Abstract
Objective: To investigate whether the prolonged physiological elevation of non-esterified fatty acids (NEFA) seen in man during fasting associates with an altered acute insulin response to NEFA. Subjects and methods: Fourteen non-diabetic subjects, age 18-25 years, BMI 23.2 - 0.8 kg/m 2 underwent hyperglycemic clamps (blood glucose 11 mM) for 120 min, during which either saline or Intralipid was administered in the last 60 min. Subjects were tested after an overnight as well as after a 58 h fast. Results: After the overnight fast, insulin levels increased during Intralipid infusion, at min 120 reaching an increment of 33.0 - 8.5 muU/ml vs. 9.5 - 4.4 muU/ml during saline; p < 0.05 for difference. Conversely, after the 58 h fast, Intralipid failed to promote a successive increase of insulin levels (increment during Intralipid at min 120: 0.5 - 5.8 muU/ml vs.- 4.3 - 2.5 muU/ml during saline, NS). Insulin sensitivity as assessed by the amount of infused glucose and its ratio to insulin was enhanced by Intralipid after an overnight fast, but was decreased after a 58 h fast. Conclusion: Long-term elevated NEFA during fasting associates with diminished beta cell responsiveness to an acute elevation of fatty acids in conjunction with negative effects on insulin sensitivity.