Reducing Cholesterol and Fat Intake Improves Glucose Tolerance by Enhancing β Cell Function in Nondiabetic Subjects

Context: A diet low in cholesterol and fat is commonly recommended to prevent metabolic and cardiovascular diseases; however, its effect on glucose tolerance is largely unknown. Objective: We examined whether and by which mechanisms a chronic reduction of cholesterol and fat intake affects glucose tolerance in nondiabetic individuals, independently of weight changes. Design and Participants: In this crossover, randomized clinical trial, 30 healthy subjects, including 15 with family history of type 2 diabetes (T2D) (T2D offspring), underwent a 75-g oral glucose tolerance test (OGTT) after two 14-day isocaloric high-cholesterol, high-fat (HChF) or low-cholesterol, and low-fat (LChF) diets. Main Outcome Measures: We evaluated changes in glucose tolerance, beta cell function, insulin clearance, and insulin sensitivity by modeling plasma glucose, insulin, and C-peptide levels during the OGTT. Results: The shift from the HChF to the LChF diet was neutral on body weight but increased glucose tolerance (mean glucose25%, P = 0.01) and three components of beta cell function: glucose sensitivity (+17%, P = 0.01), insulin secretion at fasting glucose (+20%, P = 0.02), and potentiation (+19%, P = 0.03). The LChF diet improved insulin sensitivity (+7%, P = 0.048) only in T2D offspring, who tended to be more susceptible to the positive effect of the diet on glucose tolerance. Conclusions: A chronic and isocaloric decrease in dietary cholesterol and fat intake improves glucose tolerance by diffusely ameliorating b cell function in nondiabetic subjects. Individuals genetically predisposed to develop T2D tend to be more susceptible to the positive effect of this dietary intervention on glucose tolerance and insulin sensitivity.