Abstract

Background: Childhood obesity has become a growing health problem in Egypt
and other countries in the world. The prevalence of albuminuria is higher in obesity,
and could represent an early indicator for cardiovascular diseases (CVD) in obese
adolescents. Whether there is a real association between albuminuria and other CVD
risk factors remains a matter of debate.
Purpose: In an attempt to answer this debate question, this study aims to assess
the association of urinary albumin with central obesity, blood pressure, fasting lipid
profile, and insulin resistance in obese adolescents.
Methods: Forty obese adolescents aged 10-18 years, diagnosed with simple obesity
were recruited from the National Nutrition Institute in Egypt. Exclusion criteria were
adolescents with diabetes, kidney or liver prob-lems, and/or hormonal abnormalities.
Measurements included anthropometric assess-ment, blood pressure measurement;
and lab analysis for urinary albumin, fasting blood glucose, fasting insulin, and fasting
lipid profile. The Spearman correlation coefficient was used for statistical analysis.
Results: Statistically significant p ositive c orrelations h ave b een f ound o nly between
albuminuria and each of: duration of obesity (r=0.93, p= 0.00), waist/height ratio
(r=0.65, p=0.00), and/or systolic blood pressure (r=0.33, p= 0.041).
Conclusions: Urinary albumin has been significantly a ssociated w ith t he long-term
exposure to excess body weight, central fatness, and systolic blood pressure, but not
with diastolic blood pressure, dyslipidemia or insulin resistance in obese
adolescents. Early detection of al-buminuria can have a protective role against
future hypertension and related target organ damage in this young population. The
observations of our study may aid efforts directed to planning better health care
system for obese children and/or adolescents in Egypt.

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Hala M Abdel-Salam,Eman Okasha AMAMAE-G. Association of Urinary Albumin with Selected Cardiovascular Disease Risk Factors in Obese Adolescents. ijmhs [Internet]. 9Mar.2019 [cited 24Mar.2019];9(3):323-7. Available from: http://innovativejournal.in/index.php/ijmhs/article/view/2469
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Introduction

Obesity in childhood and/or adolescence life has become one of the most common health problems worldwide, and has been associated with metabolic syndrome in this younger population 1 , 2 . A number of chronic medical problems such as type2 diabetes, dyslipidemia, cardiovascular disease (CVD), and hypertension in children and adolescents could be attributed to obesity 3 . In adult obesity, evidence shows a significant association between albuminuria and other cardiovascular risk factors 4 . In childhood obesity, there are conflicting results; while some research work found a significant correlation between albuminuria and CVD risk factors 5 , 6 , 7 , 8 , other studies did not 9 , 10 , 11 .

Therefore, this study was conducted to re-investigate the association between urinary albumin and selected CVD risk factors in obese adolescents in Egypt, in an attempt to resolve this controversy. The results of this study may help recent interests about the addition of microalbuminuria screening to the routine assessment of cardiovascular risk factors in obese children and adolescents, for early detection and prevention of future cardiovascular and metabolic problems in this population.

Methods

2.1. Ethical consideration

This study was approved by the ethical committee of Al-Azhar University. Informed consents were obtained from subjects or from their parents before getting them involved in the study.

2.2. Subjects

Forty obese adolescents (25 boys, and 15 girls) were included in this study; they were selected from the National Nutritional Institute in Egypt. The inclusion criteria included both boys and girls, aged 10-18 year, and/or diagnosed with simple obesity, according to the BMI percentile for age and sex 12 . Full medical history taking was done, and accordingly, the exclusion criteria were secondary obesity due to hormonal abnormalities, diabetes, and liver or kidney problems. The anthropometric and clinical characteristics of the subjects are presented in Table 1 .

2.3. Measurements

2.3.1. Anthropometric measurements

Anthropometric data were interpreted and presented by using the z-score classification system which is recognized as the best method for anthropometric data analysis compared to other methods 10 . This system uses the following formula for calculating the Z-score: Z-score = (observed value - median value of the reference population) / standard deviation value of reference population 13 .

2.3.1.1. Body weight (BW)

All our participants were asked to take off shoes, all outerwear clothing, such as jackets, sweaters or sweatshirts. The participant stood on the weight scale with both feet in the center of the platform with the body upright and arms hanging at their sides naturally.

2.3.1.2. Height

First, the participants were asked to remove shoes and to stand straight, looking forward with heels close together, shoulders relaxed, and hands at sides. Then the height was measured from the right side of the participant by using a wall-mounted stadiometer. The calculated height was adjusted for age and sex, according to WHO references 12 , to determine height z-score.

2.3.1.3. Body mass index (BMI)

Body mass index was calculated for each participant by the following formula: BMI = weight (in kg) / height (in meters) 2 . Then, according to WHO charts of BMI z-score for boys and girls, the calculated BMI was plotted against the age and BMI-Z score was determined 12 .

