14
November
2007
Type 2 Diabetes means the body is resistant to insulin. The body makes insulin, but usually due to obesity the body doesn’t respond to insulin well anymore. So the pancreas cranks out more and more insulin to compensate for this need, but in time it is not enough.
Over 7% American adults have diabetes. Since 1990 Type II diabetes has been dramatically increasing in children and adolescents due to obesity. 14% of US health care costs are from diabetes. Overall costs to USA is about 132 billion dollars as of 2002. Fasting blood glucose of 126 or more is diabetes, or a HbA1C of 6% or more.
So, Januvia (sitagliptin) has been out in the market for over the past year to help those with Type II diabetes who aren’t getting enough control on metformin (a commonly used medicine for type 2 diabetes). So what is it? Oh, boy, here is my best explanation.
Incretins are intestinal hormones that are released when there is food in the gut. Incretins GLP-1 (glucoagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) do the following: lowers glucagon secretion, slows the GI system, and increases satiety. Also they stimulate secretion of insulin
Dipeptidyl peptidase-4 (DDP-4) “digests” GLP-1 and GIP, so Januvia inhibits
drjohnhong 
diabetes, Endocrinology 
Comments (0) » |
23
May
2007
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. NEJM 5/21/07; 356
Avandia (generic name rosiglitazone) is a thiazolidinedione medication for type II diabetes. It is an agonist for peroxisome-proliferator-activated receptor gamma (PPAR-gamma) and has been around since 1999.
In diabetics, 65% of deaths are cardiovascular related. The meta-analysis of this study was done to increase the power to see what are the cardiovascular outcomes.
116 studies were investigated and 42 studies were analyzed for this meta-analysis. Criteria for entry included more than 24 weeks of drug exposure, randomized studies, MI (heart attack) or cardiovascular deaths had to be reported. Outcomes: MI. Cardiovascular Deaths.
15,560 people were in the Avandia treatment group and 12,283 in the control group (control group were divided into those taking insulin, sulfonylurea, metformin, and placebo). Most of the subjects were men around 57 years old, and diabetes control was relatively poor in both groups (HbA1C average 8.2%)
The trials had very few MIs or cardiovascular deaths, so they used some statistical method I have never heard of, the Peto Method. I’m not sure how they determined what would be clinically significant and statistically significant between Avandia group and control group.
Results are pretty similar. In the Avandia group, there were 86 MIs (0.55%) and in the Control group 72 MIs (0.58%). For cardiovascular deaths, the Avandia group had 39 deaths (0.25%) and the Control group had 22 deaths (0.18%).
So for MIs, Avandia had a 1.43 times increased risk of MI compared to control (43%) that is statistically significant. But in epidemiology, 43% increase risk is a weak to mild association. You need more of a 200-300% increase risk to be a strong association. Also if you just look at the numbers, 86 heart attacks out of 15,560 isn’t a whole lot in particular vs. 72 heart attacks out of 12,283 controls.
For cardiovascular, there is no increased risk of cardiovascular death that is statistically proven.
I think the findings are interesting but it is too soon to “jump the gun” like the media is doing. A study needs to be done and powered correctly to see if Avandia does indeed cause heart attacks and/or cardiovascular deaths. But I don’t think anyone can say for sure at this point that Avandia does cause heart attacks. We do know Avandia can’t be used in Stage III or IV congestive heart failure and I wonder if the heart attacks were due to this. Many questions have been raised from this meta-analysis.
© John S. Hong, MD, MS May 22, 2007
drjohnhong diabetes, medicines, cardiovascular Comments (0) » |
16
May
2007
Obesity and fructose - how are they related? 2/3 of Americans are overweight or obese. It is getting worse the past couple of decades. High fructose is very common over the past couple of decades as well. High fructose is added to most sweet drinks and foods.
Fructose is a simple sugar similar in structure to glucose (the main sugar). Metabolism is
unique – mostly done by the gut organs. Digested into glucose, glycogen, lactate, or lipids. Does use insulin – so initially was studied in type II diabetics to see if was good alternative to sugar (glucose or sucrose). Initially digested appeared to be beneficial. Low dose fructose increase glucokinase and lowers liver production of glucose.
However, later in metabolism shown to associate with Metabolic Syndrome X: insulin resistance (diabetes or glucose intolerance) , bad cholesterol (high LDL and triglycerides), increased body fat, and high blood pressure. Increased uric acid as well that increases risk of gout and kidney stones. Nurses’ Health Study 1999 showed high-fructose correlated with high c-peptide levels (~insulin). Stimulates sympathetic nervous system which is why people might get a “boost” with high sugar/fructose.
Unlike sucrose (2 glucoses combined), fructose doesn’t signal to brain that the body is full – so overeating is common. High-fructose corn syrup in mice – drink more of this than sucrose sweetened water
drjohnhong Uncategorized, obesity, diabetes, food, weight Comments (0) » |
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