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

Saturday, July 4, 2009

Januvia Causes Precancerous Changes in Transgenic Rats with Human Pancreas Cells

Page Changed: Januvia

A study published in July 2009 found evidence that while Januvia improved pancreatic beta cell function in the short term, it did so while producing pre-cancerous changes in the pancreatic duct cells.

You can read the abstract of this study here:

Beneficial Endocrine but Adverse Exocrine Effects of Sitagliptin in the Human Islet Amyloid Polypeptide Transgenic Rat Model of Type 2 Diabetes: Interactions With Metformin Aleksey V. Matveyenko et al. Diabetes. doi: 10.2337/db09-0058 Diabetes July 2009 vol. 58 no. 7 1604-1615

This study was conducted in human islet amyloid polypeptide transgenic (HIP) rats which have had human genes inserted into their pancreata. The HIP rats were treated with Januvia, or metformin, the combination of sitagliptin plus metformin, or no drug as controls for 12 weeks.

It found that "Metformin more than sitagliptin [Januvia] inhibited ß-cell apoptosis [cell death]. Metformin enhanced hepatic insulin sensitivity;"

But when Januvia was added to the mix, there was a small improvement in insulin sensitivity and in beta cell function. Note that "beta cell function" is only a measure of insulin secretion. It is not a sign that more beta cells are growing, only that existing beta cells are pumping out more insulin.

In fact, the finding, reported above was that beta cells survived better in the transgenic rats given metformin alone compared to those given Januvia.

But any benefit that might have come from increased insulin secretion was cancelled out by a very troubling finding. Here is the way the researchers report it:
sitagliptin enhanced extrahepatic insulin sensitivity with a synergistic effect in combination. ß-Cell function was partially preserved by sitagliptin plus metformin. However, sitagliptin treatment was associated with increased pancreatic ductal turnover, ductal metaplasia, and, in one rat, pancreatitis [emphasis mine].
"Metaplasia" is defined this way in Mosby's Medical Dictionary, 8th edition. © 2009, Elsevier:
the reversible conversion of normal tissue cells into another, less differentiated cell type in response to chronic stress or injury. With prolonged exposure to the inducing stimulus, cancerous transformation can occur.

New Study Sheds Light on the Function of a Common Diabetes Gene Allele

Page changed: You Did Not Eat Your Way to Diabetes

Added citation to a study published in July of which 2009 sheds light on what exactly it is that an allele (gene variant) often found associated with diabetes does. The allele in question is one of TCF7L2 transcription factor gene.

The study involved 81 normal healthy young Danish men whose genes were tested. They were then given a battery of tests to examine their glucose metabolisms. The researchers found that:
Carriers of the T allele were characterised by reduced 24 h insulin concentrations ... and reduced insulin secretion relative to glucose during a mixed meal test ... but not during an IVGTT [intravenous glucose tolerance test].
This is an interesting finding, because what damages our bodies is the blood sugar we experience after eating "a mixed meal" but so much research uses the artificial glucose tolerance (GTT) test to assess blood sugar health. This result suggests that the GTT may be missing important signs of early blood sugar dysfunction and that the mixed meal test may be a better diagnostic test than the GTT. I have long believed this to be true, since so many people experience reactive lows when they take the GTT which produces a seemingly "normal reading" though they routinely experience highs after eating meals. These highs are what damage our organs.

Young men with the TCF7L2 allele also responded with weak insulin secretion in response to the incretin hormone GLP-1 and "Despite elevated hepatic [liver] glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations ... suggesting altered alpha cell function."

Here again we see evidence that long before obesity develops, people with this common diabetes gene variant show highly abnormal blood sugar behavior. Abnormal production of glucose by the liver may also contribute to obesity as metformin, a drug that that blocks the liver's production of glucose blocks weight gain and often causes weight loss.

The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. K. Pilgaard et al. Diabetologia, Issue Volume 52, Number 7 / July, 2009. DOI 10.1007/s00125-009-1307-x

Wednesday, July 1, 2009

New Epidemiological Evidence Suggsts SSRI Use but Not Depression Causes Obesity

Page Changed: You Did Not Eat Your Way To Diabetes

Added citation to ten year Canadian epidemiological study liking the use of SSRI and Effexor but NOT Major Depressive Episode (i.e. evidence of clinical depression) to increased rates of obesity.

The study found that, "MDE [Major Depressive Episode] does not appear to increase the risk of obesity. ...Pharmacologic treatment with antidepressants may be associated with an increased risk of obesity. [emphasis mine]. The study concludesed,
Unexpectedly, significant effects were seen for serotonin-reuptake-inhibiting antidepressants [Prozac,Celexa, Lovox, Paxil, Zoloft] and venlafaxine [Effexor], but neither for tricyclic antidepressants nor antipsychotic medications.

Scott B. Patten et al. Psychother Psychosom 2009;78:182-186 (DOI: 10.1159/000209349)

This is not the first time the often prescribed antidepressants have been linked to pathological weight gain. But the media have bought into drug company spin that claimed that the underlying depression that required the drug use was what caused obesity.

This new data appears to disprove that claim.

Given the current high prescription level of SSRIs this is very likely a major cause of the so-called "obesity epidemic."

Don't expect the media to pick up on this fact, though, as they earn so much from drug company advertising. They'll continue to blame the victims for gluttony and sloth.