Nocturnal and postprandial free fatty acid kinetics in normal and type 2 diabetic subjects - Effects of insulin sensitization therapy

Whether free fatty acid (FFA) rate of appearance (R.) is increased in type 2 diabetes is controversial. To characterize nocturnal and postprandial abnormalities in FFA kinetics and to determine the effects of treatment with insulin sensitizers on lipolysis, we measured palmitate R-a in control subjects (n = 6) and individuals with poorly controlled, sulfonylurea-treated type 2 diabetes (HbA(1)c = 8.7 +/- 0.2%, n = 20), the latter before and at the end of 12 weeks of treatment with troglitazone (600 mg/day, n = 4), metformin (similar to2,000 mg/day, n = 8), or placebo (n = 8). Subjects consumed a standard breakfast at 0800 h. Results in control subjects and type 2 diabetic subjects were compared at baseline. Integrated nocturnal FFA R-a (AUC(1:00-8:00 A.M.)) was similar to50% higher in type 2 diabetic subjects than in control subjects (29.4 +/- 3.0 vs. 19.4 +/- 3.9 mmol . m(-2) . 7 h(-1), respectively, P < 0.05), whereas postprandial palmitate R-a (AUC(0-240) min) Was almost threefold higher in type 2 diabetic subjects than in control subjects (14.2 +/- 1.7 vs. 5.3 +/- 1.0 mmol . m(-2) . 4 h(-1), respectively, P < 0.01). After troglitazone treatment, nocturnal palmitate R-a did not change, but postprandial palmitate R-a decreased by similar to30% (P < 0.05). Palmitate kinetics did not change with metformin or placebo treatment. In summary, nocturnal and postprandial FFA R-a is increased in type 2 diabetes. Postprandial lipolysis appears to be preferentially improved by thiazolidinediones compared with nocturnal lipolysis.