CORRELATION BETWEEN MICROALBUMINURIA AND HBA 1 C AMONG TYPE 2 DIABETIC PATIENTS IN JAMMU , J AND K STATE , INDIA

Dr. Bawana Raina 1 , Dr. Puneeta Gupta 2 , Dr. Nawaf Khurshid Sheikh 3 and Dr. Kapil Gupta 4 . 1. Associate Professor, Deptt of Pathology, Acharya Shri Chander College of Medical Sciences. 2. Professor of Medicine, Acharya Shri Chander College of Medical Sciences. 3. Post graduate student, Deptt of Pathology, Acharya Shri Chander College of Medical Sciences. 4. Post graduate student, Deptt of Medicine, Acharya Shri Chander College of Medical Sciences. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


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Microalbuminuria is defined as urinary albumin excretion rate of 20 -200 µg/min or urinary protein excretion rate of 30-300 mg/day. 3 Microalbuminuria (MAU) represents the simplest and most sensitive prognostic factor to evaluate the risk of overt nephropathy in diabetes, as it represents the first stage of progressive diabetic renal disease. Diabetic nephropathy has been defined as clinical syndrome, characterized by persistent albuminuria (>300 mg/d or >200 μg/min), that is confirmed on at least 2 occasions 3-6 months apart, progressive decline in the glomerular filtration rate (GFR) and elevated arterial blood pressure 4 .
Currently, diabetic nephropathy is the leading cause of chronic kidney disease and is responsible for 30-40% of all the end-stage renal disease (ESRD). It is also one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes 5 . The data available from United States shows that, the prevalence of diabetic kidney disease increased directly in proportion to the prevalence of diabetes mellitus from the year 1988 to 2008. 5 In India similar studies have been conducted by Chowta et al. (2010) 6 9 , from Puducherry. As far as the authors are aware, the present study is the first from Jammu and Kashmir State.

Materials and Methods:-
A total of 110 diabetes mellitus Type 2 patients (70 males, 63.6 % and 40 females, 36.3 %), with age ranging from 40 to 70 years (Mean age 50.57), who either attended the outpatient Department or were admitted in the Department of Medicine ASCOMS and Hospital, Sidhra, Jammu, during the period from January to June 2017, were selected for the present study. The written and informed consent was taken from all tese patients as per the prevalent norms and an Institutional Ethical Committee clearance was also obtained.
Subjects, diagnosed and confirmed by specialists, as suffering from Type 2 Diabetes Mellitus (DM), were included in the present study. The diagnosis of Diabetes Melitus was based on the following Criteria. 10 Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h or 12 h. Post prandial ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test or HbA1C ≥ 7%.
Parameters taken as inclusion criteria are as follows: age of onset > 40 years of age; Serum Creatinine < 1.5 mg/dl; serum triglyceride < 400 mg/dl; negative urine culture.
Patients with systemic disease like, Hypertension, Ischemic heart disease, Valvular heart disease, Congestive cardiac failure, hemoglobinopathies, and severe anemia were excluded from the study.
Venous blood samples after fasting were taken for plasma glucose (Glucose-Oxidase Peroxidase Method). Samples for HbA1C were taken in EDTA containers (Turbidimetric Inhibition Immunoassay). All urine samples were tested for glucose and albumin by reagent strip test. Albumin negatives were further tested quantitatively for microalbumin by Immune Turbidimetric Method. HbA1C levels ≤ 7 and Microalbumin levels ≤ 30mg/day were considered to be normal. The subjects were divided into two groups according to glycemic control, based on their levels of plasma glucose, both in fasting condition and two hours after ingestion of 75g glucose, and glycated hemoglobin as per the following criteria:

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Data were analysed using SPSS version 18. Pearson Correlation Coefficient was calculated to find the linear relation between HbA1C and Microalbuminuria, and also between duration of diabetes and Microalbuminuria. Chi-square Test was also used to find relationship. p value was taken as significant at 5% confidence level (p<0.05 ).
A positive correlation was found amongdiabetic patients with uncontrolled glycaemic status, with HbA1C ≥ 7% and microalbumin >30mg/day and this was evidenced by Pearson's Correlation Co-efficient (r = 0.818) and Chi-square test. p value of 0.001 i.e. less than p<0.05 was considered statistically significant (Fig. 2).
Mean duration of diabetes in microalbuminuric patients was 11.5years while in normoalbuminuric patients it was 4.6years, which is statistically highly significant. Pearson Correlation Analysis showed statistically significant correlation of microalbuminaria with duration of diabetes i. e. r =0.622, p= < 0.0001. Correlation of duration of DM with albuminuria, + P value

