While a metabolic syndrome severity Z-score (MetS-Z) predicts incident type 2 diabetes (T2D) in observational cohorts, it is unclear whether MetS-Z can track response to medical intervention and whether changes in MetS-Z during treatment reflect altered risk for T2D. We evaluated data from the Diabetes Prevention Program, which randomized individuals with glucose intolerance (age 51±11 years) to receive: placebo (n=882), metformin 850 mg bid (n=867), or an intensive lifestyle modification program (n=827). We assessed levels of MetS-Z and the individual MetS components during 3 years of intervention (Figure), revealing 1-year decreases in MetS-Z among those treated with lifestyle (effect size -0.6), metformin (-0.3) and placebo (-0.1), driven by improvements in the individual MetS components. We assessed how change in MetS-Z affected T2D risk, finding that each 1-point increase in a participant’s effect size of MetS Z between 0 and 1 year (difference per participant/baseline SD) increased odds of incident T2D by year 3 by 70% (adjusting for intervention group; Figure). This positive association was found in individual models and in a joint model that included changes in MetS-Z and in each MetS component—suggesting independent associations of changes in MetS-Z with future T2D risk. These data support MetS-Z as an important outcome to follow for response to medical treatment in research studies and clinical care.


M.D. DeBoer: None. S.L. Filipp: None. M.J. Gurka: None.

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