EFFECT OF OBESITY ON CIRCULATING INTERMEDIARY METABOLITE CONCENTRATIONS IN THE ABSENCE OF IMPAIRED GLUCOSE-TOLERANCE

The published literature on the influence of obesity on intermediary metabolite concentrations does not adequately address the potential confounding effects of the increased prevalence of impaired glucose tolerance in obese subjects. In order to remove this, we studied 109 subjects with proven normal glucose tolerance ranging from underweight to grossly obese (range 15.3-80.9 body mass index). All had blood intermediary metabolites, plasma insulin and C-peptide measured after an overnight fast. Thirty-six (18 from each end of the range of body mass index) received a 3-hour oral glucose tolerance test for metabolites and insulin. Fasting plasma insulin was highly significantly associated with body mass index (r = 0.72; P < 0.001). Concentrations of lipid intermediaries were better associated with body mass index than with fasting plasma insulin: non-esterified fatty acids (r = 0.36; P < 0.001), glycerol (r = 0.47; P < 0.001) and ketone bodies (r = 0.45; P < 0.001). Fasting concentrations of carbohydrate intermediaries were, however, better correlated with fasting plasma insulin: lactate (r = 0.29; P < 0.01), pyruvate (r = 0.24; P < 0.01) and alanine (r = 0.36; P < 0.001). Glucose concentrations were associated with both to a similar degree (r = 0.33, r = 0.32, respectively; P < 0.001). After oral glucose, exaggerated rises in plasma insulin and blood glucose were observed in obese subjects but a lesser rise was seen for lactate. Non-esterified fatty acids and ketones, although having higher fasting concentrations in obese subjects, fell to similar concentrations in the two groups after glucose whereas blood glycerol did not fall so far in the obese subjects. The results suggest, even if those subjects with impaired glucose tolerance are excluded, insensitivity to insulin in several aspects of intermediary metabolism in obesity the degree of which may vary in different metabolic pathways or tissues.