In this double-blind randomized controlled trial, 80 individuals (35-65y) with pre-diabetes (IGT/IFG) will receive either a diet containing slow digestible starch (amylose;N=40) or "control" starch (amylopectin;N=40) for 3 months. Our data in rodents (supported by others) have shown that the ingestion of slow digestible starch: a) enhances the gut microbial profile; b) reduces metabolic endotoxemia; c) increases fermentation and production of butyrate &propionate; d) increases beneficial gut hormones such as GLP-1 and PYY; e) lowers the glycemic load and; f) suppresses appetite Therefore, we propose to feed a slowly digestible starch to simultaneously target several mechanisms known to be important in glucose homeostasis with emphasis on insulin sensitivity, fat oxidation and ectopic fat. We will test the hypothesis that improved composition of the gut microbiota with a daily intake of 45 g of amylose for 3 months in individuals with IGT and/or IFG will in turn improve risk factors for the development of T2DM such as: a) enhancement of insulin sensitivity (FSIGTT;
Aim1); b) decrease appetite and food intake (Aim2); c) decrease ectopic fat depots (1H-MRS;
Aim1); d) decrease inflammation (serum markers;
Aim1) and; e) modify the composition of large intestine microbiota in a metabolically favorable way (Aim3). This dietary intervention approach (addition of slowly digestible starch in yogurts) may prove more tolerable than daily caloric restriction and exercise and therefore more practically applicable for the treatment of T2DM.

Public Health Relevance

People with impaired glucose tolerance (IGT) suffer from insulin resistance and low grade inflammation and are at high risk of developing type 2 diabetes. Intensive lifestyle changes (reduced energy intake and increased physical activity) decrease the incidence of diabetes in people with IGT. However such lifestyle changes are difficult to maintain over the long-term and most people who lose weight regain it over subsequent years. The identification of a non-pharmacological intervention to improve insulin sensitivity in individuals could have a significant impact in an increasingly obese population. We therefore propose to study the effect of 3- month of dietary supplementation with 45-g of slowly digestible starch on risk factors for the development of type 2 diabetes in people with pre-diabetes (IGT). Preliminary data indicate that these starches may influence the gut microbial species which in turn may enhance insulin sensitivity and protect against the development of diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK092575-01A1
Application #
8372789
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Leschek, Ellen W
Project Start
2012-07-01
Project End
2017-04-30
Budget Start
2012-07-01
Budget End
2013-04-30
Support Year
1
Fiscal Year
2012
Total Cost
$433,140
Indirect Cost
$133,060
Name
Lsu Pennington Biomedical Research Center
Department
None
Type
Organized Research Units
DUNS #
611012324
City
Baton Rouge
State
LA
Country
United States
Zip Code
70808