A Study of Micro-Albuminuria in Type 1 and Type 2 Diabetes Mellitus

INTRODUCTION

Type 1 Diabetes mellitus is an autoimmune disease in which pancreatic islet β cell destruction occurs by T lymphocytes reacting against poorly defined β- cell antigens. This form of Diabetes is characterized by severe lack of insulin. Type one Diabetes most commonly develops in childhood, progresses with age and symptoms develop at puberty. Type 2 Diabetes mellitus is characterized by two metabolic defects which are as follows: (i) Decreased ability of peripheral tissues to respond to insulin (insulin resistance) (ii) β cell dysfunction which is manifested as inadequate insulin secretion in the face of insulin resistance and hyperglycemia. In most cases insulin resistance is the primary event and is followed by increasing degrees of β cell dysfunction. Currently, 19.4 million Indians are affected by this deadly disease.[1] According to the study in the Diabetes Indian Group, an overall prevalence of Diabetes mellitus was reported to be 4.3%, The prevalence in urban and rural areas was 5.6% and 2.7% respectively.[2] Diabetes Mellitus is becoming a pandemic in times to come, more percentage being affected in urban area as compared to rural. The prevalence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. Around 80% of population is suffering with Diabetes above the age of 20 years in India. The percentage of adult population suffering from this disease in urban areas ranges between 10.9% and 14.2% and prevalence in rural India was 3.0-7.8% with a much higher prevalence among individuals with the age group of 50 years and above.[3] Diabetes mellitus is also called as a disease of complications. Almost every organ of the body is directly or indirectly involved in this disease. The morbidity associated with long standing Diabetes of either type results from a number of serious complications involving both large and medium sized muscular arteries (macrovascular disease), as well as capillary dysfunction in target organs (microvascular disease). Macrovascular disease causes accelerated atherosclerosis among diabetics, resulting in increasing risk of myocardial infarction, stroke and lower extremity gangrene, whereas the effects of microvascular disease are most profound in the retina, kidneys and peripheral nerves resulting in diabetic retinopathy, nephropathy and neuropathy respectively. Most of the available experimental and clinical evidence suggests that the complications of Diabetes mellitus are a consequence of the metabolic derangements in the patients suffering with mainly hyperglycemia for more than 10 years. Increased intracellular glucose will be converted to the glycosylated end products that crosslink proteins to promote glomerular dysfunction.[4] Chronic renal disease is associated with long term diabetes mellitus (DM) and hypertension that leads to end-stage renal disease (ESRD). It has been found that around 20-30 % of population with both

However, due to prevalent nature of type two Diabetes-mellitus, such patients constitute over half of those which convert to chronic kidney disease. Nearly 30% of chronic renal failure patients in India are due to diabetic nephropathy.[5]

Microalbuminuria is accepted as a CV risk marker for myocardial infarction and stroke, regardless of diabetes status. Although there is good evidence in those with type 2 diabetes that the presence of MA >100 mg/day is associated with higher CV events and greater likelihood of kidney disease development. Patients with long-standing, poorly controlled diabetes are more likely to have MA than those without diabetes[6,7]. Likewise, people with MA are at greater risk for developing hypertension, a risk factor known to increase CV risk.[8-10] The appearance of microalbuminuria in type 1 Diabetes mellitus is a very important predictor of progression to overt proteinuria (> 300 mg/day). The present study was designed to study mean albumin creatinine ratio in patients of type one and type two diabetes mellitus and study the effect of long-term diabetes on the mean albumin creatinine ratio.

The present study was conducted in the Department of Biochemistry, Santosh Medical College & Hospital, Ghaziabad, India. The subjects were identified cases of diabetes-mellitus from department of medicine, Santosh hospital, Ghaziabad. Urinary albumin estimation and urinary creatinine estimation was done in 200 cases of Diabetes mellitus with a history of the disease for 10 years or more and 100 cases of normal healthy individuals. The subjects were divided into three different groups.

Urinary albumin estimation and urinary creatinine estimation was done in 100 normal healthy individuals of both sexes in the age group ranging from 20-50 years. This group comprised of 59 males and 41 females.

Albumin creatinine ratio was estimated in 90 cases of type I Diabetes mellitus. The cases were selected as per inclusion criteria from Outpatient and inpatient department of Medicine, Santosh Medical College & Hospital, Ghaziabad.

