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      Association between blood glucose variability and coronary plaque instability in patients with acute coronary syndromes

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          Abstract

          Background

          Blood glucose variability is receiving considerable attention as a new risk factor for coronary artery disease. This study aimed to investigate the association between blood glucose variability and coronary plaque tissue characteristics.

          Methods

          In 57 patients with acute coronary syndrome, integrated backscatter intravascular ultrasound (IB-IVUS) and gray-scale IVUS were performed before balloon dilatation or stent implantation in the culprit vessels. Standard IVUS indices were evaluated for volume index (volume/length), and plaque components were measured by IB-IVUS for percent tissue volume. In addition to conventional glucose indicators, blood glucose variability in a stable state was determined by calculating the mean amplitude of glycemic excursions (MAGE) using a continuous glucose monitoring system.

          Results

          Higher MAGE values were significantly correlated with larger percent plaque volumes (r = 0.32, p = 0.015), and increased lipid (r = 0.44, p = 0.0006) and decreased fibrous (r = −0.45, p = 0.0005) plaque components. In contrast, HbA1c or fasting plasma glucose values were not significantly correlated with plaque volumes and percent plaque components. Homeostasis model assessment of insulin resistance values were positively correlated with vessel (r = 0.35, p = 0.007) and plaque (r = 0.27, p = 0.046) volumes, but not with percent plaque components. In multiple regression analysis, higher MAGE values were independently associated with increased lipid (β = 0.80, p = 0.0035) and decreased fibrous (β = -0.79, p = 0.0034) contents in coronary plaques.

          Conclusions

          Among all glucose indicators studied, only higher blood glucose variability was an independent determinant of increased lipid and decreased fibrous contents with larger plaque burden, suggesting blood glucose variability as one of the important factors related to coronary plaque vulnerability.

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          Most cited references38

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          Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c).

          The exact contributions of postprandial and fasting glucose increments to overall hyperglycemia remain controversial. The discrepancies between the data published previously might be caused by the interference of several factors. To test the effect of overall glycemic control itself, we analyzed the diurnal glycemic profiles of type 2 diabetic patients investigated at different levels of HbA(1c). In 290 non-insulin- and non-acarbose-using patients with type 2 diabetes, plasma glucose (PG) concentrations were determined at fasting (8:00 A.M.) and during postprandial and postabsorptive periods (at 11:00 A.M., 2:00 P.M., and 5:00 P.M.). The areas under the curve above fasting PG concentrations (AUC(1)) and >6.1 mmol/l (AUC(2)) were calculated for further evaluation of the relative contributions of postprandial (AUC(1)/AUC(2), %) and fasting [(AUC(2) - AUC(1))/AUC(2), %] PG increments to the overall diurnal hyperglycemia. The data were compared over quintiles of HbA(1c). The relative contribution of postprandial glucose decreased progressively from the lowest (69.7%) to the highest quintile of HbA(1c) (30.5%, P < 0.001), whereas the relative contribution of fasting glucose increased gradually with increasing levels of HbA(1c): 30.3% in the lowest vs. 69.5% in the highest quintile (P < 0.001). The relative contribution of postprandial glucose excursions is predominant in fairly controlled patients, whereas the contribution of fasting hyperglycemia increases gradually with diabetes worsening. These results could therefore provide a unifying explanation for the discrepancies as observed in previous studies.
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            American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents.

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              Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria.

              (2001)
              New diagnostic criteria for diabetes based on fasting blood glucose (FBG) level were approved by the American Diabetes Association. The impact of using FBG only has not been evaluated thoroughly. The fasting and the 2-hour glucose (2h-BG) criteria were compared with regard to the prediction of mortality. Existing baseline data on glucose level at fasting and 2 hours after a 75-g oral glucose tolerance test from 10 prospective European cohort studies including 15 388 men and 7126 women aged 30 to 89 years, with a median follow-up of 8.8 years, were analyzed. Hazards ratios for death from all causes, cardiovascular disease, coronary heart disease, and stroke were estimated. Multivariate Cox regression analyses showed that the inclusion of FBG did not add significant information on the prediction of 2h-BG alone (P>.10 for various causes), whereas the addition of 2h-BG to FBG criteria significantly improved the prediction (P<.001 for all causes and P<.005 for cardiovascular disease). In a model including FBG and 2h-BG simultaneously, hazards ratios (95% confidence intervals) in subjects with diabetes on 2h-BG were 1.73 (1.45-2.06) for all causes, 1.40 (1.02-1.92) for cardiovascular disease, 1.56 (1.03-2.36) for coronary heart disease, and 1.29 (0.66-2.54) for stroke mortality, compared with the normal 2h-BG group. Compared with the normal FBG group, the corresponding hazards ratios in subjects with diabetes on FBG were 1.21 (1.01-1.44), 1.20 (0.88-1.64), 1.09 (0.71-1.67), and 1.64 (0.88-3.07), respectively. The largest number of excess deaths was observed in subjects who had impaired glucose tolerance but normal FBG levels. The 2h-BG is a better predictor of deaths from all causes and cardiovascular disease than is FBG.
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                Author and article information

                Contributors
                kozookada@gmail.com
                +81-45-261-5656 , hibikiyo@yokohama-cu.ac.jp
                gocchi3@hotmail.com
                skykks1118@yahoo.co.jp
                kgossy@aol.com
                e-akiyam@kumamoto-u.ac.jp
                matsu@yokohama-cu.ac.jp
                kenichiros76@gmail.com
                nmaejima@yokohama-cu.ac.jp
                mitsuendy@yahoo.co.jp
                wsnorikun@yahoo.co.jp
                k-tsuka@urahp.yokohama-cu.ac.jp
                masami.kosuge@gmail.com
                tebina@med.yokohama-cu.ac.jp
                pfitz@stanford.edu
                honda@stanford.edu
                umemuras@med.yokohama-cu.ac.jp
                c-kimura@urahp.yokohama-cu.ac.jp
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                20 August 2015
                20 August 2015
                2015
                : 14
                : 111
                Affiliations
                [ ]Division of Cardiology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, 232-0024 Japan
                [ ]Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, USA
                [ ]Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
                Article
                275
                10.1186/s12933-015-0275-3
                4546046
                26289581
                e8bd9b5b-fd95-426f-aca1-eeb58c6d3b1d
                © Okada et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 May 2015
                : 8 August 2015
                Categories
                Original Investigation
                Custom metadata
                © The Author(s) 2015

                Endocrinology & Diabetes
                glucose variability,vulnerable plaque,acute coronary syndrome,ib-ivus
                Endocrinology & Diabetes
                glucose variability, vulnerable plaque, acute coronary syndrome, ib-ivus

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