PREVALENCE OF MICROALBUMINURIA AND ITS ASSOCIATION WITH GLYCEMIC CONTROL IN TYPE 2 DIABETIC PATIENTS: A CROSS SECTIONAL STUDY AT a cross sectional

Background : Diabetes mellitus has become one of the biggest health problems of this era. The resultant microvascular and macrovascular complications add to significant amount of morbidity and mortality. Urine microalbumin is considered as an early marker for microvascular complications among diabetic patients. The aim of this study was to find out the prevalence of microalbuminuria among type 2 diabetic patients attending Kathmandu Medical College and its relation with glycemic control, age, sex, duration of diabetes. Methods : A total of 208 previously diagnosed type 2 diabetic patients attending medical outpatient department of Kathmandu Medical College, Sinamangal were included in the study over a period of 1 year (October 2017 - September 2018). Fasting and 2-hour postprandial venous blood for blood glucose and HbA1c measurement and early morning urine sample (after overnight fast) was collected for detection of microalbuminuria. Statistical analysis was done using SPSS version 23. Results : The prevalence of microalbuminuria among the study population (mean age: 54.22 ± 11.76 years, mean HbA1c: 7.62 ± 1.53 %) was 42.8%. Microalbuminuria had significant correlation with HbA1c and duration of diabetes (p<0.001), but not with age, sex and type of medication. There was positive correlation between urine microalbumin and fasting and post-prandial blood glucose. Conclusions : Our present study found high prevalence of microalbuminuria among diabetic patients with poor glycemic control. It is suggested that tighter glycemic control with regular urine microalbumin testing should be integral part of diabetic management plan to prevent long term complications such as diabetic nephropathy


INTRODUCTION
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia resulting from variable degree of insulin resistance, impaired insulin secretion or both. 1,2 The global prevalence of diabetes mellitus is on a steady rise, with the world population with this condition projected to reach 592 million by 2035. 3 In Nepal, the pooled prevalence of type 2 diabetes mellitus (T2DM) has been reported to be 8.4 %, the variability being seen in rural and urban population 4 , and is bound to increase in the coming years, driven by rapid urbanization, shift towards sedentary lifestyles and nutrition transition leading to overweight and obesity. Complications from diabetes mellitus can be divided into microvascular (such as retinopathy, neuropathy, nephropathy) and macrovascular (such as acute myocardial infarction, peripheral vascular disease, stroke) varieties that result in significant morbidity and mortality, adding to the burden of disease. Diabetic nephropathy, as defined as diabetes with albuminuria or impaired glomerular filtration rate, or both is one of the frequent microvascular complications with variable prevalence (2.2% -14.2 %) in different population. 5,6 Microalbuminuria is considered as an early marker of diabetic nephropathy, with higher levels of urinary albumin representing a generalized vascular damage rather than renal microvascular injury alone. 7 In recent years, the incidence of end stagerenal disease (ESRD) has increased drastically that has been attributed to increased incidence of diabetes mellitus in the general population. 8 Diabetic nephropathy has been reported as one of the leading etiologies of ESRD in Nepal. 9 Glycosylated hemoglobin (HbA1c) is used as a marker of blood glucose controlin the diabetic patients.It determines average glycemic control over a period of 8-12 weeks and its higher values correlate with the development of microvascular complications in the diabetic patients. 10 The Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetic Study (UKPDS) highlighted the fact that careful monitoring and control of glycemia (HbA1c<7.0 %) in patients with T2DM decreased the possibility of developing microalbuminuria by 34% and therefore, maintaining optimal HbA1c has been advised for all diabetic patients to prevent such complications. 11,12 With the rise in the patients with T2DM in Nepal and the well-known importance of early diagnosis, treatment and prevention of microalbuminuria in this population, this study was aimed at describing the prevalence of microalbuminuria in T2DM patients, the patient characteristics and evaluating the relationship between microalbuminuria and glycemic control. College, Sinamangal. Exclusion criteria were patients with newly diagnosed diabetes mellitus, patients with other causes of proteinuria, hematuria and renal failure, recent history of urinary tract infection and presence of any self-reported acute illness or fever after taking detailed history and observing previous medical records.

