Targeting LDL Dyslipidemia for Controlling Progression of Nephropathy in Diabetic Population: A Cross Sectional Analytical Study
Keywords:
Diabetes, Dyslipidemia, LDL-Cholesterol, MicroalbuminuriaAbstract
Objectives:
The purpose of the current study was to find out the correlation and cause effect relationship between LDL cholesterol and nephropathy in diabetic population.
Design:
Retrospective cross sectional analytical study. Patients and Methods: A total of 883 adult diabetic patients were selected for this study. Serum LDL cholesterol, creatinine, urine macroalbumin and microalbumin were measured by standardized laboratory methodology. LDL>100mg/dl was labeled as dyslipidemia and presence of microalbuminria or macroalbuminuria was defined
as nephropathy.
Results:
Out of 883 patients, 630 patients (71.3%) showed dyslipidemia while 253 patients (28.7%) were found to have nephropathy. Subjects with dyslipidemia (LDL>100) showed slightly higher serum creatinine levels with mean 1.022±0.74 mg/dl as compared to those without dyslipidemia with mean creatinine 1.004±0.63 mg/dl. However subjects labeled with nephropathy demonstrated marked elevated serum LDL cholesterol with mean 125.7±44.8 mg/dl as compared to those without nephropathy where LDL mean was 114±39 mg/dl. Spearman's correlation for cause effect relationship between serum LDL and nephropathy was highly significant (p <0.001). Conclusion: The observed data indicate that higher LDL levels are associated with raised creatinine levels, development and progression of nephropathy. Controlling LDL dyslipidemia is one of the effective strategies
towards diabetes management to prevent diabetic nephropathy.
Downloads
References
Ritz E, Rychlik I, Locatelli F, Halimi S: End stage renal failure in type 2 diabetes: a medical catastrophe of worldwide dimensions. Am J Kidney Dis 34:795–808, 1999.
Schena FP. Epidemiology of end stage renal disease: international comparisons of renal replacement therapy. Kidney Int Suppl 2000;57:S39-S45.
Warram JH, Scott LJ, Hanna LS, et al. Progression of microalbuminuria to proteinuria in type 1 diabetes: nonlinear relationship with hyperglycemia. Diabetes 2000; 49: 94–100.
Fried LF, Orchard TJ, Kasiske BL. Effect of lipid reduction on the progression of renal disease: A metaanalysis. Kid Intl 2001;59: 260–269.
Harris K, Thomas M, Short C, Moore R: Assessment of the efficacy of treatment of dyslipidaemia in renal outpatients. J Nephrol 15:263–269, 2002.
Keane WF, Lyle PA: Kidney disease and cardiovascular disease: implications of dyslipidemia. Cardiol Clin 23:363–372, 2005.
Diamond J. Analogous pathobiologic mechanisms in glomerulosclerosis and atherosclerosis. Kid Intl 1991; 31 [suppl]: S29–S34.
Borch-Johnsen K, Kreiner S: Proteinuria: Value as a predictor f cardiovascular mortality in insulin dependent diabetes mellitus. BMJ 294:1651–1654, 1987.
Perkins BA, Krolewski AS: Early nephropathy in type 1 diabetes: a new perspective on who will and who will not progress. Curr Diab Rep 5:455– 463, 2005.
Eknoyan G, Hostetter T, Bakris GL, Hebert L, Levey AS, Parving HH, Steffes MW, Toto R: Proteinuria and other markers of chronic kidney disease: a position statement of the National Kidney Foundation (NKF) and the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK). Am J Kidney Dis 42:617– 622, 2003.
Kannel W, McGee D: Diabetes mellitus and cardiovascular disease risk factors: the Framingham study. Diabetes Care 2:120–126, 1979.
Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, Mitch W, Smith SC Jr, Sowers JR: Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 100:1134–1146,1999.
Dinneen S, Gerstein H. The association of microalbuminuria and mortality in non-insulin dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med 157:1413–1418, 1997.
Neil A, Hawkins M, Potok M, Thorogood M, Cohen D, Mann J: A prospective population based study of microalbuminuria as a predictor of mortality in NIDDM. Diabetes Care 16:996–1003, 199.
Miettinen H, Haffner S, Lehto S, Ronnemaa T, Pyorala K, Laakso M: Proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non-insulin-dependent diabetic subjects. Stroke 27:2033–2039, 1996.
