This blog tracks updates to the Blood Sugar 101 Web site.

Wednesday, December 24, 2008

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

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 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.

Wednesday, December 17, 2008

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

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

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.

Friday, December 12, 2008

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

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.

Tuesday, December 9, 2008

Heart Attack Risk with Different Sulfonylurea Drugs Quantified

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%

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

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

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

Monday, December 8, 2008

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

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.

Sunday, December 7, 2008

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

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.