Albumin creatinine ratio was estimated in 110 case of type 2 Diabetes mellitus. The cases were selected as per inclusion criteria from OPD and IPD, Department of Medicine, Santosh Medical College & Hospital, Ghaziabad. This group was comprised of 62 males and 48 females.

i. chronic Diabetes mellitus for 10 years or more who are being treated for Diabetes. ii. Normotensive subjects {BP-≤120/80mm of Hg} iii. Age- 20-50 years.

i. Cases having proteinuria detectable by dipstick tests. ii. Cases having any evidence of infection.

1. Spot urinary albumin. 2. Spot urinary creatinine. 3. Fasting Plasma Glucose. Collection of Urine Sample Urine sample was collected in clean, sterile plastic container. Patients were told to take rest and not to do physical exercise before the collection of urine sample. Collected urine sample was tested by dipsticks for the presence of frank proteinuria. Dipstick negative urine samples, were used for quantitation of albumin and creatinine within 4 hours of voiding. Collection of Blood Sample Blood samples were collected after 12 hours of fasting after cleaning the antecubital fossa with all antiseptic precautions. Approximately 1 ml of venous blood was drawn by a dry and sterilized syringe, it was transferred to sodium fluoride vial and then mixed gently. Then it was centrifuged at 3000 rpm for 5 minutes. Plasma was pipetted out and kept in a clean sterile vial. Urinary albumin was estimated by immunoturbidimetric method. [Diasys Diagnostic system, Holzhein, Germany] Urinary creatinine was estimated by Jaffe‘s Method (Modified).

Data obtained during study were recorded in tabulated forms and were analyzed by student‘s t test. The p-value is obtained from standard table value of t distribution based on degree of freedom and level of significance.

S.E.M- Standard error of mean. (ACR= Albumin creatinine ratio) TABLE-IV Numbers of cases, range, mean, standard deviation and standard error of mean values of fasting plasma glucose in healthy controls, in comparison with type 1 and type 2 diabetes mellitus cases.

Table – VI Mean values of Urinary Albumin and Urinary creatinine with respect to duration of diabetes in cases of type 2 DM.

million people worldwide are affected by this disease. It has found that phenotype in Asia and India has an increased susceptibility to Diabetes mellitus.11 As per WHO, the maximum cases of diabetes have been reported from South East Asian countries. 12 India comprises of around 85-90% of the adult population of South Asia and hence the major contributor of diabetic population in this area with around forty million diabetic patients with an increase of 20% in another decade. As adult diabetes is reflected in chronic kidney disease, India becomes the major contributor in CKD patient load also and has been described as the Diabetes capital of the world.[13] It has reported that nearly one third of chronic renal failures in India are due to diabetic nephropathy that has to be controlled.

As diabetes mellitus is associated with chronic CKD as well as increased morbidity and mortality, the present study was undertaken to know the effective role of a marker in patients for early detection of Diabetes mellitus Albumin/creatinine ratio was calculated by spot urinary estimation of both in randomly selected cases. Earlier studies have also reported that estimation of albumin creatinine in random urine samples have highly significant correlation with results using 24-hour urine collection with a sensitivity of around 80% and specificity of 81%.[14]

Interestingly, in comparison to control group, spectrum of Diabetes mellitus including type I Diabetes mellitus and type II Diabetes mellitus there is marked increase in the albumin creatinine ratio and it is significant (P<0.001) for type I Diabetes mellitus and for type II Diabetes mellitus also (P<0.001) but in comparison between type I Diabetes mellitus and type II Diabetes mellitus, difference of mean the albumin-creatinine ratio is found to be statistically insignificant (P>0.05) clearly indicating that albumin creatinine ratio is not affected by type of Diabetes Mellitus in spite of the fact that in both the types around 43% cases were shown to have positive reports for microalbuminuria. Hyperglycemia is the major factor initiating the changes in the kidney. The tissue damage caused by hyperglycemia can be attributed to the hemodynamic factor due to adversely affected filtration process, high blood pressure and together this can lead to cardiovascular disease. Hyperglycemia increases the expression of transforming growth factor beta (TGFβ) in the glomeruli and of matrix proteins. TGFβ contributes to It can be concluded that microalbuminuria can be used as an early marker in Diabetes nephropathy and its early detection can significantly reduce the progression of renal complications associated with Diabetes mellitus

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Dean Research & Professor of Biochemistry, Santosh Deemed to be University, Ghaziabad