Advertisement

The association of insulin resistance measured through the estimated glucose disposal rate with predictors of micro-and macrovascular complications in patients with type 1 diabetes

Published:October 20, 2022DOI:https://doi.org/10.1016/j.pcd.2022.10.003

      Highlights

      • The estimated glucose disposal rate (eGDR) may quantify insulin resistance.
      • Insulin resistance is associated with an increased incidence of cardiovascular disease in type 1 diabetes.
      • The eGDR correlates with cardiovascular predictors; an additional target in preventing type 1 diabetes complications.

      Abstract

      Background and aim

      Insulin resistance (IR) is associated with a higher rate of type 1 diabetes (T1D) complications. We aimed to examine the relationship between estimated glucose disposal rate (eGDR), a readily available marker of IR in clinical practice and early predictor biomarkers of macrovascular and microvascular complications in patients with T1D.

      Design

      A cross-sectional study.

      Methods

      A total of 165 consecutive patients with T1D free of cardiovascular, eye, and renal complications were included in the study from 2016 to 2020. Participants were characterized as insulin resistant if their eGDR value was ≤ 8 mg/kg/min. Pulse wave velocity (PWV) and global longitudinal strain (GLS) were used as surrogates for subclinical atherosclerosis and left ventricular systolic dysfunction (LVSD), respectively. Four previously standardized tests based on the calculation of heart rate variability (HRV) were used to evaluate subclinical cardiac autonomic neuropathy (CAN). Early nephropathy was assessed by assessing urinary albumin to creatinine ratio (ACR).

      Results

      The population sample (n = 165) included a majority of female patients (63%) and had a median age of 32 years (24−43), median disease duration of 14 years ( ± 9.5–21.5), a median BMI value of 23.7 kg/m2 (21.4–26.6), an HbA1C of 7.2% (6.7–8.2) and median eGDR (lower values indicate higher insulin resistance) of 9.2 mg/kg/min (8.2–9.9), while 21.8% (n = 36) of the participants were characterized as insulin resistant. After adjustment for age, gender, and the duration of diabetes, the presence of IR was significantly associated with higher prevalence of subclinical atherosclerosis (OR:2.59, 95% CI: 1.06–6.30, p = 0.036), CAN (OR:3.07, 95% CI: 1.02–9.32, p = 0.047) and subclinical LVSD (OR: 4.9, 95% CI: 1.94–12.79, p = 0.001). No association was shown with ACR.

