Stage of Diabetic Nephropathy:

Patients of diabetes mellitus are at greatest risk for microvascular complications such as nephropathy, retinopathy and peripheral neuropathy and macrovascular complications. Clinical proteinuria has commonly been detected by dipstick measurement. Microalbuminuria refers to a urinary albumin concentration below the level detected by dipsticks⁷. Increased intraglomerular pressure may be caused by an imbalance in afferent and efferent renal vascular tone, increased blood flow and extracellular fluid volume. Together, elevated hydrostatic and oncotic pressures initially cause renal hyper filtration, mesangial hypertrophy and proliferation, as well as changes in the polyanionic charge and porosity of the glomerular basement membrane in the kidney and in other vascular sites (eg. retina, arteries, nerve) by deposition of advanced glycation end products. Perhaps the most studied marker of diabetes mellitus and diabetes related complication is microalbuminuria. In Diabetes Mellitus, microalbuminuria develops in 20-40% of both IDDM and NIDDM patients. The underlying physiology of microalbuminuria and its effect on clinical outcome in diabetes mellitus is unclear. However, persistent microalbuminuria may reflect a systemic, endothelial and vascular disorder rather than reflect only glomerular structural abnormalities⁸. The present study is carried out to assess HbA1c, lipid profile and urine microalbumin in Type 2 diabetic patients.

MATERIALS AND METHODS

Study design: Prospective case control study was conducted.

Setting: This study was conducted at Biochemistry department with collaboration with Nephrology department. We included A total of 60 (30 type 2 diabetic patients, and 30 healthy controls) age and sex matched subjects were participated in the study by giving informed consent form from government General hospital, Kurnool. Patients with chronic renal failure, glomerular nephritis due to other systemic conditions and hypertensives were excluded from the study.

Sample collection and analysis: After an overnight fast of 12 to 14 hrs, 5 ml blood was collected by venipuncture. 2ml of blood was collected in anticoagulant (EDTA and fluoride) vacutainer. The remaining 3ml is taken into another test tube and allowed to clot. Serum and plasma were separated. The fasting blood sugar by GOD-POD method and Glycated Hemoglobin by Micro column method on RA-50 instrument, Lipid profile was estimated and patient is given a clean container without preservative and early morning mid stream urine sample (10ml) was collected.

Selection of cases for microalbumin test: Type 2 diabetic patients (NIDDM) were screened for overt proteinuria by strip Test. Those cases which were negative for Strip test were taken up for microalbumin study.

Statistical analysis: All values obtained will be expressed as Mean (± SEM). Unpaired two-tailed student t-test will be performed to compare the difference in the means between controls and study group. A ‘P’ value <0.05 will be considered as statistically significant. Statistical Analysis will be done by using Microsoft excel spread sheets.

RESULTS

A total number of 60 subjects, 30 healthy controls (Males: 18, and Females: 12) and 30 cases (Type 2 diabetic patients: Males: 19, and Females: 11) were include in the study.

Table1: shows comparison of fasting blood glucose, Glycosylated haemoglobin (HbA1c), Urinary microalbumin, Lipid profile in between cases and controls.

Table 2: shows the correlation between the various parameters

DISCUSSION

In the present study we considered 60 subjects, including 30 T2DM patients and 30 controls. We estimated HbA1c, lipid profile and urinary microalbumin in random urine sample. There was a significant increase in the FBS levels and HbA1c levels in diabetic patients when compared to the control group. The mean FBS level in diabetic patients was 182.4 ­± 13.62 mg /dl, and in the controls, it was 92.76 ±4.37 mg/dl. Our findings are comparable with the previous studies done by Meigs jb et al⁹, who have found that there was a significant association between FBS levels with the severity of diabetic nephropathy. The mean HbA1c levels in diabetic patients were 9.043 ± 1.33 % and in the controls, it was 5.95 ± 0.14%. Our findings are comparable with the previous studies done by” Nathan DM et al,¹⁰ who have observed increased HbA1c levels in diabetic patients when compared to the control group. Studies have also shown that in patients with type 2 diabetes mellitus, every 1%increase in HbA1c would result in an increase in the micro vascular complications (such as diabetic nephropathy) by 37%. The findings of the present study and the previous studies show that hyperglycemia, as indicated by the increase in the FBS and HbA1c levels, is a potent predictor of progression of diabetic nephropathy. The possible mechanism is hyperglycemia leads to glycation of virtually all proteins, resulting in the formation of advanced glycation end products. These advanced glycation end products induce cross linking of collagen and other extracellular matrix proteins in many tissues including arterial vessel walls. Hyperglycemia-induced vascular injury leads to increased glucose flux through the polyol pathway, resulting in cellular damage, thereby resulting in the various micro vascular and macro vascular complications. HbA1c is also shown to have a special affinity for oxygen thereby causes tissue anoxia and plays a role in causation of micro and macroangiopathy. The interaction of advanced glycation end products and their receptors have been implicated as mediators of micro vascular permeability, ischemia and angiogenesis. In the present study the mean total cholesterol level in diabetic cases was 193.4 ±10.73 mg/dL and in controls it was 164 ± 6.5 mg/dL. In the present study serum total cholesterol levels corresponds to observations made by Mogensen et. al,¹¹ in diabetic nephropathy patients. The mean triglyceride level in diabetic patients was 196.6 ± 18.26 mg/dL, and in controls it was 135.86 ± 10.80 mg/dL, this increased triglyceride values were comparable with study done by Magda.S et al,¹² and Cederholm et al,¹³ in diabetic nephropathy patients when compared to control group. In the present study, the mean microalbumin levels in urine, in diabetic patients was 94.10 ± 12.80mg/l and in the control group it was 18.86 ± 1.50 mg/l. There was a significant increase in the microalbumin levels in urine in diabetic patients when compared to the control group. The findings of the present study and the previous studies show that microalbuminuria is strongly related to the degree of hyperglycemia, which leads to the formation of advanced glycation end products. These advanced glycation end products result in the various micro vascular complications. In the present study, we found that there was statistically significant correlation between the various parameters i.e., FBS, HbA1c, total cholesterol, triglyceride, and microalbuminuria. We found positive correlation microalbuminuria with FBS, HbA1c, total cholesterol, and triglyceride. Our findings are comparable with previous studies done by Meig jb et.al,⁹ Nathan DM et al,¹⁰ that the poor control of blood sugar and microalbuminuria increase the risk for the development of nephropathy. Early diagnosis and prompt treatment in these patients can reduce the onset and progression of nephropathy.

CONCLUSION

Microalbuminuria in T2DM patients is associated with hyper lipidemia. This association may represent a risk factor for cardiovascular disease and may contribute to the progression of renal disease. Early detection and treatment of diabetic nephropathy prevent development of end stage renal disease which is a major cause of morbidity and mortality in diabetic patients, and also improve the quality of life and increase life expectancy.

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