Updates to Blood Sugar 101

Januvia Causes Precancerous Changes in Transgenic Rats with Human Pancreas Cells

2009-07-04T07:11:00.001-07:00

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].

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

2009-07-04T06:19:00.000-07:00

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

2009-07-01T08:54:00.000-07:00

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

2009-06-19T05:10:00.000-07:00

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

2009-06-11T07:41:00.001-07:00

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

2009-06-11T07:20:00.001-07:00

Page Changed: Byetta

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

2009-06-08T13:48:00.000-07:00

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.

Metastudy Documents Metabolic Advantages of Ketogenic Diets

2009-06-04T07:34:00.000-07:00

Page Changed: Studies Studies Proving The Safety and Efficacy of the Low Carb Diet

Added link to metastudy published in 2005 documenting the effect of the very low carb, ketogenic diet on various metabolic markers including leptin.

Cardiovascular and Hormonal Aspects of Very-Low-Carbohydrate Ketogenic Diets. Jeff S. Volek and Matthew J. Sharman. Obesity Research (2004) 12, 115S–123S; doi: 10.1038/oby.2004.276

Also added warning note to readers explaining that many recently published diet studies making claims of the inferiority of the "low carb diet" define the "low carb diet" as a diet containing anywhere from 120 to 180 grams of carbohydrate a day, an amount far higher than most people with diabetes can process.

Reference Removed: Metformin May Prevent Beta Cell Apoptosis

2009-05-27T13:17:00.001-07:00

Page Changed: Metformin, Acarbose, Sulfonylureas: The Truth About Oral Diabetes Drugs

Removed citation to human pancreas autopsy study with findings that metformin might help prevent beta cell apoptosis (cell suicide). Reading the full study made it clear that the researchers were not discussing the actual impact of metformin taken as a drug on humans, but instead describing a highly artificial situation created in cultured cells taken from dead pancreata and bathed in fat and a metformin solution.

This is the study:
Autophagy in human type 2 diabetes pancreatic beta cells M. Massini et al. Diabetologia Volume 52, Number 6 / June, 2009, DOI 10.1007/s00125-009-1347-2.Pages 1083-1086

New Evidence on How Metformin Works

2009-05-27T12:56:00.000-07:00

Page Changed: The Truth about Oral Diabetes Drugs

Added citation to new study which suggests that metformin stops the liver from dumping glucose by directly stimulating a gene in the liver which should be stimulated by insulin but in many Type 2s apparently isn't. This suggests that it isn't lowering insulin resistance so much as doing the job itself insulin isn't doing.

Metformin and Insulin Suppress Hepatic Gluconeogenesis through Phosphorylation of CREB Binding Protein Ling He et al,, Cell Volume 137, Issue 4, 635-646, 15 May 2009. doi:10.1016/j.cell.2009.03.016

This is explained in layman's language in this week's release of Diabetes in Control:

New Information on how Metformin works. Diabetes in Control May 27, 2009.

Google Search box added to Foot of Blood Sugar 101 Pages

2009-05-05T06:05:00.000-07:00

Pages Changed: Most

The site has grown huge over the past several years so to help you find what you are looking for, I've put a Google Search box on the bottom of every page. It's set up to default to search the site.

Pesticide Atrazine Maps to Obesity and Causes IR and Weight Gain Even Without Dietary Change

2009-05-04T06:49:00.000-07:00

Page Changed: You Did Not Eat Your Way to Diabetes

Added cite to new study which found that the herbicide Atrazine, the use of which maps closely to the prevalence of obesity in the U.S., causes insulin resistance, weight gain and mitochondrial dysfunction in rats who get a lot concentration of it in their water. The weight gain is independent of diet, though a high fat/high carb diet leads to more weight gain.

Metformin and Radiological Contrast Medium

2009-04-15T05:19:00.000-07:00

Page changed: The Truth about Oral Diabetic Drugs

Added information from updated Metformin prescribing information explaining that metformin should be discontinued at the time of or slightly before radiological procedures involving injected dye and not taken for the next 2 days. After that kidney function should be evaluated with a serum creatinine test before metformin is started again. The latter recommendation is courtesy of a radiologist who pointed me to these updated guidelines.

In rare cases in people with marginal kidney function the use of contrast dyes may cause kidney failure if a dose of metformin is taken after the dye is used. It is also possible to develop lactic acidosis when this happens. This is rare, but because many people with poorly controlled diabetes have significant kidney damage, it is important for people taking metformin to be aware of this.

These recommendations have changed from what they were a few years ago.

Stop it or you'll go blind: Actos Definitely Linked to Increased Blindness in Well Controlled Diabetics

2009-04-13T06:27:00.000-07:00

Page changed: Actos and Avandia - Dangerous Diabetes Drugs

Cited brand new study published in an Opthalmology journal--not read by family doctors, alas, that demonstrated dramatically that Actos and Avandia both raise the risk of vision loss dramatically.

