Effects of Basal Insulin Supplementation on Disposition of Mixed Meal in Obese Patients With NIDDM

Basal insulin supplementation has been used as a therapy for patients with non-insulin-dependent diabetes mellitus (NIDDM) who require insulin. To determine whether basal insulin supplementation in addition to lowering postabsorptive plasma glucose concentration also improves the postprandial pattern of glucose disposition, glucose metabolism after ingestion of a solid mixed meal was assessed in obese patients with NIDDM before and after treatment with ultralente and compared with glucose metabolism observed in nondiabetic subjects. Splanchnic uptake of ingested glucose clearance was assessed by including [2-3H]glucose (a tracer that only minimally cycles through glycogen) in a solid mixed meal. Postprandial gluconeogenesis was estimated by measuring the rate of incorporation of carbon dioxide into glucose. Net glucose and lipid oxidation were measured by indirect calorimetry. Both splanchnic uptake of ingested glucose (27 +/- 1 vs. 14 +/- 2 g) and postprandial hepatic glucose release (51 +/- 5 vs. 24 +/- 3 g) were greater (P less than .001) in diabetic than in nondiabetic subjects. Although the percentage of postprandial hepatic glucose release accounted for by glucose synthesis from bicarbonate was similar in the two groups (25 +/- 2 vs. 35 +/- 5%), the absolute rate was greater in the diabetic patients (13 +/- 1 vs. 8 +/- 1 g; P less than .05). Postprandial glucose oxidation and glucose disposal (measured either isotopically or by the forearm-catheterization technique) were similar in both groups. However, total lipid oxidation was increased in the diabetic patients. (P less than .05). Two weeks of basal insulin supplementation lowered fasting glucose concentrations (from 219 +/- 22 to 144 +/- 21 mg/dl; P less than .01) and integrated postprandial glycemic response (from 814 +/- 68 to 621 +/- 72 min.mg.ml-1) but not to normal. Although circulating insulin concentrations were two- to threefold greater (P less than .02) after 3 mo of basal insulin supplementation, the postprandial pattern of glucose metabolism remained essentially the same. Basal insulin supplementation decreased (P less than .05) both splanchnic uptake of ingested glucose and hepatic glucose release. The addition of a preprandial injection of soluble insulin to basal insulin supplementation further suppressed (P less than .05) postprandial hepatic glucose release, thereby further improving postprandial glucose tolerance. These studies indicate that initial splanchnic glucose clearance, hepatic glucose release, and new glucose synthesis, as well as extrahepatic substrate metabolism, are altered in NIDDM after ingestion of a mixed meal.(ABSTRACT TRUNCATED AT 400 WORDS)