|Year : 2020 | Volume
| Issue : 2 | Page : 109-114
A study on prevalence and risk factors of diabetic nephropathy in newly detected type 2 diabetic patients
Rahul Ravindran1, S Kalaivalli1, S Srinivasagalu1, Lakshminarayanan Karthik2
1 Department of General Medicine, Meenakshi Medical College Hospital and Research Institute, Chennai, Tamil Nadu, India
2 Central Research Laboratory, Meenakshi Academy of Higher Education and Research, Chennai, Tamil Nadu, India
|Date of Submission||02-May-2019|
|Date of Decision||23-Aug-2019|
|Date of Acceptance||21-Sep-2019|
|Date of Web Publication||24-Jun-2020|
Dr. Lakshminarayanan Karthik
Meenakshi Academy of Higher Education and Research, K.K. Nagar West, Chennai 600078, Tamil Nadu.
Source of Support: None, Conflict of Interest: None
Aims and Objectives: This clinical study aimed to find out the prevalence of diabetic nephropathy in newly detected type 2 diabetic patients and also the risk factors associated with the development of the diabetic nephropathy. Settings and Design: The study group comprised 200 subjects diagnosed with type 2 diabetes mellitus. The patients were explained about the study and the study was conducted over a period of 18 months as a cross-sectional study. Materials and Methods: A progressive kidney disease diabetic nephropathy involves damaging the capillaries in the kidneys’ glomeruli. Patients were investigated for the presence of diabetic nephropathy with several risk factors such as hypertriglyceridemia, dyslipidemia, smoking, body mass index, hypertension, family history of diabetes, and kidney diseases. Statistical Analysis Used: Chi-squared test, two-sample t-test, and binary logistic regression model were used for data analysis using the Statistical Package for Social Sciences software version 11.5. Results: The prevalence found in this study was 13%. Of 200 patients, 26 were found to have diabetic nephropathy. Among these patients, 12% had microalbuminuria and 1% had macroalbuminuria. Incidence of nephropathy was higher in associated risk factors such as hypertension, obesity, and hypercholesterolemia. Conclusion: Effective measures to create awareness among the people and educate them for a healthy life style are to be taken. The effective control of the risk factors in type 2 diabetic patients will prevent the development of nephropathy and also retard its progression.
Keywords: Albuminuria, chronic kidney disease, diabetic nephropathy, end-stage renal disease, risk factors, type 2 diabetes
|How to cite this article:|
Ravindran R, Kalaivalli S, Srinivasagalu S, Karthik L. A study on prevalence and risk factors of diabetic nephropathy in newly detected type 2 diabetic patients. J Diabetol 2020;11:109-14
| Introduction|| |
Diabetes mellitus (DM) is a major health problem and causes considerable morbidity and mortality, primarily due to micro and macrovascular complications. The prevalence of diabetes is increasing globally and the maximum increase is expected to be in developing countries like India. Several distinct types of DM are caused by a complex interaction of genetics and environmental factors. Depending on the etiology of the DM, factors contributing to hyperglycemia include reduced insulin secretion, decreased glucose use, and increased glucose production. Diabetic nephropathy is the leading cause of chronic kidney disease (CKD), end-stage renal disease (ESRD), and CKD requiring renal replacement therapy. Furthermore, the prognosis of diabetic patients on dialysis is poor, with survival comparable to many forms of cancer. Albuminuria in individuals with DM is associated with an increased risk of cardiovascular disease. Individuals with diabetic nephropathy commonly have diabetic retinopathy. Like other microvascular complications, the pathogenesis of diabetic nephropathy is related to chronic hyperglycemia. Primary prevention of diabetic nephropathy is possible with vigorous glucose and blood pressure control. The American Diabetic Association in concert with National Kidney Foundation recommended screening for microalbuminuria starting at diagnosis of type 2 diabetes and patients with type 1 diabetes longer than five years.
