1. Background
One of the long- term complications of diabetes mellitus (DM) is diabetic nephropathy (DN), and it is the leading cause of end-stage renal disease worldwide (American Diabetes Association, 2012) (1). Microalbuminuria is the first clinical detectable sign of DN and is considered as an independent predictor of diabetic nephropathy (2). In addition, microalbuminuria is a marker of the increase of cardiovascular disease (1).
Different epidemiological studies revealed marked variation in the prevalence of microalbuminuria in Type 2 diabetic patients, ranging from less than 10% in the United Kingdom (3), 36.3% in Southern India (4), 40.8% in Albania (5), and to more than 41% in China (6).
The prevalence of diabetes is increasing worldwide, particularly in developing countries (7). Among the developing countries, Iran is a leading country with the highest number of diabetic patients. Moreover, further rising is expected in this country in the coming years (8). Hence, studies on diabetes related complications are essential to reduce preventable burden of diabetes. To our knowledge, no report had been published on the prevalence and risk factors of micro- and microalbuminuria in patients with Type 2 diabetes in north of Iran at the time of this study.
2. Objectives
The present study aimed at assessing the prevalence and risk factors associated with albuminuria in Iranian patients with Type 2 diabetes who referred to a diabetes center in north of Iran.
3. Methods
This cross - sectional study was conducted on patients with Type 2 diabetes who referred to the diabetes clinic of Razi hospital in Rasht - north of Iran- from August 2008 to January 2009. Type 2 diabetes were diagnosed and then confirmed according to American diabetes association criteria (9). Data including age, gender, duration of DM, most recent level of fasting plasma glucose (FPG), systolic (SBP), diastolic blood pressure (DBP), blood urea nitrogen (BUN), and serum creatinine were collected from patients’ medical records. Hemoglobin A1c (HbA1c) was recorded as national Glycohemoglobin standardization program (NGSP), and international federation of clinical chemistry (IFCC) units. Moreover, the extent of albumin in urine was routinely measured and recorded. The study protocol was approved by the Guilan University of Medical sciences, School of medicine research and ethics committee.
3.1. Urine Analysis
Urinary albumin excretion rate (UER) per 24 hours was measured by immunoturbidimetric assay using Dako (Glostrop, Denmark) kit. Microalbuminuria was defined as ranging from 30 to 300 mg in a 24-hour urine collection. Macroalbuminuria and normoalbuminura were defined as a urinary albumin excretion of more than 300 mg /24-h and less than 30 mg/24- h, respectively. Patients with hematuria, bacteriuria, acute febrile illness, congestive heart failure, and age under 30 years were excluded.
3.2. Statistical Analysis
The quantitative variables were assessed for normality using the Kolmogorov-Smirnov test. Descriptive statistics were expressed as mean ± standard deviation. Student’s t test and Mann-Whitney test were used for continuous variables, and categorical variables were compared using the chi-square test. Risk factors associated with albuminuria were evaluated by backward stepwise logistic regression. The odd ratio and 95% confidence interval (95% Confidence Interval) were reported. Data were analyzed using SPSS Version 16, and statistical significance was set at P < 0.05.
4. Results
In the present study, out of the 225 eligible patients, 21 (9.3%) were excluded from the statistical analysis because of missing data. The mean age of 204 patients (154 females and 50 males) was 54.35 ± 0.7 years, and the duration of diabetes was 8.3 ± 0.45 years. The prevalence of microalbuminuria and macroalbuminuria were 17.2% (95% CI: 12 - 22.4) and 17.6% (95% CI: 12.4 - 22.8), respectively. The prevalence of microalbuminuria among females was 20.3%, but it was 22.5% in males.
4.1. Albuminuria and Its Associated Risk Factors
The microalbuminuric and macroalbuminuric patients had higher SBP (P < 0.01), DBP (P < 0.05), FPG (P < 0.05), HbA1c (P < 0.01), and longer duration of diabetes (P < 0.01) compared to the normoalbuminuric patients. Furthermore, the macroalbuminuric patients were older (P < 0.01), had higher BUN (P < 0.001) and serum creatinine (P < 0.001) than patients with normal albumin. The demographic and clinical characteristics of the patients are presented in Table 1.
| Parameters | Normoalbuminuria | Microalbuminuria | Macroalbuminuria |
|---|---|---|---|
| Number | 133 | 35 | 36 |
| Age (years) | 53.1 ± 10 | 55.3 ± 10.4 | 58.1 ± 8.5b |
| Female/total | 102/133 | 26/35 | 26/36 |
| Duration (years) | 7.1 ± 6.2c | 9.6 ± 5.3 | 11.5 ± 7.7 |
| SBP (mmHg) | 130.5 ± 19.1c | 138.8 ± 18 | 145.4 ± 23.5 |
| DBP (mmHg) | 77.5 ± 9.3c | 82 ± 9.9 | 83.9 ± 12 |
| FPG (mg/dL) | 165 ± 62.2c | 195.2 ± 68.5 | 200.1 ± 80.5 |
| BUN (mg/dL) | 12.9 ± 8.1 | 17.1 ± 9.2 | 27.4 ± 14.8b |
| Serum creatinine (mg/dL) | 1.1 ± 0.7 | 1.3 ± 0.8 | 1.4 ± 0.7b |
| Cholesterol (mg/dL) | 189.3 ± 63.9 | 202.4 ± 46.1 | 209.8 ± 66.1 |
| Triglyceride (mg/dL) | 180 ± 104.3 | 199.5 ± 83 | 193 ± 80.1 |
| LDL (mg/dL) | 108.5 ± 36 | 112 ± 45.9 | 128 ± 45.2 |
| HDL (mg/dL) | 44.9 ± 11 | 43.2 ± 8 | 42.8 ± 9.6 |
| HbA1c | |||
| % | 7.4 ± 2.2c | 8.4 ± 2.4 | 8.6 ± 2.8 |
| mmol/mol | 57 ± 23c | 68 ± 26 | 70 ± 30 |
The Demographic and Clinical Characteristics among the Normo, Micro, and Macroalbuminuria Groupsa
4.2. Regression Analysis
Binary logistic regression with backward elimination of risk factors revealed diabetes duration (OR: 1.032, 95% CI: 1.006-1.141, P = 0.032), DBP (OR: 1.055, 95% CI: 1.014 - 1.098, P = 0.009), and FPG (OR: 1.007, 95% CI: 1.001 - 1.013, P = 0.023) to be associated with microalbuminuria. Higher FPG (OR: 1.013, CI: 1.005 - 1.022, P = 0.003), and BUN (OR: 1.143, CI: 1.072 - 1.218, P = 0.05) were picked as the main predicators for macroalbuminuria by stepwise regression based on backward elimination (Table 2).
