Transforming Growth Factor-β1 and Incident Type 2 Diabetes: Results from the MONICA/KORA case-cohort study, 1984–2002

OBJECTIVE: Subclinical inflammation leads to insulin resistance and β-cell dysfunction. This study aimed to assess whether levels of circulating transforming growth factor-β1 (TGF-β1)—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-β1 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-β1 concentrations were associated with higher, not lower, risk for type 2 diabetes (age-, sex-, and survey-adjusted hazard ratios [95% CI] for increasing TGF-β1 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-β1 indicate an increased risk for type 2 diabetes. TGF-β1 may be upregulated to counterbalance metabolic and immunological disturbances preceding type 2 diabetes.