Glucose Fluctuations and Oxidative Stress—Reply

Abstract

As I noted in the cover story, Kantor loved ambiguity, "especially when he can hide it behind a cloud of facts." It seems he was successful. M. Therese Southgate, MD therese.southgate@jama-archives.orgTo the Editor: The study of activation of oxidative stress in patients with type 2 diabetes by Dr Monnier and colleagues 1 identifies an interesting association between glycemic variability and oxidative stress. However, it is important to highlight some limitations of the tools used in this study and the data reported.Continuous glucose monitoring systems (CGMSs) may be inaccurate or even intermittently fail to record. The authors report the accuracy of CGMSs for a single fasting time point but do not report whether a minimum accuracy criterion was applied prior to accepting a 24-hour glucose profile, such as a maximum permitted mean relative absolute difference between all concurrent CGMSs and capillary glucose measurements, or a maximum gap in the CGMS recording.The study examined only 1 marker of oxidative stress, urinary 8-iso prostaglandin F 2␣ (8-iso-PGF 2␣ ). Although most studies demonstrate elevated urinary 8-iso-PGF 2␣ in patients with diabetes, some studies have indicated normal values, even in the setting of type 1 diabetes, where glycemic variability is invariably high. 2 Little is known about the relationship between urinary excretion of 8-iso-PGF 2␣ and acute changes in blood glucose. It would be very helpful to know the day-to-day intraindividual variability of urinary 8-iso-PGF 2␣ excretion and whether urinary excretion responds acutely to improvement in glycemic control. If this is not the case, it raises questions about the significance of their data.While smoking is known to increase urinary 8-iso-PGF 2␣ , 3 the study does not report the number of smokers in the diabetes or control groups. Furthermore, urine albumin excretion rate was not reported. The association between urinary 8-iso-PGF 2␣ and urine albumin excretion rate has not been studied in the setting of diabetes, but microalbuminuria is associated with elevated oxidative stress. 4 Finally, the authors chose to measure glycemic variability over a 48-hour period using an average of day 1 and 2, even though the urine collection was only performed on day 1. It appears that no effort was made to standardize the patient's diet or physical activity during the study. Therefore, glucose variability may have differed substantially between the 24 hours of urinary 8-iso-PGF 2␣ collection and the second day. These data should be provided. LETTERS Louis Monnier, MD

Glycemic Variability Determined by Continuous Glucose Monitoring System Predicts Left Ventricular Remodeling in Patients With a First ST-Segment Elevation Myocardial Infarction

“…Impaired glucose metabolism is associated with coronary microvascular dysfunction, 27 poor collateral development, 28 prevention of ischemic preconditioning, 29 inflammation, 30 and decreased mitochondrial ATP, 31 all of which may lead to LVR. Because MAGE has a more specific triggering effect on oxidative stress than sustained hyperglycemia, 19 it may be associated with these factors more strongly and thus have an effect on LVR. Therefore we might be able to demonstrate that MAGE is an independent predictor of LVR despite a small sample size.…”

“…18 Monnier et al showed that MAGE had a more specific triggering effect on oxidative stress than sustained hyperglycemia and that oxidative stress was reduced by blunting GV. 19 Oxidative stress causes complications related to impaired glucose metabolism through 4 molecular mechanisms. 20 In addition, Quagliaro et al showed that intermittent hyperglycemia induces a higher degree of apoptosis in endothelial cells than does sustained hyperglycemia.…”

Mechanistic Insights Into Diabetes Mellitus and Oxidative Stress

“…In addition, free fatty acids which can lead to ROS, have been shown to also contribute to mitochondrial DNA damage and impaired pancreatic β-cell function [88]. (1)), illustrating the importance for therapeutic interventions during acute and sustained hyperglycemic episodes [83]. Recent clinical correlates support these experimental studies to show that acute glucose swings in addition to chronic hyperglycemia can trigger oxidative stress mechanisms during Type 2 DM (Fig.…”

Model-Based Insulin and Nutrition Administration for Tight Glycaemic Control in Critical Care

“…In particular, recent analyses have indicated that the tighter the control obtained, the lower the standardized mortality [97]. Hence, the primary measurements to date that are of statistical significance are based on glycemic time in band and variability, the latter of which is also becoming well related to inflammatory cascade and reduced insulin sensitivity seen in critical care [16,[98][99][100], and the resulting poor response to infection [101,102].…”

“…By reducing variability, it decreases the risk of hypoglycaemia. In addition, evidence is showing that minimizing exposure to hyperglycaemia has a significant effect on a variety of cell functions and immune response [16,22,94,100,101,104,105]. Hence, tight control may also have positive impact on clinical outcomes by minimising exposure to hyperglycaemic levels.…”