Glucose resistance contributes to diabetes mellitus in cirrhosis

Authors

  • Alexander S. Petrides M. D.,

    Corresponding author
    1. Division of Gastroenterology, Department of Internal Medicine, Heinrich-Heine University, 4000 Düsseldorf 1, Germany
    • Division of Gastroenterology, Department of Internal Medicine, University of Tennessee–Memphis, 951 Court Avenue, Room 555D, Memphis, TN 38163
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  • Dirk Schulze-Berge,

    1. Division of Gastroenterology, Department of Internal Medicine, Heinrich-Heine University, 4000 Düsseldorf 1, Germany
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  • Christoph Vogt,

    1. Division of Gastroenterology, Department of Internal Medicine, Heinrich-Heine University, 4000 Düsseldorf 1, Germany
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  • Dwight E. Matthews,

    1. The New York Hospital–Cornell Medical Center, Cornell University, New York, New York 10021
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  • Georg Strohmeye

    1. Division of Gastroenterology, Department of Internal Medicine, Heinrich-Heine University, 4000 Düsseldorf 1, Germany
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Abstract

Insulin resistance is a characteristic feature of glucose-intolerant and diabetic cirrhotic patients. The pathogenic factors, however, that are responsible for the development of impaired glucose tolerance in cirrhosis, remain unclear. To examine whether the ability of hyperglycemia per se to enhance glucose uptake (by means of mass-action effect) is impaired in cirrhosis, we measured (insulin-independent) whole-body glucose disposal during hyperglycemia (hyperglycemic clamp studies, +125 mg/dI, in combination with an infusion of somatostatin (500 μg/hr), insulin (0.1 mU/kg min) and glucagon (0.5 ng/kg min) to “clamp” hormone levels at baseline), whole-body glucose oxidation (indirect calorimetry) and glucose turnover (prime-continuous infusion of [6,6-2H2-]glucose in a clinically homogenous group of cirrhotic patients with glucose intolerance (n = 7) or frank diabetes mellitus (n = 7) and in control individuals (n = 7). Fasting plasma glucose concentrations were normal in glucose-intolerant patients but were significantly increased in diabetic patients (158 ± 19 vs. 87 ± 2 mg/dl in controls; p < 0.01). Plasma glucose concentrations were clamped at 214 ± 4 mg/dI in controls, at 212 ± 4 mg/dI in glucose-intolerant patients and at 287 ± 19 mg/dI in diabetic patients; plasma insulin and glucagon concentrations were maintained at baseline levels. In the basal state, total-body glucose disposal (which equals basal hepatic glucose output) was normal in glucose-intolerant patients (2.25 ± 0.11 mg/kg min) but was increased in diabetic patients compared with controls (3.32 ± 0.26 mg/dI vs. 2.45 ± 0.10 mg/dI p < 0.01). Hyperglycemia significantly stimulated whole-body glucose uptake in glucose-intolerant cirrhotic patients (+ 0.97 ± 0.23 mg/kg/min p < 0.01 vs. baseline), similar to control values (+1.18 ± 0.26; p < 0.01 vs. baseline). In controls and glucose-intolerant patients, stimulation of glucose oxidation and nonoxidative glucose disposal were responsible for the increase in glucose utilization (both p < 0.01 vs. baseline in both groups, respectively). In diabetic patients, however, hyperglycemia did not enhance glucose disposal. In summary, the effect of hyperglycemia per se to promote whole-body glucose uptake is unaltered in cirrhotic patients with glucose intolerance but is blunted in those with frank diabetes mellitus. We conclude that glucose resistance contributes to the development of diabetes mellitus in cirrhosis. (HEPATOLOGY 1993;18:284–291).

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