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.
Friday, December 12, 2008
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:
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
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
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.
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
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:
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.
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.
Subscribe to:
Posts (Atom)