Glitazone Use Associated with Diabetic Macular Edema Donald S. Fong. Am J OphthVolume 147, Issue 4, Pages 583-586.e1 (April 2009)

This study analyzed the records of 170,000 people with diabetes treated by Kaiser Permanente Southern California. The researchers found that

In 2006, there were 996 new cases of ME. Glitazone users were more likely to develop ME in 2006 (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.4 to 3.0). After excluding patients who did not have the drug benefit, did not have an eye exam, and had a HgA1c <7.0, glitazone use was still associated with an increased risk of developing ME (OR, 1.6; 95% CI, 1.4 to 1.8).

This means you are 60% more likely to develop retinal swelling leading to vision loss even with well controlled blood sugars if you take Actos or Avandia than if you don't.

It's worth noting, too, that the Science News report of this study adds, "Most of the glitazone users in the study were taking pioglitazone (Actos)."

Since the whole point of lowering blood sugar in diabetes is to avoid blindness, this study makes it crystal clear that no person with diabetes should be taking Actos or Avandia.

PRINT OUT THE ABSTRACT OF THIS STUDY AND GIVE IT TO YOUR FAMILY DOCTOR AT YOUR NEXT APPOINTMENT. YOU COULD SAVE SOMEONE'S VISION.

Benfotiamine May Not Live up to Claims: Cheaper Thiamine May Be Equivalent

2009-04-08T06:56:00.001-07:00

Page changed: Helpful Supplements for Diabetes

Added link to study calling into question whether Benfotiamine is really lipid soluble as claimed and whether it has any advantages over much cheaper, regular thiamine supplements.

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivativesMarie-Laure Volvert et al. BMC Pharmacology 2008, 8:10doi:10.1186/1471-2210-8-10

New Web Page Added: Dementia and Diabetes - A Confusing Relationship

2009-03-19T07:37:00.000-07:00

Page Added: Dementia and Diabetes - A Confusing Relationship

This page pulls together information previously scattered through several posts on the Diabetes Update blog. It discusses various research studies that have been cited in the press as linking Diabetes and Alzheimer's Disease or dementia. It also cites research pointing to other, stronger, and often avoidable risk factors for dementia that should be of interest to people with diabetes.

Study: Diabetes that Starts with IGT Different From That Which Starts with IFG

2009-03-03T10:54:00.000-08:00

Page Changed: The Patterns in Which Diabetes Develops

Added this information: The Inter99 Study was a five year study. 3,145 subjects who started out with normal glucose tolerance but developed some form of abnormal blood sugar who were given glucose tolerance tests and Insulin sensitivity index (ISI), homeostasis model assessment of insulin sensitivity (HOMA-IS), early-phase insulin release (EPIR), and insulin secretion relative to insulin action (disposition index) were estimated. The researchers conclude,

A stationary reduced insulin secretion followed by a decline in primarily hepatic insulin sensitivity characterizes the transition from N[ormal] G[lucose] T[olerance] to i-I[impaired]F[asting]G[lucose]. In contrast, low whole-body insulin sensitivity with a secondary lack of ß-cell compensation is associated with the development of i-I[mpaired]G[lucose]T[olerance]. Thereby, i-IFG and i-IGT appear to result from different underlying mechanisms, which may have implications for the prevention and treatment of the diabetes that succeeds them.

Natural History of Insulin Sensitivity and Insulin Secretion in the Progression From Normal Glucose Tolerance to Impaired Fasting Glycemia and Impaired Glucose Tolerance: The Inter99 Study.
Kristine Færch, et al. Diabetes Care, 32:439-444, 2009.

Actual Statistics on Prevalence of Diabetes and Prediabetes in the U.S. Population

2009-01-28T08:36:00.000-08:00

Page Changed: The Patterns in Which Diabetes Develops

Added citation to a journal article published in Diabetes Care which analyzes data from the 2006 NHANES survey give an accurate idea of what the actual incidence of diabetes and prediabetes are in the American population.

Full Accounting of Diabetes and Pre-Diabetes in the U.S. Population in 1988–1994 and 2005–2006. Catherine C. Cowie et al. Diabetes Care 32:287-294, 2009.

This study reports,

In 2005–2006, the crude prevalence of total diabetes in people aged ≥20 years was 12.9%, of which ~40% was undiagnosed. In people aged ≥20 years, the crude prevalence of impaired fasting glucose was 25.7% and of impaired glucose tolerance was 13.8%, with almost 30% having either. Over 40% of individuals had diabetes or pre-diabetes. Almost one-third of the elderly had diabetes, and three-quarters had [either] diabetes or pre-diabetes.

Though the incidence of diagnosed diabetes had increased, the increase was slightly over 2% which may be due to better diagnosis, not more diabetes.

