The hypoglycemic effect of fat and protein is not attenuated by insulin resistance

Background: The glucose-lowering effect of fat and protein is attenuated or absent in diabetic patients, which suggests that the same may occur in insulin-resistant subjects without diabetes. Objective: The objective was to determine whether the postprandial metabolic responses elicited by fat and protein were influenced by the insulin sensitivity of the subjects and whether fat and protein modulate glucose responses through different mechanisms. Design: Healthy nondiabetic subjects aged 18-45 y took 50 g oral glucose with 0-30-g doses of canola oil and whey protein on 11 separate mornings after fasting overnight. The subjects were classified into 3 fasting serum insulin (FSI) groups: FSI < 40 pmol/L (n = 9), 40 <= FSI < 70 pmol/L (n = 8), and FSI >= 70 pmol/L (n = 8). The relative glycemic response was expressed as the incremental area under the curve (AUC) after each test meal divided by the mean AUC of the glucose control in each subject. Results: Protein significantly decreased glucose (P < 0.0001) and hepatic insulin extraction (P < 0.0001) and increased insulin (P < 0.0001) and glucagon-like peptide 1 (P = 0.004); however, protein had no significant effect on C-peptide (P = 0.69) or on the insulin secretion rate (P = 0.13). No significant FSI x fat (P = 0.19) or FSI x protein (P = 0.08) interaction effects on glucose AUC were observed. In addition, the changes in relative glycemic response per gram of fat (r = -0.05, P = 0.82) or protein (r = -0.08, P = 0.70) were not related to FSI. Conclusions: The hypoglycemic effect of fat and protein was not blunted by insulin resistance. Protein increased insulin but had no effect on C-peptide or the insulin secretion rate, which suggests decreased hepatic insulin extraction or increased C-peptide clearance. Am J Clin Nutr 2010; 91: 98-105.