1516-P: Epigenetic Changes in Insulin Signaling Genes and Cancer Pathway Genes with Remission of Prediabetes

Prediabetes or impaired glucose tolerance (IGT) is often seen in conjunction with obesity and both are associated with increased incidence of various diseases. The purpose of this study was to determine if epigenetic changes of DNA occur in patients that convert from prediabetic to normal glucose tolerance(NGT) by determining DNA methylation at baseline and at remission of prediabetes at 6 months (mo).

Methods: 24 obese adults with prediabetes were randomized to a High Protein (HP)(30% protein(P), 30% fat(F), 40% carbohydrates(C)) or High Carbohydrate (HC)(15%P, 30%F, 55%C) diet for 6 mo with all food provided. Oral Glucose Tolerance Test (OGTT) was performed at Baseline (BL) and 6 mo to determine IGT/NGT status. DNA was extracted from BL and 6 mo OGTT 0-minute blood samples. Specific site DNA methylation was determined.

Results: The HP diet group had 100%(12/12) conversion to NGT while the HC diet had 33%(4/12) conversion. Both diet groups had weight loss and improvement in insulin sensitivity determined by Matsuda Index [HP(BL 2.3 ± 0.3; 6 mo 6.5 ±1.1)], [HC(2.3±0.3; 6 mo 3.2±0.4)]. Changes in DNA methylation of numerous genes were observed from BL to 6 mo with remission of prediabetes and weight loss. Some of these genes with altered DNA methylation include the KEGG pathways of: insulin signaling(IS)(11 genes), cardiovascular disease(CV)(15 genes), inflammation(IF)(18 genes), metabolic pathways(MP)(32 genes), and cancer pathways(31 genes). Changes in DNA methylation of genes involved in IS, CV, MP, correlate with the improvements in IS, CV and IF in the subjects after 6 months on the diets. Of the cancer pathway genes and insulin signaling and inflammation genes 18 of the changes in DNA methylation of the genes were the same.

Conclusions: The HP diet was the most effective with respect to DNA methylation changes and clinical parameters. The DNA methylation changes of specific genes may be important for reduction of certain disease states and can be improved by diet and weight loss.