Analysis of factors influencing nitrogen balance during acute starvation in obese subject with and without type 2 diabetes

Abstract

Patients with type 2 diabetes (T2DM) tend to loose more lean body mass during both long-term weight reduction and short-term very-low-calorie diet. We ask what factors influence protein loss during acute starvation in T2DM. In a prospective in-hospital observational study, we compared 10 subjects with T2DM and 10 age-weight-sex matched obese controls (OB) during 60 h of fasting and used frequent blood sampling and indirect calorimetry to describe metabolic and endocrine response. We analyzed factors influencing nitrogen balance using stepwise multiple regressions. Despite comparable pattern of plasma insulin, free fatty acid, 3-hydroxybutyrate and almost identical behavior of growth hormone axis, our T2DM subjects remained hyperglycaemic and in contrast to OB subjects they failed to reduce the rate of protein oxidation, even though muscle protein breakdown rate declined similarly in both groups. Regression analysis revealed that protein oxidation rate in T2DM group was enhanced by hyperglycemia and sympathetic activity and suppressed by circulating insulin and 3-hydroxybutyrate. Liver insulin resistance increases peripheral insulin concentrations and enhances the conversion of non-esterified fatty acids (NEFA) to ketones and thus it might be a protein-saving factor. Relative deficiency of circulating insulin and hyperglycemia play a pivotal role in the impairment of protein sparing in T2DM during a short-term fasting.