Thirty-One Novel Biomarkers as Predictors for Clinically Incident Diabetes

Abstract

BackgroundThe prevalence of diabetes is increasing in all industrialized countries and its prevention has become a public health priority. However, the predictors of diabetes risk are insufficiently understood. We evaluated, whether 31 novel biomarkers could help to predict the risk of incident diabetes.Methods and FindingsThe biomarkers were evaluated primarily in the FINRISK97 cohort (n = 7,827; 417 cases of clinically incident diabetes during the follow-up). The findings were replicated in the Health 2000 cohort (n = 4,977; 179 cases of clinically incident diabetes during the follow-up). We used Cox proportional hazards models to calculate the relative risk of diabetes, after adjusting for the classic risk factors, separately for each biomarker. Next, we assessed the discriminatory ability of single biomarkers using receiver operating characteristic curves and C-statistics, integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Finally, we derived a biomarker score in the FINRISK97 cohort and validated it in the Health 2000 cohort. A score consisting of adiponectin, apolipoprotein B, C-reactive protein and ferritin almost doubled the relative risk of diabetes in the validation cohort (HR per one standard deviation increase 1.88, p = 2.8 e-5). It also improved discrimination of the model (IDI = 0.0149, p<0.0001) and reclassification of diabetes risk (NRI = 11.8%, p = 0.006). Gender-specific analyses suggested that the best score differed between men and women. Among men, the best results were obtained with the score of four biomarkers: adiponectin, apolipoprotein B, ferritin and interleukin-1 receptor antagonist, which gave an NRI of 25.4% (p<0.0001). Among women, the best score included adiponectin, apolipoprotein B, C-reactive protein and insulin. It gave an NRI of 13.6% (p = 0.041).ConclusionsWe identified novel biomarkers that were associated with the risk of clinically incident diabetes over and above the classic risk factors. This gives new insights into the pathogenesis of diabetes and may help with targeting prevention and treatment.

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

“…The Malmö Diet and Cancer (MDC) study showed that copeptin, independently of a wide range of clinical risk factors, predicts the risk of type 2 diabetes in the general population [6]. However, the FINRISK97 study could not find an independent association [32]. The fact that we found a stronger association between copeptin and the risk of type 2 diabetes in women than in men might partly be explained by differences in population characteristics compared with other studies.…”

“…The FINRISK97 study from a cohort of 7,827 participants with 417 incident cases included similar numbers of women and men [32]. In the FINRISK97 study, a higher but non-significant risk of type 2 diabetes per one SD increase in copeptin was found in the total and sex-stratified population [32]. In this latter study, the range of copeptin levels was smaller than in the MDC study and our study, for both women and men.…”

“…More generally, it is worth noting that most prediction models including data on common risk factors have shown a better performance in women compared with men [26]. Various known biomarkers, such as hs-CRP, insulin and endogenous sex hormone, improved the risk prediction for type 2 diabetes differently in women and in men [16,32,33].…”

“…Likewise, all these conditions are known to be predictors for the risk of type 2 diabetes [13]. In an extension of these studies, two previous studies have investigated the association of copeptin with the risk of type 2 diabetes [6,32]. The Malmö Diet and Cancer (MDC) study showed that copeptin, independently of a wide range of clinical risk factors, predicts the risk of type 2 diabetes in the general population [6].…”

“…In the MDC study, including a higher number of women who had comparable copeptin levels to those in our study, a potential sex-related effect on the association of copeptin with diabetes risk was not addressed. The FINRISK97 study from a cohort of 7,827 participants with 417 incident cases included similar numbers of women and men [32]. In the FINRISK97 study, a higher but non-significant risk of type 2 diabetes per one SD increase in copeptin was found in the total and sex-stratified population [32].…”