Updates to Blood Sugar 101

Why Thousands of Unregulated Supplements May Contain Dangerous Substances

2012-01-26T06:34:00.000-08:00

Page changed: Worthless or Dangerous Supplements

Added this text (note reference to a NEJM article documenting these problems):
To cite only one example, in 2011, a large "well respected" Utah supplement company marketed a product, Zotrex supposedly containing an natural herb, Ophioglossum polyphyllous, it claimed could enhance potency. What the pills actually contained was sulfoaildenafil, a drug analog of Viagra that has never been tested in humans. Quite a few drug analogs of safe drugs, are toxic for humans, for example, phenformin, which is a close relative to the very safe, well-tested drug metformin.

In another case, a supposedly "herbal" diabetes supplement, when taken to the lab turned out to contain a cheap first generation sulfonyurea drug--one that can cause dangerous hypos and, which is also now known to act on the heart in a way that promotes heart attack.

The 1994 law stipulated that supplement makers were supposed to submit safty data to the FDA for any new ingredient they introduced that wasn't on sale prior to 1994. But the New England Journal of Medicine reported in January of 2012 (HERE) that since 1994,

..the number of available dietary supplements has skyrocketed from an estimated 4000 to more than 55,000...but the FDA has received adequate notification for only 170 new supplement ingredients since 1994 — undoubtedly a small fraction of the ingredients for which safety data should have been submitted.

Any time there is any attempt to reintroduce even the feeblest oversight into the marketing of bottles that can contain literally anything, the supplement companies send paid minions out who post all over the web about how big gumint's trying to take away your freedom. People deluge their congresspeople with complaints, and the supplement companies go back to earning billions selling you whatever they feel like putting into their magic pills this month.

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Also removed paragraph about vitamins being manufactured in China.

Statins May Actually Cause Diabetes

2012-01-25T07:09:00.000-08:00

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Statins May Cause Diabetes

The highly respected Womens Health Initiative study found that women without diabetes who were taking statins at the start of the study had almost twice the risk of developing diabetes. To quote from the study:

Statin use at baseline was associated with an increased risk of DM (hazard ratio [HR], 1.71; 95% CI, 1.61-1.83). This association remained after adjusting for other potential confounders (multivariate-adjusted HR, 1.48; 95% CI, 1.38-1.59) and was observed for all types of statin medications.

It is possible that the high cholesterol that motivated doctors to put these women on statins occurred because they had abnormally high blood sugars already that were missed because they manifested as high readings after high carb meals, rather than abnormally high fasting glucose. However, given the other studies that show a mechanism by which statins decrease insulin sensitivity, it is very possible that taking statins does independently worsen blood sugar control to the point it could push people into diabetes who would otherwise only be insulin resistant or pre-diabetic.

Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative. Annie L. Culver et al. Arch Intern Med. 2012;172(2):144-152. doi:10.1001/archinternmed.2011.625

This echoes the findings of a study published earlier in 2011 in the Journal of the American Medical Association which found that people taking high dose statins were 12% more likely to get diabetes than people who took lower doses. However, in this study there was no control group of people taking no statins, which might have shown that even the people taking low doses had a higher risk of getting diabetes.

Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy: A Meta-analysis David Preiss et al. JAMA. 2011;305(24):2556-2564. doi: 10.1001/jama.2011.860

Ironically, the response of mainstream docor/thought leaders as reported in the media is that since statins help prevent the main diabetic complication--heart attack, this is nothing to worry about. Not so surprisingly, the doctors quoted are always those who get large speaking fees from, or are associated with organizations that get large research grants from, the drug companies that make statins. Apparently it doesn't matter that people with diabetes get nerve damage, diabetic blindness and kidney failure none of which are improved by taking statins.

Supplementing with Megadoses of Vitamin B6, B12 and Folic Acid Correlates with Double Stroke Risk and GFR Worsening

2012-01-13T06:47:00.000-08:00

Page changed: Diabetic Kidney Disease

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Do NOT Supplement with Higher than Normal Doses of Vitamins B6, B12 and Folic Acid

A study of people with both Type 1 and Type 2 diabetes who had been diagnosed with diabetic kidney disease found that supplementing daily with a "Single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B6 (25 mg/d), and vitamin B12 (1 mg/d)" for three years was associated with faster deterioration in GFR and a doubling of stroke risk.

Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy:A Randomized Controlled Trial. Andrew A. House et al. JAMA 2010;303(16):1603-1609. doi: 10.1001/jama.2010.490

It's important to note that the amounts used in this study were megadoses many times greater than the RDA (Recommended Daily Allowance) for each.

If you are eating a diet that does not include grains or other foods that supply natural forms of these vitamins you won't be getting them in your diet and will need to supplement, but when you do, confine your supplementation to the RDA. You can find the RDA for the B vitamins HERE.

Tight Control Decreases Kidney Deterioration by 50% in People with Type 1 Involved in DCCT

2011-11-13T05:38:00.000-08:00

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Another study, that followed people with Type 1 diabetes for more than a decade found that those who had achieved "Tight control" in the DCCT (defined as A1cs near 7%) had half the risk of developing the condition leading to kidney failure than those who did not. The full text article explains that it took ten years for the impact of that early tight control to become evident.

Lower A1cs, in the 5% range--which are easier for people with Type 2 to achieve than for those with Type 1--would likely reduce this risk a lot further.

Intensive Diabetes Therapy and Glomerular Filtration Rate in Type 1 Diabetes: The DCCT/EDIC Research Group New England Journal of Medicine, November 12, 2011 (10.1056/NEJMoa1111732)

Free Antibody Testing Available for People with Family Members Diagnosed with Type 1

2011-10-28T07:32:00.000-07:00

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Free Antibody Testing Available from TrailNet

An organization called Type 1 Diabetes TrialNet is sponsoring several studies which offer those with relatives diagnosed with Type 1 the opportunity to get free antibody testing. Those who have already tested positive for the antibodies can be enrolled in studies involving experimental treatments intended to delay the destruction of beta cells.

To be eligible for the screening test you must meet one of the following criteria:

1 to 45 years of age and have a brother, sister, child, or parent with type 1 diabetes
1 to 20 years of age and have a cousin, aunt, uncle, niece, nephew, half sibling, or grandparent with type 1 diabetes

More information about the TrialNet screening and studies can be found at:
Type 1 Diabetes TrialNet: Information for Study Participants

Added Discussion of The Toxic Effect of ACCORD Study Misinterpretations to the Blood Sugar Targets Page

2011-10-16T07:40:00.000-07:00

Page Changed: Healthy Blood Sugar Targets

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But My Doctor Says Lowering Blood Sugars is Dangerous

If you are told that lowering your blood sugars is dangerous or can cause a heart attack, the chances are that your doctor read about a study called ACCORD in a newsletter. This was a study that followed a large group of people who attempted to reach an A1c of 6.5. It was reported as concluding that those who achieved the lower A1c had a slightly higher risk of heart attack.

Subsequent analysis of the ACCORD data found two things:

Those who had heart attacks were those in the group attempting to lower A1c who did not achieve the lower blood sugars, and

The excess heart attacks occurred in those who took Avandia, a drug now known to raise heart attack risk.

Unfortunately, though the original finding received a great deal of press, the subsequent analyses explaining the result did not.

The only other study that found a problem with lowering A1c was in a group of elderly veterans who were also using the sulfonylurea drugs glipizide and glimepiride, two drugs that, like Avandia and Actos, have also been found to damage the heart over time.

There is not a single piece of research, anywhere, that suggests it's harmful to lower blood sugar by cutting down on carbohydrates. In addition, there's a lot of research suggesting that lowering blood sugars without the use of the drugs known to be harmful to the heart prevents or reverses neuropathy, retinal damage, and heart disease.

For further insight into ACCORD and links to the actual research visit:

Diabetes Update: ACCORD Redux, It's the High Blood Sugars Stupid

Diabetes Update: Avandia is sufficient to explain the excess deaths in ACCORD

You can learn more about this issue by typing "ACCORD" into the Google Search box at the upper left corner of this page.

New Study Confirms that Post-Meal Sugars and A1c Predict Heart Disease & Mortality

2011-10-05T06:11:00.000-07:00

Page changed: A1c and High Post-Meal Blood Sugars Predict Heart Attack

Moved discussion about cholesterol as a predictor of heart attack to the bottom of the page and edited it.

Added the following:

Post-Meal Blood Sugar and A1c Predict Cardiovascular Events and Deaths

A study conducted in Italy which analyzed 14 years of blood sugar data taken from people recently diagnosed with Type 2 diabetes concluded "A1C and blood glucose 2 h after lunch but not FBG [fasting blood glucose] predict cardiovascular events and all-cause mortality." The reason only sugars after lunch were cited here is that the study did not analyze post-dinner readings, only pre-dinner readings. The methodology of this study was crude--basically they compared people who met the anemic ADA blood sugar targets with those who didn't, classifying those with post-meal readings under 180 mg/dl (10 mmol/L) as "good" and comparing them with those that were over and hence "bad." Even with this crude filter, the post-meal reading was predictive.

Postprandial Blood Glucose Predicts Cardiovascular Events and All-Cause Mortality in Type 2 Diabetes in a 14-Year Follow-Up Lessons from the San Luigi Gonzaga Diabetes StudyFranco Cavalot et al. Diabetes Care October 2011 vol. 34 no. 10 2237-2243.doi: 10.2337/dc10-2414

New Page Added: Charcot's Foot

2011-09-02T07:32:00.001-07:00

Page added: Charcot's Foot

Charcot's Foot: A Foot Complication Caused by Clogged Blood Vessels

Most of us know that people with diabetes are prone to getting clogged arteries. But this is often portrayed as being caused by a build up of cholesterol in the large arteries of the heart, which doctors treat by prescribing statins. (Whether this works is discussed in great detail HERE.)

But what most people with diabetes don't understand is that damage to your blood circulation which causes the worst diabetic complications comes not from having high cholesterol, but from the toll high blood sugars take on the tiny capillaries that carry blood, oxygen, and immune system cells throughout all our tissues, including our nerves, bones, tendons, kidneys, and retinas.

Prolonged exposure to high blood sugars cause sugars to bond to the walls of tiny blood vessels which stiffen and narrow to where blood and immune system cells can't pass through them. Over time capillaries become incapable of carrying nutrients to your cells. Nerves die when capillaries don't bring them enough oxygen and nutrients. Tendons become brittle, kidneys stop filtering our urine, retinas grow a tangled network of fragile new blood vessels to replace the ones that don't work which rupture, causing blindness, and feet become gangrenous.

But one of the more serious diabetic complications that afflicts those who have experienced years of exposure to very high blood sugars--and one that few people know about, including many doctors--is Charcot's Foot.

In this condition, the long bones of the foot which have been deprived of nutrients because of damage to the circulatory system (and possibly to the nerves) break, causing the foot to collapse. This condition is crippling and can lead to gangrene because damage to the circulatory system also keeps the immune system from sending infection-fighting cells to the foot.

This complication usually occurs only after you have experienced decades of exposure to very high blood sugars. So if you are newly diagnosed it isn't something to worry about every time you feel a twinge in your foot. But it is a very good reason to ensure that you don't expose your circulatory system to decades of exposure to blood sugars that can cause this kind of damage.

Keeping your blood sugars under 140 mg/dl at all times will prevent this and other complications from developing. You can learn more about how you can do this, and join many thousands of people with diabetes who have already done this, by following the technique you'll see described HERE.

But you have already had diabetes for a decade or more and have been a victim of mediocre care that let you maintain fasting blood sugars well over 140 mg/dl and A1cs above 7% or worse, damage to your bones may be underway. If so, take foot pain seriously and get help. Many family doctors are not familiar with this complication and may ignore it until you have no option left but amputation.

Help is available, even if Charcot's Foot is developing. Dr. Richard K. Bernstein reports in his book, Dr. Bernstein's Diabetes Solution:
that he reversed early changes associated with this complication by lowering his blood sugar to normal levels.

Even if your foot has progressed to where you have been told you need an amputation because of the damage to your bones, there are clinics that specialize in preventing amputation, and they are having success in treating Charcot's Foot with new treatments that can preserve your foot.

You can read about Charcot's Foot and the treatments that can heal it in this excellent article:

Science Daily: Crippling Condition Associated With Diabetes Is Often Misdiagnosed and Misunderstood.

The article in Diabetes Care cited in the Science Daily article, which discusses this condition in more technical terms, can be found at the link below.The full text should be available for free after April 1, 2012.

The Charcot Foot in Diabetes. Lee C. Rogers, et al., Diabetes Care September 2011 34:2123-2129

NSAIDS Linked to Increased Incidence of Atrial Fibrillation Especially in People with Kidney Disease

2011-07-11T05:34:00.000-07:00

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NSAIDS (Advil, Ibuprofen, Celebrex, etc.) Linked to Higher Risk of Atrial Fibrillation

Evidence from a study of 32,602 patients from the Danish National Registry found that a history of taking first generation Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) such as Advil or ibuprofen was associated with a 40% higher risk of developing an abnormal heart rhythm.The newer COX-2 inhibitors like Celebrex were associated with a 70% higher risk.The risk was greatest for older people and people with kidney disease. This makes it likely that these drugs are more dangerous for people with Diabetes, many of whom have signs of kidney damage.

Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter: population based case-control study. M. Schmidt, et al. BMJ, 2011; 343 (jul04 1): d3450 DOI: 10.1136/bmj.d3450

Discussed in detail here:

Science Daily: Common Pain Killers Linked to Irregular Heart Rhythm

Kombiglyze and Tradjenta--Ineffective, Expensive, DPP-4 Inhibitors with Scary Side Effects

2011-06-24T11:49:00.000-07:00

Page Changed: Onglyza, Kombiglyze, Tradjenta -- Just like Januvia but Worse

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Onglyza is now being being marketed as Kombiglyze, a pill that combines Onglyza and Metformin. Easily swayed doctors are therefore prescribing to newly diagnosed patients only the very expensive combo pill instead of the extremely cheap generic Metformin pill. Don't let your doctor prescribe this combo drug.

And added this:

As of Summer 2011 there is yet another FDA-approved DPP-4 inhibitor drug available that is very similar to Onglyza. It is named Tradjenta. Based on its prescribing information, which you can read HERE, it it shares with Onglyza the characteristics that it makes very little change in blood sugar, costs a fortune, and causes the same significant immune-system related side effects--most notably the permanent sinus headache/runny nose that is a result of DPP-4 inhibition in the sinues--as well as raising the risk of pancreatitis.

In patients whose A1cs averaged 8.1% and whose fasting blood sugar averaged 178.4 mg/dl Trajenta lowered A1c to a still dangerous average 7.5% and lowered the fasting blood sugar to a rampantly damaging average of 165.1 mg/dl.

You can lower your blood sugar far more just by following the advice you'll find HERE.I have heard from hundreds of people who have done just that without any drugs except generic metformin--or no drugs at all.

Chances are there will soon be a metformin-Trajenta combo drug. Avoid it. If you feel that despite the risks you want to take a DPP-4 inhibitor Januvia appears to be the one that lowers blood sugar the best, though it doesn't do all that good a job of it and will end up giving you significant side effects.

Actos Associated with Higher Bladder Cancer Risk & FDA Administers Avandia Wrist Slap

2011-06-16T06:34:00.000-07:00

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In June of 2011 the FDA confirmed that there was a heightened risk of bladder cancer with Actos.

FDA Drug Safety Communication: Update to ongoing safety review of Actos (pioglitazone) and increased risk of bladder cancer

FDA Imposes Tight Restrictions on Avandia Prescribing
In May of 2011 the FDA tightened the restrictions on prescribing Avandia but they did not take it off the market, and doctors can and do still prescribe it. The new restrictions state that patients who are now taking the drug will have to sign an informed consent statement acknowledging that they understand all the risks before they will be allowed to refill their prescriptions and that new patients will not be able to receive the drug unless their doctors certify that they are unable to control their blood sugar levels with other therapies and that medical problems preclude them from taking Avandia's primary competitor, Actos.

As you can see, this means nothing. Doctors who prescribe Avandia will keep on prescribing it. The FDA is not likely to take either of these dangerous drugs off the market until weeks before their patents expire. They are just too profitable.

Avandia (rosiglitazone): REMS - Risk of Cardiovascular Events includes Avandia, Avandamet, and Avandaryl

Glycated LDL May Explain LInk of A1c to Heart Disease Risk

2011-05-28T08:20:00.000-07:00

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Glycated LDL May Be The Culprit

An intriguing study published in May, 2011 may explain both why measuring cholesterol gives such confusing correlations with heart disease and why the A1c predicts it so much better.

The study is Glycation of LDL by Methylglyoxal Increases Arterial Atherogenicity: A Possible Contributor to Increased Risk of Cardiovascular Disease in Diabetes. Naila Rabbani et al. Diabetes. Published online before print May 26, 2011, doi: 10.2337/db11-0085

You can read a good explanation of what this study means here:

Science Daily: Super-Sticky 'Ultra-Bad' Cholesterol Revealed in People at High Risk of Heart Disease

In brief the finding is this: LDL becomes dangerous when it becomes glycated--i.e. when sugar molecules become bonded to it. When that happens it is more likely to stick to the artery walls. It is very likely given the correlation between heart attack and A1c that LDL becomes dangerously glycated at a rate that corresponds to the rate at which hemoglobin becomes glycosylated--which is what the A1c measures. (Glycosylation is permanent glycation.)

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Also deleted suggestion to get a CRP test as recent research suggests it is not a good predictor of the value of statins in people who don't already have significant heart disease.

Huge Long-Term Study: Glibenclimide, Glipizide, Glimipiride, and Tolbutamide Associated with Increased Risk of Death and Heart Attack.

2011-04-12T05:19:00.000-07:00

Page Changed Amaryl, Glyburide, Prandin, Starlix: Drugs that Stimulate Insulin Secretion

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Then in 2011, a study analyzed the health records of "All Danish residents >20 years, initiating single-agent I[nsulin] S[ecretogogues, ie. Sulfs and glinides] or metformin between 1997 and 2006 were followed for up to 9 years (median 3.3 years)." It found the following drugs were as safe as Metformin: Prandin (repaglinide), and Diamicron (gliclazide, not sold in the U.S.).

All the other sulfonylurea drugs raised the risk of death, whether or not people had had a heart attack before taking them. The study concludes:

Monotherapy with the most used I[nsulin]S[ecretagogues]s, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular risk compared with metformin. Gliclazide and repaglinide appear to be associated with a lower risk than other I[nsulin]S[ecretagogues]s.

Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study. Tina Ken Schramm et al. Eur Heart J (2011) doi: 10.1093/eurheartj/ehr077

Statin effectiveness doess not correlate with CRP in people at very high risk of heart attack

2011-04-08T05:29:00.000-07:00

Page changed: A1c and Post-Meal Blood Sugars Predict Heart Attack

Added the following reference to this new study to the discussion of the relationship of CRP and statin effectiveness.

A larger analysis published in 2011 in the Lancet seems to contradict this finding because it found statins prevented a significant number of cardiovascular events regardless of CRP level.

C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20 536 patients in the Heart Protection Study. Heart Protection Study Collaborative Group. The Lancet Volume 377, Issue 9764, Pages 469 - 476, 5 February 2011 doi:10.1016/S0140-6736(10)62174-5

However, that is not quite what the study really showed, because all the participants in that study were at high risk of heart attack. The earlier study, in contrast, was a study of people who did not have a higher than normal risk of heart attack.

No one argues that statins don't help people who are at very high risk of heart attack--but it is a mistake to include people with diabetes who have been in excellent control for years and maintain A1cs below 6% in that group. The Lancet study treated people with a diabetes diagnosis as "high risk" but in the UK people with diabetes are considered to be in "excellent control" if they have A1cs approaching 8% and those wishing to achieve tighter control receive little support, no medication, and often no test strips.

Metformin reduces the invasiveness of endometrial cancer cells by 25%

2011-04-06T06:08:00.000-07:00

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A study conducted in women with PCOS published in 2011 found that six months of treatment with metformin decreased the invasiveness of endometrial cancer cells by 25% compared to the activity of the same cells in women with PCOS who had not taken metformin. The design of this study makes it more likely that it is the drug itself, not correlated factors, that explain the anti-cancer effect of metformin.

Metformin Treatment Exerts Antiinvasive and Antimetastatic Effects in Human Endometrial Carcinoma Cells. Journal of Clinical Endocrinology & Metabolism , 2010; 96 (3): 808 DOI: 10.1210/jc.2010-1803

10 Year Study Reveals BG Levels that Lead to Retinopathy

2011-03-17T10:41:00.000-07:00

Page changed: Research Connecting Blood Sugar Levels with Organ Damage

Added this new study:

The French DESIR study of people diagnosed with pre-diabetes confirmed what the studies cited above have found. Subjects who developed retinopathy over a 9 year period had an average fasting blood sugar of 130 mg/dl and an average A1c of 6.4%. Those who did not develop retinopathy over this period had an average fasting blood sugar of 108 mg/dl and an average A1c of 5.7%.

Hemoglobin A1c and Fasting Plasma Glucose Levels as Predictors of Retinopathy at 10 Years: The French DESIR Study. Massin P. et al. Arch Ophthalmol.2011 Feb;129(2):188-195.

Diabetic Retinopathy Occurs at Prediabetic Blood Sugar Levels

2010-12-11T05:38:00.000-08:00

Pages Changed: Research Connecting Blood Sugar Level with Organ Damage

Rewrote retinopathy section as follows:

Diabetic Retinopathy Develops at "Prediabetic" Blood Sugar Levels

The first conclusive evidence for this finding was reported based on Diabetes Prevention Project data at the ADA 65th Annual Scientific Sessions. It found that:

Over three years of subsequent follow-up of 302 DPP participants, 13% of prediabetics who developed type 2 disease were found to have diabetic retinopathy, and nearly 8% of "prediabetics" also were found to have diabetic retinopathy, though they never developed diabetes per diagnostic criteria.

The diagnostic criteria used by the DPP to define "prediabetic" was a fasting plasma glucose test result that ranged between 100 and 125 mg/dl (5.5-6.9 mmol/l and/or a glucose tolerance test result showing impaired glucose tolerance: glucose tolerance test values at two hours that fell between 150 and 199 mg/dl (8.3-11 mmol/l).

This finding would suggest that prolonged exposure to post-challenge blood sugars over 150 mg/dl are highly dangerous to your retina, with or without a diabetes diagnosis, but even more so with a type 2 diabetes diagnosis.

ADA Scientific Sessions: Retinopathy Found in Pre-Diabetes. Elizabeth Thompson Beckley. DOC News August 1, 2005. Volume 2 Number 8 p. 1

Even more worrisome is the meta analysis published by Tien Y. Wong, that found that "More than 60% of retinopathy cases were among patients with fasting plasma glucose levels below 7.0 mmol/L (126 mg/dL). This review of many published studies found that the three studies [with over 11,000 participants] together, 7.4% to 13.4% of participants had retinopathy at glucose levels below 5.6 mmol/L (100 mg/dL).

Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies Wong TY, et al Lancet 2008; 371: 736-743.

That means something like one in ten people who were most likely to have only abnormalities of post-meal blood sugars, since the most common pattern of developing diabetes is for fasting blood sugars to remain near normal for years while post-meal blood sugars rise into the prediabetic and even diabetic range.

You can read more about patterns in which diabetes develops on this page on this web site: The Patterns in which Diabetes Develops

Further confirmation that diabetic retinopathy occurs at blood sugar levels well below those defined as "diabetic" by the Amerian Diabetes Association was provided by an analysis of 2005-2006 NHANES data which was published in October 2009.

This study looked at 1,066 individuals with or without diabetes aged 40 years or more. "A1C, FPG, and 45° color digital retinal images were assessed."

This study found a prevalence of retinopathy of 11% in the whole group and 36% in those with diabetes diagnoses.

Most significantly, this study found that:

The steepest increase in retinopathy prevalence occurs among individuals with A1C equal to or greater than 5.5% and FPG equal to or greater than 5.8 mmol/l [104 mg/dl]. A1C discriminates prevalence of retinopathy better than FPG.

Association of A1C and Fasting Plasma Glucose Levels With Diabetic Retinopathy Prevalence in the U.S. Population: Implications for diabetes diagnostic thresholds Yiling J. Cheng et al. Diabetes Care November 2009 vol. 32 no. 11 2027-2032. doi: 10.2337/dc09-0440

An even larger metastudy, published in late 2010 based on he records of "44,623 participants aged 20 to 79 years with gradable retinal photographs" examined the correlations between signs of retinopathy and the subjects' fasting, 2 hour glucose tolerance test, and A1c results.

Glycemic Thresholds for Diabetes-Specific Retinopathy: Implications for Diagnostic Criteria for Diabetes:The DETECT-2 Collaboration Writing group. Stephen Colagiuri et al. Diabetes Care Published online before print October 26, 2010, doi: 10.2337/dc10-1206

The conclusion of the 2010 study was this:

A narrow threshold range for diabetes-specific retinopathy was identified for FPG and HbA1c but not for 2-h PG. The combined analyses suggest that the current diabetes diagnostic level for FPG could be lowered to 6.5 mmol/L [117 mg/dl] and that an HbA1c of 6.5% is a suitable alternative diagnostic criterion.

This was because

glycemic thresholds for diabetes-specific retinopathy were observed over the range 6.4-6.8 mmol/L [115 - 122 mg/dl] for F[asting]P[lasma]G[lucose] 9.8-10.6 mmol/L [176.4 - 191 mg/dl] for 2-h PG, and 6.3-6.7% for HbA1c.

More Evidence that Vitamin D Supplementation Does NOT Lower Blood Sugar, IR or Improve Endothelial Function.

2010-10-04T07:31:00.001-07:00

Page Changed: Helpful Supplements for People with Diabetes

This result [that supplementing with large infusions of Vitamin D3] was duplicated in a second placebo-controlled study of 61 participants given placebo, 100,000 IU or 200,000 IU of Vitamin D3.
Though the Vitamin D made a very small difference in their blood pressure (which was still too high after supplementation) the study found

here was no significant difference in the primary outcome of endothelial function at 8 weeks (placebo 5.2%, n=22; 100,000 IU 4.3%, n=19; 200,000 IU 4.9%, n=17) or at 16 weeks. Insulin resistance and glycosylated haemoglobin did not improve with either dose of vitamin D3.

The effect of different doses of vitamin D3 on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial.M. D. Witham et al. Diabetologia Volume 53, Number 10, 2112-2119, DOI: 10.1007/s00125-010-1838-1

FDA Investigating Evidence of Increased Risk of Bladder Cancer with Actos

2010-09-17T12:06:00.001-07:00

Page changed: Actos and Avandia: Dangerous Diabetes Drugs

FDA Investigating Actos Link to Bladder Cancer:

On Sept 17, 2010, the FDA announced that it was conducting a safety review of Actos, because prelimnary (5 year) results from a 10 year study found

...there was an increased risk of bladder cancer in patients with the longest exposure to Actos and in those with the highest cumulative dose of the drug.

This should be a huge concern to anyone taking either Actos or Avandia because the mechanism of the drugs is so similar.

FDA Press Release: FDA reviewing preliminary saftey information on Actos

Added New Evidence That Vitamin D Supplementation is Overhypped and Possibly Dangerous

2010-09-02T10:09:00.001-07:00

Page Changed: Helpful Supplements for People with Diabetes

Here is the revised text of the section on Vitamin D:

Vitamin D is Low in People Diagnosed with Diabetes But Supplementation Doesn't Help

Evidence is accumulating that suggests that Vitamin D is low in people who develop Type 2 diabetes. Because of this there has been speculation that Vitamin D improves insulin sensitivity. Unfortunately, there is not a scintilla of evidence that supplementing with Vitamin D in any form will reverse diabetes.

I am temporarily leaving Vitamin D in the "helpful" category, because it is possible it has some value in countering heart disease, but the evidence is accumulating that it may be just another overhyped simplistic cure promoted by unscrupulous celebrity doctors looking to earn fortunes selling products to people suffering serious chronic illnesses.

The early enthusiasm for Vitamin D as a treatment for diabetes occurred after a November 2007 a study headed by Dr. Paul Knekt published in Diabetes Care found that over 17 years in a population of roughly 4,000 Finnish men and women, individuals with higher blood levels of vitamin D had a 40 percent lower risk of developing type 2 diabetes than those with lower levels of this vitamin.

Serum 25-Hydroxyvitamin D Concentration and Subsequent Risk of Type 2 Diabetes. Catharina Mattila, Paul Knekt, et al. Diabetes Care 30:2569-2570, 2007

A review of earlier work pointing to the same conclusion can be found in:

The Role of Vitamin D and Calcium in Type 2 Diabetes. A Systematic Review and Meta-Analysis. Anastassios G. Pittas, Joseph Lau, Frank B. Hu and Bess Dawson-Hughes.J Clin Endo & Metab Vol. 92, No. 6 2017-2029.

Vitamin D Has No Effect On Early Type 1 Diabetes

Low levels of Vitamin D have also been linked with increased incidence of autoimmune disease, including both Type 1 diabetes and multiple schlerosis. One meta-study concluded that supplementation with Vitamin D had a preventative effect on the development of Type 1 (autoimmune) diabetes.

Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis.C S Zipitis, A K Akobeng. Archives of Disease in Childhood 2008;93:512-517

Unfortunately, Vitamin D in this context is preventative, but does not reverse the condition.

Giving Vitamin D to people recently diagnosed with Type 1 (autoimmune) diabetes for two years made zero difference in their outcomes.

No Protective Effect of Calcitriol on ß-Cell Function in Recent-Onset Type 1 Diabetes
The IMDIAB XIII trial Diabetes Care September 2010 vol. 33 no. 9 1962-1963. doi: 10.2337/dc10-0814

Vitamin D Infusion Does NOT Improve Glucose Metabolism

Here's another result that points to the possibility that it may be that something about having diabetes lowers Vitamin D levels, rather than that Vitamin D improves insulin sensitivity.

A study in which people who were deficient in Vitamin D were given glucose tolerance tests and then given a massive dose of Vitamin D which raised their levels to normal after which they were given follow up glucose tolerance tests found no change in blood sugar or insulin sensitivity after Vitamin D was normalized.

Glucose tolerance and vitamin D: Effects of treating vitamin D deficiency Kamilia Tai. Nutrition. Volume 24, Issue 10, Pages 950-956 (October 2008).

Vitamin D May Not Be Significant in Loss of Blood Sugar Control

A study of 446 European subjects diagnosed with metabolic syndrome found no relationship between blood concentrations of vitamin D and insulin secretion or sensitivity. In this group 20% had vitamin D levels over 30 ng/ml (75 nmol/L). This may suggest that the low vitamin D levels seen in people with diabetes are a result, not a cause of their blood sugar disorder.

Serum Vitamin D Concentration Does Not Predict Insulin Action or Secretion in European Subjects With the Metabolic Syndrome. Hanne L. Gulseth et al. Diabetes Care April 2010 vol. 33 no. 4 923-925. doi: 10.2337/dc09-1692

Womens Health Study Finds No Effect on Diabetes of Vitamin D and Calcium Supplementation

The Womens Health Study--the people who put an end to the myth that the low fat diet prevents heart disease--came up with the finding that, in 33,951 women, supplementation with 400 IU Vitamin D and 1000 mg Calcium made no difference in the number of people who developed diabetes. The finding was described as "robust."

Calcium Plus Vitamin D Supplementation and the Risk of Incident Diabetes in the Women's Health Initiative. WHI investigators. Diabetes Care 31:701-707, 2008

Those who champion Vitamin D claim that much higher doses are required to see an effect. This may be true as the amount of Vitamin D used in this study was well under the amount that is necessary to raise low levels into the normal range.

High Dose Vitamin D Increased Fractures in Older Women

Adouble-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, given Intervention 500,000 IU of cholecalciferol or placebo by injection saw a 26% higher risk of fracture in the group receiving the supplementation. So much for the theory that doses were too low in other studies.
Annual High-Dose Oral Vitamin D and Falls and Fractures in Older WomenKerrie M. Sanders et al. JAMA 2010;303(18):1815-1822.

Vitamin D's Connection with Cardiovascular Disease

Recent research has linked low levels of Vitamin D with higher risk of cardiovascular disease. An analysis of the Framingham data found that "Vitamin D deficiency is associated with incident cardiovascular disease."

Vitamin D Deficiency and Risk of Cardiovascular Disease. Thomas J. Wang et al.Circulation. 2008;117:503-511 The research that has not yet been done is the well-conducted study that would investigate whether supplementing with Vitamin D would lower the incidence of heart disease. Dr. Davis of The Heart Scan Blog claims to have seen vitamin D supplementation improve cardiac health. He believes that it is a vital part, along with Vitamin K, of the metabolic process that directs dietary calcium where it belongs--on the bones, rather than being deposited in arterial plaque which is part of the process that leads to heart attack.

Vitamin D May Have an Effect on Mood

There is some evidence that Vitamin D reverses the depression many people experience in the dark months of winter.

Vitamin D3 enhances mood in healthy subjects during winter Allen T. G. Lansdowne, S. C. Provost. Psychopharmacology, DOI 10.1007/s002130050517

Because Vitamin D has a positive effect on mood--similar to that burst of good feeling we experience when we step out into the sun, it is possible that the low levels of Vitamin D found in people with Diabetes may be related to the increased incidence of depression associated with Type 2 diabetes.

Vitamin D Improves Outcome in Chronic Kidney Disease

A study published in May of 2008 found that patients with chronic kidney disease given Calcitriol (a form of Vitamin D) had a 26% lower mortality and a 20% lower rate of going onto dialysis over a period of almost two years.

Association of Oral Calcitriol with Improved Survival in Nondialyzed CKD Abigail B. Shoben et. al. Journal of the American Society of Nephrology Published online May 7, 2008. doi: 10.1681/ASN.2007111164

A Danger with Vitamin D: High Blood Calcium Which May Cause Hardened Arteries

If you supplement with the very high Vitamin D levels being promoted by celebrity doctors you run the risk of experiencing very high blood calcium levels if you take calcium supplements. Even blood calcium levels in the high normal level have been associated with increased heart disease so this is a serious concern.

Rampant Vitamin D supplementation is causing a revival in what used to be a rare condition, Milk Alkali syndrome, which can be fatal.

Got Calcium? Welcome to the Calcium-Alkali Syndrome Ami M. Patel and Stanley Goldfarb. J Am Soc Nephrol 21: 1440-1443, 2010

I personally experienced a serious problem with a high blood calcium level after supplementing with 2000 IU of Vitamin D for about 9 months in my doctor's suggestion. I was NOT taking any calcium supplements, but I was eating several servings of cheese each day as part of my lower carbohydrate diet. My Vitamin D level tested well above the low end of normal but at a level that the lab considered normal, but the lab high is the level at which Vitamin D toxicity occurs.

If you do supplement with more than 1000 IU a day of calcium you must get your blood calcium levels checked from time to time and if they are at the high end, you should back off both Vitamin D and foods high in calcium until they come down.

As is always the case, our metabolisms are too complex to be "cured" with any supplement. It is possible that supplementation with Vitamin D in those with measured low levels is helpful for heart disease, but it is foolish to supplement with massive doses of Vitamin D when you don't know your levels and are not tracking your blood calcium.

In addition, I have see a healthy person experience a hormonal reaction similar to "roid rage" when they supplemented with high doses of Vitamin D. Dr. William Davis confirmed to me, via email that Vitamin D can raise Testosterone levels.

