EFFECTS OF KETONE-BODIES ON CARBOHYDRATE-METABOLISM IN NON-INSULIN-DEPENDENT (TYPE-II) DIABETES-MELLITUS

The ability of ketone bodies to suppress elevated hepatic glucose output was investigated in eight postabsorptive subjects with non-insulin-dependent diabetes mellitus (NIDDM). Infusion of sodium acetoacetate alone (20 μmol/kg/min) for 3 hours increased total serum ketones (β-hydroxybutyrate and acetoacetate) to approximately 6 mmol/L, but did not reduce plasma glucose (14.0 ± 0.8 to 12.3 ± 0.9 mmol/L) or isotopically determined hepatic glucose output (17.5 ± 1.4 to 12.7 ± 1.0 μmol/kg/min) more than saline alone. Plasma C-peptide concentrations were unchanged, while serum glucagon increased from 131 ± 13 to 169 ± 24 ng/mL (P < .015) and free fatty acids were suppressed by 43% (0.35 ± 0.08 to 0.20 ± 0.06 mmol/L, P < .025). When sodium acetoacetate was infused with somatostatin (0.10 μg/kg/min) to suppress glucagon and insulin secretion, the decrease in both plasma glucose (13.3 ± 0.9 to 10.2 ± 0.7 mmol/L) and hepatic glucose output (17.2 ± 1.6 to 9.4 ± 0.6 μmol/kg/min) was greater than either sodium acetoacetate or somatostatin infusion alone. Infusion of equimolar amounts of sodium bicarbonate had no effect on glucose metabolism. In conclusion, these results demonstrate that ketone bodies can directly suppress elevated hepatic glucose output in NIDDM independent of changes in insulin secretion, but only when the concomitant stimulation of glucagon secretion is prevented. Ketone bodies also suppress adipose tissue lipolysis in the absence of changes in plasma insulin and may serve to regulate their own production. © 1990.