Nelson R, Pettitt D, Carraher M, Baird H, Knowler W: Effect of proteinuria on mortality in NIDDM. Diabetes 37:1499–1504, 1988.
Herman WH, Crofford OB: Diabetic control and complications, chapter 41, in Chronic Complication of Diabetes (vol 1), edited by Pickup JC, Williams G, 2nd
edition, Melbourne, Blackwell Press, 1994, pp
1–41.11.
Austin MA , Rodriguez BL , McKnight B , McNeely MJ, Edwards KL , Curb JD , et al. Low density lipoprotein particle size, triglycerides, and high density lipoprotein cholesterol as risk factors for coronary heart disease in older Japanese - American men . Am J Cardiol
; 86 : 412 – 416.
Coresh J , Kwiterovich POJ , Smith HH , Bachorik PS. Association of plasma triglyceride concentration and LDL particle diameter, density, and chemical composition with premature coronary artery disease in men and women. J Lipid Res 1993 ; 34 : 1687–1697.
Gardner CD , Fortmann SP , Krauss RM . Association of small low density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA 1996 ; 276 : 875 – 881.
Henriksen T, Mahoney EM, Steinberg D. Interactions of plasma lipoproteins with endothelial cells. Ann NY Acad Sci 401: 102–116, 1982.
Brasen JH, Nieminen-Kelha M, Markmann D, Malle E, Schneider W, Neumayer HH, Budde K, Luft FC, Dragun D. Lectin-like oxidized low density lipoprotein
(LDL) receptor (LOX-1) mediated pathway and vascular
oxidative injury in older age rat renal transplants. Kidney
Int 67: 1583–1594, 2005.
Jenkins AJ, Lyons TJ, Zheng D, Otvos JD, et al. Lipoproteins in the DCCT/EDIC cohort: Associations with diabetic nephropathy. Kidney International, Vol. 64 (2003), pp. 817–828.
American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care, Volume 34, Supplement 1, January 2011.
Baigent C, Keech A, Kearney PM, et al. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and
safety of cholesterol-lowering treatment: prospective
meta-analysis of data from 90,056 participants in 14
randomised trials of statins. Lancet 2005;366:1267–1278.
Pyorälä K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 1997;20:614–620.
Shepherd J, Barter P, Carmena R, et al. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care 2006;29:1220–1226.
Garg JP, Bakris GL. Microalbuminuria: marker of vascular dysfunction, risk factor for cardiovascular disease. Vasc Med 2002;7:35–43.
Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, et al. Very low levels of microalbuminuria areassociated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 2004;110:32–35.
Gall MA, Hougaard P, Borch-Johnsen K, Parving HH. Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus: prospective, observational study. BMJ 1997;314:783–788.
Ravid M, Lang R, Rachmani R, Lishner M. Long-term renoprotective effect of angiotensin-converting enzyme nhibition in non-insulin-dependent diabetes mellitus. A 7-year follow-up study. Arch Intern Med 1996;156:286–289.
UKPDS: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 317:703–713, 1998.
Thomas MC, Forsblom C, Mills V, et al. Serum Lipids and the Progression of Nephropathy in Type 1 Diabetes. Diabetes Care, Volume 29, Number 2, February 2006.
Kamanna VS: Low density lipoproteins and mitogenic signal transduction processes: role in the pathogenesis of renal disease. Histol Histopathol 17:497–505,2002.
Sibley SD, Hokanson JE, Steffes MW, et al: Increased small dense LDL and intermediate-density lipoprotein with albuminuria in type 1 diabetes. Diabetes Care 22:1165–1170, 1999.
Cominacini L, Pasini AF, Garbin U, et al. Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-B through an increased production of intracellular reactive oxygen species. J Biol Chem 275:12633–12638,
Dominguez JH, Mehta JL, Hawes JW, et al. Anti-LOX1 therapy in rats with diabetes and dyslipidemia: ablation of renal vascular and epithelial manifestations. Am J Physiol Renal Physiol 294: F110–F119, 2008
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Kamran Mahmood Aziz
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Articles published in the Journal of Dow University of Health Sciences are distributed under the terms of the Creative Commons Attribution Non-Commercial License https://creativecommons.org/ licenses/by-nc/4.0/. This license permits use, distribution and reproduction in any medium; provided the original work is properly cited and initial publication in this journal. 
