Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2021

Open Access 01-12-2021 | Stroke | Original investigation

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

Authors: Alexander Zabala, Vladimer Darsalia, Marcus Lind, Ann-Marie Svensson, Stefan Franzén, Björn Eliasson, Cesare Patrone, Magnus Jonsson, Thomas Nyström

Published in: Cardiovascular Diabetology | Issue 1/2021

Login to get access

Abstract

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 R2 (± SE) values calculating the explainable log-likelihoods in the Cox regression.

Results

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 R2 (± 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.

Conclusion

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14.CrossRef Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14.CrossRef
2.
go back to reference Cederholm J, Eeg-Olofsson K, Eliasson B, Zethelius B, Nilsson PM, Gudbjörnsdottir S. Risk prediction of cardiovascular disease in type 2 diabetes: a risk equation from the Swedish National Diabetes Register. Diabetes Care. 2008;31(10):2038–43.CrossRef Cederholm J, Eeg-Olofsson K, Eliasson B, Zethelius B, Nilsson PM, Gudbjörnsdottir S. Risk prediction of cardiovascular disease in type 2 diabetes: a risk equation from the Swedish National Diabetes Register. Diabetes Care. 2008;31(10):2038–43.CrossRef
3.
go back to reference Collaboration APCS. The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific Region. Diabetes Care. 2003;26(2):360–6.CrossRef Collaboration APCS. The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific Region. Diabetes Care. 2003;26(2):360–6.CrossRef
4.
go back to reference Zabala A, Darsalia V, Holzmann MJ, Franzén S, Svensson A-M, Eliasson B, et al. Risk of first stroke in people with type 2 diabetes and its relation to glycaemic control: a nationwide observational study. Diabetes Obes Metab. 2020;22(2):182–90.CrossRef Zabala A, Darsalia V, Holzmann MJ, Franzén S, Svensson A-M, Eliasson B, et al. Risk of first stroke in people with type 2 diabetes and its relation to glycaemic control: a nationwide observational study. Diabetes Obes Metab. 2020;22(2):182–90.CrossRef
5.
go back to reference Ormazabal V, Nair S, Elfeky O, Aguayo C, Salomon C, Zuñiga FA. Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol. 2018;17(1):122.CrossRef Ormazabal V, Nair S, Elfeky O, Aguayo C, Salomon C, Zuñiga FA. Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol. 2018;17(1):122.CrossRef
6.
go back to reference Eddy D, Schlessinger L, Kahn R, Peskin B, Schiebinger R. Relationship of insulin resistance and related metabolic variables to coronary artery disease: a mathematical analysis. Diabetes Care. 2009;32(2):361–6.CrossRef Eddy D, Schlessinger L, Kahn R, Peskin B, Schiebinger R. Relationship of insulin resistance and related metabolic variables to coronary artery disease: a mathematical analysis. Diabetes Care. 2009;32(2):361–6.CrossRef
7.
go back to reference DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237(3):E214-223.PubMed DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237(3):E214-223.PubMed
8.
go back to reference Williams KV, Erbey JR, Becker D, Arslanian S, Orchard TJ. Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes. 2000;49(4):626–32.CrossRef Williams KV, Erbey JR, Becker D, Arslanian S, Orchard TJ. Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes. 2000;49(4):626–32.CrossRef
9.
go back to reference Nyström T, Holzmann MJ, Eliasson B, Svensson A-M, Sartipy U. Estimated glucose disposal rate predicts mortality in adults with type 1 diabetes. Diabetes Obes Metab. 2018;20(3):556–63.CrossRef Nyström T, Holzmann MJ, Eliasson B, Svensson A-M, Sartipy U. Estimated glucose disposal rate predicts mortality in adults with type 1 diabetes. Diabetes Obes Metab. 2018;20(3):556–63.CrossRef
10.
go back to reference Nyström T, Holzmann MJ, Eliasson B, Svensson A-M, Kuhl J, Sartipy U. Estimated glucose disposal rate and long-term survival in type 2 diabetes after coronary artery bypass grafting. Heart Vessels. 2017;32(3):269–78.CrossRef Nyström T, Holzmann MJ, Eliasson B, Svensson A-M, Kuhl J, Sartipy U. Estimated glucose disposal rate and long-term survival in type 2 diabetes after coronary artery bypass grafting. Heart Vessels. 2017;32(3):269–78.CrossRef
