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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 6  |  Page : 924-928
Association between diabetic nephropathy and other diabetic microvascular and macrovascular complications

1 Department of Internal Medicine, Christian Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Nephrology, Christian Medical College and Hospital, Ludhiana, Punjab, India
3 Department of Community Medicine, Christian Medical College and Hospital, Ludhiana, Punjab, India

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Diabetic nephropathy is found to be significantly associated with diabetic retino­pathy and coronary artery disease. Few studies have also shown an association between diabetic nephropathy and neuropathy, and peripheral vascular disease. A cross sectional study was done among consecutive type 2 diabetics presenting to Christian Medical College and Hospital, Ludhiana from June 2004 to May 2005. Patients were subjected to the clinical and laboratory investigations 174 patients were studied over a period of one year. Diabetic nephropathy was found to be associated with proliferative diabetic retinopathy, neuropathy and cardiovascular disease by univariate analysis. In multivariate analysis, diabetic nephropathy was again significantly asso­ciated with proliferative diabetic retinopathy and coronary artery disease. We conclude that close association between diabetic nephropathy and other micro and macrovascular complications exists in our Indian patients also.

Keywords: Nephropathy, Retinopathy, Neuropathy, Peripheral vascular disease

How to cite this article:
Chandy A, Pawar B, John M, Isaac R. Association between diabetic nephropathy and other diabetic microvascular and macrovascular complications. Saudi J Kidney Dis Transpl 2008;19:924-8

How to cite this URL:
Chandy A, Pawar B, John M, Isaac R. Association between diabetic nephropathy and other diabetic microvascular and macrovascular complications. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2022 Jan 18];19:924-8. Available from: https://www.sjkdt.org/text.asp?2008/19/6/924/43466

   Introduction Top

Diabetes mellitus, due to its effect on small and large blood vessels is known to cause various microvascular and macrovascular com­plications. The incidence of microvascular com­plications, namely, nephropathy, retinopathy and peripheral neuropathy increase with the duration of diabetes. [1] Macrovascular compli­cations associated with diabetes, namely, coro­nary artery disease, cerebrovascular disease and peripheral vascular disease are mainly due to accelerated atherosclerosis.

A close association between diabetic nephro­pathy and retinopathy exits in majority of patients, and one might entertain another cause for nephropathy in the absence of retinopathy.

A similar association also exists between coronary artery disease and diabetic nephro­pathy.

This study was undertaken to document asso­ciation between diabetic nephropathy and other microvascular and macrovascular complications in type 2 diabetics presenting to our center.

   Materials and Methods Top

Consecutive type 2 diabetic patients visiting Christian Medical College and Hospital, Lud­hiana were studied in a cross sectional design from June 1, 2004 to May 31, 2005. Ethics co­mmittee approval was obtained before starting the study.

Patients with acute and chronic infections, valvular heart disease, collagen vascular di­sease and malignancies were excluded.

Patients were subjected to the following clinical and laboratory tests: direct ophthal­moscopy, clinical examination for pain, touch and vibration, tendon reflexes, ankle brachial index with hand held Doppler, ECG, Echocar­diography when evidence of coronary artery disease, serum creatinine, urinary protein (urine albumin to creatinine ratio or 24 hour urine protein) and fasting lipid profile.

Type 2 Diabetes mellitus was defined as Fas­ting blood glucose of > 126 mg/dL or Random Blood Sugar of > 200 mg/dL with symptoms of diabetes.

Nephropathy was diagnosed by the presence of microalbuminuria, macroalbuminuria or Creatinine clearance of < 90 mL/min. Micro­albuminuria was diagnosed by the presence of 30-300 mg albumin in a 24 hour urine sample or 30-300 mg albumin per gm creatinine; albu­min creatinine ratio (ACR). Macroalbuminuria was diagnosed by the presence of more than 300 mg albumin in urine over 24 hours, or more than 300 mg/gm urine ACR. [1]

Chronic Kidney Disease (CKD): K/DOQI criteria for the definition of CKD were used to estimate prevalence of chronic kidney disease stages 1 to 5. [2] GFR estimation was done by Cockroft and Gault formula. [3]

Non-proliferative retinopathy was diagnosed by the presence of cotton wool spots, micro aneurysms and boat shaped hemorrhages on direct ophthalmoscopic examination. Prolifera­tive retinopathy was diagnosed by the presence of neovascularization in the retina.

Peripheral sensory neuropathy was assessed clinically by history of paresthesias in the peri­pheries or decreased pain by pin-prick testing, or decreased touch by fine cotton wisp or decreased vibration sense by tuning fork of frequency 256Hz or absent ankle reflexes.

