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Study Of Microalbuminuria In Patients With Type 2 Diabetes
Mellitus
K.J.Brahmbhatt1*, K.J.Upadhyay2 1
M.D. (Medicine) Associate Professor, Department of Medicine, Baroda Medical College,Vadodara, 2M.D. (Medicine) Professor, Department of Medicine, B.J.Medical College,Ahmedabad.
INTRODUCTION
Diabetes Mellitus (DM) is increasing globally particularly in developing countries. About 347 Million people worldwide have diabetes. In 2014, the global prevalence of DM was estimated to be 9% among the adults aged >18 years (1). In 2012, an estimated 1.5 million deaths were directly caused by diabetes (2). More than 80% of diabetic death occurs in low and middle income countries
*Corresponding Author:
Dr.K.J.Brahmbhatt 149-A1, Shreejivilla-1,
Near Motibhai Park, New VIP road, Sayajipura,Vadodara-390019 Contact no-9879520600
E-mail-krutik.brahmbhatt@gmail.com
(2).WHO projects that diabetes will be 7th leading cause of death by 2030(3). There is an emerging epidemic of diabetes in India with more than 62 million diabetics with diagnosed disease (4, 5). It is predicted that by 2030 diabetes may affect 79.4 million individuals in India (6). The cause for increasing prevalence of diabetes in India is multifactorial and includes genetic factors and other factors such as obesity, increasing living standard, urban migration, physical inactivity and lifestyle changes. India has high prevalence of DM as compared to western countries despite having low overweight and obesity rate suggest that a lean Indian adult with low BMI may be at equal risk as those who are obese(7,8,9). Diabetic kidney disease occurs in 20-40%of patients with diabetes
ORIGINAL ARTICLE
ABSTRACT
BACKGROUND: According to World Health Organization (WHO), diabetes mellitus is one of the biggest health concerns that the world faced with. According to International Diabetic Federation (IDF), India has highest number of diabetics than any other country in the world. Diabetic nephropathy is the leading cause of chronic kidney disease (CKD), ESRD, and CKD requiring renal replacement therapy. Albuminuria in individuals with DM is associated with an increased risk of cardiovascular diseases. Individuals with diabetic nephropathy commonly have retinopathy. Early detection of microalbuminuria is important for early diagnosis and prevention of diabetic nephropathy. AIMS AND OBJECTIVES: We carried out this study to see correlation between microalbuminuria and other cardiovascular factors in patient with type 2 diabetes mellitus. MATERIAL AND METHODS: Spot urine albumin to creatinine ratio was measured in 75 patients with type 2 diabetes mellitus (DM), who are attending medicine OPD or admitted in Medicine ward at B.J. Medical College. Various parameters like symptoms, duration of diabetes, family history of diabetes, glycemic control, hypertension and other microvascular or macrovascular complications were compared between patients with microalbuminuria and without microalbuminuria. RESULTS: Total seventy five patients were enrolled in the study. Twenty five patients had microalbuminuria. Family history of DM was present in 40% of patients with MAU as compared to 30% in patients without MAU. Duration of DM in patients with MAU was more than in patients without MAU. Systolic Blood pressure and diastolic blood pressure was more in patients with MAU as compared patients without MAU. Fasting blood sugar, postprandial blood sugar and glycosylated hemoglobin was more in patients with MAU as compared to patients without MAU. Retinopathy was present in 76% patients with MAU as compared to 12% patients without MAU. Cardio vascular disease was present in 20% patients with MAU and 14% in patients without MAU. Cerebrovascular disease was present in 4% patients with MAU as compared to 2% patients without MAU. CONCLUSION: In our study we found that patient with microalbuminuria had longer duration of diabetes, higher fasting and postprandial blood sugar level, poor glycemic control, higher systolic and diastolic blood pressure as compared to patients without microalbuminuria. Incidence of retinopathy was also more in patient with microalbuminuria. Macrovascular complication like stroke, cardiovascular disease and peripheral vascular diseases were also more in patient s with microalbuminuria.
