We have examined the regulation of lipid and glucose metabolism in the postabsorptive and postprandial states in six subjects with insulin-treated diabetes mellitus, and compared them with eight nondiabetic subjects. Blood or plasma concentrations of metabolites and fluxes across forearm and subcutaneous adipose tissue were studied after an overnight fast and for 6 hours after a mixed meal (3.1 MJ, 41% from fat). In the postabsorptive state, regulation of lipid metabolism in the two groups appeared basically similar except that a wider spread of plasma (free) insulin concentrations in the diabetic group led to a wider range of values of plasma nonesterified fatty acid (NEFA) release from adipose tissue, plasma NEFA concentrations, and blood ketone body concentrations. Extraction of ketone bodies across adipose tissue was positively correlated with arterial concentration in both groups (as it was in the forearm), confirming the ability of human adipose tissue to utilize ketone bodies. A single subcutaneous injection of insulin before the meal in the diabetic group produced a plasma free-insulin profile that was blunted and prolonged compared with the postprandial response in the control group. Postprandial forearm glucose uptake followed very closely the plasma (free) insulin concentration. Postprandial suppression of NEFA release from adipose tissue was essentially normal in the diabetic group, and the normal postprandial decrease in plasma NEFA concentrations was reproduced extremely closely. Forearm and adipose tissue blood flow did not differ between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)