11.
go back to reference Fonville S, Zandbergen AAM, Koudstaal PJ, den Hertog HM. Prediabetes in patients with stroke or transient ischemic attack: prevalence, risk and clinical management. Cerebrovasc Dis Basel Switz. 2014;37(6):393–400.CrossRef Fonville S, Zandbergen AAM, Koudstaal PJ, den Hertog HM. Prediabetes in patients with stroke or transient ischemic attack: prevalence, risk and clinical management. Cerebrovasc Dis Basel Switz. 2014;37(6):393–400.CrossRef
12.
go back to reference Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI. Insulin resistance and risk for stroke. Neurology. 2002;59(6):809–15.CrossRef Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI. Insulin resistance and risk for stroke. Neurology. 2002;59(6):809–15.CrossRef
13.
go back to reference Eliasson B, Gudbjörnsdottir S. Diabetes care—improvement through measurement. Diabetes Res Clin Pract. 2014;1(106):S291–4.CrossRef Eliasson B, Gudbjörnsdottir S. Diabetes care—improvement through measurement. Diabetes Res Clin Pract. 2014;1(106):S291–4.CrossRef
14.
go back to reference Cederholm J, Gudbjörnsdottir S, Eliasson B, Zethelius B, Eeg-Olofsson K, Nilsson PM, et al. Blood pressure and risk of cardiovascular diseases in type 2 diabetes: further findings from the Swedish National Diabetes Register (NDR-BP II). J Hypertens. 2012;30(10):2020–30.CrossRef Cederholm J, Gudbjörnsdottir S, Eliasson B, Zethelius B, Eeg-Olofsson K, Nilsson PM, et al. Blood pressure and risk of cardiovascular diseases in type 2 diabetes: further findings from the Swedish National Diabetes Register (NDR-BP II). J Hypertens. 2012;30(10):2020–30.CrossRef
15.
go back to reference Appelros P, Terént A. Validation of the Swedish inpatient and cause-of-death registers in the context of stroke. Acta Neurol Scand. 2011;123(4):289–93.CrossRef Appelros P, Terént A. Validation of the Swedish inpatient and cause-of-death registers in the context of stroke. Acta Neurol Scand. 2011;123(4):289–93.CrossRef
16.
go back to reference Ludvigsson JF, Svedberg P, Olén O, Bruze G, Neovius M. The longitudinal integrated database for health insurance and labour market studies (LISA) and its use in medical research. Eur J Epidemiol. 2019;34(4):423–37.CrossRef Ludvigsson JF, Svedberg P, Olén O, Bruze G, Neovius M. The longitudinal integrated database for health insurance and labour market studies (LISA) and its use in medical research. Eur J Epidemiol. 2019;34(4):423–37.CrossRef
17.
go back to reference Hoelzel W, Weykamp C, Jeppsson J-O, Miedema K, Barr JR, Goodall I, et al. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem. 2004;50(1):166–74.CrossRef Hoelzel W, Weykamp C, Jeppsson J-O, Miedema K, Barr JR, Goodall I, et al. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem. 2004;50(1):166–74.CrossRef
18.
go back to reference Heller G. A measure of explained risk in the proportional hazards model. Biostat Oxf Engl. 2012;13(2):315–25. Heller G. A measure of explained risk in the proportional hazards model. Biostat Oxf Engl. 2012;13(2):315–25.
19.
go back to reference O’Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. The Lancet. 2010;376(9735):112–23.CrossRef O’Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. The Lancet. 2010;376(9735):112–23.CrossRef
20.
go back to reference Lee Y, Cha SJ, Park J-H, Shin J-H, Lim Y-H, Park H-C, et al. Association between insulin resistance and risk of atrial fibrillation in non-diabetics. Eur J Prev Cardiol. 2020;27(18):1934–41.CrossRef Lee Y, Cha SJ, Park J-H, Shin J-H, Lim Y-H, Park H-C, et al. Association between insulin resistance and risk of atrial fibrillation in non-diabetics. Eur J Prev Cardiol. 2020;27(18):1934–41.CrossRef
21.
go back to reference Hu G, Sarti C, Jousilahti P, Peltonen M, Qiao Q, Antikainen R, et al. The impact of history of hypertension and type 2 diabetes at baseline on the incidence of stroke and stroke mortality. Stroke. 2005;36(12):2538–43.CrossRef Hu G, Sarti C, Jousilahti P, Peltonen M, Qiao Q, Antikainen R, et al. The impact of history of hypertension and type 2 diabetes at baseline on the incidence of stroke and stroke mortality. Stroke. 2005;36(12):2538–43.CrossRef
22.