      Conclusions

      In patients with T1D, insulin resistance, as measured by eGDR, correlates well with early CVD predictors and CAN. These associations appear independent of the effects of gender, aging, and disease duration.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Primary Care Diabetes
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Fullerton B.
        • Jeitler K.
        • Seitz M.
        • Horvath K.
        • Berghold A.
        • Siebenhofer A.
        Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus.
        Cochrane Database Syst. Rev. 2014; https://doi.org/10.1002/14651858.CD009122.pub2
        • Conway B.
        • Miller R.G.
        • Costacou T.
        • Fried L.
        • Kelsey S.
        • Evans R.W.
        • Orchard T.J.
        Temporal patterns in overweight and obesity in Type 1 diabetes.
        Diabet. Med. 2010; https://doi.org/10.1111/j.1464-5491.2010.02956.x
        • Nathan D.M.
        Influence of intensive diabetes treatment on body weight and composition of adults with type 1 diabetes in the diabetes control and complications trial.
        Diabetes Care. 2001; https://doi.org/10.2337/diacare.24.10.1711
        • Gregory J.M.
        • Smith T.J.
        • Slaughter J.C.
        • Mason H.R.
        • Hughey C.C.
        • Smith M.S.
        • Kandasamy B.
        • Greeley S.A.W.
        • Philipson L.H.
        • Naylor R.N.
        • et al.
        Iatrogenic hyperinsulinemia, not hyperglycemia, drives insulin resistance in type 1 diabetes as revealed by comparison with GCK-MODY (MODY2.
        Diabetes. 2019; https://doi.org/10.2337/db19-0324
        • Kilpatrick E.S.
        • Rigby A.S.
        • Atkin S.L.
        Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes: “Double diabetes” in the diabetes control and complications trial.
        Diabetes Care. 2007; https://doi.org/10.2337/dc06-1982
        • Orchard T.J.
        • Olson J.C.
        • Erbey J.R.
        • Williams K.
        • Forrest K.Y.Z.
        • Kinder L.S.
        • Ellis D.
        • Becker D.J.
        Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh epidemiology of diabetes complications study.
        Diabetes Care. 2003; https://doi.org/10.2337/diacare.26.5.1374
        • Porta M.
        • Sjoelie A.K.
        • Chaturvedi N.
        • Stevens L.
        • Rottiers R.
        • Veglio M.
        • Fuller J.H.
        Risk factors for progression to proliferative diabetic retinopathy in the EURODIAB Prospective Complications Study.
        Diabetologia. 2001; https://doi.org/10.1007/s001250100030
        • Finegood D.T.
        • Bergman R.N.
        • Vranic M.
        Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates.
        Diabetes. 1987; https://doi.org/10.2337/diab.36.8.914
        • Williams K.V.
        • Erbey J.R.
        • Becker D.
        • Arslanian S.
        • Orchard T.J.
        Can clinical factors estimate insulin resistance in type 1 diabetes.
        Diabetes. 2000; https://doi.org/10.2337/diabetes.49.4.626
        • Olson J.C.
        • Erbey J.R.
        • Forrest K.Y.Z.
        • Williams K.
        • Becker D.J.
        • Orchard T.J.
        Glycemia (or, in women, estimated glucose disposal rate) predict lower extremity arterial disease events in type 1 diabetes.
        Metabolism. 2002; https://doi.org/10.1053/meta.2002.30021
        • Tesfaye S.
        • Chaturvedi N.
        • Eaton S.E.M.
        • Ward J.D.
        • Manes C.
        • Ionescu-Tirgoviste C.
        • Witte D.R.
        • Fuller J.H.
        Vascular risk factors and diabetic neuropathy.
        N. Engl. J. Med. 2005; https://doi.org/10.1056/nejmoa032782
        • Miller R.G.
        • Costacou T.
        • Orchard T.J.
        Risk factor modeling for cardiovascular disease in type 1 diabetes in the pittsburgh epidemiology of diabetes complications (EDC) study: a comparison with the diabetes control and complications trial/epidemiology of diabetes interventions and complication.
        Diabetes. 2019; https://doi.org/10.2337/db18-0515
        • Nadeau K.J.
        • Regensteiner J.G.
        • Bauer T.A.
        • Brown M.S.
        • Dorosz J.L.
        • Hull A.
        • Zeitler P.
        • Draznin B.
        • Reusch J.E.B.
        Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function.
        J. Clin. Endocrinol. Metab. 2010; https://doi.org/10.1210/jc.2009-1756
        • Chillarón J.J.
        • Goday A.
        • Flores-Le-Roux J.A.
        • Benaiges D.
        • Carrera M.J.
        • Puig J.
        • Cano-Pérez J.F.
        • Pedro-Botet J.
        Estimated glucose disposal rate in assessment of the metabolic syndrome and microvascular complications in patients with type 1 diabetes.
        J. Clin. Endocrinol. Metab. 2009; https://doi.org/10.1210/jc.2009-0960
        • Kim H.L.
        • Kim S.H.
        Pulse wave velocity in atherosclerosis.
        Front Cardiovasc Med. 2019; https://doi.org/10.3389/fcvm.2019.00041
        • Russo C.
        • Jin Z.
        • Elkind M.S.V.
        • Rundek T.
        • Homma S.
        • Sacco R.L.
        • Di Tullio M.R.
        Prevalence and prognostic value of subclinical left ventricular systolic dysfunction by global longitudinal strain in a community-based cohort.
        Eur. J. Heart Fail. 2014; https://doi.org/10.1002/ejhf.154
        • Gerritsen J.
        • Dekker J.M.
        • Tenvoorde B.J.
        • Kostense P.J.
        • Heine R.J.
        • Bouter L.M.
        • Heethaar R.M.
        • Stehouwer C.D.A.
        Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease: the hoorn study.
        Diabetes Care. 2001; https://doi.org/10.2337/diacare.24.10.1793
      1. Chapter 1: Definition and classification of CKD Kidney Int Suppl. 2013.doi:10.1038/kisup.2012.64.

        • Yingchoncharoen T.
        • Agarwal S.
        • Popović Z.B.
        • Marwick T.H.
        Normal ranges of left ventricular strain: a meta-analysis.
        J. Am. Soc. Echocardiogr. 2013; https://doi.org/10.1016/j.echo.2012.10.008
        • Nagueh S.F.
        • Smiseth O.A.
        • Appleton C.P.
        • Byrd B.F.
        • Dokainish H.
        • Edvardsen T.
        • Flachskampf F.A.
        • Gillebert T.C.
        • Klein A.L.
        • Lancellotti P.
        • et al.
        Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
        J. Am. Soc. Echocardiogr. 2016; https://doi.org/10.1016/j.echo.2016.01.011
        • Ewing D.J.
        • Martyn C.N.
        • Young R.J.
        • Clarke B.F.
        The value of cardiovascular autonomic function tests: 10 years experience in diabetes.
        Diabetes Care. 1985; https://doi.org/10.2337/diacare.8.5.491
        • Howorka K.
        • Pumprla J.
        • Schabmann A.
        Optimal parameters of short-term heart rate spectrogram for routine evaluation of diabetic cardiovascular autonomic neuropathy.
        J. Auton. Nerv. Syst. 1998; https://doi.org/10.1016/S0165-1838(98)00015-0
      2. Kahn R. Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Diabetes Care (1992).

