Circulating ghrelin level is higher in HNF1A-MODY and GCK-MODY than in polygenic forms of diabetes mellitus.

Abstract

Ghrelin is a hormone that regulates appetite. It is likely to be involved in the pathophysiology of varying forms of diabetes. In animal studies, the ghrelin expression was regulated by the hepatocyte nuclear factor 1 alpha (HNF1A). Mutations of the HNF1A gene cause maturity onset diabetes of the young (MODY). We aimed to assess the circulating ghrelin levels in HNF1A–MODY and in other types of diabetes and to evaluate its association with HNF1A mutation status. Our cohort included 46 diabetic HNF1A gene mutation carriers, 55 type 2 diabetes (T2DM) subjects, 42 type 1 diabetes (T1DM) patients, and 31 glucokinase (GCK) gene mutation carriers with diabetes as well as 51 healthy controls. Plasma ghrelin concentration was measured using the immunoenzymatic assay with polyclonal antibody against the C-terminal fragment of its acylated and desacylated forms. Ghrelin concentrations were 0.75 ± 0.32, 0.70 ± 0.21, 0.50 ± 0.20, and 0.40 ± 0.16 ng/ml in patients with HNF1A–MODY, GCK–MODY, T1DM, and T2DM, respectively. The ghrelin levels were higher in HNF1A–MODY and GCK–MODY than in T1DM and T2DM (p < 0.001 for all comparisons) but lower than in non-diabetic controls (1.02 ± 0.29 ng/ml, p < 0.001 for both comparisons). In the multivariate linear model, the differences between both MODY groups and common diabetes types remained significant. Analysis by a HNF1A mutation type indicated that ghrelin concentration is similar in patients with different types of sequence differences. Plasma ghrelin level is higher in HNF1A–MODY and GCK–MODY than in the common polygenic forms of diabetes.