Substrate utilization and thermogenic responses to beta-adrenergic stimulation in obese subjects with NIDDM

OBJECTIVE: This study intended to investigate disturbances in beta-adrenerg ically-mediated substrate utilization and thermogenesis in obese subjects w ith mild non insulin-dependent diabetes mellitus (NIDDM). DESIGN: Following a baseline period of 30 min, the beta-agonist isoproteren ol (ISO) was administered in increasing doses of 6, 12, and 24 ng/kg(FFM).m in, each dose for 30 min. SUBJECTS: Nine healthy lean males (CON, 50.6+/-2.4 y, % body fat: 16.0+/-1. 8) and 10 obese subjects with NIDDM (51.8+/-2.4 y, % body fat 34.1+/-1.9). RESULTS: Basal non esterified fatty acid concentrations (NEFA) and basal fa t oxidation (absolute or expressed per unit fat free mass, FFM) were signif icantly higher in NIDDM as compared to CON, whereas basal carbohydrate (CHO ) oxidation was significantly lower. The ISO-induced increase in NEFA-conce ntrations was blunted in NIDDM (Delta at 24 ng/kg(FFM).min: CON: 717 +/- 59 mu mol/l vs NIDDM: 358 +/- 97 mu mol/l, P < 0.01). The non-protein respira tory exchange ratio (RER) did not change in NIDDM and significantly decreas ed in CON during ISO-infusion (P < 0.05), reflecting the tendency towards a blunted increase in fat oxidation in NIDDM (Delta fat ox at 24 ng; CON: 0. 025 +/- 0.005 g/min vs NIDDM 0.016 +/- 0.007 g/min). The ISO-induced thermo genic response was comparable in NIDDM and CON (at 24 ng %increase above ba seline: CON: 16.8 +/- 2.2% vs NIDDM: 14.7 +/- 0.9%). At all time points, th ere were no significant differences in circulating ISO and noradrenaline co ncentrations, Basal adrenaline (A) concentrations and A concentrations duri ng ISO-infusion were significantly lower in NIDDM (basal A; CON: 64 +/- 15 pg/ml vs NIDDM: 25 +/- 2 pg/ml, P < 0.001). CONCLUSION: There appear to be deviations in beta-adrenoceptor mediated fat utilization and adrenal medulla function in obesity-associated NIDDM, The impairments in sympathetically mediated fat utilization have previously bee n observed in 'simple' obese subjects, indicating that these disturbances a re confined to the obese state per se.