METHODS
After taking written consent from the research participants during their outpatient visits, an interviewer-administered questionnaire was completed that included socio-demographic data and detailed medical history including the list of current medication. Two blood samples (5 ml) weredrawn by venipuncture under aseptic conditions by trained laboratory personnel. The first sample was collected in the morning after overnight fasting (minimum 8 hours) for estimation of serum fasting blood glucose (FBG) and whole-blood HbA1c whereas the second blood sample was drawn 2 h after an average meal by the patients for estimation of serum postprandial blood glucose (PPBG). A single spot urine sample was collected in the early morning after overnight fasting. Blood glucose was determined by Selectra Pro M analyzer (EliTech Clinical Systems) using enzymatic colorimetric method (GOD/POD/ PAP method).
HbA1c(Glycated hemoglobin) was measured using chromatographic technique by D-10TM Hemoglobin analyzer(Bio-Rad Laboratories, Inc.). Based on HbA1c values, the glycemic control was categorized into: a) good control (≤ 7.0 %), b) fair control (7.01 -8.20 %),and c) poor control (> 8.20 %).Urinary albumin was measured by point-of-care NycocardTM urinaryalbumin test.In controlled laboratory testing, a precision of <10% expressed by the coefficient of variation (CV) is usually achieved for the test. A diagnosis of microalbuminuria was made if urinary albumin was≥ 20 mg/L up to 200 mg/L. Values above 200 mg/L were classified as clinical albuminuria.
Data was collected, compiled and analyzed by using Statistical Package of Social Science (SPSS) software version 23. The data were expressed as mean ± SD or median (minimum-maximum) as appropriate. The mean and median comparisons of different variables between no-microalbuminuria and microalbuminuria-present groups was done by student's t-test and Mann-Whitney U-test respectively. The difference in proportions was analyzed by chi-square test. The association between HbA1c and microalbuminuria was determined by Spearman's rank correlation coefficient. P-value of < 0.05 was considered to be statisticallysignificant.

RESULTS
A total of 208 diabetic patients (mean age: 54.22 ± 11.76 years, age ranging from 29 -84 years) were included in the study. There were 97 males (46.6 %) and 111 females (53.4 %).The median duration of diabetes was 5 years (Range: 0.5 -21 years). 81.3 % of the patients were using oral hypoglycemic agents (OHAs), and the remaining 18.8 % were using insulin.
The mean HbA1c of the study population was 7.62 ± 1.53 %. Sub-dividing the study group based on glycemic control, approximately only one-third of the patients (36.5 %) had good glycemic control [ Table 1].

DISCUSSION
Diabetes mellitus has a long natural history, because of which there is a high prevalence of micro-and macrovascular complications in the patients with this condition. These have added burden to the patients, health care providers and the national health system.It's an unarguable fact that the risks of complications in patients with diabetes mellitus are significantly reduced by improving the glycemic control (which is done by targeting HbA1c in the patient to remain in the desired range). 13 The present study shows that only one-third of the patients had good glycemic control which is alarming, increasing the susceptibility of the patients to develop diabetic complications.
In the present study, 208 patients were studied and the overall prevalence of microalbuminuria was found to be 42.8%. A study conducted by Sigdel et al 14 6,14 Therefore, it can be concluded from our study that good glycemic control and early diagnosis of diabetes and institution of therapy are the two important predictors of development of microalbuminuria in these patients.
In our study, we found significant correlation between HbA1c and microalbuminuria as supported by earlier studies. 7,17,18 However, there are studies that did not show significant association between these two. 19 These differences in findings may be due to limited sample size, less time allocation for the duration of study or variationin stage of the disease in study population.The urine microalbumin had significant positive correlations with both fasting and post-prandial blood glucose, supporting the outcome of previously conducted studies. 7,18 This highlights the fact that diabetic patients should have tighter control of blood glucose to minimize microvascular complications.
One important aspect to consider is the hospitalbased nature of our study that has introduced selection bias and therefore, might not be true representative of the diabetic population. There is scope of further study including important variables among larger diabetic population.

CONCLUSION
There is a high prevalence of microalbuminuria in patients with type 2 diabetes mellitus, which is associated with longer duration of disease and poor glycemic control.Regular testing of HbA1c and urine microalbumin should be an integral part of diabetic patient management (particularly for the patients with long duration of disease) to prevent and earlydiagnose renal complications associated with the condition.