EFFECTS OF AGING AND EPIGENETIC PREDISPOSITION OF EARLY ONSET OBESITY AND T2DM ON THE EXPRESSION OF GLYCEMIC RESPONSES INCORPULENT RAT STRAINS

To determine the effects of epigenetic predisposition of early onset obesity,aging and T2DM on glycemicparameters, groups of congenic male lean, obese, and obese-diabetic rats (n= 5-6 rats/group) that share thesame genetic trait for obesity (the -cp trait) were reared under normal laboratory conditions and fed stockPurina Rodent chowad libitum throughout. Rats were subjected to measures of fasting glucose, insulin,amylin, insulin:glucose ratios, and glycated hemoglobin concentrations and on the glycemic response to anoral glucose tolerance (OGT) and Area Under the curve (AUCglc) at 4 and again at 12 months of age. Obeseanimals weighed more than their lean littermates (p = < 0.05). Fasting plasma glucose, insulin, and amylinconcentrations of obese > lean, and in increased further in NIDDM-prone animals, with the greatestincreases in the oldest animals. Hemoglobin A1c trended higher in obese than in lean littermates and wasmarkedly greater in the NIDDM-prone animals of both ages.(p = < 0.05) Oral glucose tolerance andAUCglucose of obese > lean, and was markedly greater in NIDDM-prone animals, with the greatestincrease in the oldest animals. The AUCglc was greater in obese than in lean littermates and increasedsignificantly on T2DM-prone animals at both ages. In conclusion, these results demonstrate the effects ofaging on the obese trait on development and expression of insulin resistance may occur independently ofT2DM in these closely related congenic strains and thattheglycemic responses deteriorate further with agingwhen left untreated.