IMPAIRED POSTPRANDIAL GLUCOSE-UTILIZATION IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

The importance of impaired glucose utilization in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) is controversial. Three methods were used to assess glucose ut ilization following ingestion of a mixed meal in 18 NIDDM and 12 nondi abetic subjects. Dual glucose isotopes were used to determine first-pa ss splanchnic glucose uptake, suppression of endogenous glucose produc tion, and systemic glucose utilization. Leg balance was used to evalua te skeletal muscle glucose metabolism, and systemic and limb indirect calorimetry were used to assess glucose and lipid oxidation. NIDDM sub jects had marked postprandial hyperglycemia as compared with nondiabet ics (15.35 +/- 0.72 v 5.83 +/- 0.28 mmol, P < .001), accompanied by lo wer postprandial insulin (179 +/- 25 v 253 +/- 46 pmol, P 4.01) and el evated plasma free fatty acids ([FFA] 569 +/- 34 v 314 +/- 20 mu mol/L , P < .001). Cumulative postprandial glucose appearance was nearly two fold greater in NIDDM (82.2 +/- 4.7 v 48.7 +/- 4.9 g.5h, P <.001) due to increased endogenous glucose production (56.4 +/- 4.8 v 24.5 +/- 1. 9 g, P < .001), whereas first-pass splanchnic uptake of ingested gluco se was normal in NIDDM. Cumulative postprandial glucose utilization in NIDDM, after correction for urinary glucose, was unchanged from posta bsorptive rates, a pattern also found for postprandial glucose oxidati on. Cumulative leg glucose uptake was somewhat less in NIDDM subjects (123 +/- 18 v 173 +/- 14 mu mol/100 mL leg tissue.5h, P = .06), wherea s lactate and alanine net release across the leg were nevertheless two fold greater in NIDDM (P = .04) and accounted for nearly half of the l eg glucose metabolism in NIDDM. Leg glucose oxidation was similar in n ondiabetics and NIDDM subjects (89.5 +/- 15.2 v 73.4 +/- 9.5 mu mol/10 0 mt leg tissue 5h, NS). Nondiabetic subjects had leg glucose storage of 39 +/- 17 mu Lmol/100 ml leg tissue 5 h, whereas the respective val ue in NIDDM (-21.1 +/- 14.2) was not significantly different from zero . In summary, although impaired suppression of endogenous glucose prod uction in patients with NIDDM is the major quantitative factor driving postprandial hypergtycemia, postprandial glucose utilization is chara cterized by little if any change from postabsorptive glucose metabolis m. Copyright (C) 1994 by W.B. Saunders Company