Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study

• Published in: Diabetic medicine Vol. 23; no. 6; pp. 685 - 689
• Main Authors: Mager, U., Lindi, V., Lindström, J., Eriksson, J. G., Valle, T. T., Hämäläinen, H., Ilanne-Parikka, P., Keinänen-Kiukaanniemi, S., Tuomilehto, J., Laakso, M., Pulkkinen, L., Uusitupa, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-06-2006; Blackwell
• Subjects: Biological and medical sciences; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - prevention & control; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Finland; genetics of Type 2 diabetes; Ghrelin; Glucose Intolerance - genetics; Health Surveys; Humans; Leu72Met; Male; Medical sciences; Middle Aged; Multicenter Studies as Topic; Peptide Hormones - genetics; polymorphism; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Prospective Studies; Risk; Europe; Finland; Endocrinopathy; Type 2 diabetes; Human; genetics of Type 2 diabetes; Genetic variability; Metabolic diseases; Genotype; Epidemiology; Prevention; Leu72Met; Ghrelin; Risk factor; Impaired glucose tolerance; Polymorphism
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2006.01870.x

Aims  Ghrelin is a gut–brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS).
Methods  DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method.
Results  There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10–0.79; P = 0.016).
Conclusions  Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first‐phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.