Abnormal meal carbohydrate disposition in insulin-dependent diabetes. Relative contributions of endogenous glucose production and initial splanchnic uptake and effect of intensive insulin therapy

Abstract

Postprandial hyperglycemia in insulin-deficient, insulin-dependent diabetic subjects may result from impaired suppression of endogenous glucose production and/or abnormal disposition of meal-derived glucose. To investigate the relative contributions of these processes and to determine whether 2 wk of near normoglycemia achieved by using intensive insulin therapy could restore the pattern of glucose disposal to normal, meal-related and endogenous rates of glucose appearance were measured isotopically after ingestion of a mixed meal that contained deuterated glucose in seven lean insulin-dependent and five lean nondiabetic subjects. Diabetic subjects were studied once when insulin deficient and again during intensive insulin therapy after 2 wk of near normoglycemia. Total glucose production was determined by using tritiated glucose and the contribution of meal-related glucose was determined by using the plasma enrichment of deuterated glucose. The elevated basal and peak postprandial plasma glucose concentrations (252 ± 33 and 452 ± 31 mg/dl) of diabetic subjects when insulin deficient were decreased by intensive insulin therapy to values (82 ± 6 and 193 ± 10 mg/dl, P < 0.01) that approximated those of nondiabetic subjects (93 ± 3 and 140 ± 15 mg/dl, respectively). Total and endogenous rates of glucose appearance (3,091 ± 523 and 1,814 ± 474 mg/kg per 8 h) in the diabetic subjects were significantly (P < 0.02) greater than those in nondiabetic subjects (1,718 ± 34 and 620 ± 98 mg/kg per 8 h, respectively), whereas meal-derived rates of glucose appearance did not differ. Intensive insulin therapy decreased (P < 0.01) both total (1,581 ± 98 mg/kg per 8 h) and endogenous (478 ± 67 mg/kg per 8 h) glucose appearances to rates that approximated those observed in the nondiabetic subjects, but did not alter meal-related glucose appearance. Thus, excessive entry of glucose into the peripheral circulation in insulin-deficient diabetic patients after ingestion of a mixed meal resulted from a lack of appropriate suppression of endogenous glucose production rather than impairment of initial splanchnic glucose uptake. Intensive insulin therapy restored postprandial suppression of endogenous glucose production to rates observed in nondiabetic subjects.