A diet enriched in protein accelerates diabetes manifestation in NOD mice

Diet modifies the development of insulin-dependent diabetes mellitus in animals and in humans. We examined female non-obese-diabetic (NOD) mice, a diabetes-prone mouse strain with 70% spontaneous diabetes incidence and metabolic abnormalities in non-overtly diabetic litters. They were fed a diet containing 55% (n = 27) or 15% (n = 26) protein, respectively, after weaning. At an age of 30 weeks, non-diabetic NOD mice were submitted to an intravenous glucose tolerance test (0.5 g/kg body weight; blood samples were taken after 2, 4, 8, 10, 15, 20 and 30 min) and to perfusion of the pancreas (stimulation media were Krebs-Ringer-Hepes buffer with 5 mmol/l glucose, 30 mmol/l glucose and 5 mmol/l glucose plus 19 mmol/l arginine). Diabetic mice were removed from the experiment. Serum glucose concentration and body weight were monitored weekly. Food ingestion was checked at an age of 11 weeks. On average, the onset of diabetes was diagnosed in mice on a high-protein diet (19.7 +/- 1.3 weeks) 4 weeks earlier than in mice on a low-protein diet (23.5 +/- 1.1 weeks; P < 0.05). Non-diabetic NOD mice on a high-protein diet showed significantly better glucose tolerance (as determined by the glucose disappearance rate) and mean insulin secretion (at 30 mmol/l glucose). No difference in the serum glucose concentration between non-diabetic mice on the low-protein diet or high-protein diet could be proved. In non-diabetic mice on the high-protein diet the body weight and food ingestion exceeded those of mice on the low-protein diet (P < 0.05). High insulin secretion and glucose tolerance in non-diabetic mice may reflect the capacity of beta-cells to adapt; however, beta-cells tend to be destroyed under such circumstances. Thus, a high-protein diet promoted the onset of diabetes, but it did not increase significantly the incidence of the disease.