Januvia Causes Precancerous Changes in Transgenic Rats with Human Pancreas Cells

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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

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.

Drug Makers Study Shows Avandia Odds of Serious Heart Failure Worse Than Russian Roulette

Page Changed: Actos and Avandia: Dangerous Diabetes Drugs

Added link to published study in the Lancet (reported previously at the ADA Scientific Sessions).

Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Philip D Home, et al. The Lancet, The Lancet, Volume 373, Issue 9681, Pages 2125 - 2135, 20 June 2009. doi:10.1016/S0140-6736(09)60953-3

This study found that the risk of "Heart failure causing admission to hospital or death" was much higher in people taking Avandia, and that the incidence of "Heart failure causing admission to hospital or death" was extremely high.

Sixty-one out of 321, or one out of every five people in this study who were taking Avandia, ended up in the hospital or dead thanks to heart failure. In the control group the incidence was 9 out of 100.

One in five is worse odds than Russian Roulette.

And this study was completely funded by the makers of Avandia.

Remember in reading this that Actos, the other TZD drug, has also been linked conclusively with causing heart failure in younger patients who had never shown signs of it before taking the drug.

Heart failure is a class effect of the TZD drugs and a very dangerous one.

I find it interesting that they lump "hospitalization and death" together rather than breaking out how many people died as a direct result of heart failure attributable to Avandia. You'd want to see how many deaths due to heart failure occurred in the control group and compare that number to the deaths from heart failure in the Avandia group.

But since the study was published by the drug maker, that is one data analysis you are not likely to see.

Confirmation of Causative Link of Avandia and Actos to Fractures and Heart Failure

Page Changed: Avandia and Actos: Dangerous Diabetes Drugs

Added information from three new studies, two presented at ADA and one described in Science News based on German publication which confirm these drugs double risk of heart failure and cause fractures in both men and women. The German study explains the underlying mechanism by which Avandia and Actos cause heart failure. Stimulating PPAR-gamma turns out to change the way the heart metabolises fats in a way that weakens heart muscle.

Health Clamis Database Suggests Byetta Doesn't Cause Pancreatitis

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Added information from Medco study presented at 2009 ADA sessions showing no increase in incidence of pancreatitis in a large population of those taking it compared to a huge population of controls.

Changed Layout

Pages changed: Most

I have tweaked the Blood Sugar 101 site page layout to put ads in a column down the side and below the text rather than at the top where there were a bit annoying. I've been meaning to do this for a while, but it required more code tweaking than I felt like doing until now, since this site runs on a site host that shares code with other customers.

Let me know if you run into any problems with page display that I might not have caught viewing the site on my computers.