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.
Highlights
Obesity usually has a negative metabolic impact associated to an excessive and abnormal adipose tissue deposition and function [1], which affects several physiological processes such as glucose homeostasis and insulin sensitivity [2].Insulin resistance (IR) is characterized by complete or partial insufficiency of insulin action on target tissues, being one of the first physiological abnormalities that precede the development of type 2 diabetes (T2D) and being usually related to concomitant metabolic chronic diseases such as obesity, non-alcoholic fatty liver disease, and atherosclerosis [3]
Major exclusion criteria were a clinical history of type 1 diabetes or cardiovascular disease; T2D patients treated with insulin; pregnant or lactating women; and use of medication that could affects body weight or lipid/glucose levels
The results showed a statistically significant protein-protein interaction (PPI) enrichment p-value of 5.71 × 10−14, indicating that the proteins are at least in some way biologically connected, as a group
Summary
Insulin resistance (IR) is characterized by complete or partial insufficiency of insulin action on target tissues, being one of the first physiological abnormalities that precede the development of type 2 diabetes (T2D) and being usually related to concomitant metabolic chronic diseases such as obesity, non-alcoholic fatty liver disease, and atherosclerosis [3]. This condition is associated with concomitant pathological processes including hyperlipidemia, ectopic lipid accumulation, low-grade inflammation, endoplasmic reticulum stress, and oxidative cell damage [4]. Metabolically healthy and unhealthy phenotypes have emerged in subjects with excessive adiposity [7]
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