Given the close relationship between endothelial dysfunction and diabetes risk, Wannamethee et al. sought to determine whether markers of endothelial dysfunction, such as tissue plasminogen activator (tPA) and von Willebrand factor (vWF), were associated with incident diabetes in a prospective study of 3,562 men aged 60-79 years initially free from diabetes. During a mean follow-up of 7 years, 162 men eventually developed diabetes. At baseline, tPA variation was positively associated with triglyceride, C-reactive protein (CRP), and g-glutamyltransferase (GGT) levels and with the homeostasis model assessment for insulin resistance (HOMA-IR), even after adjusting for waist circumference. vWF was only associated with CRP levels after adjusting for waist circumference. After adjusting for age, social class, smoking, alcohol intake, physical activity, parental history of diabetes, pre-existing coronary heart disease, stroke, and use of statins, men in the top tPA tertile had a relative risk (RR) of diabetes of 4.54 (95% CI, 2.76-7.47) and men in the top vWF tertile had a RR of 1.39 (95% CI, 0.94-2.03) compared to men in the bottom tertile. The relationship between tPA and diabetes risk remained significant despite additional adjustments for waist circumference along with interleukin-6 and adiponectin levels, but not after further adjustment for GGT levels or the HOMA-IR index. In this epidemiological study, tPA was found to be an independent predictor of diabetes, but not vWF. The authors also noted by way of conclusion that the role of tPA in diabetes development needs to be investigated further.
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