Discussion:-
According to a report of World Health Organisation (WHO), 2 the number of people with diabetes has risen from 108 million to 422 million, and the global prevalence of diabetes among adults, over 18 years, has risen from 4.7 % to 8.5 % from the year 1980 to 2014. In addition it has been the major cause of blindness, kidney failure, heart attacks, strokes and lower limb amputations. India also has a vast population of diabetics, about 69 million, second largest after China; most of them being, illiterate and medically ill informed about this disease and are unaware about its serious implications and complications, adding to their woes. In many cases, it is often too late, as the patients are already victims of most of its complications, by the time the disease is diagnosed. This is evident from the findings of WHO, that 46 % of people with diabetes are undiagnosed globally.
The prevalence of microalbuminaria in Type 2 diabetes is variable and ranges from as low as 25 % (Ghai et al. 1994) 11 to as high as 84.21 % (Kumaret al. 2014). 7 In the present study, the prevalence of microalbuminaria in Jammu was 59 %, whereas, it has been reported to be 37% in Mangalore by Chowta et al. 6 6 , one of the main causes is, " irregular treatment with poor glycemic control and also may be due to the "small sample size" in their study. The sample size in the above report and the present study is almost similar, being 100 and 110 respectively. However, we feel that, sample size does not play much role in this and agree with them in suggesting that, "the level of glycemic control seems to be the strongest factor influencing transition from normoalbuminuria to microalbuminuria." They further suggest that, "ethinical differences also play a role in giving a higher prevalence of microalbuminuria" with which the present authors agree.
Mean age of patients with diabetes in the present study was 50.57 years, which is similar to that, reported by Chowta et al 6 , Kanakmani et al. 12 and Maskari et al. 13 whereas, in the studies of Tandon et al. 8 the patients belonged to a younger age group with mean age of 52.2 years. Generally, diabetic nephropathy affects both males and females equally. This was also confirmed by the present study.
The level of HbA1C has been widely accepted as an indicator of mean daily blood glucose concentration over the preceding 8-12 weeks. The glycated hemoglobin (HbA1C) assay is the most commonly used measure of chronic glycaemia, since its introduction more than 25 years ago. 14 HbA1C levels equal to or less than 6.5% in diabetes, reflects good glycemic control and more than 7.5% will put patient at greater risk of developing disease related complications, including nepthropathy. 15 The observation that, 60 patients, 54.5 % showed microalbuminuria and had HbA1C≥ 7% and only 25 patients, 22.7 % were normoalbuminuric inspite of HbA1C ≥ 7, is due to the fact that the former had DM for more than seven years and in the latter, it was for less than seven years. Significant correlation was found in the present study between HbA1C, microalbuminaria and duration of T2 DM. Baig et al 16 have also shown significant correlation between long duration of T2 DM with high level of microalbumin.In addition the studies of Muraliswaran et al. 9 and Gupta et al. 17 lend support to the present study.
Out of a total 65 microalbuminaria patients, maximum30 patients (46.1 %) had DM for a duration of 10 to 15 years, whereas, 20 patients (30 %) had DM for a duration of more than 15 years, 10 patients (15.3%) for 5 to 10 years and minimum 5 patiens(7%) had DM for 1to 5 years which is in conformity with the findings of Chowta etal 6 and Acharya et al. 18 In contrast Tandon et al. 8 had maximum cases (79.8 %) with microalbuminaria, who had DM for a duration of 6 to 10 years .
In the present study, it is found that diabetics with poor glycemic control had higher microalbumin levels compared with those of diabetics with good glycemic control. This study also highlights that there is a significant correlation 600 between microalbumin levels and HbA1C.Varghese et al. 19 carried out study among type 2 diabetic people and found a positive correlation between microalbuminuria and HbA1C but did not find any statistical difference between microalbuminuria and two sexes.
Impaired glycemic control is associated with significant elevations in urinary microalbumin levels. Furthermore, there is an increased urinary microalbumin level with increased duration of diabetes, which suggests that the detection of increased urinary microalbumin levels at the initial stage can avert, reduce the clinical and economic burden of diabetic complications in future. 20

Conclusion:-
Screening for urine albumin among persons with diabetes is widely recommended for the detection and treatment of incipient diabetic nephropathy and affects the physician's implementation of therapy to slow progression of kidney disease. Despite widespread recommendations for screening of persons with diabetes for both glycemic control and urine albumin, there has not been a systematic assembly of the literature to assess the risk relation between tests assessing long-term glycemic control or tests assessing the presence of microalbuminuria with cardiovascular, peripheral vascular, renal, and neurological outcomes (all of which represent end-organ effects of long-term diabetes). Despite its devastating consequences, microalbuminuria is still a largely unrecognized risk factor, and a large proportion of individuals with diabetes are not regularly screened.  Recommendations:monitoring of glycemic status is considered a cornerstone of diabetes care and affects how physicians and patients adjust medical therapy as well as behavioral therapy (e.g., diet and exercise). Use of audio-visual media should be introduced both at Government level and at the level of N.G.Os. to propagate and educate the public about the short and long term complications of D.M.