2.3.1.4. Waist circumference (WC)

Each participant was asked to remove his/her clothes, to stand with their feet fairly close together, and to breathe normally. WC was measured using a flexible, non-stretchable tape around the waist in a horizontal position to the nearest 0.5 after normal expiration 14 .

2.3.1.5. Waist to height ratio (W/HtR)

W/HtR is a reliable method used to identify central fatness and related cardio-metabolic risks in children and adolescents. Waist circumference of each participant (in Cm) was divided by his/her height (in Cm) and waist/height ratio was then calculated 15 , 16 .

2.3.2. Blood pressure measurement

Systolic and diastolic blood pressures were measured in the sitting position using a standardized mercury sphygmomanometer with an appropriate blood pressure cuff. The data of the systolic and diastolic blood pressure were compared to the Blood pressure tables for adolescents of the fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents 17 .

2.3.3. Lab analysis

2.3.3.1. Urinary microalbumin

Morning spot urine samples collected from the children were assessed by ELIZA kits, Micro-albumin ORG5MA (ORGENTEC Diagnostika, Germany), for determination of urinary microalbumin. Immunometric Enzyme Immunoassay for the quantitative determination of Micro-Albumin in urine was done by using an immunoassay device (State fax, USA).

2.3.3.2. Fasting blood glucose (FBG)

FBG was measured by colorimetric enzymatic method GOD- POD using a fully automated biochemistry device BT 1500 (Biotecnica instruments, Italy).

2.3.3.3. Fasting insulin

Fasting insulin levels were measured by ELISA kits (Monobind, USA) using an immunoassay device (State fax, USA). After measurement of fasting insulin, homeostatic model assessment (HOMA) score was calculated for assessment of insulin resistance, according to the following formula: HOMA-IR = Fasting blood glucose (mg/dL) × fasting insulin (μIU/ mL) /405 18 .

2.3.3.4. Fasting lipid profile

Total cholesterol, serum triglyceride and high-density lipoprotein (HDL) were measured by colorimetric enzymatic method CHOD- PAP by using a fully automated biochemistry device BT 1500 (Biotecnica instruments, Italy). While low-density lipoprotein (LDL) was calculated by this equation: [total cholesterol – HDL – (triglyceride/5)] 19 .

2.4. Statistical Analysis

Data were collected, revised, coded and entered to the Statistical Package for Social Science (IBM SPSS) version 23. The Spearman correlation coefficient was used for statistical analysis. P values of less than 0.05 were considered as statistically significant. Data were presented as means ± standard deviations.

Results

As shown in table 1, the mean values of urinary albumin, fasting insulin, and insulin resistance (HOMA-IR) are higher than normal. The mean values of cholesterol, triglycerides, and LDL are above the acceptable reference range (I.e. at the border lines). As shown in Table 2 , a statistically significant positive correlation did exist between microalbuminuria and each of duration of obesity, waist/height ratio and systolic blood pressure.

Table 1 Anthropometric and clinical characteristics of the subjects
Characteristics Study group(n=40)
Age (Years) 12.48 ± 1.99
Height Z-score 0.32±1.02
Body mass index Z-score 3.21±0.44
Waist circumference Z-score 0.87±0.88
Waist/height ratio z-score 0.94±0.95
Urinary microalbumin (μg/ml) 88.35±85.21
Systolic blood pressure Z-score 0.62±1.21
Diastolic blood pressure Z-score 0.55±1.02
Fasting blood glucose (mg/dL) 95.59 ± 15.81
Fasting insulin (μIU/ mL) 44.25±34.92
Insulin resistance (HOMA-IR) 10.5±8.42
Cholesterol (mg/dL) 177.90 ± 32.79
Triglyceride (mg/dL) 114.98 ± 56.00
HDL (mg/dL) 46.90 ± 8.26
LDL (mg/dL) 107.93 ± 33.04
Creatinine (mg/dL) 0.70 ± 0.13
Data are presented as means ± standard deviationsNormal reference ranges: Albuminuria ≤ 25 μg/ml; FBG = 70- 115 mg/dl; Fasting insulin = 0.7- 25 μIU/ml; HOMA < 3; Cholesterol < 170 mg/dL; Triglyceride (10-19 years) < 90 mg/dL; HDL > 45 mg/dl; LDL < 100 mg/dL; Creatinine = 0.6-1.1 mg/dL

Table 2 Correlation between albuminuria and each of the anthropometric and the clinical parameters
Study group(n=40)
Variables Albuminuria
r P-value
Duration of obesity (years) 0.933 0.000*
Body mass index ( kg/m2) 0.293 0.067
Waist/height ratio 0.646 0.000*
Systolic blood pressure (mmHg) 0.325 0.041*
Diastolic blood pressure (mmHg) 0.274 0.087
Insulin resistance (HOMA-IR) 0.146 0.368
Cholesterol (mg/dL) 0.071 0.665
Triglyceride (mg/dL) 0.070 0.668
HDL (mg/dL) -0.094 0.562
LDL (mg/dL) 0.069 0.671
* significant p value (< 0.05)

Discussion

Obesity in children and adolescents has become a major health concern worldwide in both developed and developing societies. Childhood obesity is now considered as an independent risk factor for the development of future metabolic and cardiovascular diseases 3 . High level of urinary albumin is quite common in obese children and adolescents 20 . Whether this condition is related to other risk factors co-existing with obesity remains a matter of debate. Some studies 5 , 6 , 7 , 8 , have found an association between albuminuria and the traditional cardiovascular risk factors. The purpose of this study was to re-explore this association in a sample of Egyptian children and adolescents in an attempt to solve this debate.

