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Effect of the interaction between diet composition and the PPM1K genetic variant on insulin resistance and β cell function markers during weight loss: Results from the Nutrient Gene Interactions in Human Obesity: Implications for dietary guidelines (NUGENOB) randomized trial

American Journal of Clinical Nutrition Aug 09, 2017

Goni L, et al. – The impact of dietary fat and carbohydrate intakes on the link between the rs1440581 protein phosphatase Mg2+/Mn2+ dependent 1K (PPM1K) genetic variant and glucose–metabolism traits during weight loss was assessed in this current study. According to findings, PPM1K rs1440581 may impact alterations in glucose metabolism during weight loss, and this effect was dependent on dietary fat and carbohydrate intakes.

Methods

  • In this study, the rs1440581 PPM1K genetic variant was genotyped in a total of 757 nondiabetic individuals who were randomly assigned to 1 of 2 energy-restricted diets that differed in macronutrient composition (low-fat diet: 20–25% fat, 15% protein, and 60–65% carbohydrate; high-fat diet: 40–45% fat, 15% protein, and 40–45% carbohydrate).
  • Researchers measured changes in fasting glucose, fasting insulin, insulin resistance (homeostasis model assessment of insulin resistance) and homeostasis model assessment of β cell function (HOMA-B) after a mean ± SD weight loss of 6.8 ± 3.4 kg over 10 wk and analyzed according to the presence of the T allele of rs1440581.

Results

  • Findings demonstrated that the rs1440581 T allele was associated with a smaller improvement in glucose concentrations after the 10-wk dietary intervention (β ± SE: 0.05 ± 0.02 mg/dL; P = 0.03).
  • Data showed significant gene-diet interactions for the rs1440581 PPM1K genetic variant in relation to changes in insulin and HOMA-B (P-interaction = 0.006 and 0.002, respectively).
  • Researchers observed that in response to the high-fat diet, the T allele was associated with a higher reduction of insulin (β ± SE: -0.77 ± 0.40 μU/mL; P = 0.04) and HOMA-B (β ± SE: -13.2 ± 3.81; P = 0.003).
  • They observed an opposite effect in the low-fat diet group, although in this group the T allele was marginally (P = 0.10) and not significantly (P = 0.24) associated with insulin and HOMA-B, respectively.

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