title: 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.
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Krakow, Poland.|Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, MA, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Nowak
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Krakow, Poland.|University Hospital, Krakow, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Hohendorff
authors.affiliation: University Hospital, Krakow, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Solecka
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Krakow, Poland.|University Hospital, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Szopa
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Krakow, Poland.|University Hospital, Krakow, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Krakow, Poland.|University Hospital, Krakow, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Kiec-Wilk
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Krakow, Poland. malecki_malecki@yahoo.com.|University Hospital, Krakow, Poland. malecki_malecki@yahoo.com.
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Malecki
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005260:Female; D054439:Ghrelin / Q000097:blood*; D005941:Glucokinase / Q000235:genetics*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D054439:Ghrelin; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D005941:Glucokinase
keywords: GCK–MODY; Ghrelin; HNF1A–MODY; T1DM; T2DM