title: Association between impaired cardiovascular autonomic function and hypoglycemia in patients with type 1 diabetes.
abstract: OBJECTIVE
  We studied the association between glycemic variability (GV) reflecting hypoglycemic stress and cardiovascular autonomic function in subjects with type 1 diabetes.
  
  
  METHODS
  Forty-four type 1 diabetic patients (mean age 34 ± 13 years, 40% male, 86% Caucasian, mean diabetes duration 13 ± 6 years, mean hemoglobin A1c [HbA1c] 8.0 ± 1.2% [64 ± 5 mmol/mol]) without cardiovascular disease, dyslipidemia, or hypertension participated in this pilot study. Indices of GV reflective of hypoglycemic stress (low blood glucose index [LBGI] and area under the curve [AUC] for hypoglycemia) were computed using data obtained during 5-day continuous glucose monitoring. Cardiovascular autonomic neuropathy (CAN) was assessed using standardized cardiovascular reflex testing and measures of heart rate variability (HRV), which were analyzed as time and frequency domain measures.
  
  
  RESULTS
  Both LBGI and AUC hypoglycemia had a significant negative association with the low-frequency power of HRV (r = -0.47, P = 0.002; r = -0.43, P = 0.005, respectively) and with the high-frequency power of HRV (r = -0.37, P = 0.018; r = -0.38, P = 0.015, respectively). These inverse associations persisted after adjusting for HbA1c, although they were attenuated in multivariable analysis after adjustment for age, diabetes duration, and several other covariates.
  
  
  CONCLUSIONS
  Increased GV promoting hypoglycemic stress was associated with reduced HRV independent of glycemic control as assessed by HbA1c. These pilot data suggest that glucose variability may contribute to cardiovascular autonomic dysfunction among adults with type 1 diabetes.
authors: Department of Neurology, University of Michigan, Ann Arbor, MI.
authors: Mamta
authors: M
authors: Jaiswal
authors: Department of Biomedical Engineering, Boston University, Boston, MA.
authors: Katherine
authors: K
authors: McKeon
authors: Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI.
authors: Nicholas
authors: N
authors: Comment
authors: Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI.
authors: James
authors: J
authors: Henderson
authors: Department of Radiology, University of Michigan, Ann Arbor, MI.
authors: Scott
authors: S
authors: Swanson
authors: Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI.
authors: Cynthia
authors: C
authors: Plunkett
authors: Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI.
authors: Patrick
authors: P
authors: Nelson
authors: Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI rpbusui@umich.edu.
authors: Rodica
authors: R
authors: Pop-Busui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000378:metabolism / Q000473:pathology*; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents