Abstract
BackgroundRecent research has demonstrated that Type 2 Diabetes (T2D) risk is influenced by a number of common polymorphisms, including MC4R rs17782313, PPARG rs1801282, and TCF7L2 rs7903146. Knowledge of the association between these single nucleotide polymorphisms (SNPs) and body weight changes in different forms of prediabetes treatment is still limited. The aim of this study was to investigate the association of polymorphisms within the MC4R, PPARG, and TCF7L2 genes on the risk of carbohydrate metabolism disorders and body composition changes in overweight or obese patients with early carbohydrate metabolism disorders.Methods and resultsFrom 327 patients, a subgroup of 81 prediabetic female patients (48.7 ± 14.8 years) of Eastern European descent participated in a 3-month study comprised of diet therapy or diet therapy accompanied with metformin treatment. Bioelectrical impedance analysis and genotyping of MC4R rs17782313, PPARG rs1801282, and TCF7L2 rs7903146 polymorphisms were performed. The MC4R CC and TCF7L2 TT genotypes were associated with increased risk of T2D (OR = 1.46, p = 0.05 and OR = 2.47, p = 0.006, respectively). PPARG CC homozygotes experienced increased weight loss; however, no additional improvements were experienced with the addition of metformin. MC4R TT homozygotes who took metformin alongside dietary intervention experienced increased weight loss and reductions in fat mass (p < 0.05).ConclusionsWe have shown that the obesity-protective alleles (MC4R T and PPARG C) were positively associated with weight loss efficiency. Furthermore, we confirmed the previous association of the MC4R C and TCF7L2 T alleles with T2D risk.
Highlights
Type 2 Diabetes (T2D) develops as a result of a complex interaction between adverse environmental and certain genetic factors [1]
We found that the C allele is associated with a more pronounced weight loss and decrease of waist/hip ratio among patients undertaking diet therapy, which is aligned with the results of earlier studies from Adamo et al and Matsuo et al.; here, the G allele was more common among patients resistant to diet therapy [43, 44]
We detected that MC4R rs17782313 and PPARGrs1801282 genotypes play an important role in body composition changes
Summary
Type 2 Diabetes (T2D) develops as a result of a complex interaction between adverse environmental and certain genetic factors [1]. It is well established that T2D may develop through various different pathways, including insulin resistance (IR) and beta-cell function deficiency, suggesting that different gene polymorphisms may be involved in T2D pathogenesis. These genes include CDKAL1, CDKN2A, CDKN2B, TCF7L2, KCNJ11, UCP2, WFS1, and ABCC8, amongst many others [6]. Recent research has demonstrated that Type 2 Diabetes (T2D) risk is influenced by a number of common polymorphisms, including MC4R rs17782313, PPARGrs1801282, and TCF7L2 rs7903146. The aim of this study was to investigate the association of polymorphisms within the MC4R, PPARG, and TCF7L2 genes on the risk of carbohydrate metabolism disorders and body composition changes in overweight or obese patients with early carbohydrate metabolism disorders. We confirmed the previous association of the MC4R C and TCF7L2 T alleles with T2D risk
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