Weight loss by very-low-calorie diets: effects on substrate oxidation, energy expenditure, and insulin sensitivity in obese subjects.

Weight reduction improves glucose utilization, but it is not known whether this occurs primarily through the oxidative or nonoxidative pathways of glucose metabolism. We studied this question in 12 obese subjects [whose body mass index (BMI) was 33.4 +/- 1.1 kg/m2)] before and after 6 wk on a very-low-calorie diet of 1680 kJ/d with the euglycemic insulin clamp technique in combination with indirect calorimetry. The mean body weight decreased from 105.3 +/- 4.6 to 94.1 +/- 4.0 kg (P less than 0.001). This was mainly due to a reduction in fat mass from 47.2 +/- 3.6 to 37.7 +/- 3.0 kg (P less than 0.001), whereas lean body mass decreased only slightly (from 58.0 +/- 2.0 to 56.4 +/- 1.8 kg). The basal energy expenditure decreased with weight loss by 10.7%. This was associated with a reduced rate of lipid oxidation (P less than 0.05). Weight loss increased glucose utilization by 26%, primarily by enhancing insulin-stimulated glucose oxidation (P less than 0.05), whereas the effect on nonoxidative glucose metabolism was less pronounced (P greater than 0.05). Substantial weight loss increases glucose utilization by enhancing glucose oxidation.