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

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

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

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

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.