Growth hormone, insulin-like growth factor-1 and insulin resistance in cirrhosis.
Cirrhosis is characterized by paradoxical growth hormone secretion in response to glucose and insulin infusion. To ascertain whether this abnormality contributes to insulin resistance, euglycemic hyperinsulinemic glucose clamps were performed on six patients with cirrhosis and six normal control subjects. Each patient with cirrhosis underwent two clamps in random order, a clamp with somatostatin (250 micrograms/hr) together with insulin and glucagon replacement, and a control clamp without somatostatin. The normal subjects underwent the control clamp only. During the control clamp, growth hormone levels were considerably higher in the patients with cirrhosis (6.1 +/- 0.4 vs. 0.5 +/- 0.4 mU/L, p < 0.02), and glucose uptake was considerably lower (3.29 +/- 0.56 vs. 9.52 +/- 1.14 mg/kg/min, p < 0.001). Indirect calorimetry indicated that the defect was accounted for by lower nonoxidative glucose disposal (1.23 +/- 0.45 vs. 6.00 +/- 0.73, p < 0.001). Peripheral glucose uptake, exemplified by forearm glucose uptake (0.27 +/- 0.04 vs. 1.22 +/- 0.42 mg/100 ml/min, p < 0.02), and calculated insulin sensitivity (24 +/- 8 vs. 114 +/- 20 microliters/kg/min per mU/L) were particularly diminished. In the patients with cirrhosis somatostatin suppressed growth hormone levels (6.1 +/- 1.2 to 1.2 +/- 0.4 mU/L, p < 0.05). However, no significant changes occurred in whole-body glucose uptake (3.29 +/- 0.56 vs 3.01 +/- 0.54 mg/kg/min), forearm glucose uptake (0.27 +/- 0.04 vs 0.30 +/- 0.01 mg/100 ml/min) or insulin sensitivity (24 +/- 8 vs, 35 +/- 10 microliters/kg/min/mU/L, p = 0.42).(ABSTRACT TRUNCATED AT 250 WORDS)
Shmueli
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Gastroenterology and Liver Unit, Royal Victoria Infirmary, Newcastle Upon Tyne, United Kingdom.
Stewart
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Alberti
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Record
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D000328:Adult; D002096:C-Peptide / Q000097:blood; D002153:Calorimetry, Indirect; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008099:Liver / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013004:Somatostatin / Q000494:pharmacology
D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005947:Glucose