Severity of Metabolic Syndrome Indicates Risk for T2D, CVD in Prediabetes Treatment

overweight man with measuring tape around his stomach
overweight man with measuring tape around his stomach
Researchers analyzed how improvements in metabolic syndrome may impact the risk of developing type 2 diabetes and cardiovascular disease in patients with prediabetes.

Changes in indicators of metabolic syndrome severity during the Diabetes Prevention Program altered patients’ risk of developing type 2 diabetes and cardiovascular disease, according to a study published in Diabetes Care.

To determine the impact of improvements in metabolic syndrome on the risk of patients with prediabetes developing type 2 diabetes and cardiovascular disease, researchers analyzed data from a cohort of 2476 adults in the Diabetes Prevention Program from 1996 to 1999. Participants in this program had been randomly placed into 3 treatment groups and treated for 2 to 3 years with metformin, placebo, or lifestyle modification. Outcomes for type 2 diabetes and cardiovascular disease were monitored yearly for a mean follow-up period of 13.4 ± 4.8 years.

Metabolic syndrome as a concept has been criticized as not providing additional risk information past its individual components (eg, high waist circumference). To serve as a continuous biomarker of severity of metabolic disarray, researchers developed a metabolic syndrome severity z Score (MetS-Z). 

After calculating 1-year “effect sizes” (1-year change/baseline standard deviation) for MetS-Z severity as well as scores for the individual components of metabolic syndrome, investigators used hazard ratios to assess the relationships between 1-year effect size and the development of type 2 diabetes and cardiovascular disease. In addition, they performed mediation analysis to understand causal relationships between change in metabolic syndrome severity and effect of study interventions (lifestyle, metformin) on disease outcomes.

High baseline MetS-Z and individual component scores were unsurprisingly associated with increased risk for incident diabetes and cardiovascular disease. During the first 3 years of follow-up, severity effect sizes had the greatest decrease in the lifestyle modification group, followed by the metformin and placebo groups. Type 2 diabetes risk within 1 to 5 years was most significantly associated with 1-year changes in waist circumference and MetS-Z (hazard ratio for a standard deviation increase, 1.80), and cardiovascular disease risk was associated with 1-year changes in glucose level, systolic blood pressure, and MetS-Z. Mediation analyses indicated that the effects of both lifestyle modification and metformin treatment on reduced risk for diabetes were mediated by metabolic syndrome severity and glucose levels. Waist circumference was also a strong mediator of the effect of lifestyle modification.

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Study investigators concluded that “these data suggest that risk indicators of metabolic disarray… can be followed over time to document both baseline risk and subsequent alterations in risk during treatment, providing the potential to identify the effects of treatments earlier, or to motivate patients toward greater adherence and improved outcomes.”


DeBoer MD, Filipp SL, Gurka MJ. Use of a metabolic syndrome severity z score to track risk during treatment of prediabetes: an analysis of the diabetes prevention programDiabetes Care. 2018;41(10):dc181079.