Inter-relationships between the Severity of Metabolic Syndrome, Insulin and Adiponectin and their Relationship to Future Type 2 Diabetes and Cardiovascular Disease

BACKGROUND: The severity of the metabolic syndrome (MetS) is related to future incidence of type 2 diabetes (T2DM) and cardiovascular disease (CVD). However, the relationship between MetS severity and levels of fasting insulin and adiponectin—markers of insulin resistance—is unclear. METHODS: We used linear and logistic regression to analyze data from 711 participants of the Princeton Lipid Research Cohort with information regarding levels of insulin, adiponectin, and MetS severity during 1998–2003 (mean age 39.5y); 595 participants had MetS severity data from childhood (1973–1976, mean age 12.9y), and 417 had updated disease status from 2010–2014 (mean age 50.9y). RESULTS: Childhood MetS-Z-scores were positively associated with adult insulin levels (p<0.001) and negatively associated with adiponectin levels (p=0.01). In individual analyses, higher insulin levels and MetS-Z-score as adults were related to higher odds of incident diabetes and CVD over the next 11.2y (all p<0.001), while lower adiponectin levels were only related to odds of future T2DM (p<0.0001). In a model including insulin, adiponectin and MetS-Z-score, adiponectin was not linked to future disease; both insulin (p=0.027) and MetS-Z-score (p=0.002) were related to risk of future T2DM, while only MetS-Z-score was related to future CVD (p<0.001). CONCLUSIONS: The severity of MetS exhibits long-term links to levels of insulin and adiponectin, suggesting potential genetic and environmental influences on insulin resistance over time. As a long-term predictor of T2DM and CVD, the severity of MetS exhibited consistent independent correlations. This supports clinical utility in evaluating MetS severity as a predictor of risk for future disease.