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

Abstract

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.

Hypoglycemia at Admission in Patients With Acute Myocardial Infarction Predicts a Higher 30-Day Mortality in Patients With Poorly Controlled Type 2 Diabetes Than in Well-Controlled Patients

“…In particular, hyperglycemia after hypoglycemia was shown to cause more severe pathophysiologic changes than those observed during recovery to euglycemia, for a so-called "reperfusionlike effect" (38,39). These pathologic processes might be more relevant to patients with poorly controlled diabetes if they also have micro-or macrovascular complications (40).…”

Reactive Oxygen Species in Inflammation and Tissue Injury

“…Continuous positive airway pressure treatment of these patients decreased basal ROS production in monocytes and concomitantly decreased the expression of CD15 and CD11c on monocytes (105). The circulating levels of ICAM-1, VCAM-1, and E-Selectin are elevated in hyperlipidemic and hyperglycemic and noninsulin-dependent diabetic-patients in direct correlation with increased oxidative stress (58,69,86,313,352). Reducing oxidative stress by GSH administration or NAC or low-fat diet improved the circulating levels of adhesion molecules (5,57,85,86).…”

Hypoglycemia in Type 2 Diabetes - More Common Than You Think

“…Since GV also measures changes of glucose levels in both the hyperglycemic and hypoglycemic ranges, the tissue damage from hypoglycemia is postulated to be mediated via increased catecholamine production and/or their effects on blood vessel and endothelial function as well as induction of proinflammatory and prothrombotic pathways. 22,23 Increased GV has also been shown to be a predictor of hypoglycemia 24 and increased risk of cardiac death in critically ill patients with T2DM. 25,26 Hypoglycemia-induced increases in blood pressure and heart rate, triggering of blood vessel constriction or acute thrombosis are probable explanations of these adverse events.…”