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and is leading cause of end stage renal disease .Increase in albuminuria, in range of urine albumin to creatinine ratio of 30-299mg/g is an early indicator of diabetic kidney disease in type 1 diabetes and a marker of development of diabetic kidney disease in type 2 diabetes . It is also a marker of increased cardiovascular disease (10, 11, and 12). Microalbuminuria is also risk factor for diabetic retinopathy in type 1 diabetes mellitus patients but not in type 2 diabetics. Overt nephropathy is correlated with retinopathy (13). We undertook this study in tertiary care teaching hospital to observe correlation between microalbuminuria and other cardiovascular factors in patients with type 2 diabetes mellitus.
MATERIAL AND METHODS
A total 75 patients of type 2 diabetes mellitus attending medical OPD or admitted to medical ward at B.J. Medical College, Ahmadabad were included in the study. Patients with uncontrolled hypertension, urinary tract infection, fever, strenuous exercise, congestive cardiac failure, abnormal urinary sediments, microalbuminuria on dipstick test, abnormal blood urea or serum creatinine were excluded from study. An individual patient consent was also taken. A detail clinical history and physical examination was done in all patients including haemogram, fasting blood glucose, postprandial blood glucose, Glycosylated hemoglobin, renal function test, liver function test, serum electrolytes, urine routine examination, serum lipid profile, electrocardiogram, chest X-ray and abdominal ultrasound was done in all patient. Microalbuminuria was tested by doing spot urinary albumin to creatinine ratio. The range of 30-299mg/gm creatinine was considered normal. Echocardiography, lower limb arterial Doppler and nerve conduction study was done in selected number of patients as indicated. Fundus examination was done in all patients. The presence or absence of microalbuminuria was compared in type2 diabetic patients. The occurrence of microalbuminuria was correlated with other parameters like hypertension, dyslipidemia, retinopathy, neuropathy,
coronary artery disease and peripheral vascular disease. The statistical data was analyzed using Microsoft excel worksheet. To compare continuous variables, unpaired t-test for independent sample was used. Z test was use for proportion. p value <0.05 was considered significant.
RESULTS
Total seventy five patients were enrolled in the study of which fifty two were male and twenty three were female. Twenty five patients had microalbuminuria of which fourteen were males and eleven were females. Mean age of patients with microalbuminuria was 51.68±3.26years and patients without microalbuminuria were 50.48±10.54 years. BMI in patients with microalbuminuria was 22.63±1.03 kg/m2 and in patients without microalbuminuria was 22.19±1.17 kg/m2.
Table 1: Comparison of Demographic Data, Symptoms and Examination in Patients with and Without MAU
Patient with MAU
Patient without MAU
Statistical test
p value
No. Of patients
25 50
Age(years) 51.68±3.26 50.48±10.54 Male 14 38
Female 11 12
BMI(kg/m2) 22.63±1.03 22.19±1.17 Smoking 8(32%) 22(44%) Alcohol 7(28%) 19(38%)
Polyuria 4(16%) 7(14%) Z=3 p<0.05 Polydepsia 4(16%) 7(14%) Z=3 p<0.05 Polyphagia 4(16%) 7(14%) Z=2 p<0.05 Tingling in
lower limbs
5(20%) 15(30%) Z=1.7 p<0.05
Claudication pain in lower limbs
5(20%) 7(14%) Z=4.26 p<0.05
Recurrent infection
2(8%) 5(10%) Z=1.14 p >0.05 Visual
disturbances
19(76%) 6(12%) Z=5.5 p<0.05
Edema feet 5(20%) 10(20%) Z=3.2 p<0.05 Family
history
10(40%) 15(30%) Z=16.3 p<0.05
Duration of DM(years)
7.92±3.92 5.4±4.13 t=2.53 p<0.05
Systolic blood pressure (mm of Hg)
141.42±10.55 126±10.56 t=5.9 p<0.05
Diastolic blood pressure (mm of Hg)
85.04±5.35 81.72±5.14 t=2.6 p<0.05
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patients without microalbuminuria. Tingling in lower limb was present in 20% patients with microalbuminuria and 30% in patients without microalbuminuria. Visual disturbances were present in 76% patients with MAU as compared to 12% in patients without MAU. Family history of DM was present in 40% of patients with MAU as compared to 30% in patients without MAU. Duration of DM in patients with MAU was 7.92±3.92 years as compared to 5.4±4.13 years in patients without MAU. Systolic Blood pressure was 141.42±10.55 mm of Hg in patients with MAU as compared to 126±10.56 mm of Hg in patients without MAU. Diastolic Blood pressure was 85.04±5.35 mm of Hg in patients with MAU as compared to 81.72±5.14 mm of Hg in patients without MAU.