Recommended Dose:

1000 IU per day. The oil based versions of Vitamin D are better absorbed than those found in hard calcium-based pills. There is no need to buy overpriced special versions of Vitamin D, such as Vitamin D2,as they may actually be less effective than the regular ones.

There is some controversy about what level constitutes an overdose but if you are not getting a lot of sun, adults should be fine taking 1000 IU. If you are taking Vitamin D, ask your doctor to test your Vitamin D level when you get your other blood tests just to be safe.
Doses higher than 1000 IU may cause problems if you already have normal levels of Vitamin D and may unbalance your blood calcium levels.

hs-CRP successfully identifies MODY-3 80% of the Time: Good Screening Test

2010-09-02T09:12:00.000-07:00

Page Changed: MODY It's Not Type 1 or Type 2 but Something Else

ADDED:

People with MODY-3 have been found to have very low Cardiac Specific C-Reactive Protein. (hs-CRP) with the mean of 0.20 mg/l and a range of 0.03 to 1.14 mg/l. This may actually be a cheap and effective screening test for this specific form of MODY as it appears to identify 80% of people with diabetes who actually have MODY. Hs-CRP in people with MODY 2, however, is very close to that of people with regular Type 2 diabetes.

Assessment of High-Sensitivity C-Reactive Protein Levels as Diagnostic Discriminator of Maturity-Onset Diabetes of the Young Due to HNF1A MutationsKatharine R. Owen, et al. Diabetes Care September 2010 vol. 33 no. 9 1919-1924 doi: 10.2337/dc10-0288

Yet Another Huge Study Proves Longterm Actos/Avandia Use Causes Fractures

2010-08-08T05:18:00.000-07:00

Page Changed: Actos and Avandia: Dangerous Diabetes Drugs

Added this text to the long list of studies showing Actos and Avandia damage bone in ways that long term lead to a significantly higher number of fractures:

Analysis of results in 19,070 patients in the huge TRIAD study confirm this finding.

Thiazolidinedione Use and the Longitudinal Risk of Fractures in Patients with Type 2 Diabetes Mellitus Zeina A. Habib et al. J. Clin Endo & Metab.Vol. 95, No. 2 592-600. doi:10.1210/jc.2009-1385

The real scandal here is the way that American Diabetes Association, as usual devoted to the interests of its sponsors, the drug companies, not those of the people in whose name it collects money continues to urge patients to ignore this data and continue on taking these damaging drugs. David Kendall, the ADA's Chief Medical and Scientific officer was quoted saying the following:

This is certainly not the first of these larger studies where I would say this unanticipated event was noted... Depending on the study, it appears that people who take TZDs for longer periods of time have about a one-and-a-half to twofold increase in their risk of fractures..

These are very effective medicines for some patients. We have to understand there are potential risks. Certainly anyone already considered to be at fracture risk -- a woman with osteoporosis -- or someone who suffers from instability or frequent falls, you should think carefully about the use of the medications. On the other hand, fractures in total [in Herman's study] were generally rare. Far more people didn't have fractures than did have.

By the same logic, we should be giving Thalidomide to pregnant women, because more of them did not have babies with flipper limbs than did. Or we should encourage smoking because not all smokers get lung cancer.

Given the weight of evidence against Actos and Avandia, and the poor evidence that they do much for patients beyond making them permanently fatter, the ADA's continued advice to patients "Those with diabetes on TZD drugs should not stop these medicines without talking to their doctor," is indefensible.

Remember, this is the same organization that continues to warn people that the long term effects of the low carb diet are "unknown" and hence it should be avoided, though every bit of evidence from all studies shows it to be safe and much more effective for people with Type diabetes than either Actos or Avandia.

Long Term Low Carb Diet Better for Health than Low Fat in Randomized Trial

2010-08-03T05:08:00.000-07:00

Page Changed: Studies Proving the Safety and Efficacy of the Low Carb Diet

A 2010 Study Finds Low Carb Diet Beats Low Fat at Improving Health Long Term

An NIH-funded study published in 2010 compared an Atkins type low carb diet to a low fat/low calorie diet over a 2 year period. This study was distinguished from earlier studies in that participants were given ongoing support to help them stay on track.

Both groups lost the same amount of weight over the two years on average. However, as stated in the results:

During the first 6 months, the low-carbohydrate diet group had greater reductions in diastolic blood pressure, triglyceride levels, and very-low-density lipoprotein cholesterol levels, lesser reductions in low-density lipoprotein cholesterol levels, and more adverse symptoms than did the low-fat diet group. The low-carbohydrate diet group had greater increases in high-density lipoprotein cholesterol levels at all time points, approximating a 23% increase at 2 years.

Though this study excluded people with diabetes, the finding confirms what people with diabetes have been reporting, anecdotally for years and removes any basis on which doctors and nutritionists can rest their oft repeated claim that the low carb diet is dangerous.

Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet: A Randomized Trial Gary D. Foster et al. Annals of Internal Medicinevol. 153 no. 3 147-157 Aug 3, 2010.

Added Onglyza Page

2010-07-13T06:20:00.000-07:00

Page Added: Onglyza

Added this page, adapted from this post on Diabetes Update.

Onglyza: Just Like Januvia but with More Serious Side Effects?

When the FDA approves a new drug it requires no proof that the drug is more effective than similar, existing drugs, only that it is better than placebo. Which is something to keep in mind about Bristol-Myers Squibb's new DPP-4 inhibitor, Onlgyza.

This mellifluous moniker is the brand name for Saxagliptin, which alert followers of drug news remember as the Januvia clone developed at the same times as Januvia whose release has been blocked due to its ability to cause "skin lesions" some of which necrotized (i.e. died and fell off) in monkeys.

The Prescribing Information for Onglyza does not reveal that it offers any benefit in comparison to Januvia, the other DPP-4 inhibitor currently on the market.

Both drugs inhibit the expression of the DPP-4 gene for a full 24 hours--which means that if your body was fighting a new, very small, DPP-4 sensitive tumor, like ovarian cancer, melanoma, prostate cancer or lung cancer, the drug would keep DPP-4 from killing off the tumor cells.

In addition, the Onglyza Prescribing Information reveals:

1. Feeble impact on blood sugar: Onglyza lowered A1cs that averaged 8% by .5%, which does not bring them anywhere near a safe level even by the anemic standards of the ADA. When the highest dose of Onglyza was compared to a placebo, it allowed only 14% more of those taking it to achieve 7% A1cs.

To better understand how "Effective" it is, consider what that A1c really meant: Onglyza lowered the average fasting glucose in those who took it from 171 mg/dl to 162 mg/dl (9.5 mmol/L) to 162 mg/dl (9 mmol/L). It lowered the average two hour post-meal blood sugar reading from a damaging 278 mg/dl (15.4 mmol/L) to an equally complication-guaranteeing 235 mg/dl (13 mmol/L).

So why take this drug which is likely to cost 3 or 4 dollars a day to "achieve" blood sugars that are still high enough to lead to amputation, blindness and kidney failure when for the same money or less you could use insulin to get normal blood sugars?

2. Negative impact on the immune system. Inhibiting the DPP-4 gene, which produces an enzyme that rids the body of GLP-1 by chopping it up, lowers blood sugar because GLP-1 lowers blood sugar. However DPP-4 is used by the immune system for other functions most doctors know nothing about. Januvia's initial testing showed that it caused changes in white blood cell counts which the drug company dismissed as being of unknown significance.

Onglyza has a stronger impact on your immune system's white blood cells. In the prescribing information we read:

There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA. From a baseline mean absolute lymphocyte count of approximately 2200 cells/microL, mean decreases of approximately 100 and 120 cells/microL with ONGLYZA 5 mg and 10 mg, respectively, relative to placebo were observed at 24 weeks in a pooled analysis of five placebo-controlled clinical studies. Similar effects were observed when ONGLYZA 5 mg was given in initial combination with metformin compared to metformin alone. There was no difference observed for ONGLYZA 2.5 mg relative to placebo. The proportion of patients who were reported to have a lymphocyte count =750 cells/microL was 0.5%, 1.5%, 1.4%, and 0.4% in the saxagliptin 2.5 mg, 5 mg, 10 mg, and placebo groups, respectively. In most patients, recurrence was not observed with repeated exposure to ONGLYZA although some patients had recurrent decreases upon rechallenge that led to discontinuation of ONGLYZA.

Translated into English, this means than in 1 person in 100 who take it, Onglyza lowers the white blood count to a dangerously low level.

If your doctor prescribes Onglyza without requiring that you have a blood count periodically, you can be sure the doctor has not read the prescribing information. Few doctors do.

3. Onglyza conflicts with common drugs and grapefruit juice Because of the way it is removed from the body Onglyza may build up in the blood stream when taken with common yeast medication, ketoconazole, as well as with erythromycin, calcium channel blocker verapamil, and grapefruit juice. Onglyza levels also rise in people with poorly functioning kidneys. The manufacturer says that dose must be cut back in people using these drugs. Whether busy doctors will know this and warn patients about lowering the dose when needed is another story.

4. Onglyza raises the peak Concentration of Sulfonylureas and TZDs. This makes it more likely people whose doctors prescribe this new drug with a sulfonylurea drug will experience hypos. Onglyza also reduces the peak concentration of metformin.

5. Side effects The main side effects reported with Onglyza are the headache and runny nose that are also found with Januvia and which result from the inhibition of the immune system these drugs cause. Over time, my experience with taking Januvia for several months was that the headaches increased in intensity in a way that made me glad to stop taking the drug.

However, Onglyza also causes other immune reactions: As reported, "Hypersensitivity-related events, such as urticaria [rash] and facial edema [swelling] in the 5-study pooled analysis up to Week 24 were reported in 1.5%, 1.5%, and 0.4% of patients."

Januvia also turns out to cause rashes, including, very rarely, the life threatening Stevens-Johnson syndrome where people's skin peels off the body. It is significant, though that rash did not appear as a side effect of Januvia until after the approval testing was complete. That Onglyza produced such a high rate of rash during testing seems to suggest that it has a higher potential to disrupt the immune system.

6. No evidence that this or any other DPP-4 inhibitor preserves beta cells I mention this because the drug reps are selling these drugs to doctors claiming, based on weak animal evidence that these drugs preserve beta cells. No drug can preserve or regenerate beta cells when blood sugars are rising over 140 mg/dl for long periods of time, because sustained high blood sugars cause glucotoxicity--poisoning of beta cells. With the many years that BMS has been testing Onglyza you can be sure they have run every test they could find to demonstrate beta cell preservation and the complete lack of any cite to this in the prescribing information suggests they could not find it.

Why Take Onglyza?

Nothing in the prescribing information suggests any advantage in taking Onglyza compared to Januvia, while at the same time suggesting strongly that Onzglya's impact on the immune system is stronger than Januvia's. No research was done into whether Onglyza increases the incidence of tumors in those who take it, and because of the very small numbers involved in the clinical trials and the way the drug companies bury tumor incidence (combining benign and cancerous tumors in one category, as in the Januvia trials), that data is not likely to emerge.

Nevertheless, I'm sure a BMS drug rep is hard at work motivating doctors to switch patients to their new drug. Don't be surprised if your doctor suggests you enroll in a "study" using Onglyza, as this is a common way to divert patients from an existing drug. The "study" will provide you with one or two month's free supply of the drug because the companies know that once you are used to taking it you are likely to continue taking it. You'll be seeing free samples and eventually saturation advertising on diabetes web sites and TV.

The really sad part is that the net effect of all this will be only that patients with A1cs of 8% whose fasting blood sugar is well over 150 mg/dl and whose post meal blood sugars are in the range the ADA long ago defined as causing blindness (over 200 mg/dl two hours after eating) will take another expensive drug that ensures they won't get the kind of control that prevents the classic complications.

If you have blood sugars that high before you pay a couple hundred bucks a month for a potentially harmful new drug try the following:

1. Try the technique described here: How to Get Your Blood Sugar Under Control. It really works. Even for people who have had diabetes for as long as a decade.

2. Add extended release metformin if you can tolerate it and have no kidney or liver problems. Metformin is much more effective and less prone to cause digestive distress when used along with a diet lower in carbohydrate.

3. If cutting back on the carbs in your meals and adding metformin doesn't lower your blood sugar to safe levels (Under 140 mg/dl after eating) demand that your doctor send you to an endocrinologist so that you can get a tailored insulin regimen that gives you normal blood sugars.

Do not settle for the kind of insulin regimen family doctors usually prescribe which almost always leave you with blood sugars that are damagingly high. These inadequate insulin regimens are designed to keep your blood sugar high so as to avoid hypos--and to avoid the need to give you the kind of diabetes education routinely offered people with Type 1. With proper diabetes education you can avoid hypos and get great control. But for most Type 2s, to get the right kind of insulin regimen prescribed you will have to find a young, knowledgeable endocrinologist who will take the time to work with you on tuning your insulin regimen.

If your doctor won't help you get normal blood sugars, and insists that all you need are oral drugs fire him or her and find one who will give you the help you need.

Every person with diabetes can achieve normal blood sugars and normal blood sugars produce normal health.

Metformin Page Rewritten

2010-07-04T06:49:00.000-07:00

Page Changed: Metformin

I have rewritten this page to emphasize the research findings of the past few years. Metformin's mode of action is emphasized as is the weight of data pointing to metformin's strong cardioprotective and anti-cancer properties. I have eliminated the long discussion of the DPP trial because the preponderance of evidence suggests now that starting metformin very early has long term benefits that extend beyond the actual lowering of blood sugar. In fact, the evidence suggests very strongly to me that lowering blood sugar by no means the most useful function that metformin performs. Its real value is in activating AMP-kinase and in stopping the liver from synthesizing the liver fat which increases insulin resistance.

Here is the updated text of the page:

Though many people find that they can bring their blood sugar back into the normal range simply by limiting their carbohydrate intake, blood sugar control is not a short term project. When you have abnormal blood sugars you will have to spend the rest of your life keeping them under control, and not everyone is willing or even able to stick with a restrictive diet for the rest of their lives.

For this reason, most doctors assume that dietary changes will not solve their patient's blood sugar problems. So immediately after diagnosing diabetes they prescribe what are known as oral anti-diabetic drugs. Chief among these is metformin.

You may well be asking, if these drugs are effective, why bother with complex and restrictive dietary regimens?

Effective, But Not Effective Enough

Unfortunately, the catch lies in how you define "effective." Just as research has shown that the current criteria for diagnosing diabetes ignore the blood sugar levels at which damage occurs, other research shows that none of these drugs brings blood sugar levels down to anywhere near normal levels. So while an oral anti-diabetic drug might be "effective" by the FDA definition of the term, that effect might only be to lower a diabetic person's fasting blood sugar from a dangerously high 250 mg/dl (13.8 mmol/L) to an only slightly less dangerous 180 mg/dl (10 mmol/L) --a level which is still high enough to encourage the development of serious complications. Even when prescribed for people whose blood sugar is only impaired, as we will see, these drugs may only lower the OGTT 2-hour reading by 20 or 30 mg/dl (1.1 or 1.7 mmol/L)--which still leaves their blood sugars higher than a damaging 140 mg/dl (7.8 mmol/L) most of the day.

So metformin alone will not be likely to bring your blood sugars back into the normal range.

An Add-On not a Substitute for Dietary Control

But--and here's the silver lining--if you are unable to get your blood sugars back into the normal range with diet alone, but are willing to modify your diet, the addition of metformin may be what it takes to push your blood sugar levels that last bit of the way needed to normalize them.

Facts about Metformin

Metformin is the generic name of the drug also marketed as Glucophage. It has been used to control diabetic blood sugars since the 1970s in Europe. It was also the subject of a detailed study intended to see whether it could prevent impaired glucose tolerance from progressing to actual diabetes.

Diabetes Prevention Program Research Group; Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin.NEJM , Volume 346:393-403 February 7, 2002 Number 6

Metformin is available in an extended release form, Metformin ER (Glucophage XR) which is supposed to be a bit easier on the digestive system.

Metformin is a cheap generic drug. Because of it's long track record for safety, it is supposed to be the first drug doctors prescribe, Unfortunately, because of the marketing efforts of the drug companies, this doesn't always happen. All too often, doctors prescribe metformin in the form of combination pills like Janumet that cost 15 times what metformin alone costs and include relatively untested drugs that have serious side effects. You will do much better and be much safer taking the plain generic metformin rather than one of these combos. In addition, the combo pills because they include drugs whose dosage is fixed make it impossible to adjust the metformin dose to the one that is right for you. Metformin is a drug where the effective dose may vary greatly with your body size.

In the course of 2010 a series of studies emerged that document quite convincingly that Metformin alone among the diabetes drugs has "side effects" that include a dramatically lower risk of death from heart disease and a strong anti-cancer effect. In addition, Metformin helps with weight loss and appears to stop the progress of fatty liver. This makes it the one oral antidiabetes drug I recommend to people with both full fledged diabetes and prediabetes.

What Metformin Does

Metformin Inhibits the Liver's Production of Glucose

There is some scholarly debate about what exactly it is that Metformin does, but most researchers agree that in most people Metformin suppresses the production of glucose in the liver.

If you'll remember, it is the liver's tendency to dump additional glucose into the blood stream when first phase insulin response is weak or missing that can cause blood sugar to shoot up after a meal. The liver may also dump glucose in the blood stream early in the morning when fasting insulin levels are low. (To read more on this topic, visit How Blood Sugar Deteriorates)

Metformin may lower fasting blood sugar by limiting the liver's production of glucose rather than by making cells more sensitive to insulin.

A mouse study published on May 15, 2009 suggests that Metformin works to lower blood sugar by directly stimulating a gene in the liver which is how it shuts off glucose production. Rather than by improving insulin sensitivity, it bypasses the broken insulin signaling.

Metformin and Insulin Suppress Hepatic Gluconeogenesis through Phosphorylation of CREB Binding Protein Ling He et al,, Cell Volume 137, Issue 4, 635-646, 15 May 2009. doi:10.1016/j.cell.2009.03.016

This study is explained in layman's language here:

New Information on how Metformin works. Diabetes in Control May 27, 2009.

Metformin Appears to Stimulate Glucose Uptake in Muscles via AMPK Activation

Though Metformin appears to increase the amount of glucose absorbed into cells this effect is observable mostly when blood sugar is high.

Mechanism of Metformin action in obese and lean noninsulin-dependent diabetic subjects. DeFronzo RA, Barzilai N, Simonson DC. J Clin Endocrinol Metab. 1991 Dec;73(6):1294-301

Research suggests that Metformin may stimulate glucose uptake by muscles and inhibit glucose production by the liver by activating an enzyme, AMP-activated protein kinase which is present in muscle, liver, and heart cells. This enzyme is usually activated when exercise has burnt off cellular energy stores. So in a way, Metformin seems to trick the body into thinking it has exercised. This may be why it can slightly elevate levels of lactate--the substance that makes your muscles ache the day after an exercise session.

Metformin Increases AMP-Activated Protein Kinase Activity in Skeletal Muscle of Subjects With Type 2 Diabetes. Nicolas Musi, Michael F. Hirshman, Jonas Nygren, Monika Svanfeldt, Peter Bavenholm, Olav Rooyackers, Gaochao Zhou, Joanne M. Williamson, Olle Ljunqvist, Suad Efendic, David E. Moller, Anders Thorell, and Laurie J. Goodyear; Diabetes 51: 2074-2081

Metformin's Activation of AMPK Blocks The Liver's Ability to Synthesize Triglycerides and Promotes Fat Burning.

For an exhaustive look at how metformin's impact on AMP-kinase works in rat tissues (and probably human tissues), read this full text study:

Role of AMP-activated protein kinase in mechanism of metformin actionZhou et al. J. Clin. Invest. 108(8): 1167-1174 (2001). doi:10.1172/JCI13505.

This study found that

metformin activates AMPK in hepatocytes [liver cells]; as a result, acetyl-CoA carboxylase (ACC) activity is reduced [ACC promotes the creation of triglycerides], fatty acid oxidation is induced [i.e. fat is burned], and expression of lipogenic enzymes is suppressed [lipogenic enzymes are needed to create triglycerides].

It also found that glucose uptake in muscles by metformin required the activation of AMPK. When it was blocked the uptake did not happen.

AMPK activation is also known to increase the breakdown of glycogen, which may be why some low carbers have observed that their glycogen stores appear already depleted when they embark on a low carb diet, so they don't lose the glycogen-associated water weight at the start of the diet that dieters lose who are not taking metformin. It may also be why when theu carb up they don't gain a lot of instant water weight either.

It is this impact of metformin on the liver, which is independent of its impact on glucose absorption that probably explains why metformin often causes modest weight loss, especially when it is first taken. It also explains why it makes weight loss maintenance much easier even in insulin sensitive dieters such as myself. Blocking the synthesis of fats and promoting the burning of fat at the liver (and possibly muscles) makes it much harder to gain weight.

Stimulation of AMPK May Be Why Metformin Appears Cardioprotective

AMPK has also been shown to have a protective effect on the heart. This review describes how AMPK may protect the body during heart attacks.

AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra Lawrence H. Young. Circulation. 2008;117:832-840
doi: 10.1161/CIRCULATIONAHA.107.713115

Metformin May Boost GLP-1 Level

GLP-1 is an incretin hormone secreted in the gut which appears to stimulate insulin release when blood sugars rise and limit glucagon production at the same time. While Byetta and Januvia are promoted as being incretin drugs, some little known research suggests that metformin may also raise the level of GLP-1 in the body. The good news is that unlike Januvia it does this without inhibiting DPP-4, a tumor suppressive drug.

Enhanced secretion of glucagon-like peptide 1 by biguanide compounds. Yasuda N et al. Biochem Biophys Res Commun. 2002 Nov 15;298(5):779-84.

UKPDS 20 Year Follow-up Study Shows Excellent Metformin Effect

The follow-up to the huge UKPDS study presented at the EASD conference in Sept 2008 followed for 20 year what happened to people who had been prescribed either a sulfonylurea drug or metformin at diagnosis. This study was one where people attempted to achieve the barely adequate blood sugar goal of a 7% A1c. Over the second ten years of the study, it was reported that few people in the study taking any drug were able to attain an A1c as low as even 7%--primarily because they were also urged to eat a very high carb/low fat diet.

Nevertheless, after twenty years, as reported by Medpage Today right after the conference found that at 20 years after the start of the study,

Patients treated with metformin had a >21% reduction in risk of any diabetes endpoint (P=0.01), a 30% reduction in risk of diabetes-related death (P=0.01), a 33% reduction in risk of MI (P=0.005), and a 27% reduction in risk of all cause mortality (P=0.002).

Of course, in this population, because of the very high blood sugars people maintained, the total rate of complications, heart attack and death was very high, so even the 33% reduction of risk left a risk far higher than you or I would wish to expose ourselves to.

Metformin May Fight Cancer

Intriguing data emerged in 2009 suggesting that metformin has cancer fighting abilities that go beyond its ability to lower insulin resistance.

Now new data from a British epidemiological study suggests that metformin may exert an anti-cancer effect. The study is:

New Users of Metformin Are at Low Risk of Incident Cancer: A cohort study among people with type 2 diabetes. Gillian Libby et al. Diabetes Care September 2009 vol. 32 no. 9 1620-1625.doi: 10.2337/dc08-2175

The study made use of medical records collected in Tayside, Scotland UK. The researchers compared 4085 people with type 2 diabetes who were new users of metformin in 1994–2003 to a group of people with diabetes diagnosed the same year who were not given metformin.

The result was that

Cancer was diagnosed among 7.3% of 4,085 metformin users compared with 11.6% of 4,085 comparators, with median times to cancer of 3.5 and 2.6 years, respectively (P < 0.001). The unadjusted hazard ratio (95% CI) for cancer was 0.46 (0.40–0.53).

This association held up even when adjusted for "sex, age, BMI, A1C, deprivation, smoking, and other drug use."

This result is intriguing, though it makes me want to ask, "What kept the doctors from prescribing metformin to the second group, the one that had so much more cancer?" Until we know the answer to that question, it is impossible to screen out the possibility that the same factor that kept doctors from prescribing the usual first line treatment for Type 2 diabetes might have also promoted cancer.

However, a mouse study supports the idea that it is metformin, not an outside factor at play here. Researchers found that metformin appears to stop breast cancer stem cells from growing in mice. You can read about this study in this article.

Science Daily: Diabetes Drug Kills Cancer Stem Cells in Combination Treatment in Mice.

More evidence that metformin is protective against cancer emerged in a second study of 1,353 people with diabetes that lasted almost ten years. It was conducted in the Netherlands as part of the ZODIAC study and published in Februrary 2010. This study found that the cancer risk of people with diabetes taking metformin was identical to that of the population at large which was not the case with those who were not taking metformin. This is significant because people with diabetes have long been known to have a higher risk of cancer.

Metformin Associated With Lower Cancer Mortality in Type 2 Diabetes: ZODIAC-16 Gijs W.D. Landman et al.Diabetes Care Diabetes Care February 2010 vol. 33 no. 2 322-326. doi: 10.2337/dc09-1380

Metformin May Be Protective Against Heart Disease

This idea has been floating around for years, though there wasn't definitive proof of it. A relatively small study published in March 2009 supports the idea.

Long-term Effects of Metformin on Metabolism and Microvascular and Macrovascular Disease in Patients With Type 2 Diabetes Mellitus. Kooy et all. Archives of Internal Medicine, 169 (6), 616-625 DOI: 19307526

A presentation at the 2009 European Association for the Study of Diabetes (EASD) described research which may point to why metformin is so effective.

You can read about it here:

Diabetes in Control: Metformin Improves Endothelial Function in Type 2 Diabetes

This study examined a series of factors associated with endothelial function--i.e. the function of the linings of the blood vessels. It demonstrated significant improvements in the 196 patients who took metformin over a period of up to 4.3 years.

Compared to those on placebo plus insulin those on metformin experienced highly significant drops in plasma levels of von Willebrand factor (vWf), soluble vascular adhesion molecule-1 (sVCAM-1), tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP), and soluble intercellular adhesion molecule-1 (sICAM-1).

The drop in C-Reactive Protein--a measure strongly linked to the risk of inflammation-related heart attack was 17%.

Since all the other oral drugs prescribed for diabetes have either been linked to increased heart attacks (sulfonylureas) or produce heart failure (Avandia and Actos) this data should reinforce the idea that metformin is the safest of the oral diabetic drugs and the one most likely to improve health outcomes long term.

Metformin Lowers Risk of All Kinds of Fatal Outcomes

A study presented at the 2010 ADA Scientific Sessions analyzed records of "19,699 patients over age 45 who had diabetes as well as documented cardiovascular disease or other atherothrombotic risk factors." It found:

patients on metformin had a significant 33% reduction in the risk of death compared with those not on the drug (95% CI 0.59 to 0.75, P less than 0.001). After adjustment with the propensity score, there was still a significant 24% reduction in death (95% CI 0.65 to 0.89, P less than 0.001).

The "propensity score" was a way of adjusting for other drugs given to control heart disease.

Diabetes in Control: ADA: Mortality Lower with Metformin

Metformin Started Early Far More Effective than Metformin Started Later

A study published of 1,799 Kaiser patients who were able to lower their A1c below 7.5% using Metformin found that when patients were started on Metformin immediately after diagnosis, they were able to stay at an A1c lower than 7% for longer than did patients whose doctors waited a year before starting them on the drug.

Secondary Failure of Metformin Monotherapy in Clinical Practice
Jonathan B. Brown. Diabetes Care Diabetes Care March 2010 vol. 33 no. 3 501-506 doi: 10.2337/dc09-1749

A more detailed discussion of this study can be found here:

Diabetes in Control: Early Treatment Doubles Chance of Success for People with Diabetes

This is important. Many people with diabetes resist taking a drug thinking that it is better to attempt to lower blood sugar with diet or exercise alone. Because the action Metformin is different from the effect of cutting carbs or exercising, this may be a mistake. It may be better to start metformin along with other approaches as soon as you receive a diagnosis of abnormal blood sugar (including a diagnosis of pre-diabetes) rather than waiting.

There's No Research Data about the Effect of Combining Metformin with Carb Restriction

Unfortunately, all studies of Metformin published to date have been performed with people who were encouraged to eat a high carbohydrate diet. So there is no definitive information about what happens when Metformin is combined with a low carbohydrate diet.

Anecdotal Evidence

Postings on newsgroups suggest that people who have a lot of weight to lose who stall out above their desired weight while on a long-term low carb diet often start losing again when they add Metformin to their diet regimen, if they continue to keep their carbohydrate intake low.

Women with PCOS have also found that the addition of Metformin to their regimen may improve both weight loss and fertility.

Metformin may prevent weigth gain independent of insulin resistance by blocking the liver's synthesis of triglycerides. It also appears to prevent the liver from storing glucose in the form of glycogen which leads to less ability to dump glucose inappropriately.

I have observed that when I am taking metformin while eating a very low carb diet and I raise my carbohydrate intake above the level that usually refills glycogen resulting in an instant water weight gain I do not see the water weight fluctuation I see when I am not taking it. I speculate that this indicates that metformin somehow interferes with the normal liver glycogen function.

In addition, studies of people with Type 1 diabetes find that metformin will lower the amount of insulin they need to use.

The Benefits of Metformin Therapy During Continuous Subcutaneous Insulin Infusion Treatment of Type 1 Diabetic Patients Laurent Meyer et. al. Diabetes Care 25:2153-2158, 2002.

The addition of metformin in type 1 diabetes improves insulin sensitivity, diabetic control, body composition and patient well-being. Moon, RJ. Diabetes Obes Metab. 2007 Jan;9(1):143-5.

What You Need To Know About Taking Metformin

Metformin takes about 3 days to kick in and 3 weeks to achieve its maximum effect. Because it can cause intense gastric problems, it's advisable to start out with a low dose and work up. Most people don't see an effect on blood sugars until they are taking between 1,000 and 1,500 mg a day. Larger people may need to take the full dose (2250 to 2500 mg depending on whether it is metformin ER or Metformin)

Timing when you take your metformin will often subtly change the impact it has on your blood sugar because even the ER form does not result in a completely smooth activity curve. Taking metformin ER it at night will often result in a stronger effect on fasting blood sugar but less action at dinner. Taking Metformin in the morning may give best coverage on lunch, decent coverage for dinner but result in the highest fasting blood sugars and the most stomach discomfort. You can experiement with the time you take metformin as long as you NEVER take more than the prescribed dose during a 24 hour period.

Side Effects

Gastric Distress

The most common side effects of Metformin are nausea, diarrhea, heartburn and gas. That's why it's been nicknamed "metfartin" by people who post on Web bulletin boards. These unpleasant digestive system symptoms often go away after a few weeks, but not always. Some people are unable to take Metformin because of the persistence of these symptoms.

The extended release form of metformin (metformin ER) often relieves gastric symptoms. Many of us find that taking metformin ER in the early afternoon after we have eaten several meals may eliminate heartburn or the stomach irritation that occurs when it is taken on a relatively empty stomach.

If your problem is gas or diarrhea, try eating less starch. These symptoms are caused by undigested starches reaching the gut where they are fermented by helpful bacteria.

Can Metformin Cause Low Blood Sugar?

Metformin is not supposed to cause dangerous hypos. A very few people have found that it causes their blood sugar to drop low enough to make them uncomfortable. This may be because of the phenomenon called False Hypo. You can read about false hypos HERE.

Lactic Acidosis?

Metformin is chemically similar to an earlier drug, Phenformin which was taken off the market bwascause it caused a fatal side effect, lactic acidosis. There is some debate about whether or not Metformin also causes this symptom.

An epidemiological study in Canada found 10 cases of hospitalization for lactic acidosis in a population of 11,797 patients who had been prescribed Metformin.

Incidence of lactic acidosis in Metformin users. Stang M, Wysowski DK, Butler-Jones D. Diabetes Care , Jun 1999, 22(6) p925-7

One review of data from published studies suggests that this frequency is a normal incidence in all populations--including those not taking the drug and probably not related to taking the drug.

Risk of fatal and nonfatal lactic acidosis with Metformin use in type 2 diabetes mellitus: systematic review and meta-analysis. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE.Arch Intern Med. 2003 Nov 24;163(21):2594-602.

Further confirmation that Metformin does not cause lactic acidosis at a rate higher than occurs in people NOT taking the drug was found in a study of 50,048 people with diabetes taking either metformin or a sulfonylurea drug. This study found that lactic acidosis was extremely rare, occurring at the rate of "3.3 cases per 100,000 person-years among metformin users and 4.8 cases per 100,000 person-years among users of sulfonylureas." In all cases the lactic acidosis appeared to be caused by "concurrent comorbidity" which means another medical problem--usually kidney disease.

Metformin, Sulfonylureas, or Other Antidiabetes Drugs and the Risk of Lactic Acidosis or Hypoglycemia: A nested case-control analysis. Michael Bodmer et. at. Diabetes Care 31:2086-2091, 2008.

The symptoms of lactic acidosis include malaise, muscle aches, and gastric distress that comes on after a person has gotten over the initial problems associated with taking Metformin. It is possible that the incidence of lactic acidosis is higher than the statistics suggest because doctors are aware of it and take patients off the drug if they begin to exhibit symptoms.

Because they are more likely to developed lactic acidosis, people with kidney damage, liver damage, or congestive heart failure should not take Metformin. Lactic Acidosis can also occur with dehydration in people who have otherwise normal kidney and liver function. If you develop a truly dehydrating condition like severe diarrhea, stop your metformin until you recover.

Stop Metformin Before X-rays with Contrast Medium

The combination of metformin plus iodine-based contrast medium can cause kidney failure in people with marginal kidnety function. The current recommendation in the prescribing information for metformin is:

Radiologic studies involving the use of iodinated contrast materials (for example, intravenous urogram, intravenous cholangiography, angiography and computed tomography (CT) scans with intravascular contrast materials) - Intravascular contrast studies with iodinated materials can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving GLUCOPHAGE [metformin]...Therefore, in patients in whom any such study is planned, GLUCOPHAGE should be discontinued at the time of or prior to the procedure, and withheld for 48 hours subsequent to the procedure and reinstated only after renal function has been re-evaluated and found to be normal.

According to the nephrologist who pointed me to these guidelines, kidney function should be evaluated using a serum creatinine test.

Avoid Alcohol While Taking Metformin

Because of a fear that drinking alcohol, which temporarily paralyzes the liver, may enhance the risk of lactic acidosis, people taking Metformin are advised not to drink more than a very small amount of alcohol.

Metformin May Deplete Vitamin B-12 and Folate

Metformin has one more significant side effect. It may deplete Vitamin B-12 because it may alter the ability of the body to absorb vitamin B-12 from the gut. If this is the case, oral supplementation will not help. You would need to have Vitamin B-12 shots to address this deficiency.

Typically it takes about 10 years for low Vitamin B-12 levels to develop, but if you are already marginal for Vitamin B-12 or have other issues with your ability to absorb nutrients this might happen earlier. Your doctor should periodically test your Vitamin B-12 levels if you are taking Metformin.

Low vitamin B-12 causes a form of neuropathy that can be confused with diabetic neuropathy but which is something different.

Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. Wulffele MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, Donker AJ, Stehouwer CD.J Intern Med. 2003 Nov;254(5):455-63.

The ADA Scientific Sessions: Hype, Hype, and More Hype

2010-06-30T04:59:00.000-07:00

This past week the movers and shakers (and funders and product sellers) got together for their annual dog and pony show, the American Diabetes Association Scientific Sessions. As is always the case, drug and device company-funded studies presented at these sessions hit the health headlines and received far more attention in the news than they deserve.

