chapter  13
37 Pages

Management of Obesity-Associated Type 2 Diabetes

WithWanda C. Lakey, Lillian F. Lien, Mark N. Feinglos

The impact of dietary factors on metabolism in general and glycemia in particular is well established in animal models [1–4]. For example, Surwit et al. in 1988 noted that the obese (C57BL/6J ob/ob) mouse only develops significant hyperglycemia in the presence of stress [5]. Initially, the background strain (C57BL/6J) was used as a normal control animal. However, when data using both the C57BL/6J animal and another strain (A/J) were compared, it became clear that the former mouse strain was always mildly hyperglycemic and hyperinsulinemic compared to the latter. This raised the possibility that the ob/ob mutation was an obesity mutation, exacerbating the genetic predilection to hyperglycemia already present in the background strain. Thus, Surwit and Feinglos developed a nutritional experiment to explore the effect of a high-fat, high-calorie diet on the development of obesity and hyperglycemia in these mice. This would serve as a model of the development of type 2 diabetes induced by diet in human populations with a similar genetic predisposition. Both A/J and C57BL/6J mice were studied. For each strain, 10 mice were fed a control diet of ad libitum water and Purina Rodent Chow, whereas 10 mice were fed a high-fat, high-simple-carbohydrate diet ad libitum. (For more detailed nutrient composition of the diets, please see Table 13.1). The control diet and the high-fat, high-simple-carbohydrate diet were administered for 6 months. Both strains of mice developed obesity after 16 weeks, but the C57BL/6J mice were significantly more obese. Furthermore, the diet-induced obesity led to moderate glucose intolerance and insulin resistance in the A/J mice, but obesity in the C57BL/6J mice led to clear-cut diabetes with markedly increased fasting glucose and insulin levels: glucose 248 ± 8 mg/dL versus 162 ± 6 mg/dL in C57BL/6J mice versus A/J mice, respectively. The authors concluded that, on this “diabetogenic” diet, C57BL/6J 217mice appear to develop diabetes in a manner that is analogous to most cases of human type 2 diabetes in predisposed individuals [5].