Genetic variation of fasting glucose and changes in glycemia in response to 2-year weight-loss diet intervention: the POUNDS LOST trial

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Abstract

OBJECTIVE:

Weight-loss intervention through diet modification has been widely used to improve obesity-related hyperglycemia; however, little is known about whether genetic variation modifies the intervention effect. We examined the interaction between weight-loss diets and genetic variation of fasting glucose on changes in glycemic traits in a dietary intervention trial.

RESEARCH DESIGN AND METHODS:

The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial is a randomized, controlled 2-year weight-loss trial. We assessed overall genetic variation of fasting glucose by calculating a genetic risk score (GRS) based on 14 fasting glucose-associated single nucleotide polymorphisms, and examined the progression in fasting glucose and insulin levels, and insulin resistance and insulin sensitivity in 733 adults from this trial.

RESULTS:

The GRS was associated with 6-month changes in fasting glucose (P < 0.001), fasting insulin (P = 0.042), homeostasis model assessment of insulin resistance (HOMA-IR, P = 0.009) and insulin sensitivity (HOMA-S, P = 0.043). We observed significant interaction between the GRS and dietary fat on 6-month changes in fasting glucose, HOMA-IR and HOMA-S after multivariable adjustment (P-interaction = 0.007, 0.045 and 0.028, respectively). After further adjustment for weight loss, the interaction remained significant on change in fasting glucose (P = 0.015). In the high-fat diet group, participants in the highest GRS tertile showed increased fasting glucose, whereas participants in the lowest tertile showed decreased fasting glucose (P-trend < 0.001); in contrast, the genetic association was not significant in the low-fat diet group (P-trend = 0.087).

CONCLUSIONS:

Our data suggest that participants with a higher genetic risk may benefit more by eating a low-fat diet to improve glucose metabolism.

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