Impact of Obesity and Insulin Resistance on Diabetic Kidney Disease Progression
Main Article Content
Keywords
Diabetic kidney disease; Type 2 diabetes mellitus; Insulin resistance; Obesity; Glomerular filtration rate; Chronic kidney disease
Abstract
One of the primary microvascular outcomes of Type 2 Diabetes is Diabetic Kidney Disease (DKD), and it causes a significant burden on the global health care system along with the increasing prevalence of insulin resistance and obesity. Epidemiological investigation found that about one-third of people who have T2DM can acquire chronic kidney disease, with insulin sensitivity and obesity acting as key drivers of kidney injury. Obesity is related to lipotoxicity, low-grade inflammation, adipokine dysregulation, and oxidative stress, while impaired insulin sensitivity leads to renal hemodynamics, progressive glomerular injury, and hyperinsulinemia. These pathways together promote glomerular hyperfiltration, albuminuria, and ultimately a decrease in glomerular filtration rate (GFR). Several studies indicate that RAAS blockade, SGLT2 inhibitors, and weight loss can reduce Diabetic Kidney Disease progression, yet persistent risk remains. The existing research gaps have a limited pathophysiological understanding, a shortage of understanding of renal ectopic fat deposition, and insufficient stratification of patients by impaired insulin sensitivity phenotypes and obesity. To develop targeted interventions, it is essential to address the gaps through clinical research and comprehensive mechanisms. The evaluation of the collaborative impact of impaired insulin sensitivity and obesity in the advancement of diabetic kidney disease is the aim of this study. In addition, rapid diagnosis and targeted treatments are the most important goals for lowering cardiovascular and renal complications.
References
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[17] Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circulation Research. 2010; 107: 1058–1070.
[18] Siragy HM, Carey RM. Role of the intrarenal renin-angiotensin-aldosterone system in chronic kidney disease. American Journal of Nephrology. 2010; 31: 541–550.
[19] Peti-Peterdi J, Kang JJ, Toma I. Activation of the renal renin-angiotensin system in diabetes—new concepts. Nephrology Dialysis Transplantation. 2008; 23: 3047–3049.
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[21] Reidy K, Kang HM, Hostetter T, Susztak K. Molecular mechanisms of diabetic kidney disease. Journal of Clinical Investigation. 2014; 124: 2333–2340.
[22] Tonneijck L, Muskiet MH, Smits MM, van Bommel EJ, Heerspink HJ, van Raalte DH, et al. Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. Journal of the American Society of Nephrology. 2017; 28: 1023–1039.
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[27] Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME. Obesity, kidney dysfunction and hypertension: mechanistic links. Nature Reviews Nephrology. 2019; 15: 367–385.
[28] Hamdy O, Porramatikul S, Al-Ozairi E. Metabolic obesity: the paradox between visceral and subcutaneous fat. Current Diabetes Reviews. 2006; 2: 367–373.
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[32] Sasson AN, Cherney DZ. Renal hyperfiltration related to diabetes mellitus and obesity in human disease. World Journal of Diabetes. 2012; 3: 1–6.
[33] Su W, Cao R, He YC, Guan YF, Ruan XZ. Crosstalk of hyperglycemia and dyslipidemia in diabetic kidney disease. Kidney Diseases. 2017; 3: 171–180.
[34] Tu QM, Jin HM, Yang XH. Lipid abnormality in diabetic kidney disease and potential treatment advancements. Frontiers in Endocrinology. 2025; 16: 1503711.
[35] Kawanami D, Matoba K, Utsunomiya K. Dyslipidemia in diabetic nephropathy. Renal Replacement Therapy. 2016; 2: 16.
[36] Ozder A. Lipid profile abnormalities seen in T2DM patients in primary healthcare in Turkey: a cross-sectional study. Lipids in Health and Disease. 2014; 13: 183.
[37] Spoto B, Pisano A, Zoccali C. Insulin resistance in chronic kidney disease: a systematic review. American Journal of Physiology-Renal Physiology. 2016; 311: F1087–F1108.
[38] Hung CC, Zhen YY, Niu SW, Lin KD, Lin HY, Lee JJ, et al. Predictive value of HbA1c and metabolic syndrome for renal outcome in non-diabetic CKD stage 1–4 patients. Biomedicines. 2022; 10: 1858.
[39] Yan H, Zhou Q, Wang Y, Tu Y, Zhao Y, Yu J, et al. Associations between cardiometabolic indices and the risk of diabetic kidney disease in patients with type 2 diabetes. Cardiovascular Diabetology. 2024; 23: 142.
[40] Lee SY, Choi ME. Urinary biomarkers for early diabetic nephropathy: beyond albuminuria. Pediatric Nephrology. 2015; 30: 1063–1075.
[41] Kern EF, Erhard P, Sun W, Genuth S, Weiss MF. Early urinary markers of diabetic kidney disease: a nested case-control study from the Diabetes Control and Complications Trial (DCCT). American Journal of Kidney Diseases. 2010; 55: 824–834.
