Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis

Alexander S. Petrides, Leif C. Groop, Caroline A. Riely, Ralph A. DeFronzo

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Insulin secretion and insulin sensitivity were evaluated in eight clinically stable cirrhotic patients and in 12 controls. OGTT was normal in cirrhotics but plasma insulin response was increased approximately twofold compared with controls. Subjects received a three-step (0.1,0.5,1.0 mU/kg · min) euglycemic insulin clamp with indirect calorimetry, [6-3H)-glucose, and [1-14C]-palmitate. During the two highest insulin infusion steps glucose uptake was impaired (3.33±0.31 vs. 5.06±0.40 mg/ kg · min, P < 0.01, and 6.09±0.50 vs. 7.95±0.52 mg/kg · min, P < 0.01). Stimulation of glucose oxidation by insulin was normal; in contrast, nonoxidative glucose disposal (i.e., glycogen synthesis) was markedly reduced. Fasting (r = -0.553, P < 0.01) and glucose-stimulated (r = -0.592, P < 0.01) plasma insulin concentration correlated inversely with the severity of insulin resistance. Basal hepatic glucose production was normal in cirrhotics and suppressed normally with insulin. In postabsorptive state, plasma FFA cone (933±42 vs. 711±44 μmol/ liter, P < 0.01) and FFA turnover (9.08±1.20 vs. 6.03±0.53 μmol/kg · min, P < 0.01) were elevated in cirrhotics despite basal hyperinsulinemia; basal FFA oxidation was similar in cirrhotic and control subjects. With low-dose insulin infusion, plasma FFA oxidation and turnover failed to suppress normally in cirrhotics. During the two higher insulin infusion steps, all parameters of FFA metabolism suppressed normally. In summary, stable cirrhotic patients with normal glucose tolerance exhibit marked insulin resistance secondary to the impaired nonoxidative glucose disposal. Our results suggest that chronic hyperinsulinism may be responsible for the insulin resistance observed in cirrhosis.

Original languageEnglish (US)
Pages (from-to)561-570
Number of pages10
JournalJournal of Clinical Investigation
Volume88
Issue number2
DOIs
StatePublished - Aug 1991

Keywords

  • Free fatty acid cirrhosis
  • Glucose
  • Hyperinsulinemia
  • Insulin resistance

ASJC Scopus subject areas

  • Medicine(all)

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