Longitudinal changes in blood biomarkers and their ability to predict type 2 diabetes mellitus—The Tromsø study
AuthorAllaoui, Giovanni; Rylander, Charlotta; Averina, Maria; Wilsgaard, Tom; Fuskevåg, Ole Martin; Berg, Vivian
Methods: This nested case–control study included 234 participants in the Tromsø Study who gave blood samples at five time points between 1986 and 2016: 130 did not develop T2DM and were used as controls; 104 developed T2DM after the third time point and were included as cases. After stratifying by sex, we investigated changes in pre- and post-diagnostic concentrations of lipids, thyroid hormones, HbA1c, glucose and gamma-glutamyltransferase (GGT) using linear mixed models. We used logistic regression models and area under the receiver operating characteristic curve (AROC) to assess associations between blood biomarker concentrations and T2DM, as well as the predictive ability of blood biomarkers.
Results: Cases and controls experienced different longitudinal changes in lipids, free T3, HbA1c, glucose, and GGT. The combination of selected blood biomarker concentrations and basic clinical information displayed excellent (AROC 0.78–0.95) predictive ability at all pre-diagnostic time points. A prediction model that included HDL (for women), HbA1c, GGT, and basic clinical information demonstrated the strongest discrimination 7 years before diagnosis (AROC 0.95 for women, 0.85 for men).
Conclusion: There were clear differences in blood biomarker concentrations between cases and controls throughout the study, and several blood biomarkers were associated with T2DM. Selected blood biomarkers (lipids, HbA1c, GGT) in combination with BMI, physical activity, elevated blood pressure, and family history of T2DM had excellent predictive ability 1–7 years before T2DM diagnosis and acceptable predictive ability up to 15 years before diagnosis.