| Covariates | Odd Ratio | 95% CI | P Value |
|---|---|---|---|
| Microalbuminuria as a dependent variable | |||
| DBP (mmHg) | 1.053 | 1.014 - 1.098 | 0.009 |
| FPG (mg/dL) | 1.007 | 1.001 - 1.013 | 0.023 |
| Duration (years) | 1.071 | 1.006 - 1.141 | 0.032 |
| Macroalbuminuria as a dependent variable | |||
| FPG (mg/dL) | 1.013 | 1.005 - 1.022 | 0.003 |
| BUN (mg/dL) | 1.14 | 1.072 - 1.218 | 0.000 |
Backward Stepwise Logistic Regression Analysis of Micro and Macroalbuminuria Considering the Dependent Covariates
5. Discussion
Based on the results of this cross- sectional study, the prevalence of microalbuminuria and macroalbuminuria in the patients with Type 2 diabetes was found to be 17.2% and 17.6%, respectively.
Many variations in the prevalence of albuminuria have been reported by different cross- sectional and epidemiological studies 10 - 16 .The prevalence of microalbuminuria was 19.7% and 25.5% in south and north of India, respectively (10, 11). A very high prevalence of microalbuminuria was found in those Indians newly diagnosed with Type 2 diabetes (54.09 %) (12). Studies in Hong Kong revealed a prevalence of 13.4% (13) and 22.7% in young diabetic patients (14). A study by Huraib et al. in Saudi Arabia denoted a prevalence of microalbuminuria of 16.8% (15). In Kuwaiti individuals with Type 2 diabetes, the prevalence of microalbuminuria was 27.3% (16). Furthermore, few studies on Iranian patients with Type 2 diabetes revealed the prevalence of microalbuminuria to be from 14.2% to 33% (17-19). Differences in populations, the definitions of microalbuminuria, method of urine collection, and method of measurement can explain the variation in the prevalence of microalbuminuria. Differences in the ethnic susceptibility to nephropathy may also be used to explain this variation.
Similar to the study in north of India (11) and Kuwait (16), the results of the present study showed higher prevalence of macroalbuminuria than others (5, 19). This may reflect the prolonged periods of undetectable subclinical hyperglycemia, or poor diabetes control.
Although the prevalence of microalbuminuria was slightly more in males than in females, the difference was not statistically significant. Our results were similar to the findings of Varghese et al. (4) and Afkhami-Ardekani et al. (18). In contrast, some studies reported an increased prevalence of microalbuminuria in males compared to females (9, 20). Moreover, we faced a problem when using albumin creatinine ratio to compare the prevalence across genders because females had lower creatinine excretion than males and this might have affected the results (21). Therefore, we used a daily excretion rate to evaluate microalbuminuria.
In the present study, backward stepwise logistic regression analysis revealed duration of diabetes, DBP, and FPG as the independent risk factors for microalbuminuria. John et al. reported male sex, older age, longer duration of diabetes, higher plasma glucose, and raised blood pressure as risk factors of microalbuminuria (10). Age, diabetes duration, SBP, and serum creatinine were selected as predicators in a regression model by Lutale et al. (22). Various studies have found a strong association between glycemic control and microalbuminuria (23, 24), but two other studies did not find any association (17, 19). Sheng et al. revealed that microalbuminuria mainly attributed to elevated DBP and plasma glucose (25). Unlike one study (11), but similar to others (4), we did not find a significant association between HbA1c and microalbuminuria. Other factors, which had been reported to be associated with microalbuminuria, were alcohol intake (23), smoking, and HDL (19).
The results of the logistic regression analysis revealed that higher plasma glucose and BUN were risk factors of macroalbuminuria. Similar to many other studies (26, 27), our results also revealed that controlling blood glucose and maintaining an optimal blood pressure might decrease the prevalence of albuminuria.
Being a clinical based study was one of the limitations of the present study, which could have introduced some degree of referral bias.
5.1. Conclusions
The prevalence of both micro- and macroalbuminuria was high in the patients with Type 2 diabetes. Therefore, the annual screening programme for microalbuminuria should be performed for these patients. Microalbuminuria is mainly attributed to high diastolic blood pressure, high fasting plasma glucose, and longer duration of diabetes. It seems that lowering blood pressure, even in the absence of hypertension- prehypertension, and controlling blood glucose should be considered for patients with microalbuminuria. Patients with significantly high plasma glucose and higher BUN were prone to develop macroalbuminuria.
