KCNQ1 Long QT Syndrome Patients Have Hyperinsulinemia and Symptomatic Hypoglycemia

  1. Torben Hansen2,7
  1. 1Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  2. 2Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  3. 3Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark
  4. 4Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
  5. 5Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
  6. 6Gentofte, Aalborg and Herlev University Hospitals, Hellerup, Denmark
  7. 7Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
  1. Corresponding author: Signe S. Torekov, 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 β-cells. Inhibition of KCNQ1 in β-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-, and sex-matched control participants and underwent an oral glucose tolerance test (OGTT), a hypoglycemia questionnaire, and continuous glucose monitoring. KCNQ1 mutation carriers showed increased insulin release (area under the curve 45.6 ± 6.3 vs. 26.0 ± 2.8 min ⋅ nmol/L insulin) and β-cell glucose sensitivity and had lower levels of plasma glucose and serum potassium upon oral glucose stimulation and increased hypoglycemic symptoms. Prolonged OGTT in four available patients and matched control subjects revealed hypoglycemia in carriers after 210 min (range 1.4–3.6 vs. 4.1–5.3 mmol/L glucose), and 24-h glucose profiles showed that the patients spent 77 ± 18 min per 24 h 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 after 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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