Why? Because the presentations made at the ADA Scientific Sessions are not peer reviewed. The visibility of this blog has risen to whee I have been getting PR releases intended for the health media. When I write back and ask the PR people if the studies they are touting will be published in a journal, the answer is often that no, no such publication is planned. This makes sense. Why bother, when the goal has already been achieved? The studies have been featured in the New York Times and on TV where the companies funding them can be certain no critical thought will be applied to their findings.

What most of the studies presented at the ADA Scientific Sessions that make it into the news have in common is a willingness to twist the truth to make a drug or device sound much better than it is.

For example, here's the headline about Viaject, a new formulation of R (regular human) insulin that is supposed to be absorbed faster than regular Regular. It was published in the online newsletter version of Endocrine Today. "Glycemic control similar with VIAject insulin vs. regular human insulin." The release goes on to claim that:

Patients with type 2 diabetes who took VIAject insulin, a fast-absorbed human insulin formulation, achieved similar glycemic control, but significantly better weight loss and a twofold reduction in the rate of hypoglycemia compared with patients who took regular human insulin

This sounds exciting--until you read a bit further and discover that "similar glycemic control" is an exaggerated claim and the two-fold reduction was between a very small number and an even smaller number of very mild hypos.

Here are the significant detailss:

Helena W. Rodbard, MD, and colleagues observed a –0.56% reduction in HbA1c with VIAject insulin (Biodel) vs. –0.70 with regular human insulin.

Keep in mind that the A1c change presented here is an average and that individuals vary so greatly in the extent to which their A1c maps to actual blood sugars.

Remember, too, that the A1c is the last statistic you'd want to look at when evaluating a fast acting insulin because it hides the range of variation of blood sugar. Two people can have the same A1c with blood sugars but one may have blood sugars that always stay between 95 mg/dl and 140 mg/dl white the other has blood sugars bouncing between 175 mg/dl and 60 mg/dl. The person who keeps blood sugar in the narrow range that stays under 140 mg/dl will have a very different complication risk than the person who spends hours over 140 mg/dl each day.

But that said, the A1c of the group taking Viaject was still higher than that of the people using regular insulin. And we have to assume that the average A1c was the best statistic they could come up with.

So when we read after this that "patients assigned to VIAject had an adjusted mean weight change of just 0.46 compared with 1.35 among patients assigned to regular human insulin." (no units given!) and that they had fewer mild hypos since, "The rate of non-severe hypoglycemia was significantly lower with VIAject insulin (0.33 events per month) compared with regular human insulin (0.66 events per month; P<.02)." a thinking person might ask, Is it possible they had slightly less weight gain and slightly less hypos because they were getting slightly less insulin as shown by their slightly higher blood sugars?"

Another study touting the advantages of a new inhaled insulin (view it here) sounds good until you discover they were comparing their combo of Lantus and inhaled insulin at meals against "biaspart" premix given twice a day. Biaspart is the 70/30 NPH/Novolog combo which is well known to give very poor results, since you can't titrate the Novolog in the premix to the carbohydrates in the meals the user eats. This 70/30 insulin is shot twice a day so users get a small amount of fast acting insulin that is not injected at meal times and only have the very unpredictable, hypo-causing NPH in their bodies to cover lunch. The only safe way to use 70/30 is to underdose, which explains why it produces a much higher A1c than any combo of basal and fast acting insulin used at meals. So basically this is an Apples and Oranges study. The inhaled insulin did better as a fast acting insulin than almost NO fast acting insulin would do, but that is a meaningless finding.

Comparing their inhaled insulin used with Lantus to Novolog injected at meals with Lantus would have come up with a more useful but probably damning, result. But the really important comparison to do with an inhaled insulin would have been to forget about the Lantus completely (and eliminate the possibility that the Lantus doses were not really, functionally the same) and compare the effect of the inhaled insulin used at meals against the injected fast acting insulin at meals in a crossover study where the same people used both insulins at different times.

That's not going to happen because inhaled insulin does not work predictably and if past formulations are anything to go by won't compare well head to head with fast acting insulin injected at meals.

Another study which received much play in the press was one that confirmed that Avandia appears to raise the risk of death from heart ailments compared to Actos. (See how the New York Times reported this here).

This is of course not news, but the problem with this study is that in it Avandia was compared to Actos so the reader is left with the impression that Actos is a safer drug that doesn't cause heart-related deaths.

What is left out is that Actos is known to cause heart failure in people who did not have it before they started the drug, and that neither Avandia nor Actos is as safe as taking neither drug. Comparing Avandia deaths and CV incidents, Actos deaths and CV incidents and metformin-only deaths and CV incidents would have been far more honest.

Beyond that none of the reporting mentioned the real problem with Actos: it shares with Avandia a mechanism (lowering blood sugar by stimulating the creation of new fat cells out of precursor cells that otherwise would have turned into new bone) that, over time, causes serious, probably irreversible, bone tissue loss that results in fractures as people get older. Actos, in short, is not a safe drug. But you wouldn't know that from the way this latest study was presented.

That's it for now. The main point to keep in mind is that presentations given at the ADA Scientific Sessions are not given even the anemic peer review that you see in the published studies. Many are never heard of again after the conference is over.

As far as I can tell, the main use of this huge conference is to give drug and device makers a way to fast track the poor-quality studies they've run to tout the effectiveness of their new moneymakers. And of course, to wine and dine the influential doctors and "thought leaders" the drug and device companies keep well supplied with research grants, "consulting fees" and other sweeteners to ensure doctors keep prescribing their drugs.

Vitamin B Supplementation Hastens Kidney Damage Raises Incidence of Stroke

2010-04-27T13:37:00.001-07:00

Page Changed: Worthless or Dangerous Supplements

Added the following:

B Vitamin Supplementation Increases Stroke and Kidney Damage

A study published in JAMA in April 2010 asked whether giving supplemental B vitamins to people with diabetes would improve their kidneys because they were known to have low levels of homocysteine. What the study found was very disturbing: people with diabetes who were given a single daily tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B6 (25 mg/d), and vitamin B12 (1 mg/d) ended up with significantly worse kidney function as measured by GFR and also in a higher incidence of stroke. This suggests B Vitamin supplementation is harmful to people with kidney problems.

Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy. A Randomized Controlled Trial. Andrew A. House et al. JAMA Vol. 303 No. 16, April 28, 2010.

Potentially Dangerous Drugs for People with Type 2 Diabetes and Kidney Disease

2010-04-18T15:26:00.000-07:00

Page changed: Diabetic Kidney Damage

Added this text:

Other Potentially Dangerous Pharmaceutical Drugs. The following prescription medications are capable of causing problems in people who already have significant kidney damage:

a. ACE inhibitors and ARBs. These drugs protect the kidneys in most people, but if you have a condition called "renal artery stenosis" they may be harmful.There is a test, the Captopril Scan, that can be done to ensure you respond appropriately to these kinds of drugs if there is any question that you might have renal arterial stenosis.

b. Radioacontrast agents used during angiography. According to this review published in Endocrine Today up to 35% of people with diabetes may experience acute renal failure when given these during angiograms. Proper hydration appears to be the appropriate defense. Discuss this issue with your doctor before you find yourself in a hospital having tests done by doctors who don't have your chart. If you are at risk, make sure that information is available at any hospital you might be taken to.

c. Antibiotics. These can occasionally cause kidney failure, too. Again, this is mainly a problem if you have serious kidney damage. If you do ask the doctor who treats your diabetes before you take ANY medication prescribed by another doctor who may not know the details of your case

Endocrine Today: Medications that worsen renal function in diabetes

Blood Levels of Vitamin D Do Not Predict Insulin Secretion or Sensitivity in People with Metabolic Syndrome

2010-04-02T08:31:00.001-07:00

Page Changed: Helpful Supplements for Diabetes

A study of 446 European subjects diagnosed with metabolic syndrome found no relationship between blood concentrations of vitamin D and insulin secretion or sensitivity. In this group 20% had vitamin D levels over 30 ng/ml (75 nmol/L). This may suggest that the low vitamin D levels seen in people with diabetes are a result, not a cause of their blood sugar disorder.

Serum Vitamin D Concentration Does Not Predict Insulin Action or Secretion in European Subjects With the Metabolic Syndrome. Hanne L. Gulseth et al. Diabetes Care April 2010 vol. 33 no. 4 923-925. doi: 10.2337/dc09-1692

Metformin Started At Diagnosis Far More Effective Than Metformin Prescribed Later

2010-03-26T10:30:00.000-07:00

Page Changed: Metformin

A study published of 1,799 Kaiser patients who were able to lower their A1c below 7.5% using Metformin found that when patients were started on Metformin immediately after diagnosis, they were able to stay at an A1c lower than 7% for longer than did patients whose doctors waited a year before starting them on the drug.

Secondary Failure of Metformin Monotherapy in Clinical Practice
Jonathan B. Brown. Diabetes Care Diabetes Care March 2010 vol. 33 no. 3 501-506 doi: 10.2337/dc09-1749

A more detailed discussion of this study can be found here:

Diabetes in Control: Early Treatment Doubles Chance of Success for People with Diabetes

This is important. Many people with diabetes resist taking a drug thinking that it is better to attempt to lower blood sugar with diet or exercise alone. Because the action Metformin is different from the effect of cutting carbs or exercising, this may be a mistake. It may be better to start metformin along with other approaches as soon as you receive a diagnosis of abnormal blood sugar (including a diagnosis of pre-diabetes) rather than waiting.

Another Large Study Links TZDs and Broken Bones

2010-02-18T12:40:00.000-08:00

Page changed: Actos and Avandia: Dangerous Diabetes Drugs

Added this new study.

Thiazolidinedione Use and the Longitudinal Risk of Fractures in Patients with Type 2 Diabetes Mellitus Zeina A. Habib et al. JClinEndo&Metab Vol. 95, No. 2 592-600 doi:10.1210/jc.2009-1385

In this study, as summarized in the newsletter, Endocrine Today, which gives more information than the abstract, researchers,

... studied 19,070 patients at Henry Ford Hospital in Detroit between January 2000 and May 2007. The study group included 9,620 women and 9,450 men. During the study period, 4,511 patients had at least one prescription filled for a TZD. The investigators used electronically maintained medical claims data to identify nontraumatic bone fractures.

TZD use was associated with an increased risk for fracture in the overall cohort (adjusted HR=1.35; 95% CI, 1.05-1.71) and in women (HR=1.57; 95% CI, 1.16-2.14). Men, regardless of age, were not at an increased risk for fractures (HR=1.05; 95% CI, 0.70-1.58). Women aged 65 years and older appeared to be at the greatest risk for fracture (HR=1.72; 95% CI, 1.17-2.52). They found that the increased risk for fracture in women appeared after approximately one year of TZD use.

More Proof Metformin Is Protective Against Cancer

2010-02-07T11:05:00.000-08:00

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Added this text with link to full text of a new study that found evidence that metformin protects people with diabetes against cancer.

===

More evidence that metformin is protective against cancer emerged in a second study of 1,353 people with diabetes that lasted almost ten years. It was conducted in the Netherlands as part of the ZODIAC study and published in Februrary 2010. This study found that the cancer risk of people with diabetes taking metformin was identical to that of the population at large which was not the case with those who were not taking metformin. This is significant because people with diabetes have long been known to have a higher risk of cancer.

Metformin Associated With Lower Cancer Mortality in Type 2 Diabetes: ZODIAC-16 Gijs W.D. Landman et al.Diabetes Care Diabetes Care February 2010 vol. 33 no. 2 322-326. doi: 10.2337/dc09-1380

Afro-American Genes Linked to Poor Carbohydrate Metabolism

2009-12-28T08:42:00.000-08:00

Page Changed: You Did Not Eat Your Way to Diabetes

Added the following:

Genes Linked to African Heritage Linked to Poor Carbohydrate Metabolism

It has long been known that African-Americans have a much higher rate of diabetes and metabolic syndrome than the American population as a whole. This has been blamed on lifestyle, but a 2009 genetic study finds strong evidence that the problem is genetic.

The study reports,

Using genetic samples obtained from a cohort of subjects undergoing cardiac-related evaluation, a strict algorithm that filtered for genomic features at multiple levels identified 151 differentially-expressed genes between Americans of African ancestry and those of European ancestry. Many of the genes identified were associated with glucose and simple sugar metabolism, suggestive of a model whereby selective adaptation to the nutritional environment differs between populations of humans separated geographically over time.

In the full text discussion the authors state,

These results suggest that differences in glucose metabolism between Americans of African and European may reside at the transcriptional level. The down-regulation of these genes in the AA cohorts argues against these changes being a compensatory response to hyperglycemia and suggests instead a genetic adaptation to changes in the availability of dietary sugars that may no longer be appropriate to a Western Diet.

In conclusion the authors note that the vegetarian diet of the Seventh Day Adventists, often touted as proof of the usefulness of the "Diet Pyramid" doesn't provide the touted health benefits to people of African American Heritage. Obviously, when hundreds of carbohydrate metabolizing genes aren't working properly the diet needed is a low carbohydrate diet.

The study is available in full text here:

Stable Patterns of Gene Expression Regulating Carbohydrate Metabolism Determined by Geographic AncestryJonathan C. Schisler et. al. PLoS One 4(12): e8183. doi:10.1371/journal.pone.0008183

ONE Hour GTT Result over 155 Correlates with Markers for Cardiovascular Disease

2009-12-20T07:30:00.000-08:00

Pages Changed: A1c and Post Meal Blood Sugar Predict Heart Attack and Research Connectiong Organ Damage with Blood Sugar Level

Added the following text to both pages:

One Hour OGTT Result over 155 mg/dl(8.6 mmol/L) Correlates with Markers for Cardiovascular Disease

A study published in November of 2009 linked blood sugar readings one hour after ingesting glucose with high fibrinogen and leukocytes count (WBC), which point to subclinical inflammation, and with abnormal lipid ratios, and insulin sensitivity in a population of 1062 participants with normal glucose tolerance or prediabetes. "Normal" glucose tolerance as defined by doctors and researchers means a 2 hour blood sugar reading of under 140 mg/dl on an oral glucose tolerance test.

This study found

Elevated 1hPG [one hour plasma glucose] in NGT [people with normal glucose tolerance] and pre-DM subjects is associated to subclinical inflammation, high lipid ratios and insulin resistance. Therefore, 1hPG >155 mg/dl could be considered a new 'marker' for cardiovascular risk.

This strongly supports the message I have been emphasizing on this web site since 2004 that it is essential to keep one hour blood sugar reading after meals under 140 mg/dl.

The reliance of doctors on two hour glucose tolerance test results allows people to live for years with blood sugars high enough to promote complications long before they are diagnosed even pre-diabetes.

Inflammation markers and metabolic characteristics of subjects with one-hour plasma glucose levels. Gianluca Bardini et al. Diabetes Care Published online before print November 16, 2009, doi: 10.2337/dc09-134

New Page on Non-Fat Related Weight Gain and Loss Added to Low Carb Site

2009-12-03T10:29:00.000-08:00

Page added: Don't Be Taken in By Fake Weight Loss or Fake Gain

Added a page to the Low Carb sister site of Blood Sugar 101 explaining the impact of factors including glycogen levels, dehydration, and salt on weight.

Many fad diets exploit people's misunderstanding of what causes very fast weight loss. Many people who eat low carb diets don't understand why it is so easy to "regain" a lot of weight after only eating a high carb diet for a day or two.

This page explains these phenomena.

FDA Adds Warning: Don't Take Byetta If Kidneys Seriously Impaired

2009-11-29T06:57:00.001-08:00

Page changed: Byetta.

Added the following:
In late 2009 the FDA analyzed postmarketing data for Byetta and found 78 cases of kidney failure reported between April 28, 2005 and October 29, 2008, a period in which more than 6.6 million prescriptions for Byetta had been dispensed.

Given the prevalence of kidney failure among people with established diabetes this finding may or may not be related to the drug. The FDA now states that Byetta should not be prescribed to people with "severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease." Caution should be used when prescribing it to people with "moderate renal impairment (creatinine clearance 30 to 50 ml/min)."

Because doctors are ignorant of or ignore FDA drug warnings check your creatinine clearance test results before you start Byetta. If your doctor has not given you this test once a year, find a new doctor. All people with diabetes should have their kidney function tested periodically.

Warning signals of kidney problems are: Increased serum creatinine, Changes in urination (color, frequency, amount), Unexplained swelling in the extremities, Increases in blood pressure, Lethargy, Dull ache in the mid to lower back. NOTE: Changes in appetite and digestion are also listed as symptoms of kidney dysfunction but are also normal responses to Byetta.

FDA Safety Information for Byetta

Common Herbicide and Fibrates Block Receptor That Stimulates GLP-1

2009-11-28T06:02:00.000-08:00

Page changed: You Did Not Eat Your Way to Diabetes

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In 2007 scientists at New York's Mount Sinai Hospital discovered that the intestine has receptors for sugar identical to those found on the tongue and that these receptors regulate secretion of glucagon-like peptide-1 (GLP-1). GLP-1 is the peptide that is mimicked by the diabetes drug Byetta and which is kept elevated by Januvia and Onglyza. You can read about that finding in this Science Daily report:

Science Daily: Your Gut Has Taste Receptors

In November 2009, these same scientists reported that a very common herbicide 2,4 D blocked this taste receptor, effectively turning off its ability to stimulate the production GLP-1. The fibrate drugs used to lower cholesterol were also found to block the receptor.

Science Daily: Common Herbicides and Fibrates Block Nutrient-Sensing Receptor Found in Gut and Pancreas

What was even more of concern was the discovery that the ability of these compounds to block this gut receptor "did not generalize across species to the rodent form of the receptor." The lead researcher was quoted as saying,

...most safety tests were done using animals, which have T1R3 receptors that are insensitive to these compounds,

This takes on additional meaning when you realize that most compounds released into the environment are tested only on animals, not humans. It may help explain why so many supposedly "safe" chemicals are damaging human glucose metabolisms.

Metformin's Effect Linked Strongly to Activation of AMPK

2009-11-13T08:05:00.001-08:00

Page changed: Metformin

Included findings of a fascinating study published in 2001, but previously overlooked, that provided detailed insight into Metformin's activation of AMP-kinase (AMPK) in rat tissue in ways that provide explanations for many of the anecdotally observed effects of Metformin that are not directly related to insulin resistance, most notably its ability to prevent weight regain in dieters and the way it appears to lower glycogen stores. Another study is cited that describes cardioprotective effects of the activation of AMPK that may explain metformin's observed cardioprotective effects.

Text added:

Metformin's Activation of AMPK Blocks The Liver's Ability to Synthesize Triglycerides and Promotes Fat Burning.

metformin activates AMPK in hepatocytes [liver cells]; as a result, acetyl-CoA carboxylase (ACC) activity is reduced [ACC promotes the creation of triglycerides], fatty acid oxidation is induced [i.e. fat is burned], and expression of lipogenic enzymes is suppressed [lipogenic enzymes are needed to create triglycerides].

Stimulation of AMPK May Be Why Metformin Appears Cardioprotective

More Evidence Lean Offspring of People With Type 2 Show Beta Cell Defects and IR

2009-11-12T06:18:00.000-08:00

Page Changed: You Did Not Eat Your Way to Diabetes

A new study published in Diabetologia confirms the finding of an earlier study that shows that lean, young relatives of people with Type 2 diabetes already show dramatic differences in their ability to secrete insulin and their insulin sensitivity.

This points out very clearly that people who develop diabetes didn't cause their disorder by overeating, as they already have high post-meal blood sugars when young and thin. This is attributed in the study to beta cell dysfunction.

This study compared detailed measurements of insulin secretion and resistance in 187 offspring of people diagnosed with Type 2 diabetes against 509 controls. Subjects were matched with controls for age, gender and BMI. It concluded:

The first-degree offspring of type 2 diabetic patients show insulin resistance and beta cell dysfunction in response to oral glucose challenge. Beta cell impairment exists in insulin-sensitive offspring of patients with type 2 diabetes, suggesting beta cell dysfunction to be a major defect determining diabetes development in diabetic offspring.

Beta cell (dys)function in non-diabetic offspring of diabetic patients M. Stadler et al. Diabetologia Volume 52, Number 11 / November, 2009, pp 2435-2444. doi 10.1007/s00125-009-1520-7

NHANES: Retinopathy Incidence Rises Steeply At 5.5% A1c

2009-10-30T06:21:00.000-07:00

Page Changed: Research Connecting Organ Damage with Blood Sugar Level

Added analysis of 2005-2006 NHANES data which was published in October 2009. The study looked at 1,066 individuals with or without diabetes aged 40 years or more. "A1C, FPG, and 45° color digital retinal images were assessed."

This study found a prevalence of retinopathy of 11% in those diagnosed with diabetes and 36% in those with diabetes diagnoses.

Most significantly, this study found that

The steepest increase in retinopathy prevalence occurs among individuals with A1C equal to or greater than 5.5% and FPG equal to or greater than 5.8 mmol/l [104 mg/dl]. A1C discriminates prevalence of retinopathy better than FPG.

Sulfonylurea Drugs Linked to Hemolytic Anemia Especially with Certain Genetic Condition

2009-10-14T06:21:00.000-07:00

Page Changed: Amaryl, Glyburide, Prandin, Starlix: Drugs that Stimulate Insulin Secretion

Added information on new FDA Safety Alert.

An FDA safety Alert published Auguest of 2009 reports:

Treatment of patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents can lead to hemolytic anemia. Because Glynase PresTab belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD deficiency and a non-sulfonylurea alternative should be considered. In post marketing reports, hemolytic anemia has also been reported in patients who did not have known G6PD deficiency.

Hemolytic anemia is a condition where the body stops making red blood cells. It can become an emergency. Symptoms of hemolytic anemia include Dark urine, Enlarged spleen, Fatigue, Paleness, Rapid heart rate, Shortness of breath, Yellow skin color (jaundice).

Because the G6PD deficiency is often only discovered when people react badly to a drug, it would be a good idea to get your blood count tested shortly after starting a sulfonylurea drug.

FDA Safety Alert for Glynase (micronized glyburide) tablets

Metformin Fights Heart Disease by Improving Endothelial Function

2009-10-14T06:02:00.000-07:00

Page changed: Metformin

Added section discussing the latest studies documenting Metformin's ability to prevent heart disease by improving endothelial function.

This idea has been floating around for years, though there wasn't definitive proof of it. A relatively small study published in March 2009 supports the idea.

Long-term Effects of Metformin on Metabolism and Microvascular and Macrovascular Disease in Patients With Type 2 Diabetes Mellitus. Kooy et all. Archives of Internal Medicine, 169 (6), 616-625 DOI: 19307526

A presentation at the 2009 European Association for the Study of Diabetes (EASD) described research which may point to why metformin is so effective.

You can read about it here:

Diabetes in Control: Metformin Improves Endothelial Function in Type 2 Diabetes

This study examined a series of factors associated with endothelial function--i.e. the function of the linings of the blood vessels. It demonstrated significant improvements in the 196 patients who took metformin over a period of up to 4.3 years.

Compared to those on placebo plus insulin those on metformin experienced highly significant drops in plasma levels of von Willebrand factor (vWf), soluble vascular adhesion molecule-1 (sVCAM-1), tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP), and soluble intercellular adhesion molecule-1 (sICAM-1).

The drop in C-Reactive Protein--a measure strongly linked to the risk of inflammation-related heart attack was 17%.

Since all the other oral drugs prescribed for diabetes have either been linked to increased heart attacks (sulfonylureas) or produce heart failure (Avandia and Actos) this data should reinforce the idea that metformin is the safest of the oral diabetic drugs and the one most likely to improve health outcomes long term.

FDA Adds Pancreatitis Warning to Januvia and Janumet Prescribing Information

2009-09-27T09:03:00.000-07:00

Page changed: Januvia

Added information that FDA has added a warning about the association of pancreatitis with Januvia, including the information that "Furthermore, 47 of the 88 cases (53%) resolved once sitagliptin was discontinued."

Doctors are advised to warn patients prescribed Januvia of the symptoms of pancreatitis so they can be taken off the drug.

If you are on Januvia, has your doctor warned you about the symptoms of pancreatitis? If not, ask your doctor why. The doctor probably doesn't know of this latest issue with Januvia, as they usually don't know of the others, either.

Added Fish Oil to The "Helpful Supplements" Page

2009-09-25T08:47:00.000-07:00

Page Changed: Helpful Supplements for Diabetes

Added the text from today's Diabetes Update blog post, Fish Oil Yes--But Not From Fish , to the web page about helpful supplements.

Added Onglyza to Summary Page

2009-09-16T10:03:00.000-07:00

Page Changed: Diaetes Drugs - Quick Summary

Added Onglyza to table and provided link to page discussing Onglyza.

Metformin May Have Anti-Cancer Properties

2009-09-16T09:44:00.000-07:00

Page Changed: Metformin

Added citations to two studies suggesting that metformin has anti-cancer properties, using information discussed in this Diabetes Update blog post.

Two New Studies Support Utility of Metformin

Split Metformin, Acarbose and Sulfonylurea Page to New Pages

2009-09-16T09:41:00.000-07:00

Page changed: Metformin, Acarbose and Drugs that Stimulate Insulin Secretion

Divided this page into separate pages:

Meformin

Acarbose

Sulfonylureas and glitinides

FDA Adds More Drugs to List of Those that Combine with Glyburide to Cause Hypos

2009-08-26T07:08:00.001-07:00

Page changed: Metformin, Acarbose, and Drugs that Stimulate Insulin Secretion

Added this text:

The following drugs are known to increase the effect of sulfonylurea drugs which can cause dangerous hypos:

Nonsteroidal anti-inflammatory drugs [Ibuprofen, Motril, Advil etc], clarithromycin, and other drugs that are highly protein bound, such as salicylates [aspirin], sulfonamides [Septra, Bactrim, etc], chloramphenicol, coumarins, probenecid, monoamine oxidase inhibitors, and ß-adrenergic blocking agents [Beta Blockers like Toprol and others].

In August of 2009 The FDA added a new warning about combining Glyburide with disopyramide [Norpace], fluoxetine [Prozac], and quinolones [Cipro and other "floxin" antibiotics].

Cancer Treatment and Especially Radiation Cause Diabetes Independent of BMI or Exercise

2009-08-19T06:46:00.000-07:00

Page Changed: You Did Not Eat Your Way To Diabetes

Added citation and discussion of a new large population study that found that after adjusting for BMI and exercise, there was almost double the incidence of diabetes in survivors of childhood cancer and a 7.2 times greater risk of diabetes among cancer survivors who had been treated with full body radiation.

This raises the question about whether other exposures to radiation might be a contributing cause of diabetes, especially the very high doses used in CAT scanning.

Diabetes Mellitus in Long-term Survivors of Childhood Cancer: Increased Risk Associated With Radiation Therapy: A Report for the Childhood Cancer Survivor Study.Lillian R. Meacham et al. Arch. Int. Med.Vol. 169 No. 15, Aug 10/24, 2009.

Actos Raises Fracture Risk 77% in Women 61% in Men

2009-08-19T06:31:00.001-07:00

Page Changed: Actos and Avandia Dangerous Diabetes Drugs

Added study analyzing data from 84 339 patients from British Columbia, Canada, who began treatment with a thiazolidinedione or a sulfonylurea. The study found that use of Actos conferred a 77% higher risk of periphereral fracture (i.e. broken bones in arms and legs) for women and a 61% higher risk for men.

Thiazolidinediones and fractures in men and women. Dormuth CR, et al. Arch Intern Med. 2009 Aug 10;169(15):1395-402.

Despite overwhelming evidence from many studies cited on this page, doctors still call for "more study." While they are studying, patients taking Actos and Avandia are having their osteocytes--baby bone cells--converted to fat cells, which over time makes bones porous and prone to break. Reversing this damage once it occurs may be impossible, or a very slow process.

Study Confirms Benefits of Insulin/Metformin Regimen for Newly Diagnosed Type 2s

2009-08-19T06:15:00.000-07:00

Page changed: Insulin for Type 2 Diabetes

Added link to new article which compared three years of using an Insulin with metformin regimen with a metformin, pioglitazone (Actos), and glyburide regimen. Patients had nearly identical results with less average weight gain and no more hypos in the insulin group and high patient satisfaction with insulin.

It's heartening to see that the average A1c in both groups of this study was in the very low 6% range which is a huge improvement on what we usually see in such studies.

Lantus and Cancer: Discussion Added to Site

2009-08-17T06:27:00.000-07:00

Page Changed: Insulin for Diabetes

Added discussion of the controversy surrounding whether Lantus promotes cancer including links to the original Diabetologia studies raising the question, the Diabetes Update blog post discussing this question, and a subsequent large study finding that casts further doubt on the theory.

New MODY Gene Identified

2009-08-12T05:54:00.000-07:00

Page changed: MODY It's Not Type 1 or Type 2 but Something Else

Added link to study identifying a new MODY gene, BLK, which affects the ability to secrete insulin.

For more discussion of this discovery, please read this Diabetes Update blog post: Diabetes Update: New MODY Gene Identified.

Note the second link in the blog post should go to THIS LINK.

Blogger is not letting me get into my Diabetes Update blog control panel this afternoon so I have not been able to fix it or approve comments.

Prozac and Cipro can Cause Dangerous Hypos when Combined with Sulfs like Amaryl

2009-08-05T06:27:00.000-07:00

Page changed: Metformin, Acarbose and Drugs that Stimulate Insulin Secretion

Added information about new FDA warnings (added to required Prescribing Information) about other drugs that have been found to interact with Sulfs like Amaryl and Glipizide in ways that can cause dangerous hypos. These drugs include Prozac and Cipro as well as others.

A warning is also added about interactions of Lopid and cyclosporin with Prandin.

FDA Safety Alerts (7/11/09)

Onglyza: Just Like Januvia--But Worse

2009-08-03T06:57:00.000-07:00

Page Added: Onglyza - Just Like Januvia, but Worse

Added review of FDA required Prescribing Information for newly approved DPP-4 inhibitor, Onglyza. Text of page is the same as August 3 Diabetes Update blog post on same topic.

Januvia Causes Precancerous Changes in Transgenic Rats with Human Pancreas Cells

2009-07-04T07:11:00.001-07:00

Page Changed: Januvia

A study published in July 2009 found evidence that while Januvia improved pancreatic beta cell function in the short term, it did so while producing pre-cancerous changes in the pancreatic duct cells.

You can read the abstract of this study here:

Beneficial Endocrine but Adverse Exocrine Effects of Sitagliptin in the Human Islet Amyloid Polypeptide Transgenic Rat Model of Type 2 Diabetes: Interactions With Metformin Aleksey V. Matveyenko et al. Diabetes. doi: 10.2337/db09-0058 Diabetes July 2009 vol. 58 no. 7 1604-1615

This study was conducted in human islet amyloid polypeptide transgenic (HIP) rats which have had human genes inserted into their pancreata. The HIP rats were treated with Januvia, or metformin, the combination of sitagliptin plus metformin, or no drug as controls for 12 weeks.

It found that "Metformin more than sitagliptin [Januvia] inhibited ß-cell apoptosis [cell death]. Metformin enhanced hepatic insulin sensitivity;"

But when Januvia was added to the mix, there was a small improvement in insulin sensitivity and in beta cell function. Note that "beta cell function" is only a measure of insulin secretion. It is not a sign that more beta cells are growing, only that existing beta cells are pumping out more insulin.

In fact, the finding, reported above was that beta cells survived better in the transgenic rats given metformin alone compared to those given Januvia.

But any benefit that might have come from increased insulin secretion was cancelled out by a very troubling finding. Here is the way the researchers report it:

sitagliptin enhanced extrahepatic insulin sensitivity with a synergistic effect in combination. ß-Cell function was partially preserved by sitagliptin plus metformin. However, sitagliptin treatment was associated with increased pancreatic ductal turnover, ductal metaplasia, and, in one rat, pancreatitis [emphasis mine].

the reversible conversion of normal tissue cells into another, less differentiated cell type in response to chronic stress or injury. With prolonged exposure to the inducing stimulus, cancerous transformation can occur.

New Study Sheds Light on the Function of a Common Diabetes Gene Allele

2009-07-04T06:19:00.000-07:00

Page changed: You Did Not Eat Your Way to Diabetes

Added citation to a study published in July of which 2009 sheds light on what exactly it is that an allele (gene variant) often found associated with diabetes does. The allele in question is one of TCF7L2 transcription factor gene.

The study involved 81 normal healthy young Danish men whose genes were tested. They were then given a battery of tests to examine their glucose metabolisms. The researchers found that:

Carriers of the T allele were characterised by reduced 24 h insulin concentrations ... and reduced insulin secretion relative to glucose during a mixed meal test ... but not during an IVGTT [intravenous glucose tolerance test].

This is an interesting finding, because what damages our bodies is the blood sugar we experience after eating "a mixed meal" but so much research uses the artificial glucose tolerance (GTT) test to assess blood sugar health. This result suggests that the GTT may be missing important signs of early blood sugar dysfunction and that the mixed meal test may be a better diagnostic test than the GTT. I have long believed this to be true, since so many people experience reactive lows when they take the GTT which produces a seemingly "normal reading" though they routinely experience highs after eating meals. These highs are what damage our organs.

Young men with the TCF7L2 allele also responded with weak insulin secretion in response to the incretin hormone GLP-1 and "Despite elevated hepatic [liver] glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations ... suggesting altered alpha cell function."

Here again we see evidence that long before obesity develops, people with this common diabetes gene variant show highly abnormal blood sugar behavior. Abnormal production of glucose by the liver may also contribute to obesity as metformin, a drug that that blocks the liver's production of glucose blocks weight gain and often causes weight loss.

The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. K. Pilgaard et al. Diabetologia, Issue Volume 52, Number 7 / July, 2009. DOI 10.1007/s00125-009-1307-x

New Epidemiological Evidence Suggsts SSRI Use but Not Depression Causes Obesity

2009-07-01T08:54:00.000-07:00

Page Changed: You Did Not Eat Your Way To Diabetes

Added citation to ten year Canadian epidemiological study liking the use of SSRI and Effexor but NOT Major Depressive Episode (i.e. evidence of clinical depression) to increased rates of obesity.

The study found that, "MDE [Major Depressive Episode] does not appear to increase the risk of obesity. ...Pharmacologic treatment with antidepressants may be associated with an increased risk of obesity. [emphasis mine]. The study concludesed,

Unexpectedly, significant effects were seen for serotonin-reuptake-inhibiting antidepressants [Prozac,Celexa, Lovox, Paxil, Zoloft] and venlafaxine [Effexor], but neither for tricyclic antidepressants nor antipsychotic medications.

Scott B. Patten et al. Psychother Psychosom 2009;78:182-186 (DOI: 10.1159/000209349)

This is not the first time the often prescribed antidepressants have been linked to pathological weight gain. But the media have bought into drug company spin that claimed that the underlying depression that required the drug use was what caused obesity.

This new data appears to disprove that claim.

Given the current high prescription level of SSRIs this is very likely a major cause of the so-called "obesity epidemic."

Don't expect the media to pick up on this fact, though, as they earn so much from drug company advertising. They'll continue to blame the victims for gluttony and sloth.

Drug Makers Study Shows Avandia Odds of Serious Heart Failure Worse Than Russian Roulette

2009-06-19T05:10:00.000-07:00

Page Changed: Actos and Avandia: Dangerous Diabetes Drugs

Added link to published study in the Lancet (reported previously at the ADA Scientific Sessions).

Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Philip D Home, et al. The Lancet, The Lancet, Volume 373, Issue 9681, Pages 2125 - 2135, 20 June 2009. doi:10.1016/S0140-6736(09)60953-3

This study found that the risk of "Heart failure causing admission to hospital or death" was much higher in people taking Avandia, and that the incidence of "Heart failure causing admission to hospital or death" was extremely high.

Sixty-one out of 321, or one out of every five people in this study who were taking Avandia, ended up in the hospital or dead thanks to heart failure. In the control group the incidence was 9 out of 100.

One in five is worse odds than Russian Roulette.

And this study was completely funded by the makers of Avandia.

Remember in reading this that Actos, the other TZD drug, has also been linked conclusively with causing heart failure in younger patients who had never shown signs of it before taking the drug.

Heart failure is a class effect of the TZD drugs and a very dangerous one.

I find it interesting that they lump "hospitalization and death" together rather than breaking out how many people died as a direct result of heart failure attributable to Avandia. You'd want to see how many deaths due to heart failure occurred in the control group and compare that number to the deaths from heart failure in the Avandia group.

But since the study was published by the drug maker, that is one data analysis you are not likely to see.

Confirmation of Causative Link of Avandia and Actos to Fractures and Heart Failure

2009-06-11T07:41:00.001-07:00

Page Changed: Avandia and Actos: Dangerous Diabetes Drugs

Added information from three new studies, two presented at ADA and one described in Science News based on German publication which confirm these drugs double risk of heart failure and cause fractures in both men and women. The German study explains the underlying mechanism by which Avandia and Actos cause heart failure. Stimulating PPAR-gamma turns out to change the way the heart metabolises fats in a way that weakens heart muscle.

Health Clamis Database Suggests Byetta Doesn't Cause Pancreatitis

2009-06-11T07:20:00.001-07:00

Page Changed: Byetta

Added information from Medco study presented at 2009 ADA sessions showing no increase in incidence of pancreatitis in a large population of those taking it compared to a huge population of controls.

Changed Layout

2009-06-08T13:48:00.000-07:00

Pages changed: Most

I have tweaked the Blood Sugar 101 site page layout to put ads in a column down the side and below the text rather than at the top where there were a bit annoying. I've been meaning to do this for a while, but it required more code tweaking than I felt like doing until now, since this site runs on a site host that shares code with other customers.

Let me know if you run into any problems with page display that I might not have caught viewing the site on my computers.

Metastudy Documents Metabolic Advantages of Ketogenic Diets

2009-06-04T07:34:00.000-07:00

Page Changed: Studies Studies Proving The Safety and Efficacy of the Low Carb Diet

Added link to metastudy published in 2005 documenting the effect of the very low carb, ketogenic diet on various metabolic markers including leptin.

Cardiovascular and Hormonal Aspects of Very-Low-Carbohydrate Ketogenic Diets. Jeff S. Volek and Matthew J. Sharman. Obesity Research (2004) 12, 115S–123S; doi: 10.1038/oby.2004.276

Also added warning note to readers explaining that many recently published diet studies making claims of the inferiority of the "low carb diet" define the "low carb diet" as a diet containing anywhere from 120 to 180 grams of carbohydrate a day, an amount far higher than most people with diabetes can process.

Reference Removed: Metformin May Prevent Beta Cell Apoptosis

2009-05-27T13:17:00.001-07:00

Page Changed: Metformin, Acarbose, Sulfonylureas: The Truth About Oral Diabetes Drugs

Removed citation to human pancreas autopsy study with findings that metformin might help prevent beta cell apoptosis (cell suicide). Reading the full study made it clear that the researchers were not discussing the actual impact of metformin taken as a drug on humans, but instead describing a highly artificial situation created in cultured cells taken from dead pancreata and bathed in fat and a metformin solution.

This is the study:
Autophagy in human type 2 diabetes pancreatic beta cells M. Massini et al. Diabetologia Volume 52, Number 6 / June, 2009, DOI 10.1007/s00125-009-1347-2.Pages 1083-1086

New Evidence on How Metformin Works

2009-05-27T12:56:00.000-07:00

Page Changed: The Truth about Oral Diabetes Drugs

Added citation to new study which suggests that metformin stops the liver from dumping glucose by directly stimulating a gene in the liver which should be stimulated by insulin but in many Type 2s apparently isn't. This suggests that it isn't lowering insulin resistance so much as doing the job itself insulin isn't doing.

Metformin and Insulin Suppress Hepatic Gluconeogenesis through Phosphorylation of CREB Binding Protein Ling He et al,, Cell Volume 137, Issue 4, 635-646, 15 May 2009. doi:10.1016/j.cell.2009.03.016

This is explained in layman's language in this week's release of Diabetes in Control:

New Information on how Metformin works. Diabetes in Control May 27, 2009.

Google Search box added to Foot of Blood Sugar 101 Pages

2009-05-05T06:05:00.000-07:00

Pages Changed: Most

The site has grown huge over the past several years so to help you find what you are looking for, I've put a Google Search box on the bottom of every page. It's set up to default to search the site.

Pesticide Atrazine Maps to Obesity and Causes IR and Weight Gain Even Without Dietary Change

2009-05-04T06:49:00.000-07:00

Page Changed: You Did Not Eat Your Way to Diabetes

Added cite to new study which found that the herbicide Atrazine, the use of which maps closely to the prevalence of obesity in the U.S., causes insulin resistance, weight gain and mitochondrial dysfunction in rats who get a lot concentration of it in their water. The weight gain is independent of diet, though a high fat/high carb diet leads to more weight gain.

Metformin and Radiological Contrast Medium

2009-04-15T05:19:00.000-07:00

Page changed: The Truth about Oral Diabetic Drugs

Added information from updated Metformin prescribing information explaining that metformin should be discontinued at the time of or slightly before radiological procedures involving injected dye and not taken for the next 2 days. After that kidney function should be evaluated with a serum creatinine test before metformin is started again. The latter recommendation is courtesy of a radiologist who pointed me to these updated guidelines.

In rare cases in people with marginal kidney function the use of contrast dyes may cause kidney failure if a dose of metformin is taken after the dye is used. It is also possible to develop lactic acidosis when this happens. This is rare, but because many people with poorly controlled diabetes have significant kidney damage, it is important for people taking metformin to be aware of this.

These recommendations have changed from what they were a few years ago.

Stop it or you'll go blind: Actos Definitely Linked to Increased Blindness in Well Controlled Diabetics

2009-04-13T06:27:00.000-07:00

Page changed: Actos and Avandia - Dangerous Diabetes Drugs

Cited brand new study published in an Opthalmology journal--not read by family doctors, alas, that demonstrated dramatically that Actos and Avandia both raise the risk of vision loss dramatically.

Glitazone Use Associated with Diabetic Macular Edema Donald S. Fong. Am J OphthVolume 147, Issue 4, Pages 583-586.e1 (April 2009)

This study analyzed the records of 170,000 people with diabetes treated by Kaiser Permanente Southern California. The researchers found that

In 2006, there were 996 new cases of ME. Glitazone users were more likely to develop ME in 2006 (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.4 to 3.0). After excluding patients who did not have the drug benefit, did not have an eye exam, and had a HgA1c <7.0, glitazone use was still associated with an increased risk of developing ME (OR, 1.6; 95% CI, 1.4 to 1.8).

This means you are 60% more likely to develop retinal swelling leading to vision loss even with well controlled blood sugars if you take Actos or Avandia than if you don't.

It's worth noting, too, that the Science News report of this study adds, "Most of the glitazone users in the study were taking pioglitazone (Actos)."

Since the whole point of lowering blood sugar in diabetes is to avoid blindness, this study makes it crystal clear that no person with diabetes should be taking Actos or Avandia.

PRINT OUT THE ABSTRACT OF THIS STUDY AND GIVE IT TO YOUR FAMILY DOCTOR AT YOUR NEXT APPOINTMENT. YOU COULD SAVE SOMEONE'S VISION.

Benfotiamine May Not Live up to Claims: Cheaper Thiamine May Be Equivalent

2009-04-08T06:56:00.001-07:00

Page changed: Helpful Supplements for Diabetes

Added link to study calling into question whether Benfotiamine is really lipid soluble as claimed and whether it has any advantages over much cheaper, regular thiamine supplements.

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivativesMarie-Laure Volvert et al. BMC Pharmacology 2008, 8:10doi:10.1186/1471-2210-8-10

New Web Page Added: Dementia and Diabetes - A Confusing Relationship

2009-03-19T07:37:00.000-07:00

Page Added: Dementia and Diabetes - A Confusing Relationship

This page pulls together information previously scattered through several posts on the Diabetes Update blog. It discusses various research studies that have been cited in the press as linking Diabetes and Alzheimer's Disease or dementia. It also cites research pointing to other, stronger, and often avoidable risk factors for dementia that should be of interest to people with diabetes.

Study: Diabetes that Starts with IGT Different From That Which Starts with IFG

2009-03-03T10:54:00.000-08:00

Page Changed: The Patterns in Which Diabetes Develops

Added this information: The Inter99 Study was a five year study. 3,145 subjects who started out with normal glucose tolerance but developed some form of abnormal blood sugar who were given glucose tolerance tests and Insulin sensitivity index (ISI), homeostasis model assessment of insulin sensitivity (HOMA-IS), early-phase insulin release (EPIR), and insulin secretion relative to insulin action (disposition index) were estimated. The researchers conclude,

A stationary reduced insulin secretion followed by a decline in primarily hepatic insulin sensitivity characterizes the transition from N[ormal] G[lucose] T[olerance] to i-I[impaired]F[asting]G[lucose]. In contrast, low whole-body insulin sensitivity with a secondary lack of ß-cell compensation is associated with the development of i-I[mpaired]G[lucose]T[olerance]. Thereby, i-IFG and i-IGT appear to result from different underlying mechanisms, which may have implications for the prevention and treatment of the diabetes that succeeds them.

Natural History of Insulin Sensitivity and Insulin Secretion in the Progression From Normal Glucose Tolerance to Impaired Fasting Glycemia and Impaired Glucose Tolerance: The Inter99 Study.
Kristine Færch, et al. Diabetes Care, 32:439-444, 2009.

Actual Statistics on Prevalence of Diabetes and Prediabetes in the U.S. Population

2009-01-28T08:36:00.000-08:00

Page Changed: The Patterns in Which Diabetes Develops

Added citation to a journal article published in Diabetes Care which analyzes data from the 2006 NHANES survey give an accurate idea of what the actual incidence of diabetes and prediabetes are in the American population.

Full Accounting of Diabetes and Pre-Diabetes in the U.S. Population in 1988–1994 and 2005–2006. Catherine C. Cowie et al. Diabetes Care 32:287-294, 2009.

This study reports,

In 2005–2006, the crude prevalence of total diabetes in people aged ≥20 years was 12.9%, of which ~40% was undiagnosed. In people aged ≥20 years, the crude prevalence of impaired fasting glucose was 25.7% and of impaired glucose tolerance was 13.8%, with almost 30% having either. Over 40% of individuals had diabetes or pre-diabetes. Almost one-third of the elderly had diabetes, and three-quarters had [either] diabetes or pre-diabetes.

Though the incidence of diagnosed diabetes had increased, the increase was slightly over 2% which may be due to better diagnosis, not more diabetes.

I take the high incidence of "prediabetes" compared to the modest prevalence of full fledged diabetes--much of it occurring in the elderly--as an indication that most people with "prediabetes" are not likely to become fully diabetic, though they may experience blood sugar related hunger and weight gain.

Only those with the underlying genetic flaws that prevent beta cell mass to expand or limit insulin secretion are likely to go on to become fully diabetic.

New Evidence that Post-Challege Glucose Not Fasting Plasma Glucose Accurately Predicts Future Diabetes

2009-01-28T08:11:00.000-08:00

Page Changed: What is a Normal Blood Sugar?

Research first published in 2008 that was based on studying a group of 2,442 subjects who were free of type 2 diabetes at the beginning of the study found that fasting glucose tests were a very poor predictor of who in this group would develop diabetes.

The researchers found that people whose one hour glucose tolerance test results were over 155 mg/dl and who had markers for metabolic syndrome--such as a concentration of fat around the belly and high blood pressure were those who were more accurately predicted to be likely to develop diabetes.

Fasting Versus Postload Plasma Glucose Concentration and the Risk for Future Type 2 Diabetes Muhammad A. Abdul-Ghani et al. Diabetes Care 32:281-286, 2009 DOI: 10.2337/dc08-1264

Fetal Exposure to PCBs and DDE Correlate to Obesity by Age 3

2009-01-21T08:43:00.000-08:00

Page Changed: You Did Not Eat Your Way to Diabetes

Added reference to a new study that tracked the exposure of a group of pregnant Belgian woman to several common pollutants: hexachlorobenzene, dichlorodiphenyldichloroethylene (DDE) , dioxin-like compounds, and polychlorinated biphenyls (PCBs). It found a correlation between exposure to PCBs and DDE and obesity by age 3, especially in children of mothers who smoked.

Intrauterine Exposure to Environmental Pollutants and Body Mass Index during the First 3 Years of Life Stijn L. Verhulst et al., Environmental Health Perspectives. Volume 117, Number 1, January 2009

Added My New Nutritional Calculator to the Blood Sugar 101 Low Carb Diet Site

2009-01-17T08:04:00.001-08:00

Page Changed: Use Our Nutritional Calculator to Break Through Stalls

This calculator computes calorie levels and nutrient breakdowns for people eating a ketogenic low carbohydrate diet. It gives suggested intake levels for maintenance and weight loss.

Tips for How to Keep On Eating Low Carb When Money Is Scarce

2009-01-13T16:08:00.000-08:00

Page changed: What Can You Eat When You Are Cutting The Carbs?

Added link to a discussion at The Low Carb Friends Discussion Forum with some helpful ideas for how to eat a low carbohydrate diet when money is tight.

Low carb foods may seem more expensive, but if they control your appetite you might end up spending less on a few pounds of meat and cheese than you will on the cheaper starches that leave you hungry and eating more food--at the same time as they ruin your blood sugar control.

New 24 Week Study Compares Atkins Diet to Low GI Die in People with Diabetes

2009-01-10T13:03:00.000-08:00

Page Changed: Studies Proving the Safety and Efficacy of the Low Carb Diet

Added discussion of this study:

The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Eric C Westman et al.Nutrition & Metabolism 2008,5:36doi:10.1186/ 1743-7075-5-36. December 2008.

where the classic Atkins diet was found to provide much better weight loss, blood sugar control, and Lipids compared to the Low GI diet after a 24 week trial.

Actos and Avandia Double Fracture Risk in Women with Type 2 Diabetes

2008-12-24T09:33:00.000-08:00

Page changed: Actos and Avandia--Dangerous Diabetes Drugs

Added reference to metastudy that concluded that TZD drugs double a woman's risk of fracture.

Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. Yoon K. Loke et al. CMAJ Early release, published at www.cmaj.ca on Dec. 10, 2008.

The article reporting on this study published on Science DaiIy quoted one of the researchers, stating,

In absolute terms, Singh said, if thiazolidinediones (TZDs) are used by elderly, postmenopausal women (around 70 years) with type 2 diabetes for one year, one additional fracture would occur among every 21 women. Among younger women (around 56 years), use of the drugs for one year or longer would result in one additional fracture for every 55 women.

With hip fractures representing a major cause of death for older women, this is not a trivial finding. Other studies have also found that Actos and Avandia weaken bone by turning the bone stem cells that should become new bone into new fat cells instead.

High Dose Thiamine--Vitamin B1--May Help with Diabetic Kidney Disease

2008-12-17T08:25:00.000-08:00

Page changed: Diabetic Kidney Damage and Helpful Supplements for People with Diabetes

Added link to new study that found that taking 100 mg of Vitamin B1 three times a day (a total dose of 300 mg) lowered the excretion of albumen in urine.

High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study. N. Rabbani et al. Diabetologia 10.1007/s00125-008-1224-4, Dec 05, 2008.

FDA Issues Suicide Warning For Two Drugs Widely Prescribed for Diabetic Neuropathic Pain

2008-12-17T05:26:00.000-08:00

Page Changed: Other Dangerous Drugs for People with Diabetes

Noted that the FDA is adding a warning to the labels of Lyrica and Topomax warning that these drugs, widely prescribed for neuropathic pain, cause suicidal thoughts and behavior.

Note that these drugs do not treat the underlying causes of neuropathy which will continue to worsen while people are taking these drugs. They only mask the brain's ability to perceive the pain. Ignoring neuropathic pain will lead to numbness and immune system failure. This leads to infections that will not heal, huge gaping holes in the tissue of the feet which become gangrenous, and amputation.

If you have neuropathy you can reverse the damage to your nerves by lowering your post-meal blood sugars below 140 mg/dl (7.7 mmol/L) and if possible even lower than that. Use the strategies described here:

How to Get Your Blood Sugar Under Control

If this dietary strategy is not effective insist that your doctor help you find safe drugs that will lower your blood sugar to that zone in conjunction with dietary changes. Doctors who tell you that 7% A1cs are sufficient to avoid neuropathy have not seen the evidence. If your doctor tells you this is true, ask how many of his patients with 7% A1cs have suffered severe foot infections.

Byetta and the HNF4-a Gene Defect Associated with Type 2 Diabetes

2008-12-12T07:51:00.000-08:00

Page changed: Byetta

Added link to new research which appears to explain the effect of the HNF-4a gene defect found in Ashkenazi Jewish and some Nordic populations. I had previously speculated this gene defect might have something to do with the anecdotally reported strong response of people from this population to Byetta.

Common Variants in Maturity-Onset Diabetes of the Young Genes and Future Risk of Type 2 Diabetes Johan Holmkvist et al. Diabetes 57:1738-1744, 2008

It turns out that this particular gene defect turns out to affect hepatic glucose production rather than insulin secretion, which surprised the researchers who ran this study as much as it did me. But it is always good to have a hypothesis checked out by good research.

This means the original speculation that Byetta is helpful to people with gene defect because it raises insulin secretion is wrong. However, there is also evidence that Byetta may be able to suppress this runaway production of glucose by the liver. That may be the explanation of why appears, again anecdotally, to be particularly effective in people who may carry this gene defect.

Here is a study discussing how GLP-1 also glucose production by the liver.

Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect. Ronald L. Prigeo et al. Am J Physiol Endocrinol Metab 285: E701-E707, 2003.

Heart Attack Risk with Different Sulfonylurea Drugs Quantified

2008-12-09T10:13:00.000-08:00

Page Changed: Diabetes Drugs: Quick Summary and The Truth About Oral Diabetes Drugs

Added reference to a new study which quantified the risk of cardiovascular disease with the different sulfonylurea drugs. The main finding was:

The hazard of developing CAD [coronary artery disease] associated with initial treatment increased by 2.4-fold ... with glibenclamide [glyburide]; 2-fold ... with glipizide; 2.9-fold ...with either, and was unchanged with metformin. The hazard decreased 0.3-fold ... with glimepiride, 0.4-fold ... with gliclazide, and 0.4-fold ... with either.

This would lead us to believe that that Amaryl (glimepiride) and Diamicron (gliclazide) (not available in the U.S.) are the only safe drugs in this family. The mechanism that explains that finding has to do with the fact that the older sulfonylurea drugs not only stimulate a receptor on the beta cell, but they stimulate one found in heart muscle. The newer sulf drugs are designed to be specific to the beta cell.

Here is the study:

Risk of coronary artery disease associated with initial sulphonylurea treatment of patients with type 2 diabetes: A matched case–control study Shaukat M. Sadikot et al. Diabetes Research and Clinical Practice.Volume 82, Issue 3, December 2008, Pages 391-395

Risk of Chronic Kidney Disease Rises with A1c over 6.0%

2008-12-09T08:35:00.000-08:00

Pages changed: Research Connecting Organ Damage to Blood Sugar Level
Diabetic Kidney Damage

Added reference to new 11-year study that found a straight line relationship between A1c and the risk of chronic kidney disease. The risk began to rise significantly as A1c rose over 6.0%.

The study is found here:

Poor Glycemic Control in Diabetes and the Risk of Incident Chronic Kidney Disease Even in the Absence of Albuminuria and Retinopathy: Atherosclerosis Risk in Communities (ARIC) Study. Lori D. Bash et al. Arch Intern Med. Vol. 168 No. 22, Dec 8/22, 2008

Gene Raises Risk of Heart Disease in People With Diabetes And Magnifies the Positive Impact of Very Tight Control

2008-12-09T07:43:00.001-08:00

Page Changed: A1c and High Post-Meal Blood Sugars Predict Heart Attack.

Added reference to study published in JAMA linking doubled risk of heart disease to possession of a single copy of a specific gene defect and quadrupled risk to having two copies.

The study finds that "good control" halves the incidence of heart disease in people with the gene. However, "good control" here, as always, is defined as the mediocre 7% A1c that is associated with a much higher risk of heart attack in ALL populations.

This suggests that lowering blood sugar to a truly safe level--the 5-6% A1c range would provide even greater benefits to people with this gene.

Interaction Between Poor Glycemic Control and 9p21 Locus on Risk of Coronary Artery Disease in Type 2 Diabetes Alessandro Doria et al. JAMA, 2008;300(20):2389-2397.

Varient of Gene Invovled in Circadian Rhythm Associated with Elevated Fasting Glucose and Type 2 Diabetes

2008-12-09T07:17:00.000-08:00

Page changed: You Did Not Eat Your Way to Diabetes.

Added reference to study which linked a gene abnormality involved with the secretion of melatonin and the regulation of the body clock with elevated fasting plasma glucose and increased prevalence of Type 2 diabetes.

Here's a link to the study: A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk

There's an excellent translation of what it means translated into layman's terms at Science Daily:

Body Clock Linked to Diabetes And High Blood Sugar In New Genome-wide Study

New Information about DPP-4 and Tumors with Response by Researcher

2008-12-08T10:39:00.000-08:00

Page Changed: Januvia.

Added new citations linking DPP-4 inhibition with the promotion of metastatic cancers for lung cancer, prostate cancer, ovarian cancer, melanoma, and neuroblastoma.

Added reply from a much-published DPP-4 tumor gene researcher confirming that the impact of Januvia on DPP-4 is of grave concern, especially since it has not been the target of any investigation.

The researcher who I queried about the importance of this research had this reply for me via email:

I agree that use of DPPIV inhibitors to treat diabetes patients needs further studies. Inhibiting DPPIV function in general(according to ours and others research) may not be a great idea. I believe that decrease or loss of DPPIV may be associated with cancer initiation or progression.

We have shown that loss of DPPIV is indeed associated with melanoma, prostate and lung cancers. Importantly our work has shown that restoring DPPIV can suppress the tumor growth. I have not conducted any detailed studies with DPPIV inhibitors including Januvia, in particular. DPPIV has multiple functions. It is not known if Januvia blocks all of its functions. This warrants more studies with this drug.

Study Calls DPP-4 Inhibition "Trigger" for Prostate Cancer

2008-12-07T11:26:00.000-08:00

Page Changed: Januvia

Januvia works by inhibiting DPP-4, an enzyme which is used all over the body for many different purposes, many of which are unrelated to blood sugar. The study cited here is one of several recent studies that find that inhibiting DPP-4 leads cells of various types to turn cancerous.

Other cells that become cancerous with to DPP-4 inhibition are melanocytes and ovarian cells.

Here is the study: Note the conclusion:

CD26/dipeptidyl peptidase IV regulates prostate cancer metastasis by degrading SDF-1/CXCL12.

Lots of Little Housekeeping Improvements on Blood Sugar 101

2008-11-27T12:31:00.000-08:00

Pages changed: All

It is now more than five years since the original version of Blood Sugar 101 was posted on the old Geocities web site.

Over all this time I've been adding new information to the site every few weeks as new research accumulates. Not surprisingly, as the site has grown to its current size of over 90,000 words, little text errors and formatting mistakes have crept in. In addition, quite a few links have gone dead.

So over this past week I've started going through the site and cleaning it up. You may notice small changes here and there, but mostly the changes are cosmetic.

If you happen to notice something that needs to be fixed while reading the site, just drop me a line using the email associated with this blog profile. Thanks!

Cheaper R and NPH Insulins as Effective for Type 2 as Expensive Analogs

2008-11-25T07:57:00.000-08:00

Page changed: Insulin for Type 2

Added reference to a new study of hospitalized people with Type 2 diabetes that found no significant differences in blood sugar control using R and NPH as compared to using the more expensive Levemir and Novolog combination.

Note that the target blood sugar in this study was very high, so it does not entirely answer the question of whether tighter and healthier control is easier with the newer insulins.

Since I have personally gotten very good control using R in the past--better, actually, than I get with analog insulins, my guess is that the only reason that R (regular human) insulin has been dropped from most physicians' prescribing habits is because it is not promoted by drug salespeople. Since R insulins cost less than 1/3 of what the analogs cost, this should be no surprise.

R insulin is an excellent choice for anyone who has poor insurance or who is having serious problems with post-meal hypos since its slightly slower action makes it easier to test and correct before you hypo. It also works very well with a lower carb diet or a diet rich in slow digesting carbs because of the shape of its activity curve.

More Evidence Later Onset LADA Shares Common Gene with Type 2

2008-11-25T07:28:00.000-08:00

Page changed: LADA -- Slow Onset Type 1

Added second study that finds that the incidence of the diabetic allele of TCF7L2 is similar in people over the age of 40 diagnosed as being GAD positive (i.e. having autoimmune diabetes) as it is in GAD negative Type 2s. This strengthens the concept that LADA that comes on in middle age may be a combined form of Type 1 and Type 2.

It's worth keeping in mind, though, that the presence of the antibodies mean that an autoimmune attack is present and the person diagnosed with LAD often ends up fully insulin dependent and prone to DKA without insulin.

New Study Misleadingly Suggests Actos is Safe

2008-11-24T16:08:00.000-08:00

Page changed: Actos and Avandia: Dangerous Diabetes Drugs

Added link to new journal article published in Archives of Internal Medicine which is being reported in the media as if it proves that Actos is safe while Avandia is not.

In fact, the study only compared one dangerous drug, Actos, against another even more dangerous drug, Avandia. It lacked the vital placebo group of people taking neither drug which might have shown that BOTH drugs are more dangerous than placebo re congestive heart disease and other cardiovascular problems.

In addition, this study did not track the rate of broken bones or blindness due to macular edema, both of which have been linked to Actos as well as Avandia.

My guess is that this study was funded by Takeda, makers of Actos. Since the conflict of interest paragraph does not appear in the free abstract of this article it is impossible to know. If you have a subscription to this journal, send me the "Conflict of interest" section so I can check it out. Thanks!

Please, people. Actos, like Avanida, is a dangerous drugs with life-ruining side effects that have only become evident in people who have taken them for a long time. They do not make much of a difference in blood sugars while increasing your likelihood of osteoporosis, fractures, congestive heart failure and heart attack. Avoid them!

New Study Finds Genes Predict Type 2 Diabetes As Well As or Better than Conventional Risk Factors

2008-11-23T09:17:00.000-08:00

Page changed: You Did Not Eat Your Way to Diabetes

Added citation to new large-scale study published in the New England Journal of Medicine which found that testing for alleles of 8 genes associated with Type 2 was predictive of diabetes regardless of classic risk factors and predicted as well as did those risk factors. In addition, the usefulness of the gene test for prediction became greater as time went by while that of the risk factors declined over time.

This is yet more evidence of the genetic nature of Type 2 diabetes.

Excellent Summary of Studies Showing Uselessness or Dangerousness of Vitamin Supplements

2008-11-20T10:32:00.000-08:00

Page Changed: Bad or Questionable Supplements

Added a link to and discussion of an excellent New York Times article which summarized and linked to a long list of major studies showing that antioxidant vitamins are either useless or even dangerous.

Impact of Abnormal Diabetes Genes on Beta Cell Function is Additive

2008-11-13T12:33:00.000-08:00

Page changed: You Did Not Eat Your Way to Diabetes

Added reference to new study published in Diabetologia quantifying the cumulative impact of known diabetes genes on beta cell function which found that the impact of known diabetes genes is additive.

Statins Effective Mostly in People with Elevated CRP

2008-11-09T06:59:00.000-08:00

Page changed: A1c and High Post-Meal Blood Sugar Predict Heart Attack

Added link to New York Times study reporting on major new research that shows that statins are effective in people with elevated CRP (C-reactive protein) a measure of inflammation.

Note that as reported in the New York Times HERE this study is being used to argue that EVERYONE should take statins, but in fact, it proves quite the opposite. Get your CRP tested and if it is not elevated, you probably don't need to take statins.

This study appears to confirm what many have begun to suspect--that whatever benefit there is from taking statins has nothing to do with their impact on cholesterol levels, but results from the fact that they have an anti-inflammatory effect on blood vessels.

This probably explains why half of those who have heart attacks have normal cholesterol.

More "Unpublished" Avandia Liver Deaths Revealed in FDA Data

2008-10-31T11:51:00.001-07:00

Page changed: Avandia and Actos

Added link to Reuters news story reporting on Public Citizen's discovery of 12 unpublished Avandia-related deaths due to liver failure and petition to FDA to ban the drug.

Note that Avandia and Actos are related to Rezulin which was taken off the market after it was found to have killed at least 400 people via liver failure. Orginally only 63 deaths were reported and the others only came to light after doctors were made aware that the drug caused liver failure. Some people estimate that many thousands more died or were seriously sickened since the family doctors who mostly prescribed the drug were not aware of the liver damage, even though it was listed in a black box warning on the drug.

If you are taking Avandia or Actos, you should have your liver enzymes checked every couple months, though in the case of Rezulin, checking liver enzymes often did not prevent liver failure as it can happen quickly.

Despite all the warnings that have gone out about Avandia, Reuters reports that 10,000 prescriptions a day are still being filled. That's a lot of people at risk for heart attack, broken bones, blindness caused by macular edema, and of course, weight gain--all proven side effects of Avandia.

Documentation of all these side effects is available at the Avandia and Actos web page.

Updated "How to Get Yourr Blood Sugar Under Control" Page

2008-10-31T06:14:00.000-07:00

Page changed: How To get Your Blood Sugar Under Control

Redid this page to present the updated blood sugar targets and textual editing changes previously put into the Flyer posted on our blog.

This tightens up and brings up-to-date the information found on the alt-support-diabetes.org "Newly Diagnosed" page which has not been updated in many years.

Updates to Blood Sugar 101

Why Thousands of Unregulated Supplements May Contain Dangerous Substances

Statins May Actually Cause Diabetes

Statins May Cause Diabetes

Supplementing with Megadoses of Vitamin B6, B12 and Folic Acid Correlates with Double Stroke Risk and GFR Worsening

Do NOT Supplement with Higher than Normal Doses of Vitamins B6, B12 and Folic Acid

Tight Control Decreases Kidney Deterioration by 50% in People with Type 1 Involved in DCCT

Free Antibody Testing Available for People with Family Members Diagnosed with Type 1

Free Antibody Testing Available from TrailNet

Added Discussion of The Toxic Effect of ACCORD Study Misinterpretations to the Blood Sugar Targets Page

But My Doctor Says Lowering Blood Sugars is Dangerous

New Study Confirms that Post-Meal Sugars and A1c Predict Heart Disease & Mortality

Post-Meal Blood Sugar and A1c Predict Cardiovascular Events and Deaths

New Page Added: Charcot's Foot

Charcot's Foot: A Foot Complication Caused by Clogged Blood Vessels

NSAIDS Linked to Increased Incidence of Atrial Fibrillation Especially in People with Kidney Disease

NSAIDS (Advil, Ibuprofen, Celebrex, etc.) Linked to Higher Risk of Atrial Fibrillation

Kombiglyze and Tradjenta--Ineffective, Expensive, DPP-4 Inhibitors with Scary Side Effects

Actos Associated with Higher Bladder Cancer Risk & FDA Administers Avandia Wrist Slap

Glycated LDL May Explain LInk of A1c to Heart Disease Risk

Glycated LDL May Be The Culprit

Huge Long-Term Study: Glibenclimide, Glipizide, Glimipiride, and Tolbutamide Associated with Increased Risk of Death and Heart Attack.

Statin effectiveness doess not correlate with CRP in people at very high risk of heart attack

Metformin reduces the invasiveness of endometrial cancer cells by 25%

10 Year Study Reveals BG Levels that Lead to Retinopathy

Diabetic Retinopathy Occurs at Prediabetic Blood Sugar Levels

More Evidence that Vitamin D Supplementation Does NOT Lower Blood Sugar, IR or Improve Endothelial Function.

FDA Investigating Evidence of Increased Risk of Bladder Cancer with Actos

Added New Evidence That Vitamin D Supplementation is Overhypped and Possibly Dangerous

Vitamin D Has No Effect On Early Type 1 Diabetes

Vitamin D Infusion Does NOT Improve Glucose Metabolism

Vitamin D May Not Be Significant in Loss of Blood Sugar Control

Womens Health Study Finds No Effect on Diabetes of Vitamin D and Calcium Supplementation

High Dose Vitamin D Increased Fractures in Older Women

Vitamin D's Connection with Cardiovascular Disease

Vitamin D May Have an Effect on Mood

Vitamin D Improves Outcome in Chronic Kidney Disease

A Danger with Vitamin D: High Blood Calcium Which May Cause Hardened Arteries

Recommended Dose:

hs-CRP successfully identifies MODY-3 80% of the Time: Good Screening Test

Yet Another Huge Study Proves Longterm Actos/Avandia Use Causes Fractures

Long Term Low Carb Diet Better for Health than Low Fat in Randomized Trial

A 2010 Study Finds Low Carb Diet Beats Low Fat at Improving Health Long Term

Added Onglyza Page

Onglyza: Just Like Januvia but with More Serious Side Effects?

Why Take Onglyza?

Metformin Page Rewritten

Effective, But Not Effective Enough

An Add-On not a Substitute for Dietary Control

Facts about Metformin

What Metformin Does

Metformin Inhibits the Liver's Production of Glucose

Metformin Appears to Stimulate Glucose Uptake in Muscles via AMPK Activation

Metformin's Activation of AMPK Blocks The Liver's Ability to Synthesize Triglycerides and Promotes Fat Burning.

Stimulation of AMPK May Be Why Metformin Appears Cardioprotective

Metformin May Boost GLP-1 Level

UKPDS 20 Year Follow-up Study Shows Excellent Metformin Effect

Metformin May Fight Cancer

Metformin May Be Protective Against Heart Disease

Metformin Lowers Risk of All Kinds of Fatal Outcomes

Metformin Started Early Far More Effective than Metformin Started Later

There's No Research Data about the Effect of Combining Metformin with Carb Restriction

Anecdotal Evidence

What You Need To Know About Taking Metformin

Side Effects

Gastric Distress

Can Metformin Cause Low Blood Sugar?

Lactic Acidosis?

Stop Metformin Before X-rays with Contrast Medium

Avoid Alcohol While Taking Metformin

Metformin May Deplete Vitamin B-12 and Folate

The ADA Scientific Sessions: Hype, Hype, and More Hype

More CGMS Evidence Documents the Truly Normal Blood Sugar Range

More Data Links A1c But Not Fasting Glucose to Cardiac Risk

Risk Quantified For Non-Diabetic A1cs and Heart Attack Risk

Vitamin B Supplementation Hastens Kidney Damage Raises Incidence of Stroke

B Vitamin Supplementation Increases Stroke and Kidney Damage

Potentially Dangerous Drugs for People with Type 2 Diabetes and Kidney Disease

Blood Levels of Vitamin D Do Not Predict Insulin Secretion or Sensitivity in People with Metabolic Syndrome

Metformin Started At Diagnosis Far More Effective Than Metformin Prescribed Later