Antecedent Hypoglycemia Impairs Autonomic Cardiovascular Function : Implications for Rigorous Glycemic Control

• Published in: Diabetes (New York, N.Y.) Vol. 58; no. 2; pp. 360 - 366
• Main Authors: ADLER, Gail K, BONYHAY, Istvan, FAILING, Hannah, WARING, Elizabeth, DOTSON, Sarah, FREEMAN, Roy
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.2009
• Subjects: Adolescent; Adult; Autonomic Nervous System - metabolism; Autonomic Nervous System - physiopathology; Baroreflex - physiology; Biological and medical sciences; Blood glucose; Blood Glucose - metabolism; Blood sugar; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - etiology; Cardiovascular Diseases - physiopathology; Complications and side effects; Control; Diabetes; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epinephrine - blood; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucose; Glucose Clamp Technique; Heart Rate - physiology; Humans; Hypoglycemia; Hypoglycemia - blood; Hypoglycemia - complications; Hypoglycemia - physiopathology; Hypotheses; Insulin; Male; Medical sciences; Metabolism; Middle Aged; Mortality; Nervous system; Norepinephrine - blood; Parasympathetic Nervous System - physiopathology; Research design; Risk factors; Sympathetic Nervous System - physiopathology; Womens health; Young Adult; United States; Endocrinopathy; Metabolic diseases; Hypoglycemia; Diabetes mellitus; Antecedent
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db08-1153

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. 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. 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). 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.