Objective: We evaluated metabolic parameters in Chilean women with polycystic ovary syndrome (PCOS) who were carriers and non-carriers of the glycine-to-arginine substitution at codon 972 (Gly972Arg) variant of insulin receptor substrate-1 and to assess insulin response after oral high- and low-glycemic loads
Methods: In 146 women with PCOS and 97 healthy women (HW), Gly972Arg genotypes were obtained by polymerase chain reaction, and an oral glucose tolerance test was performed with glucose and insulin measurements. An insulinogenic index, a homeostasis model assessment for insulin resistance, and whole-body insulin sensitivity index (composite) were calculated. Eight carriers and eight non-carriers (four PCOS and four HW, respectively) underwent a 50-g glucose (high glycemic) or 50-g fructose (low glycemic) load with serum glucose and insulin measurements at 15-min intervals for 3 h.
Results: The frequency of the Gly972Arg variant was higher in PCOS patients than in HW (P < 0.05). The insulinogenic index was lower in HW carriers than in non-carriers (P < 0.05). In PCOS carriers, 2-h insulin was higher than in those without the mutation. In overweight PCOS carriers, the homeostasis model assessment for insulin resistance was higher and the insulin sensitivity index was lower than in PCOS patients without the mutation. In HW carriers, a delay in the maximal response of insulin secretion was observed, with a decrease of 26.7% in insulin concentrations 30 to 60 min after the 50-g glucose load. Glucose concentrations increased by 19.7% between 60 and 120 min. Glucose concentrations between 0 and 120 min were 14.9% higher in PCOS carriers than in non-carriers after the 50-g glucose load.
Conclusions: In HW, this polymorphism appears to be associated with a decrease in insulin secretion; in PCOS women, this polymorphism interacts with obesity to influence insulin resistance, thus contributing to the pathogenesis of the metabolic component of PCOS.