The E23K variant in the Kir6.2 subunit of the ATP-sensitive K+ channel does not augment impaired glucose tolerance in Caribbean subjects with a family history of type 2 diabetes

Abstract

The E23K variant of the Kir6·2 gene has been shown to be associated with type 2 diabetes mellitus in Caucasian subjects. Because offspring of type 2 diabetic patients have a genetically increased risk of developing diabetes, we sought to identify the E23K variant of the Kir6·2 gene in offspring of Caribbean patients with type 2 diabetes and assess the contribution of this variant to impaired glucose tolerance in these subjects. Forty-six offspring of patients with type 2 diabetes and 39 apparently healthy subjects whose immediate parents were not diabetic ('control') were studied after an overnight fast. Anthropometric indices were measured and blood samples were collected. Fasting and 2 h plasma glucose, insulin and lipids were subsequently determined. Insulin resistance was calculated using the homeostatic model assessment technique. The offspring and control subjects had similar frequencies of the E23K polymorphism (52·6 vs 45·5%, P>0·05) and the frequency of the E23K variant did not differ significantly between gender and ethnic distributions, irrespectively of a family history of diabetes (P>0·05). There were no significant differences in biochemical risk factors for developing diabetes in offspring carriers of the E23K variant compared with offspring non-carriers of the mutation. Offspring with the E23K mutation had even significantly higher 2 h insulin concentrations when compared with control subjects. It is concluded that the presence of the Kir6·2 E23K genotype in Caribbean subjects with an immediate positive family history of diabetes does not confer significantly higher levels of biochemical risk factors for the development of type 2 diabetes.

Effect of genetic polymorphisms on the development of secondary failure to sulfonylurea in Egyptian patients with type 2 diabetes

“…Our observation is consistent with the studies which found that the E23K polymorphism does not increase impaired glucose tolerance in carriers of the E23K polymorphism [Ezenwaka et al 2005]. Jose and colleagues [Jose et al 2007] observed no significant longitudinal changes in fasting glucose levels across genotypic groups in the metformin arm.…”

Genetic Variations in the Kir6.2 Subunit(KCNJ11)of Pancreatic ATP-Sensitive Potassium Channel Gene Are Associated with Insulin Response to Glucose Loading and Early Onset of Type 2 Diabetes in Childhood and Adolescence in Taiwan

“…In contrast, we found that those carrying K-allele exhibited a higher insulin response after oral glucose loading in the normal glucose-tolerant children ( Figure 1(b) ). In support of our findings, studies in the glucose-tolerant offspring of T2D patients carrying the E23K variants demonstrated significantly higher 2-hour insulin concentrations compared with those with control subjects [ 51 ]. Moreover, the E23K variant has been linked to an increase in BMI in the Danish population [ 50 ].…”

Prediabetes is associated with genetic variations in the gene encoding the Kir6.2 subunit of the pancreatic ATP‐sensitive potassium channel (KCNJ11): A case‐control study in a Han Chinese youth population

“…Finally, potential confounding factors, such as family history, were not included in our analysis. Although a previous study has shown that the presence of the E23K variant in Caribbean subjects with an immediate positive family history of diabetes does not confer significantly higher levels of biochemical risk factors for the development of T2D, we cannot rule out the possibility that the E23K variant in Chinese may contribute to the development of prediabetes. Therefore, it is important that future studies analyze a wide range of potential confounding factors on the effects of the E23K variant of KCNJ11 on the development of T2D in female and male youth in China.…”