title: Cardiac Effects of Sulfonylurea-Related Hypoglycemia.
abstract: To determine the effect of sulfonylurea-related hypoglycemia on cardiac repolarization and ectopy in the setting of well-controlled type 2 diabetes.
  
  
  
  Thirty subjects with sulfonylurea-treated type 2 diabetes underwent 48 h of concurrent continuous glucose monitoring and ambulatory electrocardiography. Ventricular repolarization (QTc) and QT dynamicity were analyzed during periods of hypoglycemia (<3.5 mmol/L for >20 min) and compared with periods of euglycemia and hyperglycemia combined. Cardiac ectopy rates during hypoglycemia were compared with ectopy rates when blood glucose was 4-10 mmol/L.
  
  
  
  Mean HbA1cwas 6.9% (52 mmol/mol). Hypoglycemia was detected in 9 of 30 subjects (30%); episodes were typically nocturnal (67%) and asymptomatic (73%). Hypoglycemia-associated QTc prolongation was seen in five of nine subjects with a large variation in individual response. Higher QT dynamicity, a poor prognostic factor in cardiac disease, was seen in subjects who experienced hypoglycemia compared with subjects who did not (0.193 vs. 0.159 for the nocturnal period;P= 0.01). This finding persisted after the hypoglycemic event. The rates of ventricular and supraventricular ectopy demonstrated a nonsignificant trend toward an increase during hypoglycemia (median rate ratio 1.58 and 1.33, respectively). Similar, nonsignificant results were observed in a separate insulin-treated cohort.
  
  
  
  Hypoglycemia, often unrecognized, is a frequent finding in well-controlled sulfonylurea-treated type 2 diabetes. It is associated with the novel finding of increased QT dynamicity and QTc prolongation in some individuals. Our findings suggest sulfonylurea-related hypoglycemia can have detrimental cardiovascular sequelae. Similar effects are also seen in the setting of insulin therapy.
authors.affiliation: Diabetes Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia timothy.middleton@sswahs.nsw.gov.au.|Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Timothy L
authors.identifier: 0000-0002-9719-2306
authors.initials: TL
authors.lastname: Middleton
authors.affiliation: Diabetes Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.|Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Jencia
authors.initials: J
authors.lastname: Wong
authors.affiliation: Diabetes Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Lynda
authors.initials: L
authors.lastname: Molyneaux
authors.affiliation: Diabetes Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.|School of Nursing, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Belinda A
authors.initials: BA
authors.lastname: Brooks
authors.affiliation: Diabetes Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.|Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Yue
authors.affiliation: Diabetes Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.|Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Twigg
authors.affiliation: Diabetes Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Ted
authors.initials: T
authors.lastname: Wu
mesh_terms: D000368:Aged; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D015716:Electrocardiography, Ambulatory; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds