Elsevier

Metabolism

Volume 38, Issue 4, April 1989, Pages 387-395
Metabolism

Fasting hyperglycemia in non-insulin-dependent diabetes mellitus: Contributions of excessive hepatic glucose production and impaired tissue glucose uptake

https://doi.org/10.1016/0026-0495(89)90129-7Get rights and content

Abstract

The factors responsible for fasting hyperglycemia were investigated in 77 normal weight non-insulin-dependent diabetic (NIDD) and 72 age-, sex-, and weight-matched control individuals. In diabetic subjects with mild fasting hyperglycemia (<140 mg/dL) hepatic glucose production (1.85 ± 0.03 mg/kg · min) was similar to controls (1.84 ± 0.02); the major factor responsible for the elevated basal glucose level in the diabetic group was a decreased efficiency in the tissue uptake of glucose, as reflected by a 30% decline in the rate of glucose clearance (1.56 ± 0.03 v 2.00 ± 0.03 mL/kg · min, P < .001). In contrast, in diabetic subjects with fasting plasma glucose concentrations above 140 mg/dL, basal hepatic glucose production was significantly elevated (2.42 ± 0.08 mg/kg · min, P < .001) and correlated closely with the increase in fasting plasma glucose concentration (r = .796, P < .001). The basal rate of whole body glucose clearance reached a plateau value at fasting glucose levels of 160 to 180 mg/dL and did not contribute to the further rise in fasting plasma glucose concentrations above 160 to 180 mg/dL. Decreased efficiency of tissue glucose uptake is responsible the development of fasting hyperglycemia in patients with mild NIDDM (fasting plasma glucose < 140 mg/dL). As the diabetic state worsens, an increase in basal hepatic glucose production is the major factor responsible for the progressive rise in fasting glucose levels.

References (66)

  • SE Fineberg et al.

    Glipizide versus tolbutamide, an open trial. Effects on insulin secretory patterns and glucose concentrations

    Diabetologia

    (1980)
  • D Simonson et al.

    Mechanism of improvement in glucose metabolis following chronic glyburide therapy

    Diabetes

    (1984)
  • RG Judzewitsch et al.

    Chronic chlorporpamide therapy of noninsulin-dependent diabetes augments basal and stimulated insulin secretion by increasing islet sensitivity to glucose

    J Clin Endocrinol Metab

    (1982)
  • RA Jackson et al.

    Mechanism of metformin action in non-insulin dependent diabetes mellitus

    Diabetes

    (1987)
  • RG Firth et al.

    Effects of tolazamide and exogenous insulin on insulin action in patients with noninsulin-dependent diabetes mellitus

    N Engl J Med

    (1986)
  • H Hidaka et al.

    Improvement of insulin secretion but not insulin resistance after short term control of plasma glucose in obese type II diabetics

    J Clin Endocrinol Metab

    (1982)
  • WT Garvey et al.

    The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus

    Diabetes

    (1985)
  • RR Henry et al.

    Effects of weight loss on mechanisms of hyperglycemia in obese non-insulin dependent diabetes mellitus

    Diabetes

    (1986)
  • RA DeFronzo et al.

    Hepatic and peripheral insulin resistance: A common feature in non-insulin dependent and insulin dependent diabetes

    Diabetologia

    (1982)
  • RA DeFronzo

    The triumvirate—β-cell, liver, muscle: A collusion responsible for type II diabetes mellitus. Lilly Lecture

    Diabetes

    (1988)
  • JD Best et al.

    The effect of chronic sulfonylurea therapy on hepatic glucose production in noninsulin dependent diabetes mellitus

    Diabetes

    (1982)
  • RG Firth et al.

    Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus

    J Clin Invest

    (1986)
  • C Bogardus et al.

    Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin dependent diabetic subjects

    J Clin Invest

    (1984)
  • OG Kolterman et al.

    Receptor and postreceptor defects contribute to the insulin resistance in noninsulin dependent diabetes mellitus

    J Clin Invest

    (1981)
  • L Sacca et al.

    Hyperglycemia inhibits glucose production in man independent of changes in glucoregulatory hormones

    J Clin Endocrinol Metab

    (1978)
  • Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance

    Diabetes

    (1979)
  • H Glauber et al.

    Effects of fasting on plasma glucose and prolonged tracer measurement of hepatic glucose output in NIDDM

    Diabetes

    (1987)
  • CN Hales et al.

    Immunoassay of insulin with insulin antibody precipitate

    Biochem J

    (1963)
  • RS Sherwin et al.

    Glucose homeostasis during prolonged suppression of glucagon and insulin secretion by somatostatin

  • PM Bell et al.

    Assessment of insulin action in insulin-dependent diabetes mellitus using [614C] glucose, [33H] glucose, and [23H] glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used

    J Clin Invest

    (1986)
  • E Ferrannini et al.

    Effect of insulin on the distribution and deposition of glucose in man

    J Clin Invest

    (1985)
  • C Cobelli et al.

    Non-steady state: error analysis of Steele's model and developments for glucose kinetics

    Am J Physiol

    (1987)
  • RA DeFronzo et al.

    Regulation of splanchnic and peripheral glucose uptake by insulin and hyperglycemia

    Diabetes

    (1983)
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    Supported by NIH Grant Nos. AM 24092 and AG00233 and Clinical Research Center Grant No. RR125.

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