Protein markers and risk of type 2 diabetes and prediabetes: a targeted proteomics approach in the KORA F4/FF4 study

The objective of the present study was to identify proteins that contribute to pathophysiology and allow prediction of incident type 2 diabetesor incident prediabetes. We quantified 14 candidate proteins using targeted mass spectrometryin plasma samples of the prospective, population-based German KORA F4/FF4 study (6.5-year follow-up). 892 participants aged 42–81 years were selected using a case-cohort design, including 123 persons with incident type 2 diabetesand 255 persons with incident WHO-defined prediabetes. Prospective associations between protein levels and diabetes, prediabetesas well as continuous fasting and 2 h glucose, fasting insulin and insulin resistance were investigated using regression models adjusted for established risk factors. The best predictive panel of proteins on top of a non-invasive risk factor model or on top of HbA1c, age, and sex was selected. Mannan-binding lectinserine peptidase (MASP) levels were positively associated with both incident type 2 diabetesand prediabetes. Adiponectinwas inversely associated with incident type 2 diabetes. MASP, adiponectin, apolipoprotein A-IV, apolipoprotein C-II, C-reactive protein, and glycosylphosphatidylinositolspecific phospholipase D1were associated with individual continuous outcomes. The combination of MASP, apolipoprotein E (apoE) and adiponectinimproved diabetes prediction on top of both reference models, while prediabetesprediction was improved by MASP plus CRP on top of the HbA1c model. In conclusion, our mass spectrometric approach revealed a novel association of MASP with incident type 2 diabetesand incident prediabetes. In combination, MASP, adiponectinand apoE improved type 2 diabetesprediction beyond non-invasive risk factors or HbA1c, age and sex.