The main findings of the present study were: (a) Urinary albumin in obese children and adolescents did have a significantly positive correlation with the duration of obesity (i.e. the long-term exposure to excess weight), and with the central fat distribution pattern of obesity measured by waist/height ratio. Furthermore, urinary albumin was significantly positively associated with systolic but not diastolic blood pressure. (b) Moreover, in regard with blood lipids and insulin resistance, urinary albumin showed non-significant associations with either of them.

In accordance with our study, Csernus et al. 21 , have found significantly higher levels of albuminuria in obese children compared to normal weight peers, suggesting early renal dysfunction as a consequence of obesity. Prior research work has also reported that higher incidence of microalbuminuria was significantly related to central obesity, both in obese adolescents 22 , and obese adults 23 , suggesting weight loss as an essential goal in cardiovascular risk management and prevention of renal damage in paediatric and adult obesity. Contrary to this finding, a negative association between albuminuria and childhood obesity in some studies 24 , 25 . However, there is an additional evidence supporting this finding, as central obesity has been shown to be an important risk factor for renal function abnormalities, including albuminuria 26 ; variable degrees of albuminuria have been also found to be positively correlated with the severity of obesity 27 . Furthermore, Filler et al. 28 reported a significant increase in BMI z-score in pediatric Nephrology population, with an overall BMI z-score higher than the comparable normal USA young population in the same time span. Moreover, overweight subjects have shown an increased GFR compared with lean subjects, suggesting a significant positive relation to BMI 29 . The higher prevalence of albuminuria in obese children and adolescents could be explained by the pathophysiological changes that occur in renal hemodynamics including hyperfiltration together with hyperperfusion, both of which play an important role in renal injury 30 .

In line with our results, three studies have found that microalbuminuria was associated with hypertension in obese children and adolescents 6 , 7 , 31 , 32 . In a Chinese study by Wu et al 31 , systolic but not diastolic BP was positively correlated with urinary albumin excretion in children, and those with systolic BP of 110- 130 mm Hg had significantly higher microalbuminuria than those with systolic BP ≤90 mm Hg. Furthermore, in a Korean study, Cho and Kim 32 , have found that microalbuminuria was associated with systemic hypertension in obese adolescents. Moreover, Naughty et al 6 , have also reported an association between microalbuminuria and hypertension in obese adolescents. To add , in obese adults, it was found that albuminuria has a positive correlation with blood pressure particularly with systolic BP 33 . This association could be explained by the fact that elevation in systemic blood pressure leads to endothelial damage which increases vascular permeability resulting in the development of microalbuminuria 34 .

The routine evaluation of urinary albumin was previously proposed by the European Society of Hypertension guidelines is one of the laboratory tests, for assessing target organ damage in hypertensive adult subjects 35 . In paediatric population, the European Society of Hypertension pediatric guidelines recommended the assessment of microalbuminuria to be included in clinical practice 36 . In addition, the more recent pediatric guidelines of the Canadian Hypertension Education Program also recommend the detection of urinary albumin to assess for the existence of target organ damage in children with confirmed hypertension 37 .

Our study has also shown that, urinary albumin, insulin resistance, cholesterol, triglycerides, and LDL were above the normal range in obese adolescents. However, we did not find an association between albuminuria and either of insulin resistance or blood lipids. These findings are in accordance with Rademacher et al. 38 , who have reported that the urinary excretion of Albumin is not related to insulin resistance in adolescents. Furthermore, Radhakishun et al. 10 have reported no association of microalbumiuria with impaired glucose tolerance or serum blood lipids in overweight and obese children. Moreover, Gurecká et al. 11 has reported no association between microalbuminuria and serum blood lipids in older adolescents.

Conclusion

A significant association between albuminuria and some cardiovascular risk factors, namely systolic hypertension and central obesity has been established , with no association with other cardio-metabolic risk factors, in particular, insulin resistance and dyslipidemia. Accordingly screening for microalbumiuria in obese children and adolescents may be a useful tool for early detection of subjects at risk of future systolic hypertension with anticipated target organ damage affecting the renal and the cardiovascular systems. Nevertheless, longitudinal observation studies with large sample size are needed to confirm our results.

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