INSULIN KINETICS, INSULIN ACTION, AND MUSCLE MORPHOLOGY IN LEAN OR SLIGHTLY OVERWEIGHT PERSONS WITH IMPAIRED GLUCOSE-TOLERANCE

Glucose intolerance is influenced by body fat mass, as well as muscle fiber composition. To examine the relation between the metabolic profi le and muscle morphology in this condition, we performed muscle biopsi es and hyperglycemic clamps to determine insulin secretion and clearan ce, and the insulin effects on glucose disposal and nonesterified fatt y acids (NEFA) in 45 glucose intolerant persons (body mass index [BMI] , 27.8 +/- 3.0 kg/m(2)) and 45 normoglycemic controls (BMI, 25.8 +/- 2 .7 kg/m(2)) (P = .001). After adjustment for BMI, glucose-intolerant s ubjects had lower first-phase insulin release (726 v 954 pmol/L, P = . 04). Glucose-intolerant subjects and controls differed in fasting insu lin, insulin clearance, and insulin sensitivity to glucose disposal be fore, but not after, standardizing for BMI. During the clamp, glucose- intolerant subjects had less NEFA suppression and elevated levels of N EFA compared with controls (85% +/- 9% v 90% +/- 6%, P = .02; and 70 /- 42 mu mol/L v 45 +/- 28 mu mol/L, P = .01). Glucose-intolerant subj ects also had a higher percentage of insulin-insensitive, type 2b musc le fibers, which are not adapted for fat oxidation (7% +/- 9% v 9% +/- 9%, P = .003). BMI was not associated with NEFA suppression or the pe rcentage of type 2b muscle fibers in either group. in conclusion, gluc ose-intolerant persons have impaired first-phase insulin release, an e levated percentage of type 2b muscle fibers, and increased NEFA availa bility. Reduced insulin clearance, hyperinsulinemia, and insulin resis tance were associated with small increments in BMI. Copyright (C) 1998 by W.B. Saunders Company.