The mediating role of systolic blood pressure in the association between estimated glucose disposal rate and renal prognosis: a nationwide prospective cohort study

Abstract

Aim: Despite the well-documented pathogenic role of insulin resistance (IR) and hypertension in nephropathy progression, the prognostic value of the estimated glucose disposal rate (eGDR) for incident renal dysfunction remains unclear. This population-based longitudinal analysis specifically examined the eGDR-renal dysfunction relationship in middle-aged and elderly populations, with a particular focus on the potential mediating role of systolic blood pressure (SBP) based on a nationwide longitudinal study.

Methods: Utilizing data from 8,136 participants in the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015), we conducted multivariable-adjusted logistic regression analyses combined with a restricted cubic spline model to assess the association between eGDR and incident renal dysfunction. Mediation analysis was employed to assess the proportion of the association mediated by SBP in this relationship.

Results: Over a median follow-up period of 4 years, 2,223 participants developed renal dysfunction. Both eGDR and SBP were significantly and independently associated with incident renal dysfunction. The odds ratio (OR) for eGDR was 0.73 (95%CI: 0.58-0.92), while the OR for SBP was 1.20 (95%CI: 1.05-1.38). Restricted cubic spline analysis identified critical thresholds, with eGDR levels below 11.6 mg/kg/min and SBP levels above 125 mmHg being associated with a higher risk of renal dysfunction. Mediation analysis further demonstrated that SBP acted as a significant mediator in the relationship between eGDR and renal dysfunction, accounting for 42.6% of the total effect (95%CI: 19.9%-86.7%).

Conclusion: This prospective cohort study identifies eGDR as an independent predictor of renal dysfunction, with nearly half of its effect mediated by SBP. These findings highlight the potential benefit of integrated management strategies targeting both insulin sensitivity and blood pressure control to reduce the risk of renal dysfunction in aging populations.

Keywords

Estimated glucose disposal rate / renal dysfunction / systolic blood pressure / mediation effects / insulin resistance

References

[1] Tangri N,Bodegård J.Mortality, health care burden, and treatment of CKD: a multinational, observational study (OPTIMISE-CKD).Kidney3602024;5:352-62 PMCID:PMC11000732

[2] 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019.Lancet2020;396:1204-22 PMCID:PMC7567026

[3] De Cosmo S, Menzaghi C, Prudente S, Trischitta V. Role of insulin resistance in kidney dysfunction: insights into the mechanism and epidemiological evidence.Nephrol Dial Transplant2013;28:29-36

[4] Pham H,de Boer IH.Measurement of insulin resistance in chronic kidney disease.Curr Opin Nephrol Hypertens2011;20:640-6 PMCID:PMC3712903

[5] DeFronzo RA,Andres R.Glucose clamp technique: a method for quantifying insulin secretion and resistance.Am J Physiol1979;237:E214-23

[6] Pambianco G,Orchard TJ.The prediction of major outcomes of type 1 diabetes: a 12-year prospective evaluation of three separate definitions of the metabolic syndrome and their components and estimated glucose disposal rate: the Pittsburgh epidemiology of diabetes complications study experience.Diabetes Care2007;30:1248-54

[7] Peng J,Zhu Y.Estimated glucose disposal rate for predicting cardiovascular events and mortality in patients with non-diabetic chronic kidney disease: a prospective cohort study.BMC Med2024;22:411 PMCID:PMC11438365

[8] Mao Y.Changes of insulin resistance status and development of complications in type 1 diabetes mellitus: analysis of DCCT/EDIC study.Diabetes Res Clin Pract2022;184:109211

[9] Lonardo A,Targher G.Precision medicine approaches in metabolic disorders and target organ damage: where are we now, and where are we going?.Metab Target Organ Damage2021;1:3

[10] Yan Y,Liu B.Optimal blood pressure control target for older patients with hypertension: a systematic review and meta-analysis.CVIA2023;7:1-12

[11] Zhang F.Mendelian randomization study on insulin resistance and risk of hypertension and cardiovascular disease.Sci Rep2024;14:6191 PMCID:PMC10940700

[12] Zeng J,Yang Y.Association between a metabolic score for insulin resistance and hypertension: results from National Health and Nutrition Examination Survey 2007-2016 analyses.Front Endocrinol2024;15:1369600 PMCID:PMC11070536

[13] Niu ZJ,Wei T.The effect of insulin resistance in the association between obesity and hypertension incidence among Chinese middle-aged and older adults: data from China health and retirement longitudinal study (CHARLS).Front Public Health2024;12:1320918 PMCID:PMC10898648

[14] Zhao Y,Smith JP,Yang G.Cohort profile: the China Health and Retirement Longitudinal Study (CHARLS).Int J Epidemiol2014;43:61-8 PMCID:PMC3937970

[15] Li W,Wang M,Guo C.The effect of clean cooking on the social participation of middle-aged and older adults in China: a prospective cohort study.Sci Total Environ2024;922:171207

