LIPOLYSIS AND GLUCONEOGENESIS FROM GLYCEROL ARE INCREASED IN PATIENTS WITH NONINSULIN-DEPENDENT DIABETES-MELLITUS

The rate of lipolysis (glycerol R(a)), gluconeogenesis from glycerol, and its contribution to overall hepatic glucose production (glucose R(a)) were determined in 10 patients with noninsulin-dependent diabetes mellitus (NIDDM) [body mass index (BMI) 27.2 +/- 1.0 kg/m2, fasting plasma glucose 10.3 +/- 1.2 mmol/L], and in 6 matched control subjects (BMI 27.3 +/- 1.1 kg/m2, fasting plasma glucose 5.3 +/- 0.3 mmol/L) using infusions of [3-H-3]glucose (0-600 min) and [U-C-14]glycerol (360-600 min). Glycerol R(a) was increased in the patients with NIDDM (120 +/-16-mu-mol/m2.min) compared to the normal subjects (84 +/- 9-mu-mol/m2.min, P < 0.05). Gluconeogenesis from glycerol was 1.7-fold higher in the patients (96 +/- 16-mu-mol/m2.min) than in the normal subjects (56 +/-10-mu-mol/m2.min, P < 0.05), and explained 9 +/- 1% and 7 +/- 1% (NS) of total glucose R(a) in patients with NIDDM and normal subjects, respectively. To determine whether these abnormalities are more pronounced in overweight patients with NIDDM, glucose and glycerol R(a) were also determined in 5 obese patients with NIDDM (BMI 36.4 +/-1.0 kg/m2, fasting plasma glucose 11.3 +/- 1.3 mmol/L). Glycerol R(a) (154 +/- 26-mu-mol/m2.min) was again higher than in the normal subjects (P < 0.05) but not different from that in the less obese patients with NIDDM. The rate of gluconeogenesis from glycerol (159 +/- 20-mu-mol/m2. min) was significantly higher in the obese than in the less obese patients with NIDDM (P < 0.05) but its contribution to total glucose R(a) (10 +/- 1%) was similar to that in the less obese patients with NIDDM. When all data were analyzed together, gluconeogenesis from glycerol (r = 0.57, P < 0.01) but not lipolysis (r = 0.02, NS) correlated with the percentage of lipolysis diverted toward gluconeogenesis suggesting that the rate of gluconeogenesis from glycerol is regulated by intrahepatic mechanisms rather than by glycerol availability. Neither the rate of lipolysis nor the rate of glycerol gluconeogenesis correlated with BMI, serum triglyceride, or insulin concentrations. We conclude that gluconeogenesis from glycerol is increased in patients with NIDDM. This increase appears to be the consequence of both accelerated lipolysis and increased intrahepatic conversion of glycerol to glucose.