Abstract
Objective: Evaluate the ability of a newly developed diabetes risk score, the Diabetes Risk Index (DRI), to predict incident type 2 diabetes mellitus (T2D) in a large adult population. Methods: The DRI was developed by combining the Lipoprotein Insulin Resistance Index (LP-IR), calculated from 6 lipoprotein subspecies and size parameters, and the branched chain amino acids, valine and leucine, all of which have been shown previously to be associated with future T2D. DRI scores were calculated in a total of 6134 nondiabetic men and women in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident T2D. Results: During a median follow-up of 8.5 years, 306 new T2D cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI scores and incident T2D with the hazard ratio (HR) for the highest versus lowest quartile being 12.07 (95% confidence interval: 6.97–20.89, p < 0.001). After additional adjustment for body mass index (BMI), family history of T2D, alcohol consumption, diastolic blood pressure, total cholesterol, triglycerides, HDL cholesterol and HOMA-IR, the HR was attenuated but remained significant (HR 3.20 (1.73–5.95), p = 0.001). Similar results were obtained when DRI was analyzed as HR per 1 SD increase (HR 1.37 (1.14–1.65), p < 0.001). The Kaplan–Meier plot demonstrated that patients in the highest quartile of DRI scores presented at higher risk (p-value for log-rank test <0.001). Conclusions: Higher DRI scores are associated with an increased risk of T2D. The association is independent of clinical risk factors for T2D including HOMA-IR, BMI and conventional lipids.
Highlights
In order to curtail the growing epidemic of obesity and type 2 diabetes mellitus (T2D), new clinical practice guidelines recommend structured lifestyle modification and/or pharmacological intervention for patients who are at high risk of developing T2D [1,2]
Of the PREVEND participants that completed the second round of screening, 6134 subjects who did not have T2D and had complete data available on Diabetes Risk Index (DRI) and covariates at the time of screening were included in this study
The difference between women and men persisted in age-adjusted models, hazard ratio (HR) for women was 2.50 (2.10–2.97; p < 0.001) and HR for men 2.04 (1.75–2.37; p < 0.001) (Supplemental Tables S2 and S3). In this large prospective cohort, comprising 6134 participants, we report for the first time that higher values of DRI, a newly developed diabetes risk algorithm, are associated with incidences of T2D
Summary
In order to curtail the growing epidemic of obesity and type 2 diabetes mellitus (T2D), new clinical practice guidelines recommend structured lifestyle modification and/or pharmacological intervention for patients who are at high risk of developing T2D [1,2]. Genome-wide association studies have identified more than 200 genetic loci which are associated with development of T2D [10,11]. Application of this genetic information is more likely to be used in support of studies on pathophysiological understanding of T2D rather than to be applied in actual clinical risk prediction, where biomarkers still are most promising [12]. There remains a clinical need for diagnostic tools that identify high risk patients in order to employ therapeutic measures early in the course of worsening dysglycemia
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