Distinct genetic subtypes of adiposity and glycemic changes in response to weight-loss diet intervention: the POUNDS Lost trial

Eur J Nutr. 2021 Feb;60(1):249-258. doi: 10.1007/s00394-020-02244-x. Epub 2020 Apr 9.


Purpose: Obesity is a heterogeneous condition and distinct adiposity subtypes may differentially affect type 2 diabetes risk. We assessed relations between genetically determined subtypes of adiposity and changes in glycemic traits in a dietary intervention trial.

Methods: The four genetic subtypes of adiposity including waist-hip ratio-increase only (WHRonly+), body mass index-increase only (BMIonly+), WHR-increase and BMI-increase (BMI+WHR+), and WHR-decrease and BMI-increase (BMI+WHR-) were assessed by polygenetic scores (PGSs), calculated based on 159 single nucleotide polymorphisms related to BMI and/or WHR. We examined the associations between the four PGSs and changes in fasting glucose, insulin, β-cell function (HOMA-B) and insulin resistance (HOMA-IR) in 692 overweight participants (84% white Americans) who were randomly assigned to one of four weight-loss diets in a 2-year intervention trial.

Results: Higher BMI+WHR-PGS was associated with a greater decrease in 2-year changes in waist circumference in white participants (P = 0.002). We also found significant interactions between WHRonly+PGS and dietary protein in 2-year changes in fasting glucose and HOMA-B (P = 0.0007 and < 0.0001, respectively). When consuming an average-protein diet, participants with higher WHRonly+PGS showed less increased fasting glucose (β = - 0.46, P = 0.006) and less reduction in HOMA-B (β = 0.02, P = 0.005) compared with lower WHRonly+PGS. Conversely, eating high-protein diet was associated with less decreased HOMA-B among individuals with lower than higher WHRonly+PGS (β = - 0.02, P = 0.006).

Conclusions: Distinct genetically determined adiposity subtypes may differentially modify the effects of weight-loss diets on improving glucose metabolism in white Americans. This trial was registered at clinicaltrials.gov as NCT00072995.

Keywords: Adiposity subtypes; Body mass index; Gene–diet interaction; Glycemic traits; Polygenetic score; Waist–hip ratio.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adiposity
  • Body Mass Index
  • Diabetes Mellitus, Type 2* / genetics
  • Diet, Reducing
  • Humans
  • Insulin Resistance*
  • Obesity / genetics
  • Weight Loss

Associated data

  • ClinicalTrials.gov/NCT00072995