        • Mattace-Raso F.U.S.
        • Hofman A.
        • Verwoert G.C.
        • Wittemana J.C.M.
        • Wilkinson I.
        • Cockcroft J.
        • McEniery C.
        • Yasmina
        • Laurent S.
        • Boutouyrie P.
        • et al.
        Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ‘establishing normal and reference values.
        Eur. Heart J. 2010; https://doi.org/10.1093/eurheartj/ehq165
        • Epstein E.J.
        • Osman J.L.
        • Cohen H.W.
        • Rajpathak S.N.
        • Lewis O.
        • Crandall J.P.
        Use of the estimated glucose disposal rate as a measure of insulin resistance in an urban multiethnic population with type 1 diabetes.
        Diabetes Care. 2013; https://doi.org/10.2337/dc12-1693
        • Nyström T.
        • Holzmann M.J.
        • Eliasson B.
        • Svensson A.M.
        • Sartipy U.
        Estimated glucose disposal rate predicts mortality in adults with type 1 diabetes.
        Diabetes, Obes. Metab. 2018; https://doi.org/10.1111/dom.13110
        • Astrup A.S.
        • Tarnow L.
        • Rossing P.
        • Hansen B.V.
        • Hilsted J.
        • Parving H.H.
        Cardiac autonomic neuropathy predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy.
        Diabetes Care. 2006; https://doi.org/10.2337/diacare.29.02.06.dc05-1242
        • Biering-Sørensen T.
        • Biering-Sørensen S.R.
        • Olsen F.J.
        • Sengeløv M.
        • Jørgensen P.G.
        • Mogelvang R.
        • Shah A.M.
        • Jensen J.S.
        Global longitudinal strain by echocardiography predicts long-term risk of cardiovascular morbidity and mortality in a low-risk general population: the copenhagen city heart study.
        Circ. Cardiovasc Imaging. 2017; https://doi.org/10.1161/CIRCIMAGING.116.005521
        • Cauwenberghs N.
        • Knez J.
        • Thijs L.
        • Haddad F.
        • Vanassche T.
        • Yang W.Y.
        • Wei F.F.
        • Staessen J.A.
        • Kuznetsova T.
        Relation of insulin resistance to longitudinal changes in left ventricular structure and function in a general population.
        J. Am. Heart Assoc. 2018; https://doi.org/10.1161/JAHA.117.008315
        • Chaturvedi N.
        • Bandinelli S.
        • Mangili R.
        • Penno G.
        • Rottiers R.E.
        • Fuller J.H.
        • Karamanos B.
        • Kofinis A.
        • Petrou K.
        • Giorgino R.
        • et al.
        Microalbuminuria in type 1 diabetes: Rates, risk factors and glycemic threshold.
        Kidney Int. 2001; https://doi.org/10.1046/j.1523-1755.2001.00789.x
        • Helliwell R.
        • Warnes H.
        • Kietsiriroje N.
        • Campbell M.
        • Birch R.
        • Pearson S.M.
        • Ajjan R.A.
        Body mass index, estimated glucose disposal rate and vascular complications in type 1 diabetes: Beyond glycated haemoglobin.
        Diabet. Med. 2021; https://doi.org/10.1111/dme.14529
        • Hirose K.
        • Nakanishi K.
        • Daimon M.
        • Sawada N.
        • Yoshida Y.
        • Iwama K.
        • Yamamoto Y.
        • Ishiwata J.
        • Hirokawa M.
        • Koyama K.
        • et al.
        Impact of insulin resistance on subclinical left ventricular dysfunction in normal weight and overweight/obese japanese subjects in a general community.
        Cardiovasc Diabetol. 2021; https://doi.org/10.1186/s12933-020-01201-6
        • Laitinen T.
        • Lindström J.
        • Eriksson J.
        • Ilanne-Parikka P.
        • Aunola S.
        • Keinänen-Kiukaanniemi S.
        • Tuomilehto J.
        • Uusitupa M.
        Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance.
        Diabet. Med. 2011; https://doi.org/10.1111/j.1464-5491.2011.03278.x
        • Liu J.H.
        • Chen Y.
        • Yuen M.
        • Zhen Z.
        • Chan C.W.S.
        • Lam K.S.L.
        • Tse H.F.
        • Yiu K.H.
        Incremental prognostic value of global longitudinal strain in patients with type 2 diabetes mellitus.
