Interplay of an Obesity-Based Genetic Risk Score with Dietary and Endocrine Factors on Insulin Resistance

Nutrients. 2019 Dec 21;12(1):33. doi: 10.3390/nu12010033.

Abstract

This study aimed to nutrigenetically screen gene-diet and gene-metabolic interactions influencing insulin resistance (IR) phenotypes. A total of 232 obese or overweight adults were categorized by IR status: non-IR (HOMA-IR (homeostatic model assessment - insulin resistance) index ≤ 2.5) and IR (HOMA-IR index > 2.5). A weighted genetic risk score (wGRS) was constructed using 95 single nucleotide polymorphisms related to energy homeostasis, which were genotyped by a next generation sequencing system. Body composition, the metabolic profile and lifestyle variables were evaluated, where individuals with IR showed worse metabolic outcomes. Overall, 16 obesity-predisposing genetic variants were associated with IR (p < 0.10 in the multivariate model). The wGRS strongly associated with the HOMA-IR index (adj. R squared = 0.2705, p < 0.0001). Moreover, the wGRS positively interacted with dietary intake of cholesterol (P int. = 0.002), and with serum concentrations of C-reactive protein (P int. = 0.008) regarding IR status, whereas a negative interaction was found regarding adiponectin blood levels (P int. = 0.006). In conclusion, this study suggests that interactions between an adiposity-based wGRS with nutritional and metabolic/endocrine features influence IR phenotypes, which could facilitate the prescription of personalized nutrition recommendations for precision prevention and management of IR and diabetes.

Keywords: diet; genetic risk score; insulin resistance; metabolic factors; obesity; personalized nutrition.

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Diet*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide