Insulin resistance and β-cell dysfunction are well-established, pathophysiological mechanisms underlying the development of type 2 diabetes (T2D). Fasting proinsulin levels may serve as a marker of β-cell dysfunction and predict T2D development. The predictive value of proinsulin for the risk of developing T2D is currently unknown, and, to the best of our knowledge, there are no longitudinal studies investigating proinsulin level as a marker of incident T2D in participants with hypertension or kidney dysfunction.
In this large cohort of a predominantly middle-aged population, we found fasting proinsulin levels were independently associated with incident T2D. The association remained statistically significant after multivariable adjustment for BMI, hypertension, glucose, and relevant lipid-related biomarkers, as well as after adjustment for plasma insulin and C-peptide. The addition of proinsulin to the prdeiction model of T2Dimproved the prediction value of T2D. Moreover, the association of proinsulin with incident T2D was particularly strong in participants with hypertension or kidney dysfunction
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