KCNQ1 Long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia

  1. Torben Hansen, PhD2,7
  1. 1Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
  2. 2Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen
  3. 3Department of Clinical Biochemistry, SSI, 2300 Copenhagen
  4. 4Research Centre for Prevention and Health, Glostrup University Hospital, 2600 Glostrup
  5. 5Faculty of Health Sciences, University of Aarhus, 8000 Aarhus, Denmark. Denmark
  6. 6Gentofte, Aalborg & Herlev University Hospitals, 2950 Hellerup, Denmark
  7. 7Faculty of Health Sciences, University of Southern Denmark, 5230 Odense, Denmark
  1. Corresponding author: Signe S. Torekov, E-mail: Torekov{at}


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 (<3.9 mmol/l glucose) with 36±10 min. <2.8 mmol/l glucose vs. 0 min (<3.9 mmol/l glucose) for the control participants.

The phenotype of patients with KCNQ1 LQTS, caused by mutations in KCNQ1, includes, besides long QT, hyperinsulinemia, clinically relevant symptomatic reactive hypoglycemia and low potassium following an oral glucose challenge, suggesting that KCNQ1 mutations may explain some cases of “essential” reactive hypoglycemia.

  • Received September 20, 2013.
  • Accepted December 12, 2013.

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