Evidence That Hyperglycemia After Recovery From Hypoglycemia Worsens Endothelial Function and Increases Oxidative Stress and Inflammation in Healthy Control Subjects and Subjects With Type 1 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 11; pp. 2993 - 2997
• Main Authors: Ceriello, Antonio, Novials, Anna, Ortega, Emilio, La Sala, Lucia, Pujadas, Gemma, Testa, Roberto, Bonfigli, Anna Rita, Esposito, Katherine, Giugliano, Dario
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.11.2012
• Subjects: Adult; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Ascorbic Acid - administration & dosage; Ascorbic Acid - therapeutic use; Biological and medical sciences; Breath tests; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - etiology; Cardiovascular Diseases - prevention & control; Complications; Complications and side effects; Cross-Over Studies; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - immunology; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Experiments; Female; Glucose; Glucose - administration & dosage; Glucose - therapeutic use; Humans; Hyperglycemia; Hyperglycemia - etiology; Hyperglycemia - immunology; Hyperglycemia - physiopathology; Hypoglycemia; Hypoglycemia - chemically induced; Hypoglycemia - immunology; Hypoglycemia - physiopathology; Hypoglycemia - therapy; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Inflammation; Inflammation Mediators - blood; Infusions, Intravenous; Insulin; Insulin - administration & dosage; Insulin - adverse effects; Male; Medical sciences; Oxidative stress; Oxidative Stress - drug effects; Plasma; Risk Factors; Statistical significance; Type 1 diabetes; Vasodilation - drug effects; Vitamin C; Young Adult; Italy; Spain; Endocrinopathy; Human; Immunopathology; Oxidative stress; Autoimmune disease; Metabolic diseases; Inflammation; Hypoglycemia; Endothelium; Hyperglycemia; Type 1 diabetes; Blood vessel; Circulatory system
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db12-0224

Currently there is debate on whether hypoglycemia is an independent risk factor for atherosclerosis, but little attention has been paid to the effects of recovery from hypoglycemia. In normal control individuals and in people with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normoglycemia or hyperglycemia for another 2 h and then maintaining normal glycemia for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. Recovery with normoglycemia is accompanied by a significant improvement in endothelial dysfunction, oxidative stress, and inflammation, which are affected by hypoglycemia; however, a period of hyperglycemia after hypoglycemia worsens all of these parameters, an effect that persists even after the additional 6 h of normoglycemia. This effect is partially counterbalanced when hyperglycemia after hypoglycemia is accompanied by the simultaneous infusion of vitamin C, suggesting that when hyperglycemia follows hypoglycemia, an ischemia-reperfusion-like effect is produced. This study shows that the way in which recovery from hypoglycemia takes place in people with type 1 diabetes could play an important role in favoring the appearance of endothelial dysfunction, oxidative stress, and inflammation, widely recognized cardiovascular risk factors.