[42] Polidori N, Giannini C, Salvatore R, Pelliccia P, Parisi A, Chiarelli F, et al. Role of urinary NGAL and KIM-1 as biomarkers of early kidney injury in obese prepubertal children. Journal of Pediatric Endocrinology and Metabolism. 2020; 33: 1183–1189.
[43] De Silva PM, Mohammed Abdul KS, Eakanayake EM, Jayasinghe SS, Jayasumana C, Asanthi HB, et al. Urinary biomarkers KIM-1 and NGAL for detection of chronic kidney disease of uncertain etiology (CKDu) among agricultural communities in Sri Lanka. PLOS Neglected Tropical Diseases. 2016; 10: e0004979.
[44] Park HS, Park SH, Seong Y, Kim HJ, Choi HY, Rhee Y, et al. Adiponectin-to-leptin ratio and incident chronic kidney disease: sex and body composition-dependent association. Journal of Cachexia, Sarcopenia and Muscle. 2024; 15: 1298–1308.
[45] Shetty S, Suvarna R, Awasthi A, Bhojaraja MV, Pappachan JM. Emerging biomarkers and innovative therapeutic strategies in diabetic kidney disease: a pathway to precision medicine. Diagnostics. 2025; 15: 973.
[46] Zhang K, Zhang W, Xia F, Wang N, Lu Y, Sui C, et al. Obesity patterns, metabolic abnormality, and diabetic kidney disease in patients with type 2 diabetes. Diabetes, Metabolic Syndrome and Obesity. 2023; 16: 3999–4011.
[47] Wang J, Niratharakumar K, Gokhale K, Tahrani AA, Taverner T, Thomas GN, et al. Obesity without metabolic abnormality and incident CKD: a population-based British cohort study. American Journal of Kidney Diseases. 2022; 79: 24–35.e1.
[48] Todd JN, Dahlström EH, Salem RM, Sandholm N, Forsblom C, McKnight AJ, et al.; FinnDiane Study Group. Genetic evidence for a causal role of obesity in diabetic kidney disease. Diabetes. 2015; 64: 4238–4246.
[49] Yang S, Kwak S, Song YH, Han SS, Lee HS, Kang S, et al. Association of longitudinal trajectories of insulin resistance with adverse renal outcomes. Diabetes Care. 2022; 45: 1268–1275.
[50] Amouzegar A, Honarvar M, Masoumi S, Tohidi M, Mehran L, Azizi F. Sex-specific trajectories of insulin resistance markers and reduced renal function during 18 years of follow-up: TLGS. The Journal of Clinical Endocrinology & Metabolism. 2023; 108: e230–e239.
[51] Ma A, Liu F, Wang C, Liang K, Yan F, Hou X, et al. Both insulin resistance and metabolic syndrome accelerate the progression of chronic kidney disease among Chinese adults: results from a 3-year follow-up study. International Urology and Nephrology. 2018; 50: 2239–2244.
[52] Cheng HT, Huang JW, Chiang CK, Yen CJ, Hung KY, Wu KD. Metabolic syndrome and insulin resistance as risk factors for development of chronic kidney disease and rapid decline in renal function in elderly. The Journal of Clinical Endocrinology & Metabolism. 2012; 97: 1268–1276.
[53] Navaneethan SD, Yehnert H, Moustarah F, Schreiber MJ, Schauer PR, Beddhu S. Weight loss interventions in chronic kidney disease: a systematic review and meta-analysis. Clinical Journal of the American Society of Nephrology. 2009; 4: 1565–1574.
[54] Liakopoulos V, Franzén S, Svensson AM, Sattar N, Miftaraj M, Björck S, et al. Renal and cardiovascular outcomes after weight loss from gastric bypass surgery in type 2 diabetes: cardiorenal risk reductions exceed atherosclerotic benefits. Diabetes Care. 2020; 43: 1276–1284.
[55] DeFronzo RA, Reeves WB, Awad AS. Pathophysiology of diabetic kidney disease: impact of SGLT2 inhibitors. Nature Reviews Nephrology. 2021; 17: 319–334.
[56] Zou H, Zhou B, Xu G. SGLT2 inhibitors: a novel choice for the combination therapy in diabetic kidney disease. Cardiovascular Diabetology. 2017; 16: 65. Erratum in: Cardiovascular Diabetology. 2018; 17: 38.
[57] Dai ZC, Chen JX, Zou R, Liang XB, Tang JX, Yao CW. Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease. Frontiers in Immunology. 2023; 14: 1213473.
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Published
Jun 18, 2026
Article Details
How to Cite
Impact of Obesity and Insulin Resistance on Diabetic Kidney Disease Progression. (2026). Journal of Renal and Hepatic Disorders, 10(1), 24-33. https://doi.org/10.63268/jrenhp.v10i1.255
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Review Nephrology
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Author Biographies
Ameen Heshmat Ali Rasheedee, Department of Medical Laboratory Sciences, UIAHS, Chandigarh University, 140301 Mohali, India
Department of Medical Laboratory Technology, UIAHS, Chandīgarh University.
Amit Kumar Singh, Department of Medical Laboratory Sciences, UIAHS, Chandigarh University, 140301 Mohali, India
"Assistant Professor, Department of Medical Laboratory Technology, UIAHS, Chandigarh University"