oA novel nonparametric approach for estimating cut-offs in continuous risk indicators with application to diabetes epidemiology

Using data from a representative large multistage longitudinal epidemiological study in a primary care setting in Germany, this paper explores a novel approach for estimating optimal cut-offs of anthropomorphic parameters for predicting type 2 diabetes based on a discontinuity of a regression function in a nonparametric regression framework.The resulting cut-off corresponded to values obtained by the Youden Index (maximum of the sum of sensitivity and specificity, minus one), often considered the optimal cut-off in epidemiological and biomedical research. The nonparametric regression based estimator was compared to results obtained by the established methods of the Receiver Operating Characteristic plot in various simulation scenarios and based on bias and root mean square error, yielded excellent finite sample properties.It is thus recommended that this nonparametric regression approach be considered as valuable alternative when a continuous indicator has to be dichotomized at the Youden Index for prediction or decision purposes.Anthropometric parameters such as body mass index (BMI), waist circumference (WC) or waist to height ratio (WHtR) are often applied as indicators of obesity in epidemiological and clinical studies due to their simple application and high correlation with more complex measures [1-3]. As a case in point, decisions made from these parameters are necessarily dependent on statistically reliable derived cut-offs. For example, obesity is an established risk factor for the development of clinical type 2 diabetes [1-4] and also plays a central role in metabolic syndrome according to the National Cholesterol Education Program (NCEP) [5] and the International Diabetes Federation (IDF) [6]. The definitions of metabolic syndrome are based on the same set of risk factors (abdominal obesity, hypertriglyceridemia, low HDL, hypertension, elevated fasting glucose) in the NCEP and by the IDF, but differ in terms of what constitutes the best cut-offs for WC an