HNF1A variant, energy-reduced diets and insulin resistance improvement during weight loss: The POUNDS Lost trial and DIRECT.
Study Goal
The researchers aimed to determine if a high-fat diet could modulate the genetic effect of HNF1A rs7957197 on weight loss and insulin resistance improvement in overweight/obese adults.
Results Summary
The study found that a high-fat diet significantly enhanced weight loss and reduced waist circumference in individuals with the HNF1A rs7957197 T allele, with similar benefits observed for fasting insulin and insulin resistance. These results were replicated in an independent trial.
Population
Overweight/obese adults (722 in the POUNDS Lost trial, 280 in the DIRECT trial).
Effective Dosage
Not specified (hypocaloric high-fat diet).
Duration
2 years.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
high-fat diet | decrease | weight loss | 722 overweight/obese adults from the POUNDS Lost trial | - | significantly modified the genetic effect of HNF1A on | #1 |
high-fat diet | decrease | reduction in waist circumference | 722 overweight/obese adults from the POUNDS Lost trial | - | significantly modified the genetic effect of HNF1A on | #2 |
high-fat diet | decrease | fasting insulin | 722 overweight/obese adults from the POUNDS Lost trial | - | borderline significant interactions for | #3 |
high-fat diet | decrease | insulin resistance | 722 overweight/obese adults from the POUNDS Lost trial | - | borderline significant interactions for | #4 |
high-fat diet | decrease | weight loss | pooled results from POUNDS Lost and DIRECT trials | - | similar significant interactions with | #5 |
high-fat diet | decrease | waist circumference reduction | pooled results from POUNDS Lost and DIRECT trials | - | similar significant interactions with | #6 |
high-fat diet | decrease | improvement in fasting insulin | pooled results from POUNDS Lost and DIRECT trials | - | similar significant interactions with | #7 |
high-fat diet | decrease | improvement in insulin resistance | pooled results from POUNDS Lost and DIRECT trials | - | similar significant interactions with | #8 |
high-fat diet | decrease | weight | participants with the T allele in the high-fat diet group | - | greater decreases in | #9 |
high-fat diet | decrease | waist circumference | participants with the T allele in the high-fat diet group | - | greater decreases in | #10 |
high-fat diet | decrease | fasting insulin level | participants with the T allele in the high-fat diet group | - | greater decreases in | #11 |
high-fat diet | decrease | insulin resistance | participants with the T allele in the high-fat diet group | - | greater decreases in | #12 |
hypocaloric and high-fat diet | decrease | weight loss | individuals with the HNF1A rs7957197 T allele | - | might obtain more benefits in | #13 |
hypocaloric and high-fat diet | decrease | improvement of insulin resistance | individuals with the HNF1A rs7957197 T allele | - | might obtain more benefits in | #14 |
AIM: To determine whether weight-loss diets varying in macronutrients modulate the genetic effect of hepatocyte nuclear factor 1α (HNF1A) rs7957197 on weight loss and improvement of insulin resistance. MATERIALS AND METHODS: We analysed the interaction between HNF1A rs7957197 and weight-loss diets with regard to weight loss and insulin resistance improvement among 722 overweight/obese adults from a 2-year randomized weight-loss trial, the POUNDS Lost trial. The findings were replicated in another independent 2-year weight-loss trial, the Dietary Intervention Randomized Controlled Trial (DIRECT), in 280 overweight/obese adults. RESULTS: In the POUNDS Lost trial, we found that a high-fat diet significantly modified the genetic effect of HNF1A on weight loss and reduction in waist circumference (P for interaction = .006 and .005, respectively). Borderline significant interactions for fasting insulin and insulin resistance (P for interaction = .07 and .06, respectively) were observed. We replicated the results in DIRECT. Pooled results showed similar significant interactions with weight loss, waist circumference reduction, and improvement in fasting insulin and insulin resistance (P values for interaction = .001, .005, .02 and .03, respectively). Greater decreases in weight, waist circumference, fasting insulin level and insulin resistance were observed in participants with the T allele compared to those without the T allele in the high-fat diet group (P = .04, .03 and .01, respectively). CONCLUSIONS: Our replicable findings provide strong evidence that individuals with the HNF1A rs7957197 T allele might obtain more benefits in weight loss and improvement of insulin resistance by choosing a hypocaloric and high-fat diet.