Contribution of Abnormal Muscle and Liver Glucose Metabolism to Postprandial Hyperglycemia in NIDDM

Abstract

To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with [14C]glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O2, and CO2 (with forearm calorimetry). In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects (45.1 +/- 2.3 vs. 34.4 +/- 1.5 g, P less than 0.01), but glucose Rd was not significantly different in NIDDM (35.1 +/- 2.4 g) and nondiabetic (33.3 +/- 2.7 g) subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 +/- 1.1 vs. 6.8 +/- 1.0 g, P less than 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 +/- 1.5 vs. 27.5 +/- 0.9 g, P less than 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 +/- 3.5 vs. 41.0 +/- 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 +/- 1.0 vs. 5.2 +/- 0.3 g in nondiabetic subjects, P less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM.

Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study

“…Glucose uptake, because of the stimulating effect of hyperglycaemia per se, is normal or increased despite insulin resistance in type 2 diabetes [18,19]. Therefore blood glucose can only be decreased by inhibiting hepatic glucose production unless oxygen consumption is increased [20,21]. One may therefore expect that hepatic insulin resistance is an important determinant of the insulin dose independent of body mass.…”

Beta Cell Function, Insulin Resistance and Plasma Adiponectin Concentrations are Predictors for the Change of Postprandial Glucose in Non-diabetic Subjects at Risk for Type 2 Diabetes

“…Adiponectin might especially influence hepatic insulin sensitivity [21 ± 23], which is the most important determinant of postprandial glucose [24,25]. By estimating insulin sensitivity from the oGTT [12] using a formula derived from the euglycemic clamp, a measure of whole−body insulin sensitivity, we may have missed some specific effect of adiponectin on hepatic insulin sensitivity.…”

Insulin secretory defect plays a major role in the development of diabetes in patients with distal pancreatectomy

“…However, when insulin secretion is defective, a lack of glucagon suppression can cause substantial hyperglycemia by enhancing glucose production rates [21]. Moreover, the magnitude of the defective suppression of hepatic glucose production is correlated with increased plasma glucagon and the glucagon-insulin molar ratio [22][23][24]. In addition, 48 hours of physiological hyperglycemia, even in NGT subjects, is associated with an increased rate of basal hepatic glucose production, an impaired insulin-mediated suppression of hepatic glucose production, and defective glucose disposal by peripheral tissues [25,26].…”