go back to reference Xie X-X, Liu P, Wan F-Y, Lin S-G, Zhong W-L, Yuan Z-K, et al. Blood pressure lowering and stroke events in type 2 diabetes: a network meta-analysis of randomized controlled trials. Int J Cardiol. 2016;208:141–6.CrossRef Xie X-X, Liu P, Wan F-Y, Lin S-G, Zhong W-L, Yuan Z-K, et al. Blood pressure lowering and stroke events in type 2 diabetes: a network meta-analysis of randomized controlled trials. Int J Cardiol. 2016;208:141–6.CrossRef
23.
go back to reference Redon J, Mancia G, Sleight P, Schumacher H, Gao P, Pogue J, et al. Safety and efficacy of low blood pressures among patients with diabetes: subgroup analyses from the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). J Am Coll Cardiol. 2012;59(1):74–83.CrossRef Redon J, Mancia G, Sleight P, Schumacher H, Gao P, Pogue J, et al. Safety and efficacy of low blood pressures among patients with diabetes: subgroup analyses from the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). J Am Coll Cardiol. 2012;59(1):74–83.CrossRef
24.
go back to reference Rawshani A, Rawshani A, Franzén S, Sattar N, Eliasson B, Svensson A-M, et al. Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2018;379(7):633–44.CrossRef Rawshani A, Rawshani A, Franzén S, Sattar N, Eliasson B, Svensson A-M, et al. Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2018;379(7):633–44.CrossRef
25.
go back to reference Upadhyay J, Farr O, Perakakis N, Ghaly W, Mantzoros C. Obesity as a disease. Med Clin North Am. 2018;102(1):13–33.CrossRef Upadhyay J, Farr O, Perakakis N, Ghaly W, Mantzoros C. Obesity as a disease. Med Clin North Am. 2018;102(1):13–33.CrossRef
26.
go back to reference Oesch L, Tatlisumak T, Arnold M, Sarikaya H. Obesity paradox in stroke—Myth or reality? A systematic review. PLoS ONE. 2017;12(3):e0171334.CrossRef Oesch L, Tatlisumak T, Arnold M, Sarikaya H. Obesity paradox in stroke—Myth or reality? A systematic review. PLoS ONE. 2017;12(3):e0171334.CrossRef
27.
go back to reference Edqvist J, Rawshani A, Adiels M, Björck L, Lind M, Svensson A-M, et al. BMI, mortality, and cardiovascular outcomes in type 1 diabetes: findings against an obesity paradox. Diabetes Care. 2019;42(7):1297–304.CrossRef Edqvist J, Rawshani A, Adiels M, Björck L, Lind M, Svensson A-M, et al. BMI, mortality, and cardiovascular outcomes in type 1 diabetes: findings against an obesity paradox. Diabetes Care. 2019;42(7):1297–304.CrossRef
28.
go back to reference Eeg-Olofsson K, Cederholm J, Nilsson PM, Zethelius B, Nunez L, Gudbjörnsdóttir S, et al. Risk of cardiovascular disease and mortality in overweight and obese patients with type 2 diabetes: an observational study in 13,087 patients. Diabetologia. 2009;52(1):65–73.CrossRef Eeg-Olofsson K, Cederholm J, Nilsson PM, Zethelius B, Nunez L, Gudbjörnsdóttir S, et al. Risk of cardiovascular disease and mortality in overweight and obese patients with type 2 diabetes: an observational study in 13,087 patients. Diabetologia. 2009;52(1):65–73.CrossRef
30.
go back to reference UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet Lond Engl. 1998;352(9131):837–53.CrossRef UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet Lond Engl. 1998;352(9131):837–53.CrossRef
31.
go back to reference ORIGIN Trial Investigators, Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367(4):319–28. ORIGIN Trial Investigators, Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367(4):319–28.
32.
go back to reference Currie CJ, Peters JR, Tynan A, Evans M, Heine RJ, Bracco OL, et al. Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet Lond Engl. 2010;375(9713):481–9.CrossRef Currie CJ, Peters JR, Tynan A, Evans M, Heine RJ, Bracco OL, et al. Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet Lond Engl. 2010;375(9713):481–9.CrossRef
Metadata
Title
Estimated glucose disposal rate and risk of stroke and mortality in type 2 diabetes: a nationwide cohort study
Authors
Alexander Zabala
Vladimer Darsalia
Marcus Lind
Ann-Marie Svensson
Stefan Franzén
Björn Eliasson
Cesare Patrone
Magnus Jonsson
Thomas Nyström
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2021
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-021-01394-4

Other articles of this Issue 1/2021

Cardiovascular Diabetology 1/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.