Insulin Gene Variable Number of Tandem Repeats (INS VNTR) Genotype and Metabolic Syndrome in Childhood Obesity

Abstract Objective: The insulin VNTR polymorphism located in the insulin gene promoter (INS VNTR) has been associated with insulin levels in obese children. Hyperinsulinemia is a pivotal factor in the development of metabolic syndrome, an emerging complicance in childhood obesity. With the present study we aimed to test the associations between INS VNTR and the metabolic syndrome in juvenile-onset obesity. Materials and Methods: We screened for the INS VNTR 320 obese children (152 girls; mean age 11.2 ± 2.3 years; mean z-score BMI 3.6 ± 1.1). All of them underwent a standard oral glucose tolerance test (OGTT); baseline measurements included blood pressure, plasma lipid and fasting insulin levels. By using the data derived from the OGTT, the whole body insulin sensitivity (WBISI) and the insulinogenic index (IGI) were calculated. Results: The prevalence of metabolic syndrome reached 39 percent. No differences in INS VNTR genotype distribution were observed between obese subjects and two hundred lean, age and sex matched, children (p= 0.7). Among obeses, the prevalence of the metabolic syndrome was significantly higher in subjects with the I/I genotype (p= 0.006); the risk for developing the metabolic syndrome was significantly higher in subjects carrying the I/I genotype (OR: 2.5; 95% CI: 1.5-3.9). Obese subjects homozygotes for the class I allele showed higher insulin levels, and IGI, but lower WBISI. Conclusions: We conclude that the I variant of the insulin promoter, when expressed in homozygosis, can predispose obese children to develop the metabolic syndrome.