Nocturnal and Postprandial Free Fatty Acid Kinetics in Normal and Type 2 Diabetic Subjects

Abstract

Whether free fatty acid (FFA) rate of appearance (Ra) 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 Ra in control subjects (n = 6) and individuals with poorly controlled, sulfonylurea-treated type 2 diabetes (HbA1c = 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 (∼2,000 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 Ra (AUC1:00–8:00 a.m.) was ∼50% 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 Ra (AUC0–240 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 Ra did not change, but postprandial palmitate Ra decreased by ∼30% (P < 0.05). Palmitate kinetics did not change with metformin or placebo treatment. In summary, nocturnal and postprandial FFA Ra is increased in type 2 diabetes. Postprandial lipolysis appears to be preferentially improved by thiazolidinediones compared with nocturnal lipolysis.