KCNQ1 Long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia

Patients with loss of function mutations in KCNQ1 have KCNQ1 long QT syndrome (LQTS). KCNQ1 encodes a voltage-gated K(+) channel located in both cardiomyocytes and pancreatic beta cells. Inhibition of KCNQ1 in beta cells increases insulin secretion. Therefore KCNQ1 LQTS patients may exhibit increased insulin secretion.Fourteen patients, from six families, diagnosed with KCNQ1 LQTS were individually matched to two randomly chosen BMI-age-gender-matched control participants and underwent oral glucose tolerance test, hypoglycemia questionnaire and continuous glucose monitoring.KCNQ1 mutation carriers showed increased insulin release (AUC:45.6±6.3vs.26.0±2.8 min*nmol/l insulin), and beta cell glucose sensitivity and had lower levels of plasma glucose and serum potassium upon oral glucose stimulation and increased hypoglycemic symptoms. Prolonged oral glucose tolerance test in four available patients and matched controls revealed hypoglycemia in carriers after 210 min. (range:1.4-3.6vs.4.1-5.3 mmol/l glucose), and 24-hour glucose profiles showed that the patients spent 77±18 min. per 24-hours in hypoglycemic states (