Microalbuminuria in patients with type 2 Diabetes mellitus and its correlation with dyslipidemia

Introduction

Diabetes mellitus is characterized by metabolic abnormalities and long-term micro-andmacrovascular complications. Diabetic nephropathy is an important cause of morbidity and mortality and is now among the most common causes of end stage renal disease. However, there is an early phase of diabetic renal disease called incipient diabetic nephropathy. In this stage there is a rise in urinary excretion of albumin i.e. microalbuminuria1. But the rise is detectable only by use of sensitive assay for urinary albumin. At this stage urine is negative for macro albumin and renal function is normal by standard clinical tests. The presence of microalbuminuria precedes the development of overt diabetic nephropathy by 10 to 15 years. It is at this stage that one can hope to reverse diabetic renal disease or prevent its progression to end stage renal disease.

Risk factors for the development of diabetic nephropathy include hyperglycaemia, hypertension, dyslipidaemia, smoking, family history of diabetic nephropathy and gene polymorphisms affecting the activity of the reninangiotensin-aldosterone axis.

Dyslipidemia is one of the major risk factors for diabetic nephropathy. The relationship between alteration of serum lipids and vascular complications is more significant in diabetics than in non-diabetics amongst the general population. Lipid abnormalities will lead to microvascular and macrovascular diseases in diabetic patients². Lipoprotein abnormalities correlated with large vessel disease are seen in diabetics and non-diabetic populations, however atherogenesis is accelerated in diabetics.^3,4

As these groups of patients are at a high risk of morbidity and mortality, the need for more aggressive lipid lowering therapy have been recognized by both the National Cholesterol Education Program5 and American Diabetes Associations (ADA)⁶. The aim is to study the occurrence of microalbuminuria in patients with type 2 diabetes mellitus and to correlate its association with dyslipidemia.

Materials and Methods

One hundred patients of type 2 Diabetes Mellitus admitted to our tertiary teaching hospital, were studied. The patients were recruited from the medical wards of the hospital based on computerized random selection.

Patients were considered to be diabetic based on ADA criteria for diagnosis of diabetes mellitus were included in the study. Those following were exclusion criteria: Patients with Chronic kidney disease, Hypertension, active urinary tract infection, patients on Statins, ACE inhibitors and Angiotensin Receptor Blockers.

The selected patients were studied in detail with history and physical examination that included patient’s age, sex, age of onset and duration of diabetes,all details regarding the presenting complaints, the drugs (OHA/Insulin) patient was taking, along with the dosages, regularity and the control of diabetes as assessed by blood sugar measurement and any family history regarding diabetes.

The objectives of the study was to 1) to estimate Microalbuminuria and Dyslipidemia in patients with Type 2 DM and 2) to study the correlation between micralbuminuria and dyslipidemia in patients with Type 2 Diabetes Mellitus.

The following investigations were done in all the patients:

Urine Microalbumin. Microalbuminuria (by Immunoturbidometric test), fasting lipid profile, glycosylated haemoglobin, blood urea and serum creatinine, fasting and post-prandial blood sugar, urine routine and ultrasonography of the abdomen for evidence of renal echogenicity and size.

Immunoturbidometric test is an immunoassay for in vitro quantitative determination of microalbumin. Erbalachema Microalbumin calibrator was used to calculate microalbumin levels in all the urine samples.

Statistical methods:

Chi-square and Fisher Exact test are used to find the significance of proportion of incidence of microalbuminuria between various levels of study parameters namely, Age, Duration of DM, HbA1C, abnormal lipid profile and various complications. The odds ratio is used to find the strength of relationship between the incidence of microalbuminuria and other study parameters. P value of less than 0.05 is taken as significant. Student T test is used to find the significance of mean levels of laboratory parameters between the presence and absence of microalbuminuria.

Statistical software:

The Statistical software namely SPSS version 18 ( IBM corporation, SPSS Inc., Chicago, IL, USA) was used for the analysis of the data. Results on continuous measurements were presented on Mean-SD (Min-Max) and results on categorical measurements were presented in Frequency (Percentage). Microsoft Word and Excel have been used to generate graphs and tables.

Results

In this clinical study consisting of 100 type 2 Diabetes mellitus patients, 100 patients 56 were male and 44 females (table 1).

Of 100 patients, 46 had microalbuminuria. None in the age group of 31-40 years (7) demonstrated microalbuminuria. Of 46 patients who were in the age group 41-60 years, 13 showed microalbuminuria. Among 47 patients above age 61 years or above, 38 had microalbuminuria and it was statistically significant (Table 2).

Out of 100 patients, 64 had diabetes ≤ 5 years since diagnosis. Of them 32 were males and 32 females. 20 patients had duration of diabetes since diagnosis between 6-10 years of which 12 were males and 8 females. 16 patients had duration of diabetes since diagnosis ≥ 11 years of which 12 were males and 4 females. The mean duration of diabetes since diagnosis in the study population is 5.55 years (Table3). The incidence of microalbuminuria showed a statistically significant increase with longer duration of diabetes (p value of <0.001). 

We found 27 patients with a total cholesterol > 200 mg/dl of whom, 17 had microalbuminuria. Forty-nine patients had serum TGL > 150 mg/dl of whom 19 had microalbuminuria. Forty-three patients had serum LDL > 100 mg/dl, out of which 22 patients had microalbuminuria. Sixty-three patients had serum HDL < 40 mg/dl out of which 32 had microalbuminuria. Twenty-four patients had serum VLDL >38 mg/dl of which 6 patients had microalbuminuria. In this study, HDL is the most common deranged lipid parameter followed by triglycerides and LDL. VLDL is the least affected lipid parameter in this study (Table 5 and 6).

We found 27 patients with a total cholesterol > 200 mg/dl of whom, 17 had microalbuminuria. Forty-nine patients had serum TGL > 150 mg/dl of whom 19 had microalbuminuria. Forty-three patients had serum LDL > 100 mg/dl, out of which 22 patients had microalbuminuria. Sixty-three patients had serum HDL < 40 mg/dl out of which 32 had microalbuminuria. Twenty-four patients had serum VLDL >38 mg/dl of which 6 patients had microalbuminuria. In this study, HDL is the most common deranged lipid parameter followed by triglycerides and LDL. VLDL is the least affected lipid parameter in this study (table 5 and 6).

Correlation between microalbuminuria and lipid parameters: 

There was a statistically significant negative correlation between TGL, VLDL and microalbuminuria (Table 7).

Discussion

Type 2 Diabetes mellitus is being increasingly recognized as a disease, which is characterized by dysfunction of the endothelium. Endothelial dysfunction occurs in a generalized and widespread manner in diabetic subjects. The severity of the dysfunction is directly proportional to the age of the patient and duration of the diabetes. The clinical markers of the generalized endothelial dysfunction become manifest in several forms.

Microalbuminuria marks the onset of endothelial dysfunction related to the kidney. Microalbuminuria serves as a warning for imminent nephropathy. But its true value is that it heralds generalized endothelial dysfunction. Thus, diabetic subjects with microalbuminuria not only have ongoing progressive nephropathy but are also likely to have retinopathy, neuropathy and cardiovascular problems including coronary artery disease and hypertension. An effort has been made in this study to highlight this issue.

Even among randomly selected patients an incidence of 46% for microalbuminuria is evident. Among various other studies the prevalence of microalbuminuria ranges from 25% to 35% 8.9. A slight increase in the percentage of microalbuminuria in our study can be attributed to several factors such as large number of elderly patients, longer duration of diabetes and poor glycemic control.

Various epidemiological and cross sectional studies have reported marked variation in the prevalence of microalbuminuria.10-14 Earlier studies on Asian immigrant Indians and native Indians have suggested a high prevalence of microalbuminuria.12-14 Gupta et al reported a prevalence of 26.6% in 65 type 2 north Indian nonproteinuric patients,13 while John et al reported a prevalence of 19.7% from a tertiary hospital in Vellore, South India.¹⁵

Vijay et al reported presence of proteinuria in 15.7% among 600 type 2 diabetic patients studied at a diabetic centre in Chennai city.16 Studies in the white UK population of diabetics revealed a prevalence of microalbuminuria of 7%–9%,17-18 while it was 31% among Mexican Americans,19The prevalence among others was as follows: Pima Indians 26%,20 Nauruans 42%,127 and Hispanic Americans 35%.²¹

In our study microalbuminuria was two times more common in age group>60 years as compared to age group <60 years. There are many reasons for this phenomenon. Firstly, deterioration in the β-cell function, which occurs with increasing duration of diabetes, and is likely to contribute to worsening glycemic control. Higher values of HbA1C and longer duration of diabetes are known to be associated with increasing incidence of microalbuminuria.

In this study, out of 64 patients with duration of diabetes <5 yrs. 16 patients had microalbuminuria, out of 20 patients with duration of diabetes 5-10yrs 14 patients had microalbuminuria and out of 16 patients with duration of diabetes >10 yrs. all 16 patients had microalbuminuria indicating high prevalence of microalbuminuria with duration of diabetes.

Out of the 100 patients in the study group, 27 patients had total cholesterol > 200mg/dl,49 patients had Triglyceride levels> 150mg/dl, 43 patients had LDL > 100mg/dl, 63 patients had HDL <40mg/dl, 24 patients had VLDL > 38mg/dl. In this study the level of HDL cholesterol was the most common deranged lipid parameter followed by triglycerides and LDL. VLDL was the least affected lipid parameter in this study.

Incidence of microalbuminuria was significantly associated with total cholesterol as denoted by the P value 0.038. And a statistically significant negative correlation was observed between TGL, VLDL and microalbuminuria.

In a study, Qadir  and coworkers observed that high serum cholesterol, TGL, and LDL showed positive correlation with microalbuminuria but not with high VLDL and low  HDL levels.²² In a study by Suma and colleagues in Tumkur, Karnataka, observed no significant association between microalbuminuria and dyslipidemia.²³ Afkhami and colleagues in Iran did not find any statistically significant correlation between microalbuminuria and dyslipidemia.⁹ Mather and colleagues reported a statistically significant correlation between the prevalence of microalbuminuria and serum triglyceride levels.²⁴

Conclusion

The incidence of microalbuminuria in patients with diabetes mellitus is 46%. Incidence of microalbuminuria is significantly associated with total cholesterol levels. Statistically significant negative correlation was observed between TGL, VLDL and microalbuminuria.