Cerebrovascular disease was assessed by his­tory of previous transient ischemic attack or stroke.

Cardiovascular disease was assessed by his­tory of angina or equivalents, verified by pre­vious hospital record, or ECG changes of Q waves, or poor progression of R waves in anterior leads or Echocardiography showing evidence of wall motion abnormalities, dilated left ventricle or ejection fraction of < 40%.

Peripheral vascular disease (PVD) was asse­ssed by ankle brachial index. Ankle brachial index (ABI) was tested using Ultratec PD 1 v hand held Doppler. ABI less than 0.9 was considered as evidence of peripheral vascular disease. [4]

   Statistical Analysis Top

Chi square test, univariate and multivariate logistic regression analysis was performed. P value < 0.05 was taken as significant.

   Results Top

174 patients were studied over a period of one year, 107 were male. Mean age for males was 57.6 ± 11.78 years and 55.3 ± 10.36 years for females.

29 patients (16.6%) had normal renal function. Microalbuminuria was found in 54 (31.03%) patients, 29 (15%) patients had macroalbumi­nuria with normal estimated GFR. Chronic Kid­ney Disease (CKD) stage2-5 was present in 10 27, 11 and 20 respectively.

Distal symmetric polyneuropathy (DSPN) was detected in 124 patients (72.5%). Ankle jerk was absent in 109(63.3%) patients. Paresthe­sias was the commonest, 85 patients (45.8%), symptom of neuropathy.

Ophthalmoscopic examination was performed in 144 patients, 49.3% had normal findings, 29.16% had non proliferative diabetic retinopathy (NPDR) and 21.5% had proliferative retinopathy (PR).

Ankle brachial index was checked in 150 patients, 14% had evidence of peripheral vas­cular disease. Eighty-one (46.5%) had evidence of ischemic heart disease and 29 patients had dilated cardiomyopathy on echocardiography. Out of the 174 patients, 22 (12.6%) had evi­dence of cerebrovascular disease, by history and previous medical record.

Diabetic nephropathy was present in majority of patients with other complications, [Table 1]. Univariate analysis confirmed significant asso­ciation of diabetic nephropathy with proli­ferative diabetic retinopathy, neuropathy and cardiovascular disease, but not with cerebro­vascular disease or peripheral vascular disease, [Table 1]. Similar association was observed even with each stage of the CKD, [Table 2].

Using multivariate analysis considering dura­tion of diabetes, BMI, sex, smoking, alcohol consumption of more than 10 years duration, total cholesterol, triglycerides, HDL, LDL and hypertension, diabetic nephropathy was signi­ficantly associated with proliferative diabetic retinopathy and coronary artery disease but not significantly associated with neuropathy, ce­rebrovascular or peripheral vascular disease.

With increasing stage of CKD a significant increase in prevalence of proliferative retino­pathy, neuropathy and coronary artery disease was found. However, cerebrovascular disease and peripheral vascular disease did not show an association with the stage of CKD in dia­betic nephropathy.

   Discussion Top

Diabetic nephropathy was significantly asso­ciated with proliferative diabetic retinopathy and coronary artery disease in our patients. A linear association between the stages of CKD in diabetic nephropathy and retinopathy, coro­nary artery disease was also observed. Corro­borative data shows that in almost all diabetics with End Stage Renal Disease (ESRD) who are admitted into dialysis or transplant prog­rammes, there is clinical evidence of diabetic retinopathy on routine fundoscopic examina­tion. [5] As the renal disease advances, the prog­ression of diabetic retinopathy accelerates. [6]

Parving and associates found that the inci­dence of proliferative retinopathy rose from 12% in normoalbuminuric type1 diabetic pa­tients to 28%, 58%, and > 90% in patients with microalbuminuria, macroalbuminuria and ad­vanced renal failure respectively. [5]

Microalbuminuria is proved to be not only a harbinger of progressive kidney damage, but its presence is associated with a higher risk for coronary artery disease. [6],[7],[8],[9] Similar association between microalbuminuria and coronary artery disease(CAD) was also found in our patients (p < 0.01).

Klein et al, also confirmed the association of proliferative diabetic retinopathy with nephro­pathy and coronary artery disease. [10]

Similarly Rius Riu et al, found a significant relationship of CAD events with the new ap­pearance or worsening of diabetic retinopathy or nephropathy in Spanish patients. [11]

With progression from microalbuminuria to macroalbuminuria, the proportion of individuals with peripheral symmetric polyneuropathy in­creased progressively in our patients (67-85%) (p< 0.001). In fact majority of the patients from CKD stages II to V (74-100%) had peri­pheral symmetric polyneuropathy. However, neuropathy was not found to be significantly associated with diabetic nephropathy by multi­variate analysis.

