Do Genes Determine Our Health?
Implications for Designing Lifestyle Interventions and Drug Trials
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Belalcazar et al1 exploited a genetic variant (L446P)2 in the glucokinase regulatory (GCKR) gene, known to have inverse cardiometabolic effects, to investigate whether the effect of the 446L allele can be attenuated by an intensive lifestyle intervention (ILI) in the Look Action for Health in Diabetes (AHEAD) trial.3 Participants of Look AHEAD exhibited high adherence to the ILI, which demonstrated the success of an intensive lifestyle by significant weight loss,4 improved diabetes mellitus control,5 and reduced C-reactive protein (CRP) and triglyceride levels6 compared with usual care participants. The authors evaluated the interaction of the common variant in GCKR to treatment assignment and triglyceride or CRP levels in participants with type 2 diabetes mellitus (T2DM) and unfavorable metabolic profiles. In 3214 participants with triglyceride and 1411 with CRP levels, the GCKR 446L allele showed no benefit of participating in the ILI intervention on lowering triglyceride or CRP levels at the 1-year follow-up (49% randomized to ILI and 51% to usual care).
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