Postprandial Free Fatty Acids (FFA) Metabolism Early in the Natural History of Type 2 Diabetes Mellitus (DM2)

We have shown that reduced suppression of plasma FFA appearance during enhanced intravascular lipolysis induced by iv fat infusion is among the earliest metabolic dysfunction seen in offspring of two parents with DM2 (FH+). Whether increased postprandial plasma FFA appearance occurs that early in the natural history of DM2 is unknown. Plasma palmitate appearance rate (Rapalmitate) was determined using intravenous [U- ¹³C]-palmitate during the last 2 hours of steady oral intake of a high-fat liquid meal over 6 hours (74, 169, and 70 g of fat, carbohydrates and proteins) in five FH+subjects (1 M, 4 F, BMI=28.6±1.6 kg/m²) and compared to 10 healthy subjects without family history of DM2 (FH-: 6 M, 4 F, BMI=25.4±1.6 kg/m²) and 7 subjects with DM2 (5 M, 2 F, BMI=33.0±3.1 kg/m²). Postprandial plasma glucose, palmitate and FFA levels in FH+were similar to FHbut lower than DM2 (P<0.05) (glucose: 5.3±0.2, 4.9±0.2 and 7.0±0.5 mmol/l; palmitate: 37±6, 28±4 and 50±8 μmol/l; FFA: 197±54, 174±34 and 328±50 μmol/l). Plasma insulin levels were similar between all groups. Ra_palmitate in FH+was also similar to FH- but lower than DM2 (P=0.07) (51±6, 55±7 and 80±1 μmol/min). Plasma triglyceride levels were significantly elevated in FH+compared to FH- (P<0.05) almost to a similar degree than in DM2 (1.91±0.28, 1.12±0.16 and 2.35±0.47 mmol/l). We repeated these experiments using intravenous insulin and glucose infusion to keep postprandial glucose levels to ~6 mmol/l in all participants but found similar results. These preliminary data show that postprandial increase in plasma FFA appearance seen in DM2 is not yet fully installed in FH+. The latter group displays postprandial hypertriglyceridemia that could contribute to lipotoxicity known to occur in these subjects. Acute normalization of plasma glucose does not reverse postprandial FFA abnormalities in DM2.