The long-term effect of low-carbohydrate/high-fat diet on the development of diabetes mellitus in spontaneously diabetic rats.

The long-term effect of low-carbohydrate/high-fat diets on the development of diabetes mellitus was studied in Otsuka Long-Evans Tokushima Fatty strain (OLETF) rats. Four groups of spontaneously diabetic (type 2) male rats at 10 weeks of age were pair-fed semi-purified powder diets containing different amounts of carbohydrate (80%, 60%, 40%, 20% of total calories) for 30 weeks. The carbohydrate content was isocalorically substituted for the fat content in the diet. At the onset of experimental feeding (10 weeks of age), an oral glucose tolerance test (OGTT) was normal in each group. After 15 weeks of the test diet feeding there was no significant difference in the glucose tolerance among the 4 groups, although most of the rats were diabetic. The body weight increased with the decrease of the carbohydrate intake and increase of the fat intake (p <0.05), and the difference increased in proportion to age (p<0.05). The severity of diabetes mellitus was also increased along with the lower carbohydrate intake and higher fat intake, when the carbohydrate intake was less than 60% (in energy). On the other hand, there was a significant increase in the 20% group in the postload plasma insulin levels as compared with the other 3 groups at 40 weeks of age. Fasting plasma free fatty acid levels were increased in the lower carbohydrate content groups (20% and 40%) as compared with the higher carbohydrate content groups (60% and 80%) at the end of the experiment. Impairment of insulin secretion may be the cause of glucose intolerance induced by low carbohydrate intake rather than insulin resistance. These findings suggest that low-carbohydrate/high-fat diet aggravates diabetes mellitus in genetically diabetic rats, and that the development of diabetes mellitus is associated with the activation of the glucose-fatty acid cycle.