[16] Chen W,Chen J.Household air pollution, adherence to a healthy lifestyle, and risk of cardiometabolic multimorbidity: results from the China health and retirement longitudinal study.Sci Total Environ2023;855:158896

[17] Ren X,Han L.Estimated glucose disposal rate and risk of cardiovascular disease: evidence from the China Health and Retirement Longitudinal Study.BMC Geriatr2022;22:968 PMCID:PMC9753298

[18] Liao J,Duan L.Association between estimated glucose disposal rate and cardiovascular diseases in patients with diabetes or prediabetes: a cross-sectional study.Cardiovasc Diabetol2025;24:13 PMCID:PMC11730478

[19] Yan L,Wu X.Association between the changes in the estimated glucose disposal rate and new-onset cardiovascular disease in middle-aged and elderly individuals: a nationwide prospective cohort study in China.Diabetes Obes Metab2025;27:1859-67 PMCID:PMC11885094

[20] Helliwell R,Kietsiriroje N.Body mass index, estimated glucose disposal rate and vascular complications in type 1 diabetes: beyond glycated haemoglobin.Diabet Med2021;38:e14529

[21] Michels WM,Verduijn M,Dekker FW.Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size.Clin J Am Soc Nephrol2010;5:1003-9 PMCID:PMC2879308

[22] Zhang Z,Liu M.Association of depressive symptoms with rapid kidney function decline in adults with normal kidney function.Clin J Am Soc Nephrol2021;16:889-97 PMCID:PMC8216614

[23] Zhou W,Ning Y.Social isolation is associated with rapid kidney function decline and the development of chronic kidney diseases in middle-aged and elderly adults: findings from the china health and retirement longitudinal study (CHARLS).Front Med2021;8:782624 PMCID:PMC8674531

[24] Ran J,Zhang S.Circadian syndrome is associated with the development of chronic kidney disease and rapid decline in kidney function in middle-aged and elder adults: a China nationwide cohort study.J Nutr Health Aging2024;28:100011

[25] Penno G, Solini A, Orsi E, et al; Renal Insufficiency And Cardiovascular Events (RIACE) Study Group. Insulin resistance, diabetic kidney disease, and all-cause mortality in individuals with type 2 diabetes: a prospective cohort study. BMC Med. 2021;19:66. PMCID:PMC7962330

[26] Šimonienė D,Prakapienė E,Veličkiene D.Insulin resistance in type 1 diabetes mellitus and its association with patient’s micro- and macrovascular complications, sex hormones, and other clinical data.Diabetes Ther2020;11:161-74 PMCID:PMC6965600

[27] Ebert T, Anker SD, Ruilope LM, et al; FIDELIO-DKD and FIGARO-DKD Investigators. Outcomes with finerenone in patients with chronic kidney disease and type 2 diabetes by baseline insulin resistance. Diabetes Care. 2024;47:362-70. PMCID:PMC10909685

[28] Karamanakos G,Kapelios CJ.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.Prim Care Diabetes2022;16:837-43

[29] Wu B,Stanford A.Understanding CKD among patients with T2DM: prevalence, temporal trends, and treatment patterns-NHANES 2007-2012.BMJ Open Diabetes Res Care2016;4:e000154 PMCID:PMC4838667

[30] Wagnew F,Kibret GD.Diabetic nephropathy and hypertension in diabetes patients of sub-Saharan countries: a systematic review and meta-analysis.BMC Res Notes2018;11:565 PMCID:PMC6080368

[31] Castro L,Diniz MF.Association of hypertension and insulin resistance in individuals free of diabetes in the ELSA-Brasil cohort.Sci Rep2023;13:9456 PMCID:PMC10257662

[32] Quesada O,Rodriguez F.Associations of insulin resistance with systolic and diastolic blood pressure: a study from the HCHS/SOL.Hypertension2021;78:716-25 PMCID:PMC8650976

[33] Yamaguchi T,Takaoka S.Serum calcium is positively correlated with fasting plasma glucose and insulin resistance, independent of parathyroid hormone, in male patients with type 2 diabetes mellitus.Metabolism2011;60:1334-9

[34] Salvetti A,Di Legge V.The inter-relationship between insulin resistance and hypertension.Drugs1993;46:149-59

[35] Hu FB.Insulin resistance and hypertension: the chicken-egg question revisited.Circulation2005;112:1678-80

[36] Huh JH,Kim JS.An association of metabolic syndrome and chronic kidney disease from a 10-year prospective cohort study.Metabolism2017;67:54-61

[37] Stopford R,Ismail K.Social support and glycemic control in type 2 diabetes: a systematic review of observational studies.Patient Educ Couns2013;93:549-58

[38] Cui Y,Guo Z.Family function and self-management of patients with early chronic kidney disease: the mediating roles of self-perceived burden and ego depletion.Patient Prefer Adherence2025;19:161-72 PMCID:PMC11769855