Table2:Comparison Of Biochemical
Parameters, Microvascular And
Macrovascular Complication In
Patients With And Without MAU
Patient with MAU
Patient without MAU
Statistical test
p value
Fasting blood sugar(mg/dl)
159.6±47.17 135.2±40.5 t=2.32 p<0.05
Postprandial blood sugar(mg/dl)
202.64±39.7 7
189.45±59.3 2
t=1.003 p>0.05
Glycosylated haemoglobin (%)
10.3±2.56 7.06±1.19 t=7.5 p<0.05
Estimated GFR(ml/min )
86.77±15.56 98.32±22.92 t=2.2 p<0.05
Retinopathy 19(76%) 6(12%) Z=5.5 p<0.05 Peripheral
neuropathy
5(20%) 15(30%) Z=1.7 p<0.05
PVD 5(20%) 7(14%) Z=4.26 p<0.05 CVD 5(20%) 7(14%) Z=4.26 p<0.05 Stroke 1(4%) 1(2%) 1.8 p<0.05 Fasting Blood sugar was 159.6±47.17mg% in patients with MAU as compared to 135.2±40.5mg% in patients without MAU. Postprandial Blood sugar was 202.64±39.77mg% in patients with MAU as compared to 189.45±59.32mg% in patients without MAU. Glycosylated hemoglobin was 10.3±2.56 in patients with MAU as compared to 7.06±1.19 in patients without MAU. Estimated GFR was 86.77±15.56 in patients with MAU as compared to 98.32±22.92 in patients without MAU. Retinopathy was present in 76% patients with MAU as compared to
12% patients without MAU. Peripheral vascular disease was present in 20% patients with MAU as compared to 14% patients without MAU. Cardio vascular disease was present in 20% patients with MAU and 14% in patients without MAU. Cerebrovascular disease was present in 4% patients with MAU as compared to 2% patients without MAU.
DISCUSSION
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volume that occur during the day(21,22). One problem with measuring the urine albumin concentration or estimating it with a sensitive dipstick is that false negative and false positive results can occur, since the urine albumin concentration is determined by the urine volume as well as the amount of albuminuria (23). Thus, at a particular rate of albumin excretion, a substantial increase or decrease in urine volume will respectively lower and raise the urine albumin concentration. The confounding effect of the urine volume can be minimized by repeated measurements on early morning specimens (21). The albumin-to-creatinine ratio obtained from a first morning void sample appears to provide the best predictive value for renal disease progression. This was shown in a subset analysis of the RENAAL trial in which methods of estimating protein excretion were compared in terms of their ability to predict renal outcomes, including the time of doubling of serum creatinine or end-stage renal disease. Compared to urinary albumin excretion and urinary protein excretion from a 24 hour collection, and to urinary albumin excretion from a first morning void, the albumin-to-creatinine ratio from a first morning void demonstrated the strongest association with the risk for renal events. Measurement of the urine albumin-to-creatinine ratio in an untimed urinary sample is the preferred screening strategy for microalbuminuria in all diabetic patients. The reported prevalence of microalbuminuria among patients with type 2 diabetes approximately 10 years after the diagnosis ranges from 25 to 40 percent (24-28). In a systematic review of 28 studies in type 2 diabetes (10,298 patients), the prevalence of microalbuminuria was 26 percent at a mean diabetes duration of 10 years (24). In our study prevalence of microalbuminuria was 33.33%. The prevalence of microalbuminuria in patients with type 2 diabetes varies with ethnicity, being higher in Asians and Hispanics than in whites. At a mean duration of diabetes of almost eight years, the rate of microalbuminuria was significantly higher in Asians and
Hispanics. Some patients with type 2 diabetes have microalbuminuria at the time of diagnosis. There are at least two possible explanations for the presence of microalbuminuria at the time of diagnosis of type 2 diabetes: the patients had previously undiagnosed diabetes or some other disease (eg. benign nephrosclerosis) was responsible for the microalbuminuria. The rate of microalbuminuria at the time of diagnosis of type 2 diabetes may be higher in older patients. This was illustrated in a cross-sectional population study of older adults in Finland (29). As duration of diabetes increases, chance of development of microalbuminuria also increases. The mean duration of diabetes in patients with microalbuminuria in our study was more than in patients without microalbuminuria which was comparable with S.Saha et al study and J.Sheth et al study (30, 31). There is a close relation between the prevalence of hypertension and increasing albuminuria. The blood pressure typically begins to rise within the normal range at or within a few years after the onset of microalbuminuria and increases progressively as the renal disease progresses particularly in Type 1 diabetes. The rate of microalbuminuria was significantly higher, 39 percent of patients with hypertension (24 versus 14 percent in those without hypertension) in another report of over 3600 newly diagnosed patients who were recruited for the UKPDS. In present study there is statistically significant difference in hypertension in patients with microalbuminuria as compared to without microalbuminuria. Diabetic nephropathy is more likely to develop in patients with worse glycemic control (higher HbA1c
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precedes the onset of overt nephropathy in these patients. The relationship between diabetic nephropathy and retinopathy is less predictable in type 2 diabetes. Based upon the correlation between retinopathy and nephropathy, the 2007 K/DOQI Guidelines for diabetes and chronic kidney disease suggest that chronic kidney disease should be attributed to diabetes in most patients with diabetes if microalbuminuria or proteinuria and diabetic retinopathy are both present(36). By comparison, other causes of CKD should be entertained if diabetic retinopathy is absent. There is increase chance of other microvascular and macrovascular complication like PVD, neuropathy and CVD in patients with microalbuminuria as compare to patients without microalbuminuria. With increasing stage of CKD a significant increase in prevalence of proliferative retinopathy, neuropathy and coronary artery disease was found (37). Screening for microalbuminuria should be done in all type 2 diabetic patients at time of diagnosis and after 5 years of diagnosis in type 1 diabetic patients. Annual screening should be done in patients who had not demonstrated microalbuminuria on first time examination. Glycemic and blood pressure control, particularly with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), may reduce both microalbuminuria and progression to macroalbuminuria (38). Clinical trials have also demonstrated efficacy of ACE inhibitors and ARBs and of glycemic control for the primary prevention of microalbuminuria and subsequent overt nephropathy in patients with type 2 diabetes.
CONCLUSION
Microalbuminuria is an indicator of early nephropathy in patient with diabetes mellitus. Spot urine albumin to creatinine ratio is an effective method for detection of microalbuminuria. Development of microalbuminuria depends on ethnicity, duration of diabetes, glycemic control, associated hypertension and other macrovascular complication. Microalbuminuria is marker of macrovascular complication in patient
with type 2 diabetes mellitus. Screening for microalbuminuria is important for early detection and prevention of diabetic nephropathy.
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