A blunted initial
insulin secretory response may contribute to oral
glucose intolerance in
cirrhosis. Oral
glucose is a better stimulant to insulin secretion than intravenous (IV)
glucose in part because of release of gut
peptides, notably
glucose-dependent insulinotropic peptide (GIP) and
glucagon-like peptide 1 [7-36 amide] (
GLP-1 [7-36
amide]). Because impaired release of or resistance to these gut
peptides could explain impaired insulin secretion after oral
glucose, we measured insulin secretion, plasma GIP, and
GLP-1 [7-36
amide] levels, basally and after 75 g oral
glucose, in 10 cirrhotics and 10 controls. Insulin secretion was calculated from a two-compartment analysis of serum
C-peptide levels using kinetic parameters derived from IV injection of recombinant human
C-peptide.
C-peptide metabolic clearance rate, and the fractional rate constants for
C-peptide (using the two-compartment model) were not significantly different, but the volume of the central compartment was 15% greater in cirrhotics (P < .01). Fasting
blood glucose levels were similar (cirrhotics, 4.9 +/- 0.2; controls, 4.6 +/- 0.1 mmol/L) but serum
insulin was six times higher in cirrhotics (P < .001). Cirrhotics had higher fasting GIP (215 +/- 72 vs. 42 +/- 18 pmol/L) and
GLP-1 [7-36
amide] levels (25 +/- 3 vs. 16 +/- 1 pmol/L) (both P < .05). After oral
glucose, blood glucose levels were significantly higher in cirrhotics. The timing of the gut
peptide response to oral
glucose was similar in the two groups, but peak levels of both
peptides were approximately x2 higher in the cirrhotics.(ABSTRACT TRUNCATED AT 250 WORDS)