Dr. Ron’s Research Review – April 16, 2014

© 2014

This week’s research review focuses on diabetes and food additives.

Food is now universally shared across the globe, particularly processed food. Food is different today than it was in the past; over 4,000 new agents have entered our food supply intentionally or in-advertently: almost none of those have been evaluated as potential causes of obesity or diabetes.

Dr. Barbara E. Corkey's proposes a model that environmentally induced elevated background levels of insulin, superimposed on a susceptible genetic background, or basal hyperinsulinemia is the root cause of insulin resistance, obesity, and diabetes. (Corkey 2012)

Dr. Corkey showed that monoglycerides, artificial sweeteners, and iron were found to increase insulin secretion at basal glucose through the production of ROS. (Corkey 2012)

A recent article showed that basal-state hyperinsulinemia in healthy normoglycemic adults is predictive of type 2 diabetes over a 24-year follow-up. (Dankner, Chetrit et al. 2012)

Both human and rodent studies demonstrated that sucralose, a synthetic organochlorine sweetener, may alter glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels. In rats, sucralose alters the microbial composition in the gastrointestinal tract (GIT), with relatively greater reduction in beneficial bacteria. (Schiffman and Rother 2013)

Dr. Ron


Articles

Diabetes: have we got it all wrong? Insulin hypersecretion and food additives: cause of obesity and diabetes?

         (Corkey 2012) Download

The initial three agents studied in our laboratory, monoglycerides, artificial sweeteners, and iron, were found to increase insulin se- cretion at basal glucose through the production of ROS such as superoxide, nitric oxide, and peroxides (10). We determined that ROS could directly stimulate insulin secretion (10,54). We also found that increasing the mitochondrial redox state (NADH/NAD) increased both ROS generation and insulin secretion

Banting lecture 2011: hyperinsulinemia: cause or consequence?

         (Corkey 2012) Download

The Banting Medal for Scientific Achievement Award is the American Diabetes Association's highest scientific award and honors an individual who has made significant, long-term contributions to the understanding of diabetes, its treatment, and/or prevention. The award is named after Nobel Prize winner Sir Frederick Banting, who codiscovered insulin treatment for diabetes. Dr. Barbara E. Corkey received the American Diabetes Association's Banting Medal for Scientific Achievement at the Association's 71st Scientific Sessions, 24-28 June 2011, San Diego, California. She presented the Banting Lecture, "Hyperinsulinemia: Cause or Consequence?" on Sunday, 26 June 2011.

Basal-state hyperinsulinemia in healthy normoglycemic adults is predictive of type 2 diabetes over a 24-year follow-up: a preliminary report

         (Dankner, Chetrit et al. 2012) Download

BACKGROUND: In a preliminary report, we found an association between hyperinsulinemia in the basal (fasting) state and the development of diabetes. OBJECTIVES: The current analysis further explored the long term link between basal hyperinsulinemia and conversion to dysglycemia. METHODS: This is a prospective study with up to 24 years of follow-up of 515 normoglycemic individuals (mean age at follow up = 70.3 +/- 7.0; range 58-94) of an Israeli cohort. Fasting glucose and insulin were measured, and dysglycemia was defined as fasting glucose > 100 mg/dL. RESULTS: At the end of the follow-up period, almost half had progressed to dysglycemia. Male sex and elevated baseline levels of basal insulin, body mass index, blood glucose and blood pressure each favoured progression to dysglycemia over the subsequent two decades. A multivariate logistic regression model identified basal hyperinsulinemia as the strongest predictor for progression to dysglycemia (odds ratio = 1.79; 95% confidence interval 1.12-2.88), while controlling for ethnicity, blood pressure, fasting glucose, male sex, body mass index and age. CONCLUSIONS: Basal hyperinsulinemia in normoglycemic adults constitutes an independent risk factor for metabolic deterioration to dysglycemia over adulthood, and may help to identify apparently healthy subjects at increased risk for diabetes.

Sucralose, a synthetic organochlorine sweetener: overview of biological issues

         (Schiffman and Rother 2013) Download

Sucralose is a synthetic organochlorine sweetener (OC) that is a common ingredient in the world's food supply. Sucralose interacts with chemosensors in the alimentary tract that play a role in sweet taste sensation and hormone secretion. In rats, sucralose ingestion was shown to increase the expression of the efflux transporter P-glycoprotein (P-gp) and two cytochrome P-450 (CYP) isozymes in the intestine. P-gp and CYP are key components of the presystemic detoxification system involved in first-pass drug metabolism. The effect of sucralose on first-pass drug metabolism in humans, however, has not yet been determined. In rats, sucralose alters the microbial composition in the gastrointestinal tract (GIT), with relatively greater reduction in beneficial bacteria. Although early studies asserted that sucralose passes through the GIT unchanged, subsequent analysis suggested that some of the ingested sweetener is metabolized in the GIT, as indicated by multiple peaks found in thin-layer radiochromatographic profiles of methanolic fecal extracts after oral sucralose administration. The identity and safety profile of these putative sucralose metabolites are not known at this time. Sucralose and one of its hydrolysis products were found to be mutagenic at elevated concentrations in several testing methods. Cooking with sucralose at high temperatures was reported to generate chloropropanols, a potentially toxic class of compounds. Both human and rodent studies demonstrated that sucralose may alter glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels. Taken together, these findings indicate that sucralose is not a biologically inert compound.

References

Corkey, B. E. (2012). "Banting lecture 2011: hyperinsulinemia: cause or consequence?" Diabetes 61(1): 4-13. [PMID: 22187369]

Corkey, B. E. (2012). "Diabetes: have we got it all wrong? Insulin hypersecretion and food additives: cause of obesity and diabetes?" Diabetes Care 35(12): 2432-7. [PMID: 23173132]

Dankner, R., A. Chetrit, et al. (2012). "Basal state hyperinsulinemia in healthy normoglycemic adults heralds dysglycemia after more than two decades of follow up." Diabetes Metab Res Rev 28(7): 618-24. [PMID: 22865584]

Schiffman, S. S. and K. I. Rother (2013). "Sucralose, a synthetic organochlorine sweetener: overview of biological issues." J Toxicol Environ Health B Crit Rev 16(7): 399-451. [PMID: 24219506]