Effect of Meal Frequency on Insulin Resistance in Subjects With Type 2 Diabetes

Aims and priorities of the project The purpose of this study is to 1. test the effect of frequency of meals (six vs. two meals daily with the same daily caloric restriction of -500 kcal/day) on insulin sensitivity, insulin secretion, and hepatic fat content. 2. characterize some of the mechanisms of action of different frequencies of meals (amount of visceral fat, hepatic fat content, serum concentrations of adipokines, gut hormones, oxidation stress markers). 3. test the ability of the participants to maintain hypocaloric diet on both regimens when educated and left to prepare their meals alone in comparison with those for whom all meals during the study will be provided. It will be a randomized, crossover study, where 50 individuals with type 2 diabetes will change in a random order two regimens: six, and two meals a day. Each testing period will take three months. Glucose and lipid metabolism and its regulation will be thoroughly tested at start, and after each 3-months-period (meal test, hyperinsulinemic isoglycemic clamp, indirect calorimetry, MRI scan of the liver, DXA scan, serum concentration determination of selected adipokines, gut hormones, and oxidation stress markers). Hypothesis The investigators hypothesize that low plasma insulin levels (as achieved by periods of fasting) will reduce insulin resistance and hepatic lipid content. In contrast, frequent meals (and consequent higher plasma levels of insulin) will predispose to non-alcoholic fatty liver disease and insulin resistance. The investigators further hypothesize that the participants will increase their caloric intake with increased meal frequency (in spite of thorough education) when left to prepare their meals in comparison with those for whom all meals will be provided.