title: Reduced capacity of heart rate regulation in response to mild hypoglycemia induced by glibenclamide and physical exercise in type 2 diabetes.
abstract: OBJECTIVE
  Decreased heart rate variability (HRV) is associated with enhanced mortality due to abnormal cardiac rhythm. While hypoglycemic events are increasingly common in the treatment of type 2 diabetes, HRV is part of the counter-regulation against low blood glucose levels. We hypothesized that HRV was impaired in mild hypoglycemia in diabetic individuals.
  
  
  METHODS
  Hyperinsulinemic-hypoglycemic clamps were performed in twelve type 2 diabetic patients without cardiovascular disease and in non-diabetic subjects matched for age, sex, and weight. In an additional study, hypoglycemic events, induced by either a single morning dose of glibenclamide or physical exercise, were recorded for the subsequent 24h. Blood glucose concentrations and electrocardiograms were continuously monitored. Serum hormone levels, hypoglycemic symptoms, and forearm blood flow were measured at defined time points.
  
  
  RESULTS
  Occurrence of a symptomatic hypoglycemic episode (mean blood glucose 3.1±0.4 mmol/l) attenuated most of the time and frequency domain measurements in both healthy and diabetic individuals. The magnitude of reduction of HRV parameters was significantly lower in diabetic compared to healthy subjects. Glibenclamide taken in the morning enhanced the daily number of mild hypoglycemic events compared with placebo or moderate exercise. Concordantly, 24-h mean HRV measurements were decreased.
  
  
  CONCLUSIONS
  HRV response to hypoglycemia is impaired in type 2 diabetic subjects resulting in a higher than expected risk for sudden arrhythmia following mild hypoglycemic episodes.
authors: Medizinische Klinik und Poliklinik III, Universitätsklinikum Giessen und Marburg GmbH, Giessen, Germany.
authors: Nedim
authors: N
authors: Soydan
authors: Reinhard G
authors: RG
authors: Bretzel
authors: Britta
authors: B
authors: Fischer
authors: Florian
authors: F
authors: Wagenlehner
authors: Adrian
authors: A
authors: Pilatz
authors: Thomas
authors: T
authors: Linn
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D015536:Down-Regulation / Q000187:drug effects; D015444:Exercise / Q000502:physiology*; D005260:Female; D015309:Glucose Clamp Technique; D005905:Glyburide / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012720:Severity of Illness Index
chemical_list: D007004:Hypoglycemic Agents; D010919:Placebos; D005905:Glyburide