Metformin reduces the invasiveness of endometrial cancer cells by 25%

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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

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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

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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.

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

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

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

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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