Fifty-five (34.8%) of the 158 patients checked had evidence of PVD, more than half of these patients had evidence of Nephropathy; how­ever, no significant association was noted bet­ween albuminuria and PVD.

Tzeng et al, to the contrary did find a signi­ficant association with advanced nephropathy, frequently in patients on dialysis. [6] We did not find an association between presence of neph­ropathy and cerbrovascular disease contrary to the studies reported by Mieltinen, Wada and others. [12],[13] Studies done in South India on type 2 diabetics with peripheral vascular disease (PVD) showed that there was a linear increase in prevalence of PVD with increasing duration of diabetes. Multiple logistic regression ana­ lyses showed that serum cholesterol, serum creatinine, systolic BP, duration of diabetes and ischemic heart disease are strong predic­tive factors for PVD. [14]

In conclusion, the type II diabetic patients presenting in our hospital had high frequency of diabetic complications. Close association between diabetic nephropathy and other micro and macrrovascular complications exists in our part of the Indian patients. A larger study is further needed to explore the association of nephropathy with PVD.

   References Top

1.Keane WF, Eknoyan G. Proteinuria, albumi­nuria, risk, assessment, detection, elimination (PARADE): a position paper of the National Kidney Foundation. Am J Kidney Dis 1999; 33(5):1004-10.  Back to cited text no. 1    
2.National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2Suppl1):S1-266.  Back to cited text no. 2    
3.Coyne DW. Evaluation of the patient with renal disease, Washington Manual of medical therapeutics. In: Carey CF, Lee HH, Woeltje KF, eds. 29th ed. 12:227.  Back to cited text no. 3    
4.Zheng ZJ, Rosamond WD, Chambless LE, et al. Lower extremity arterial disease assessed by ankle-brachial index in a middle-aged population of African Americans and whites: The Atherosclerosis Risk in Communities (ARIC) Study. Am J Prev Med 2005;29(5 Suppl 1):42-9.  Back to cited text no. 4    
5.Zander E, Seidlein I, Herfurth S, et al. Increased prevalence of proliferative retinopathy and car­diovascular autonomic dysfunction in IDDM patients with proteinuria. Exp Clin Endocr 1992;99(2):102-7.  Back to cited text no. 5    
6.Tzeng TF, Hsiao PJ, Hsieh MC, Shin SJ Asso­ciation of nephropathy and retinopathy, blood pressure, age in newly diagnosed type 2 diabetes mellitus. Kaohsiung J Med Sci 2001; 17(6):294-301.  Back to cited text no. 6    
7.Gall MA, Rossing P, Skott P, et al. Prevalence of micro- and macroalbuminuria, arterial hy­pertension, retinopathy and large vessel disease in European type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1991;34:655- 61.  Back to cited text no. 7    
8.Messent JW, Elliott TG, Hill RD, Jarrett RJ, Keen H, Viberti GC. Prognostic significance of microalbuminuria in insulin-dependent dia­betes mellitus: A twenty-three year follow-up study. Kidney Int 1992;41:836-9.  Back to cited text no. 8  [PUBMED]  
9.Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984; 310:356-60.  Back to cited text no. 9  [PUBMED]  
10.Klein R, Klein BE, Moss SE. Department of Ophthalmology, University of Wisconsin, Madison 53792-3220 Epidemiology of proli­ferative diabetic retinopathy. Diabetes Care 1992;15(12):1875-91.  Back to cited text no. 10    
11.Rius Riu F, Salinas Vert I, Lucas Martin A, Romero Gonzalez R, Sanmarti Sala A. Internal Medicine Service, Hospital Universitari Arnau de Vilanova, Lleida, Spain: a prospective study of cardiovascular disease in patients with Type 2 diabetes. 6.3 years of follow-up. J Diabetes Compl 2003;17(5):235-42.  Back to cited text no. 11    
12.Miettinen H, Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non-insulin­dependent diabetic subjects. Stroke 1996;27: 2033-9.  Back to cited text no. 12    
13.Wada M, Nagasawa H, Kurita K, et al. Microalbuminuria is a risk factor for cerebral small vessel disease in community-based elderly subjects, J Neurol Sci 2007;255(1-2): 27-34.  Back to cited text no. 13    
14.Mohan V, Premalatha G, Sastry NG. Peri­pheral vascular disease in non-insulin­dependent diabetes mellitus in south India. Diabetes Res Clin Pract 1995;27(3):235-40.  Back to cited text no. 14    

Correspondence Address:
Anila Chandy
Department of Internal medicine, Christian Medical College and Hospital, Brown Road, Ludhiana-141008, Punjab
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PMID: 18974577

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