Failure of glyburide and insulin treatment to decrease leucine flux in obese type II diabetic patients

Poorly-controlled type I diabetic patients have elevated rates of leucine appearance (indicating increased proteolysis), which are reduced with insulin therapy. It also has been suggested that obesity increases leucine appearance rate by reducing sensitivity to insulin. In the present study, we examined whether non-diabetic obese women or poorly-controlled obese type II diabetic patients have elevated leucine appearance rates, and whether diabetic patients have a reduction in leucine appearance with treatment of their hyperglycemia. Among non-diabetic women, postabsorptive leucine appearance rate was positively correlated with the percentage of body weight as fat (r = 0.92, P < 0.01). Obese women with untreated type II diabetes did not have a higher mean (± s.e.m.) leucine appearance rate (2.13 ± 0.18 μmol/min/kg fat-free mass, determined by infusion of 1-[1-¹³C] leucine as a tracer) than obese non-diabetic women with a similar fat-free mass (2.49 ± 0.09 μmol/min/kg fat-free mass). After two weeks of glyburide therapy mean glucose concentrations decreased 24 percent and glucose production decreased 18 percent, but leucine appearance rate was not altered (2.08 ± 0.18 μmol/min/kg fat-free mass). After 2 weeks of insulin therapy, mean fasting glucose concentration and glucose production rate were normal (55 per cent and 46 per cent below pre-treatment levels), but leucine appearance rate remained unchanged (2.17 ± 0.18 μmol/min/kg fat-free mass). We conclude that type II diabetes in obese patients is not associated with elevated proteolysis, that treatments that significantly improve or normalize postabsorptive glucose metabolism in obese type II diabetic patients do not affect postabsorptive proteolysis, and that obesity per se (without diabetes) increases proteolysis.