Transforming Growth Factor-beta 1 and Incident Type 2 Diabetes Results from the MONICA/KORA case-cohort study, 1984-2002

OBJECTIVE - Subclinical inflammation leads to insulin resistance and P-cell dysfunction. This study aimed to assess whether levels of circulating transforming growth factor-beta 1 (TGF-beta 1)-a central, mainly immunosuppressive, and anti-inflammatory cytokine-were associated with incident type 2 diabetes, RESEARCH DESIGN AND METHODS - We measured serum levels of TGF-beta 1 from 460 individuals with and 1,474 individuals without incident type 2 diabetes in a prospective case-cohort study within the population-based MONICA (MONItoring of Trends and Determinants in CArdiovascular Disease)/KORA (Cooperative Health Research in the Region of Augsburg) cohort. RESULTS - Elevated TGF-beta 1 concentrations were associated with higher, not lower, risk for type 2 diabetes (age-, sex-, and survey-adjusted hazard ratios [95% CI] for increasing TGF-beta 1 tertiles: 1.0, 1.08 [0.83-1.42], and 1.41 [1.08-1.83]; P-for trend = 0.012). Adjustment for BMI and metabolic and lifestyle factors had virtually no impact on the effect size. CONCLUSIONS - Elevated serum concentrations of the cytokine TGF-beta 1 indicate an increased risk for type 2 diabetes. TGF-beta 1 may be upregulated to counterbalance metabolic and immunological disturbances preceding type 2 diabetes.