Plasma acetate levels in response to intravenous fat or [formula omitted] infusions in diabetic and non-diabetic subjects

Abstract

We measured plasma levels of acetate, glucose, insulin, fatty acids and ‘ketone bodies’ (KB), during fat infusion and continuous simultaneous infusion of insulin and glucose according to a computerized algorithm to maintain fasting euglycaemia and derive indices of tissue insulin sensitivity (hyperinsulinaemic euglycaemic clamping HEC). (i) Plasma acetate leels (mmol/l) approximately doubled (0.14 ± (Sem) 0.02 to 0.25 ± 0.02, p < 0.01) during INTRALIPID infusion in 7 non-diabetic individuals while total ‘ketone bodies’ and non-esterified fatty acids (NEFAs) increased 10-fold, (ii) Early in the HEC, plasma acetate levels decreased as did NEFAs in 13 non-diabetic (0.17 ± 0.01 to 0.12 ± 0.01, p < 0.001) and 9 diabetic (0.22 ± 0.02 to 0.15 ± 0.01, p < 0.005) individuals. However while acetate levels later rose to fasting values in the non-diabetics, they remained low in the diabetics. NEFA levels were low throughout the clamp but glucose flux was increased as judged from the glucose infusion even with maintained euglycaemia. The change in acetate values during the second hour of the clamp correlated with neither BMI nor two indices of insulin sensitivity (glucose metabolic clearance rate and steady state glucose infusion rate). These results accord with acetate production from glucose and fat oxidation, via acetyl CoA. The differing metabolism of acetate in the second hour of clamping between diabetics and non-diabetics may reflect altered post-receptor glucose metabolism with the onset of diabetes.