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      Estimated glucose disposal rate and risk of stroke and mortality in type 2 diabetes: a nationwide cohort study


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          Background and aims

          Insulin resistance contributes to the development of type 2 diabetes (T2D) and is also a cardiovascular risk factor. The aim of this study was to investigate the potential association between insulin resistance measured by estimated glucose disposal rate (eGDR) and risk of stroke and mortality thereof in people with T2D.

          Materials and methods

          Nationwide population based observational cohort study that included all T2D patients from the Swedish national diabetes registry between 2004 and 2016 with full data on eGDR and categorised as following: < 4, 4–6, 6–8, and ≥ 8 mg/kg/min. We calculated crude incidence rates and 95% confidence intervals (CIs) and used multiple Cox regression to estimate hazard ratios (HRs) to assess the association between the risk of stroke and death, according to the eGDR categories in which the lowest category < 4 (i.e., highest grade of insulin resistance), served as a reference. The relative importance attributed of each factor in the eGDR formula was measured by the R 2 (± SE) values calculating the explainable log-likelihoods in the Cox regression.


          A total of 104 697 T2D individuals, 44.5% women, mean age of 63 years, were included. During a median follow up-time of 5.6 years, 4201 strokes occurred (4.0%). After multivariate adjustment the HRs (95% CI) for stroke in patients with eGDR categories between 4–6, 6–8 and > 8 were: 0.77 (0.69–0.87), 0.68 (0.58–0.80) and 0.60 (0.48–0.76), compared to the reference < 4. Corresponding numbers for the risk of death were: 0.82 (0.70–0.94), 0.75 (0.64–0.88) and 0.68 (0.53–0.89). The attributed relative risk R 2 (± SE) for each variable in the eGDR formula and stroke was for: hypertension (0.045 ± 0.0024), HbA1c (0.013 ± 0.0014), and waist (0.006 ± 0.0009), respectively.


          A low eGDR (a measure of insulin resistance) is associated with an increased risk of stroke and death in individuals with T2D. The relative attributed risk was most important for hypertension.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12933-021-01394-4.

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          Most cited references30

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          Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

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            Global estimates of the prevalence of diabetes for 2010 and 2030.

            We estimated the number of people worldwide with diabetes for the years 2010 and 2030. Studies from 91 countries were used to calculate age- and sex-specific diabetes prevalences, which were applied to national population estimates, to determine national diabetes prevalences for all 216 countries for 2010 and 2030. Studies were identified using Medline, and contact with all national and regional International Diabetes Federation offices. Studies were included if diabetes prevalence was assessed using a population-based methodology, and was based on World Health Organization or American Diabetes Association diagnostic criteria for at least three separate age-groups within the 20-79 year range. Self-report or registry data were used if blood glucose assessment was not available. The world prevalence of diabetes among adults (aged 20-79 years) will be 6.4%, affecting 285 million adults, in 2010, and will increase to 7.7%, and 439 million adults by 2030. Between 2010 and 2030, there will be a 69% increase in numbers of adults with diabetes in developing countries and a 20% increase in developed countries. These predictions, based on a larger number of studies than previous estimates, indicate a growing burden of diabetes, particularly in developing countries. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
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              Glucose clamp technique: a method for quantifying insulin secretion and resistance.

              Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.

                Author and article information

                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                6 October 2021
                6 October 2021
                : 20
                : 202
                [1 ]Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, 11883 Stockholm, Sweden
                [2 ]GRID grid.8761.8, ISNI 0000 0000 9919 9582, Institute of Medicine, , University of Gothenburg, ; Gothenburg, Sweden
                [3 ]GRID grid.459843.7, ISNI 0000 0004 0624 0259, Department of Medicine, , NU Hospital Group, ; Uddevalla, Sweden
                [4 ]Centre of Registers in Region Västra Götaland, Gothenburg, Sweden
                [5 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Department of Molecular Medicine and Surgery, , Karolinska Institutet, ; Stockholm, Sweden
                [6 ]GRID grid.24381.3c, ISNI 0000 0000 9241 5705, Department of Vascular Surgery, , Karolinska University Hospital, ; Stockholm, Sweden
                Author information
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                : 29 June 2021
                : 29 September 2021
                Funded by: FundRef http://dx.doi.org/10.13039/501100003793, hjärt-lungfonden;
                Award ID: 20190298
                Award Recipient :
                Funded by: alf stockholms läns landsting and karolinska institutet (grant 20170120).
                Award ID: 20170120
                Award Recipient :
                Funded by: Karolinska Institute
                Original Investigation
                Custom metadata
                © The Author(s) 2021

                Endocrinology & Diabetes
                type 2 diabetes,estimated glucose disposal rate,insulin resistance,stroke,all-cause mortality


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