Distinct genetic subtypes of adiposity and glycemic changes in response to weight-loss diet intervention: the POUNDS Lost trial.
Study Goal
The researchers aimed to determine how genetically determined adiposity subtypes influence the effects of weight-loss diets, including high-protein diets, on glucose metabolism.
Results Summary
The study found that distinct adiposity subtypes modified the effects of dietary protein on glucose metabolism, with higher WHR-only polygenic scores showing less increase in fasting glucose and less reduction in β-cell function when consuming an average-protein diet, while high-protein diets were associated with less decrease in β-cell function among those with lower WHR-only scores.
Population
692 overweight participants (84% white Americans)
Effective Dosage
Not specified
Duration
2 years
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
higher BMI+WHR- polygenetic score | decrease | 2-year changes in waist circumference | white participants | - | associated with a greater decrease | #1 |
higher WHRonly+ polygenetic score with average-protein diet | increase | fasting glucose | participants | β = -0.46 | showed less increased | #2 |
higher WHRonly+ polygenetic score with average-protein diet | decrease | HOMA-B | participants | β = 0.02 | showed less reduction | #3 |
high-protein diet with lower WHRonly+ polygenetic score | decrease | HOMA-B | individuals | β = -0.02 | associated with less decreased | #4 |
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.