Diagnosis and stages of diabetic nephropathy. The diagnosis of diabetic nephropathy can be made by (1) urinary albumin excretion rate, (2) glomerular filtration rate (GFR) estimation, (3) serum creatinine, and (4) renal biopsy. The presence of these findings would support diagnosis of diabetic nephropathy in a diabetic patient who has (1) minimal proteinuria, (2) active urine sediment with RBC casts in urine, (3) the duration of diabetes is short, and (4) absence of diabetic retinopathy. The characteristic clinical stages of diabetic nephropathy are best understood in the setting of type 1 diabetes. Patients with type 2 diabetes may have other coexisting disease including hypertension, and renal disease in these patients can be attributed to diabetes only in 75% cases. Furthermore, type 2 diabetes is usually diagnosed after actual onset of the disease, which is often indolent, so the characteristic of the early clinical stages of kidney involvement is often difficult to delineate. Diabetic nephropathy can be conveniently characterized into different stages as described in [Table 1]. This study mainly focuses on determining the prevalence of diabetic nephropathy in newly detected patients with type 2 diabetes and the subsequent analysis of the risk factors associated with the development of diabetic nephropathy.
| Materials and Methods|| |
This study was carried out in the Department of Diabetology and General Medicine following the approval from the institute’s ethical committee. The study group comprised newly detected type 2 diabetes subjects (n = 200) from where it was conducted as a cross-sectional study over an 18-month period. They were explained about the study and a written informed consent was obtained from all the study subjects. The body mass index (BMI) was calculated with height and weight of the subject using the formula BMI = weight (kg)/height (m). Right upper arm blood pressure was taken in supine position by using sphygmomanometer under appropriate condition. Triglyceride (TGL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels were estimated and calculated using standard methods in the early-morning fasting blood sample. Blood samples collected for blood urea and serum creatinine were analyzed in the institute’s respective laboratory. The blood urea in this study was estimated using diacetyl monoxime (DAM) method, whereas serum creatinine was estimated using modified Jaffe’s method. GFR was calculated using Modification of Diet in Renal Disease Study formula. Urine sample was collected to estimate protein creatinine ratio (PCR) using sulfo salicylic precipitation method. Micral-Test strips were used to detect the presence of microalbuminuria in the early-morning sample. Fundus examination was carried out for all the subjects with direct ophthalmoscope. Ultrasound (USG) KUB was performed to find out renal size and to rule out nondiabetic causes of nephropathy.
The inclusion criteria of the study included the following:
Detection of DM in patients within six months from the time of enrolment for the study.
The inclusion criteria of the study included the following:
Patients not willing for study.
Patients with uncontrolled hypertension (average systolic blood pressure (SBP) ≥ 150mm HG or diastolic blood pressure (DBP) ≥ 90mm Hg).,
Patients with poor glycemic control (HbA1c ≥ 7%).
Patients with urinary tract infection.
Patients with cardiac failure.
Patients suspected to have nondiabetic nephropathy such as USG KUB showing contracted kidney and cystic renal disease.
Patients with other medical illness.
Micro and macroalbuminuria. It is defined as urinary albumin excretion >30 mg/24h (20 µg/min) and ≤300 mg/24h (200 µg/min) irrespective of how the urine is collected. At least two of three samples collected within six-month period under optimal conditions should be positive to call it as persistent microalbuminuria. In this study, Micral dip stick showing positivity of more than 20 mg/L has taken as microalbuminuria. PCR was also correlated with this result where a value of >0.03 to 0.3 was considered as excretion of about 30–300 mg in 24h. Both showed one/one correlation in our study. Macroalbuminuria can be defined as persistent albuminuria found >300 mg/24h or 200 µg/min (AER). Presence of at least one definite microaneurysm in any of the visualized fields was considered as the minimum criterion for diagnosis of diabetic retinopathy.
Systemic and controlled hypertension. Subjects with self-reported hypertension and those who had SBP of ≥ 150mm Hg and/or DBP ≥ 90mm Hg in adults were considered to have hypertension. JNC VIII recommends cut-off value of ≤ 140/90 mmHg for good control of systemic hypertension in diabetic subjects. There has been no evidence that treating patients with CKD to a lower blood pressure goal slows the progression of the disease. Similarly, no evidence is available from randomized controlled trials showing that treatment to a systolic pressure of <140mm Hg improves health outcomes in adults with diabetes and hypertension. Angiotensin-converting enzyme (ACE) inhibitors and nondihydropyridine CCBs were not used for the control of blood pressure as they have modifying effect on proteinuria. In this study, only normotensive and controlled hypertensive patients are taken as study subjects. Those who had uncontrolled hypertension are not included in this study so that false positivity because of uncontrolled hypertension while the detection of albuminuria is eliminated.