        Cardiovasc Diabetol. 2016; https://doi.org/10.1186/s12933-016-0333-5
        • Llauradó G.
        • Cano A.
        • Albert L.
        • Ballesta S.
        • Mazarico I.
        • Luchtenberg M.F.
        • González-Sastre M.
        • Megía A.
        • Simó R.
        • Vendrell J.
        • et al.
        Arterial stiffness is highly correlated with the scores obtained from the steno type 1 risk engine in subjects with T1DM.
        PLoS One. 2019; https://doi.org/10.1371/journal.pone.0220206
        • Maser R.E.
        • Mitchell B.D.
        • Vinik A.I.
        • Freeman R.
        The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes a meta-analysis.
        Diabetes Care. 2003; https://doi.org/10.2337/diacare.26.6.1895
        • Sarkar G.
        • Alattar M.
        • Brown R.J.
        • Quon M.J.
        • Harlan D.M.
        • Rother K.I.
        Exenatide treatment for 6 months improves insulin sensitivity in adults with type 1 diabetes.
        Diabetes Care. 2014; https://doi.org/10.2337/dc13-1473
        • Shah A.S.
        • Black S.
        • Wadwa R.P.
        • Schmiege S.J.
        • Fino N.F.
        • Talton J.W.
        • D’Agostino R.
        • Hamman R.F.
        • Urbina E.M.
        • Dolan L.M.
        • et al.
        Insulin sensitivity and arterial stiffness in youth with type 1 diabetes: the SEARCH CVD study.
        J. Diabetes Complicat. 2015; https://doi.org/10.1016/j.jdiacomp.2015.02.004
        • Soedamah-Muthu S.S.
        • Chaturvedi N.
        • Fuller J.H.
        • Toeller M.
        Do European people with type 1 diabetes consume a high atherogenic diet? 7-year follow-up of the EURODIAB prospective complications study.
        Eur. J. Nutr. 2013; https://doi.org/10.1007/s00394-012-0473-7
        • Tynjälä A.
        • Forsblom C.
        • Harjutsalo V.
        • Groop P.H.
        • Gordin D.
        Arterial stiffness predicts mortality in individuals with type 1 diabetes.
        Diabetes Care. 2020; https://doi.org/10.2337/dc20-0078
        • Wadén J.
        • Forsblom C.
        • Thorn L.
        • Saraheimo M.
        • Rosengård-Bärlund M.
        • Heikkilä O.
        • Lakka T.
        • Tikkanen H.
        • Groop P.-H.
        Physical activity and diabetes complications in patients with type 1 diabetes.
        Diabetes Care. 2008;
        • Zairi I.
        • Mzoughi K.
        • Kamoun S.
        • Ben Moussa F.
        • Rezgallah R.
        • Maatoug J.
        • Mazigh S.
        • Kraiem S.
        Impairment of left and right ventricular longitudinal strain in asymptomatic children with type 1 diabetes.
        Indian Heart J. 2019; https://doi.org/10.1016/j.ihj.2019.04.008
        • Köken Ö.Y.
        • Kara C.
        • Yilmaz G.C.
        • Aydin H.M.
        Utility of estimated glucose disposal rate for predicting metabolic syndrome in children and adolescents with type-1 diabetes.
        J. Pedia Endocrinol. Metab. 2020; https://doi.org/10.1515/jpem-2020-0012
        • De Boer I.H.
        • Kestenbaum B.
        • Rue T.C.
        • Steffes M.W.
        • Cleary P.A.
        • Molitch M.E.
        • Lachin J.M.
        • Weiss N.S.
        • Brunzell J.D.
        Insulin therapy, hyperglycemia, and hypertension in type 1 diabetes mellitus.
        Arch. Intern Med. 2008; https://doi.org/10.1001/archinternmed.2008.2
        • De Boer I.H.
        • Bangalore S.
        • Benetos A.
        • Davis A.M.
        • Michos E.D.
        • Muntner P.
        • Rossing P.
        • Zoungas S.
        • Bakris G.
        Diabetes and hypertension: a position statement by the American diabetes association.
        Diabetes Care. 2017; https://doi.org/10.2337/dci17-0026
        • Spallone V.
        • Ziegler D.
        • Freeman R.
        • Bernardi L.
        • Frontoni S.
        • Pop-Busui R.
        • Stevens M.
        • Kempler P.
        • Hilsted J.
        • Tesfaye S.
        • et al.
        Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management.
        Diabetes Metab. Res. Rev. 2011; https://doi.org/10.1002/dmrr.1239