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

Sunday, November 29, 2009

FDA Adds Warning: Don't Take Byetta If Kidneys Seriously Impaired

Page changed: Byetta.

Added the following:
In late 2009 the FDA analyzed postmarketing data for Byetta and found 78 cases of kidney failure reported between April 28, 2005 and October 29, 2008, a period in which more than 6.6 million prescriptions for Byetta had been dispensed.

Given the prevalence of kidney failure among people with established diabetes this finding may or may not be related to the drug. The FDA now states that Byetta should not be prescribed to people with "severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease." Caution should be used when prescribing it to people with "moderate renal impairment (creatinine clearance 30 to 50 ml/min)."

Because doctors are ignorant of or ignore FDA drug warnings check your creatinine clearance test results before you start Byetta. If your doctor has not given you this test once a year, find a new doctor. All people with diabetes should have their kidney function tested periodically.

Warning signals of kidney problems are: Increased serum creatinine, Changes in urination (color, frequency, amount), Unexplained swelling in the extremities, Increases in blood pressure, Lethargy, Dull ache in the mid to lower back. NOTE: Changes in appetite and digestion are also listed as symptoms of kidney dysfunction but are also normal responses to Byetta.

FDA Safety Information for Byetta

Saturday, November 28, 2009

Common Herbicide and Fibrates Block Receptor That Stimulates GLP-1

Page changed: You Did Not Eat Your Way to Diabetes

Added the following:

In 2007 scientists at New York's Mount Sinai Hospital discovered that the intestine has receptors for sugar identical to those found on the tongue and that these receptors regulate secretion of glucagon-like peptide-1 (GLP-1). GLP-1 is the peptide that is mimicked by the diabetes drug Byetta and which is kept elevated by Januvia and Onglyza. You can read about that finding in this Science Daily report:

Science Daily: Your Gut Has Taste Receptors

In November 2009, these same scientists reported that a very common herbicide 2,4 D blocked this taste receptor, effectively turning off its ability to stimulate the production GLP-1. The fibrate drugs used to lower cholesterol were also found to block the receptor.

Science Daily: Common Herbicides and Fibrates Block Nutrient-Sensing Receptor Found in Gut and Pancreas

What was even more of concern was the discovery that the ability of these compounds to block this gut receptor "did not generalize across species to the rodent form of the receptor." The lead researcher was quoted as saying,
...most safety tests were done using animals, which have T1R3 receptors that are insensitive to these compounds,
This takes on additional meaning when you realize that most compounds released into the environment are tested only on animals, not humans. It may help explain why so many supposedly "safe" chemicals are damaging human glucose metabolisms.

Friday, November 13, 2009

Metformin's Effect Linked Strongly to Activation of AMPK

Page changed: Metformin

Included findings of a fascinating study published in 2001, but previously overlooked, that provided detailed insight into Metformin's activation of AMP-kinase (AMPK) in rat tissue in ways that provide explanations for many of the anecdotally observed effects of Metformin that are not directly related to insulin resistance, most notably its ability to prevent weight regain in dieters and the way it appears to lower glycogen stores. Another study is cited that describes cardioprotective effects of the activation of AMPK that may explain metformin's observed cardioprotective effects.

Text added:

Metformin's Activation of AMPK Blocks The Liver's Ability to Synthesize Triglycerides and Promotes Fat Burning.

For an exhaustive look at how metformin's impact on AMP-kinase works in rat tissues (and probably human tissues), read this full text study:

Role of AMP-activated protein kinase in mechanism of metformin actionZhou et al. J. Clin. Invest. 108(8): 1167-1174 (2001). doi:10.1172/JCI13505.

This study found that
metformin activates AMPK in hepatocytes [liver cells]; as a result, acetyl-CoA carboxylase (ACC) activity is reduced [ACC promotes the creation of triglycerides], fatty acid oxidation is induced [i.e. fat is burned], and expression of lipogenic enzymes is suppressed [lipogenic enzymes are needed to create triglycerides].
It also found that glucose uptake in muscles by metformin required the activation of AMPK. When it was blocked the uptake did not happen.

AMPK activation is also known to increase the breakdown of glycogen, which may be why some low carbers have observed that their glycogen stores appear already depleted when they embark on a low carb diet, so they don't lose the glycogen-associated water weight at the start of the diet that dieters lose who are not taking metformin. It may also be why when theu carb up they don't gain a lot of instant water weight either.

It is this impact of metformin on the liver, which is independent of its impact on glucose absorption that probably explains why metformin often causes modest weight loss, especially when it is first taken. It also explains why it makes weight loss maintenance much easier even in insulin sensitive dieters such as myself. Blocking the synthesis of fats and promoting the burning of fat at the liver (and possibly muscles) makes it much harder to gain weight.

Stimulation of AMPK May Be Why Metformin Appears Cardioprotective

AMPK has also been shown to have a protective effect on the heart. This review describes how AMPK may protect the body during heart attacks.

AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra Lawrence H. Young. Circulation. 2008;117:832-840 doi: 10.1161/CIRCULATIONAHA.107.713115

Thursday, November 12, 2009

More Evidence Lean Offspring of People With Type 2 Show Beta Cell Defects and IR

Page Changed: You Did Not Eat Your Way to Diabetes

A new study published in Diabetologia confirms the finding of an earlier study that shows that lean, young relatives of people with Type 2 diabetes already show dramatic differences in their ability to secrete insulin and their insulin sensitivity.

This points out very clearly that people who develop diabetes didn't cause their disorder by overeating, as they already have high post-meal blood sugars when young and thin. This is attributed in the study to beta cell dysfunction.

This study compared detailed measurements of insulin secretion and resistance in 187 offspring of people diagnosed with Type 2 diabetes against 509 controls. Subjects were matched with controls for age, gender and BMI. It concluded:
The first-degree offspring of type 2 diabetic patients show insulin resistance and beta cell dysfunction in response to oral glucose challenge. Beta cell impairment exists in insulin-sensitive offspring of patients with type 2 diabetes, suggesting beta cell dysfunction to be a major defect determining diabetes development in diabetic offspring.
Beta cell (dys)function in non-diabetic offspring of diabetic patients M. Stadler et al. Diabetologia Volume 52, Number 11 / November, 2009, pp 2435-2444. doi 10.1007/s00125-009-1520-7