Dyslipidemia and obesity. Adult Treatment Panel III (ATP III) guidelines developed by the National Cholesterol Education Program have been used to detect dyslipidemia in the study subjects. The classification adopted from National Institute of Health, National Heart, Lung and Blood Institute recognized by WHO is used for classifying the subjects according to the weight status. Chi-squared test, two-sample t-test, and binary logistic regression model were used for the analysis. All the analyses were performed using the Statistical Package for Social Sciences software version 11.5.
| Results|| |
Of the 200 total subjects involved in the study, 70 (35%) were men and 130 (65%) were women. The statistical analysis of the age distribution among the study population diagnosed with diabetic nephropathy is represented in [Table 2]. As described in the Materials and Methods section to this paper, BMI calculation was performed for the study population. The results showed that about 57.5% of the subjects had normal BMI, 32% were overweight, and 9.5% were obese [Table 2]. Similar kind of BMI calculation was also performed for the study population diagnosed with diabetic nephropathy. Subjects having weight above the desired normal BMI were found to be 88.5% in the nephropathy group. Among them, 73.1% were overweight and 15.4% were obese [Table 2]. The mean age among the study population for diabetic nephropathy and non-nephropathy were found to be 48.46 and 49.17, respectively. The difference between the two groups was not significant (P = 0.710). Among the 26 patients who were diagnosed to have diabetic nephropathy, 24 had microalbuminuria and 2 had macroalbuminuria. The mean serum creatinine value in non-nephropathy subjects was found to be 0.7 mg/dL, whereas in nephropathy group it was found to be 0.8 mg/dL.
|Table 2: Age and BMI distribution of study population (comprises non-nephropathy and nephropathy)|
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The family history of diabetes was analyzed for the study population. In total, about 52 patients were found to have family history of diabetes. Among them, eight patients (4%) were diagnosed with nephropathy [Table 3]. Similar kind of analysis was carried out for finding the family history of kidney diseases for subjects diagnosed with nephropathy. The results showed that only two patients among the nephropathy group were having family history of kidney diseases [Table 3]. Analysis of the prevalence of dyslipidemia in the study population showed that in TGL group about 92 of them had hypertriglyceridemia. Among these 92 subjects, 16 (8%) were diagnosed with nephropathy [Table 3]. The LDL group has witnessed the highest number of patients with 198 reported to have LDL-cholesterol dyslipidemia. Incidentally, this group also comprised of all the 26 (13%) subjects diagnosed with nephropathy [Table 3]. In HDL group, about 94 subjects had HDL-cholesterol dyslipidemia in the study group. It was 8% in the nephropathy subjects [Table 3]. About 23 study subjects were found to be hypertensive. Among them, nine were diagnosed with nephropathy. All the six subjects found to have retinopathy were under the nephropathy group [Table 3]. As for the GFR analysis, about 46 (23%) patients in the study group with 1% of nephropathy group were present with hyperfiltration. Among the remaining patients with nephropathy about 6% had a normal GFR, whereas the same percentage of the nephropathy subjects possessed a decreased GFR [Table 4].
|Table 3: Prevalence of various risk factors found in the study population (comprises non-nephropathy and nephropathy)|
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Binary logistic regression. The following variables such as age group, gender, family history of diabetes, family history of kidney diseases, smoking, BMI, hypertension, TGL, LDL, and HDL groups were taken as models for which binary logistic regression model was applied to find out correlation of the risk factors [Table 5]. The results showed significant correlation between diabetic nephropathy and the following risk factors: male sex and BMI especially overweight and hypertension [Table 5].
| Discussion|| |
Early detection and adequate control remain the key focus in diabetes management. Several studies have shown that diabetes control worsens with increase in the duration of the disease. Poor glycemic control remains as one of the risk factors resulting in the development of micro and macrovascular complications. Therefore, it becomes imperative for both the patients and physicians in regulating the proper glycemic control. The results obtained from this study were compared with studies carried out in various races. A study carried out in the Chennai urban region by Unnikrishnan et al. showed the 23.9% prevalence of microalbuminuria and 2.2% of macroalbuminuria. In our study, it was 12% and 1% of microalbuminuria and macroalbuminuria, respectively. The lesser prevalence may be because uncontrolled hypertensive patients are excluded from our study, while in other studies they were included. In this study, no correlation between age and diabetic nephropathy was found. This was in contrast to the observation noted in Unnikrishnan et al. study, whereas with increasing the age the risk of diabetic nephropathy also increased. In this study, no significant difference was observed between the age of the diabetic patient and development of diabetic nephropathy. However, a significant correlation was noted between gender and diabetic nephropathy where the binary regression model showed that significant correlation exists between male sex and diabetic nephropathy (P = 0.017). In contrast, Unnikrishnan et al. study showed no such correlation between gender and diabetic nephropathy. Various western studies had shown that male patients had increased risk of development of diabetic nephropathy., Also, in other studies highly sensitive methods such as immunoturbidometric assay were used for AER detection. Moreover, as compared with those studies the sample size was relatively smaller in our study. Prevalence of macroalbuminuria has been found higher in the western population.,
As for the BMI, patients having over weight also showed significant development of diabetic nephropathy [Table 2]. Among several other factors, while significant correlation was found between family history of kidney diseases and development of diabetic nephropathy [Table 3] no such correlation was found between family history of diabetes and smoking with development of diabetic nephropathy [Table 3]. Anjana et al. too made a similar observation where they found that smoking and alcohol consumption had a negligible impact to be considered as risk factors for diabetes. On the contrary, in the study carried out by Unnikrishnan et al., significant correlation was found between smoking and development of diabetic nephropathy. But, in the present study due to the smaller size of study population with only a lesser number of patients were found to be smokers no correlation relationship was existed between smoking and diabetic nephropathy.
