Vigorous Physical Activity, Heredity, and Modulation of Risk for Obesity and Type 2 Diabetes in Postmenopausal Women

Abstract

Both obesity and type 2 diabetes are significant health burdens in our society. The prevention of these conditions is vital to individual health and to the health care system, which is inordinately stressed by these chronic diseases. Due to variations in individual response to interventions, prevention strategies may require some tailoring based on heritable traits.The objective of this study was to determine whether insulin sensitivity could be altered by resistance training, and further if body composition or insulin sensitivity response to resistance training in postmenopausal women may be influenced by adrenergic receptor genetic variants and gene-gene interactions.Completers of a 12-month randomized controlled trial of resistance training in sedentary post-menopausal (PM) women, using or not using hormone therapy, were measured for fasting plasma glucose, insulin, and non-esterified fatty acids (NEFA) at baseline and one year. These biomarkers were used to compute models of insulin sensitivity. Body composition was measured by dual x-ray absorptiometry. Subjects were also re-consented for genotyping of adrenergic receptor (ADR) gene variants, ADRA2B Glu9/12, ADRB3 Trp64Arg, ADRB2 Gln27Glu.The resistance training intervention did not have an overall effect on insulin sensitivity in the largest sample and change in insulin sensitivity was largely dependent body composition. There were small favorable effects of genotype on initial measures of both body composition and insulin sensitivity in the ADRA2B Glu9+ carriers versus non-carriers. The effects of ADRA2B alone were no longer present following intervention, but ADRB3 Arg64+ and ADRB2 Glu27+ contribute to improved insulin sensitivity with exercise, when accounting for body composition. ADRB2 Glu27+ was the key to improved biomarkers of insulin sensitivity when in combination with ADRA2B Glu9+ or ADRB3 Arg64+ and a model of insulin sensitivity was most improved by the combination ADRB3 Arg64+ by ADRB2 Glu27+, compared to other ADRB3 by ADRB2 combinations.This is the first trial of ADRA2B, ADRB3, and ADRB2 genetic variation combinations and resistance training in postmenopausal women relative to body composition and insulin sensitivity. Some specific genotypes were identified as responders and non-responders to exercise. These data support independent associations between body composition and insulin sensitivity and the ADR gene variants.