KCNJ11 E23K Affects Diabetes Risk and Is Associated With the Disposition Index: Results of two independent German cohorts

Various cross-sectional studies suggest that a polymorphism (E23K) within the ATP-sensitive K+ channel KCNJ11 gene is associated with type 2 diabetes (1). However, only two prospective studies have addressed the relation between KCNJ11 E23K and type 2 diabetes, and these studies were intervention trials based on individuals with impaired fasting glucose and impaired glucose tolerance (2–4). With respect to functional effects, recent studies have been inconsistent regarding demonstration of a relation of the polymorphism with markers of insulin secretion (3,5,6), although in vitro studies clearly suggested a defect in insulin secretion (7–9). One study proposed a relation to glucagon response, while insulin secretion itself was not affected (10). However, the relation between polymorphism and insulin secretion might have been masked in some of those studies by differences of insulin sensitivity, and detailed analysis might thus require consideration of insulin sensitivity of the study participants, such as that given in the disposition index (11). We investigated the effect of KCNJ11 E23K on diabetes risk within a prospective case-cohort study ( n = 2,945) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. We additionally tested the association with diabetes in a second independent cross-sectional study, the Metabolic Syndrome Berlin Potsdam (MeSyBePo) cohort, from the same geographical region ( n = 1,891). Within this second study, the association between polymorphism and disposition index was additionally investigated. We designed a case-cohort study within the EPIC-Potsdam study, a prospective cohort involving 27,548 Caucasian volunteers, mainly aged 35–65 years, from the general population (12–14). A total of 2,263 individuals were randomly selected for a subcohort. Because the …