Meanwhile, a highly significant correlation was found between hypertension and diabetic nephropathy in this study where hypertensive subjects having optimum controlled blood pressure are only included. Therefore, the bias of albuminuria caused by hypertension has been avoided in this study. Nonetheless, the hypertensive patients still possessed the risk of acquiring nephropathy because of hypertensive vascular pathology caused by previously uncontrolled or delayed detection of hypertension and type 2 diabetes. Therefore, this study signifies that screening and early detection of hypertensive subjects and also the effective control of systemic pressure in spite of diabetic status (including latent diabetes) becomes imperative.
The subjects presented with nephropathy had TGL, LDL, and HDL dyslipidemia with the prevalence of 8%, 13%, and 8%, respectively. The prevalence in total subjects (newly detected DM) is 46%, 99%, and 47%, respectively. This shows high prevalence of hypertriglyceridemia, high-LDL cholesterol levels, and low-HDL cholesterol levels in type 2 DM as well as in diabetic nephropathy subgroup [Table 3]. In this study, no statistical significance was observed between dyslipidemia and diabetic nephropathy. Various other studies had shown significant relation between dyslipidemia and nephropathy. This may be because of the small size of our study population and also the high prevalence of the dyslipidemia among all the newly detected patients with DM in our study. Likewise, GFR variable has also possessed significant correlation with diabetic nephropathy in this study. Fifty percent of the nephropathy subjects had lower GFR depending on the severity of the disease. Among non-nephropathic subjects, one fourth had hyperfiltration suggestive of stage-I diabetic nephropathy. The mean GFR in total subjects (newly detected type 2 DM) has been found to be 115 ± 18mL/min/1.73 m2.
Retinopathy was found to have highly significant correlation with nephropathy. Retinopathy patients had increased risk of developing nephropathy. About one fourth of the nephropathy subjects in this study had presented with diabetic retinopathy. The prevalence of retinopathy in this study was found to be lesser (3%) and it may be because of using direct ophthalmoscope for the fundus examination. However, fundus photography was used in other studies.
| Conclusion|| |
This study aimed to find out the prevalence of diabetic nephropathy in newly detected type 2 diabetic patients and also the risk factors associated with the development of the diabetic nephropathy. The study signifies the early screening of all newly diagnosed type 2 diabetic patients for diabetic nephropathy. This study has shown significant association between the development of nephropathy and risk factors such as family history of kidney diseases and BMI especially with overweight, gender, systemic hypertension, serum creatinine, GFR, and retinopathy. Binary regression model analysis showed significant association with male sex, overweight, and hypertension. This study has not shown significant association of smoking and dyslipidemia with the development of diabetic nephropathy. Albumin excretion rate is the gold standard screening as well as diagnostic tool for the early diagnosis of diabetic nephropathy. Micral dip stick test method and the cost-effective PCR can be used as the valuable screening test in setting such as our country where most of the population are in the low socioeconomic status.
The active screening and early detection of type 2 diabetes is necessary. Effective measures to control the risk factors and early detection of diabetic nephropathy to prevent it from progressing toward ESRD are the key in maintaining the quality of life in diabetic population. This not only decreases the morbidity and mortality among the diabetic patients but also lessens the financial burden faced on treating such complications enormously, in the developing countries like India. The presence of complications at the time of diagnosis of type 2 diabetes itself shows that intensive screening for early detection of DM and tight glycemic control as well as blood pressure control will prevent the development of microvascular complications.
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Conflicts of interest
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]