KCNQ1 Long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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 b-cells. Inhibition of
KCNQ1 in b-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 6.3 vs. 26.0 6 2.8 min $ nmol/L insulin)
and b-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 6 18 min
per 24 h in hypoglycemic states (<3.9 mmol/L
glucose) with 36 6 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.
Udgave nummer4
Sider (fra-til)1315-1325
Antal sider11
StatusUdgivet - apr. 2014

ID: 101010395