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Abnormal glucagon evident in patients with NAFLD

Researchers found that abnormal glucagon levels were common in patients with nonalcoholic fatty liver disease, but had intact alpha cell sensitivity to physiological doses of glucagon-like peptide-1, according to recent findings.

“Incretin physiology has been intensely studied in patients with type 2 diabetes, but no studies have investigated the role of [glucagon-like peptide-1] in glucose tolerant individuals with NAFLD. Hyperglucagonemia in NAFLD could reflect impaired regulation of glucagon by [glucagon-like peptide-1],” Tina Vilsbøll, MD, DMSc, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark, and colleagues wrote. “We studied the effects of physiological doses of [glucagon-like peptide-1] on glucagon secretion at two different plasma glucose levels.”

The researchers compared data of 10 patients with NAFLD to 10 matched controls after undergoing a 2-hour IV infusion of glucagon-like peptide-1 (GLP-1). Based on liver biopsy, five patients had mild steatosis, two had moderate and three had severe steatosis.

“We evaluated relative plasma levels of glucagon, endogenous glucose production and whole body lipolysis rates with stable isotopes and respiratory quotient using indirect calorimetry,” the researchers wrote.

The patients with NAFLD showed more resistance to insulin, with a homeostasis model assessment insulin resistance score of 3.8 ± 2.2 compared with 1.6 ± 1.5 among the controls (P = .003), as well as higher fasting hyperglucagonemia than controls (7.5 ± 5.3 vs. 5.8 ± 1.5 mmol/L; P = .045).

Both groups had similar relative glucagon suppression during GLP-1 infusion at fasting (– 97 ± 75 vs. – 93 ± 41 pmol/L × min^{– 1}; P = .566) and postprandial plasma glucose levels (– 108 ± 101 vs. – 97 ± 53 pmol/L × min^{– 1}; P = .196).

Increased insulinotropic effects of GLP-1 were seen in the patients with NAFLD. However, no effect of GLP-1 on endogenous glucose production was observed in either group.

The researchers concluded: “Patients with NAFLD exhibited fasting hyperglucagonemia, but intact GLP-1-mediated glucagon suppression independently of plasma glucose concentrations. Preserved glucagonostatic effect and increased insulinotropic effects of GLP-1 in NAFLD may be important to maintain normoglycemia in these patients.”

Disclosure: The researchers report no relevant financial disclosures.