Glucose resistance contributes to diabetes mellitus in cirrhosis.
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/dl, in combination with an infusion of somatostatin (500 micrograms/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 homogeneous 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/dl in controls, at 212 +/- 4 mg/dl in glucose-intolerant patients and at 287 +/- 19 mg/dl 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/dl vs. 2.45 +/- 0.10 mg/dl; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Petrides
A S
AS
Department of Internal Medicine, Heinrich-Heine University, Düsseldorf, Germany.
Schulze-Berge
D
D
Vogt
C
C
Matthews
D E
DE
Strohmeyer
G
G
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology; D004351:Drug Resistance; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D010084:Oxidation-Reduction
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D005934:Glucagon; D005947:Glucose