I take the high incidence of "prediabetes" compared to the modest prevalence of full fledged diabetes--much of it occurring in the elderly--as an indication that most people with "prediabetes" are not likely to become fully diabetic, though they may experience blood sugar related hunger and weight gain.

Only those with the underlying genetic flaws that prevent beta cell mass to expand or limit insulin secretion are likely to go on to become fully diabetic.

New Evidence that Post-Challege Glucose Not Fasting Plasma Glucose Accurately Predicts Future Diabetes

2009-01-28T08:11:00.000-08:00

Page Changed: What is a Normal Blood Sugar?

Research first published in 2008 that was based on studying a group of 2,442 subjects who were free of type 2 diabetes at the beginning of the study found that fasting glucose tests were a very poor predictor of who in this group would develop diabetes.

The researchers found that people whose one hour glucose tolerance test results were over 155 mg/dl and who had markers for metabolic syndrome--such as a concentration of fat around the belly and high blood pressure were those who were more accurately predicted to be likely to develop diabetes.

Fasting Versus Postload Plasma Glucose Concentration and the Risk for Future Type 2 Diabetes Muhammad A. Abdul-Ghani et al. Diabetes Care 32:281-286, 2009 DOI: 10.2337/dc08-1264

Fetal Exposure to PCBs and DDE Correlate to Obesity by Age 3

2009-01-21T08:43:00.000-08:00

Page Changed: You Did Not Eat Your Way to Diabetes

Added reference to a new study that tracked the exposure of a group of pregnant Belgian woman to several common pollutants: hexachlorobenzene, dichlorodiphenyldichloroethylene (DDE) , dioxin-like compounds, and polychlorinated biphenyls (PCBs). It found a correlation between exposure to PCBs and DDE and obesity by age 3, especially in children of mothers who smoked.

Intrauterine Exposure to Environmental Pollutants and Body Mass Index during the First 3 Years of Life Stijn L. Verhulst et al., Environmental Health Perspectives. Volume 117, Number 1, January 2009

Added My New Nutritional Calculator to the Blood Sugar 101 Low Carb Diet Site

2009-01-17T08:04:00.001-08:00

Page Changed: Use Our Nutritional Calculator to Break Through Stalls

This calculator computes calorie levels and nutrient breakdowns for people eating a ketogenic low carbohydrate diet. It gives suggested intake levels for maintenance and weight loss.

Tips for How to Keep On Eating Low Carb When Money Is Scarce

2009-01-13T16:08:00.000-08:00

Page changed: What Can You Eat When You Are Cutting The Carbs?

Added link to a discussion at The Low Carb Friends Discussion Forum with some helpful ideas for how to eat a low carbohydrate diet when money is tight.

Low carb foods may seem more expensive, but if they control your appetite you might end up spending less on a few pounds of meat and cheese than you will on the cheaper starches that leave you hungry and eating more food--at the same time as they ruin your blood sugar control.

New 24 Week Study Compares Atkins Diet to Low GI Die in People with Diabetes

2009-01-10T13:03:00.000-08:00

Page Changed: Studies Proving the Safety and Efficacy of the Low Carb Diet

Added discussion of this study:

The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Eric C Westman et al.Nutrition & Metabolism 2008,5:36doi:10.1186/ 1743-7075-5-36. December 2008.

where the classic Atkins diet was found to provide much better weight loss, blood sugar control, and Lipids compared to the Low GI diet after a 24 week trial.

Actos and Avandia Double Fracture Risk in Women with Type 2 Diabetes

2008-12-24T09:33:00.000-08:00

Page changed: Actos and Avandia--Dangerous Diabetes Drugs

Added reference to metastudy that concluded that TZD drugs double a woman's risk of fracture.

Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. Yoon K. Loke et al. CMAJ Early release, published at www.cmaj.ca on Dec. 10, 2008.

The article reporting on this study published on Science DaiIy quoted one of the researchers, stating,

In absolute terms, Singh said, if thiazolidinediones (TZDs) are used by elderly, postmenopausal women (around 70 years) with type 2 diabetes for one year, one additional fracture would occur among every 21 women. Among younger women (around 56 years), use of the drugs for one year or longer would result in one additional fracture for every 55 women.

With hip fractures representing a major cause of death for older women, this is not a trivial finding. Other studies have also found that Actos and Avandia weaken bone by turning the bone stem cells that should become new bone into new fat cells instead.

High Dose Thiamine--Vitamin B1--May Help with Diabetic Kidney Disease

2008-12-17T08:25:00.000-08:00

Page changed: Diabetic Kidney Damage and Helpful Supplements for People with Diabetes

Added link to new study that found that taking 100 mg of Vitamin B1 three times a day (a total dose of 300 mg) lowered the excretion of albumen in urine.

High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study. N. Rabbani et al. Diabetologia 10.1007/s00125-008-1224-4, Dec 05, 2008.