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

Abstract

To determine the effects of epigenetic predisposition of early onset obesity,aging and T2DM on glycemic parameters, groups of congenic male lean, obese, and obese-diabetic rats (n= 5-6 rats/group) that share the same genetic trait for obesity (the -cp trait) were reared under normal laboratory conditions and fed stock Purina 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 an oral glucose tolerance (OGT) and Area Under the curve (AUCglc) at 4 and again at 12 months of age. Obese animals weighed more than their lean littermates (p = < 0.05). Fasting plasma glucose, insulin, and amylin concentrations of obese > lean, and in increased further in NIDDM-prone animals, with the greatest increases in the oldest animals. Hemoglobin A1c trended higher in obese than in lean littermates and was markedly greater in the NIDDM-prone animals of both ages.(p = < 0.05) Oral glucose tolerance and AUCglcof obese > lean, and was markedly greater in NIDDM-prone animals,  with the greatest increase in the oldest animals.  The AUCglc was greater in obese than in lean littermates and increased significantly on T2DM-prone animals at both ages. In conclusion, these results demonstrate the effects of aging on the obese trait on development and expression of insulin resistance may occur independently of T2DM in these closely related congenic strains  and that the glycemic responses deteriorate further with aging when left untreated.