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      Effects of long-term glycemic variability on incident cardiovascular disease and mortality in subjects without diabetes : A nationwide population-based study

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          Abstract

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          Abstract

          Increased glycemic variability (GV) is an independent risk factor for cardiovascular complications in patients with diabetes. We evaluated the risk of future development of cardiovascular disease (CVD) and death according to GV in a general population without diabetes.

          We used the National Health Insurance Service, providing a population-based, nationwide database of Koreans. We included individuals without diabetes who underwent glucose measurement at least 3 times during 2002 to 2006. GV was calculated as standard deviation (SD) of fasting plasma glucose (FPG) levels. We observed development of CVD or all-cause death from 2007 to 2015, and also evaluated the mortality within 1 year after CVD.

          Among 3,211,319 people, we found 23,374 incident cases of myocardial infarction (MI), 27,705 cases of stroke, and 63,275 deaths during 8.3 years of follow-up. After multivariate adjustment, GV was found to be a significant predictor of MI, stroke and all-cause death for their highest quartile, with corresponding hazard ratios (HR) of 1.08 (95% confidence interval, CI 1.04–1.11), 1.09 (95% CI 1.06–1.13), and 1.12 (95% CI 1.10–1.15), respectively. The risk of death increased more in those who had both impaired fasting glucose and the highest quartile of GV (HR 1.24 [95% CI 1.21–1.28]). Moreover, early death rate after 1 year of CVD was higher in the highest quartile of GV compared to the lowest quartile (HR 1.21 [95% CI 1.03–1.41]).

          Long-term FPG variation was independently associated with CVD and mortality in a general population without diabetes.

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          Most cited references23

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          Mean amplitude of glycemic excursions, a measure of diabetic instability.

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            Postprandial hyperglycemia and diabetes complications: is it time to treat?

            A Ceriello (2004)
            Increasing evidence suggests that the postprandial state is a contributing factor to the development of atherosclerosis. In diabetes, the postprandial phase is characterized by a rapid and large increase in blood glucose levels, and the possibility that the postprandial "hyperglycemic spikes" may be relevant to the onset of cardiovascular complications has recently received much attention. Epidemiological studies and preliminary intervention studies have shown that postprandial hyperglycemia is a direct and independent risk factor for cardiovascular disease (CVD). Most of the cardiovascular risk factors are modified in the postprandial phase in diabetic subjects and directly affected by an acute increase of glycemia. The mechanisms through which acute hyperglycemia exerts its effects may be identified in the production of free radicals. This alarmingly suggestive body of evidence for a harmful effect of postprandial hyperglycemia on diabetes complications has been sufficient to influence guidelines from key professional scientific societies. Correcting the postprandial hyperglycemia may form part of the strategy for the prevention and management of CVDs in diabetes.
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              Variability of blood glucose concentration and short-term mortality in critically ill patients.

              Intensive insulin therapy may reduce mortality and morbidity in selected surgical patients. Intensive insulin therapy also reduced the SD of blood glucose concentration, an accepted measure of variability. There is no information on the possible significance of variability in glucose concentration. The methods included extraction of blood glucose values from electronically stored biochemical databases and of data on patient's characteristics, clinical features, and outcome from electronically stored prospectively collected patient databases; calculation of SD of glucose as a marker of variability and of several indices of glucose control in each patient; and statistical assessment of the relation between these variables and intensive care unit mortality. There were 168,337 blood glucose measurements in the study cohort of 7,049 critically ill patients (4.2 hourly measurements on average). The mean +/- SD of blood glucose concentration was 1.7 +/- 1.3 mM in survivors and 2.3 +/- 1.6 mM in nonsurvivors (P < 0.001). Using multiple variable logistic regression analysis, both mean and SD of blood glucose were significantly associated with intensive care unit mortality (P < 0.001; odds ratios [per 1 mM] 1.23 and 1.27, respectively) and hospital mortality (P < 0.001 and P = 0.013; odds ratios [per 1 mM] 1.21 and 1.18, respectively). The SD of glucose concentration is a significant independent predictor of intensive care unit and hospital mortality. Decreasing the variability of blood glucose concentration might be an important aspect of glucose management.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                July 2019
                19 July 2019
                : 98
                : 29
                : e16317
                Affiliations
                [a ]Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, Korea University
                [b ]Department of Biostatistics, College of Medicine, The Catholic University of Korea
                [c ]Department of Family Medicine, College of Medicine, Korea University, Seoul, Korea.
                Author notes
                []Correspondence: Kyung Mook Choi, Department of Internal Medicine, Division of Endocrinology and Metabolism, Korea University Guro Hospital, College of Medicine, Korea University, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea (e-mail: medica7@ 123456gmail.com ); Nan Hee Kim, Department of Internal Medicine, Division of Endocrinology and Metabolism, Korea University Ansan Hospital, College of Medicine, Korea University, 123 Jeokgeum-ro, Danwon-gu, Ansan, Gyeonggi-do 15355, Korea (e-mail: nhkendo@ 123456gmail.com ).
                Article
                MD-D-18-07050 16317
                10.1097/MD.0000000000016317
                6709246
                31335679
                6ea16c6d-6159-4fba-bf36-06c4cb2ac96f
                Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 29 September 2018
                : 20 May 2019
                : 13 June 2019
                Categories
                4300
                Research Article
                Observational Study
                Custom metadata
                TRUE

                cardiovascular disease,cardiovascular mortality,glycemic variability,mortality

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