title: Antecedent hypoglycemia impairs autonomic cardiovascular function: implications for rigorous glycemic control.
abstract: OBJECTIVE
  Glycemic control decreases the incidence and progression of diabetic complications but increases the incidence of hypoglycemia. Hypoglycemia can impair hormonal and autonomic responses to subsequent hypoglycemia. Intensive glycemic control may increase mortality in individuals with type 2 diabetes at high risk for cardiovascular complications. We tested the hypothesis that prior exposure to hypoglycemia leads to impaired cardiovascular autonomic function.
  
  
  METHODS
  Twenty healthy subjects (age 28 +/- 2 years; 10 men) participated in two 3-day inpatient visits, separated by 1-3 months. Autonomic testing was performed on days 1 and 3 to measure sympathetic, parasympathetic, and baroreflex function. A 2-h hyperinsulinemic [hypoglycemic (2.8 mmol/l) or euglycemic (5.0 mmol/l)] clamp was performed in the morning and in the afternoon of day 2.
  
  
  RESULTS
  Comparison of the day 3 autonomic measurements demonstrated that antecedent hypoglycemia leads to 1) reduced baroreflex sensitivity (16.7 +/- 1.8 vs. 13.8 +/- 1.4 ms/mmHg, P = 0.03); 2) decreased muscle sympathetic nerve activity response to transient nitroprusside-induced hypotension (53.3 +/- 3.7 vs. 40.1 +/- 2.7 bursts/min, P < 0.01); and 3) reduced (P < 0.001) plasma norepinephrine response to lower body negative pressure (3.0 +/- 0.3 vs. 2.0 +/- 0.2 nmol/l at -40 mmHg).
  
  
  CONCLUSIONS
  Baroreflex sensitivity and the sympathetic response to hypotensive stress are attenuated after antecedent hypoglycemia. Because impaired autonomic function, including decreased cardiac vagal baroreflex sensitivity, may contribute directly to mortality in diabetes and cardiovascular disease, our findings raise new concerns regarding the consequences of hypoglycemia.
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Gail K
authors.initials: GK
authors.lastname: Adler
authors.forename: Istvan
authors.initials: I
authors.lastname: Bonyhay
authors.forename: Hannah
authors.initials: H
authors.lastname: Failing
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Waring
authors.forename: Sarah
authors.initials: S
authors.lastname: Dotson
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
mesh_terms: D000293:Adolescent; D000328:Adult; D001341:Autonomic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D017704:Baroreflex / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010275:Parasympathetic Nervous System / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D009638:Norepinephrine; D004837:Epinephrine