Study of the Relationship between Abdominal Obesity and Micro-Albuminuria in Elderly

Results: Mean age of participants was 74.96 ± 5.603 years. Mean waist circumference in whole sample measured 96.78 ± 16.85, mean hip circumference was 106.31 ± 19.24, mean waist hip ratio measured 0.91 ± 0.09 and mean body mass index was 27.83 ± 9.8. All of waist circumference, waist hip ratio, systolic blood pressure, hypertension, diabetes mellitus, ischemic heart disease, renal disease were significantly related to micro-albuminuria. Also, fasting blood sugar, serum triglycerides and renal functions were related to micro-albuminuria, meanwhile on multivariate analysis abdominal obesity as measured by waist hip ratio was the strongest variable correlated with micro-albuminuria in elderly subjects in the whole sample. Aim: To study the relationship between abdominal obesity and micro-albuminuria in elderly subjects.


Introduction
Micro-albuminuria (MA) is defined when urinary albumin excretion level is between 30-300 mg/day [6].MA is not only a predictor of nephropathy in diabetic patients [7] but is also associated with renal functional abnormalities in non-diabetic subjects [8].
The important role abdominal versus peripheral fat distribution on urinary albumin excretion has been highlighted by various authors [9].Waist circumference which measures central obesity reflects metabolically active visceral fat [10,11], whereas Body mass index does not account for the wide variations in body fat distribution and has considerable limitations in prediction of intra-abdominal fat accumulation [12].Waist hip ratio is reported to be a more efficient predictor of mortality in older people [13] and also a better predictor of cardiovascular disease [14] than waist circumference or body mass index.
Abdominal obesity symbolizes a key component of the metabolic syndrome.The fundamental component that associates abdominal obesity to other features of the metabolic syndrome and end-organ damage are apparently due to elevated insulin levels, peripheral tissue resistance to the insulin-sensitizing action of leptin and increased macrophage infiltration in fat tissues with concomitant release of pro-inflammatory cytokines [15,16].This further decreases the functional integrity of the renal endothelial wall and lead to micro-albuminuria [9].
A cross sectional study was conducted on two hundred elderly subjects during the period from (January 2012 to December 2012).All patients were 60 years old and over, both males and females were included.
Participants were recruited from both Geriatrics and Gerontology department and Internal medicine department at Ain Shams University hospital in Cairo, Egypt.
All subjects had comprehensive geriatric assessment and cognitive assessment done, also anthropometric measurements and laboratorial measurements of fasting blood sugar (FBS), lipid profile (Total cholesterol, LDL, HDL, serum triglycerides), kidney functions (Blood urea nitrogen, serum creatinine) and assessment of albumin / creatinine ratio in urine.
Though the cardiovascular risks of obesity are widely acknowledged, less often identified is the relationship between obesity and renal function, also studies addressing old age group are lacking.So, this study is being undertaken to determine relationship between abdominal obesity and micro-albuminuria in elderly.
As regards anthropometric measurements, waist circumference (WC) and hip circumference (HC) were measured according to the World Health Organisation's data gathering protocol [17], the waist circumference was measured at the midpoint between the lower margin of the last palpable rib and the top of the iliac crest, using a stretch-resistant tape that provides a constant 100 g tension.Hip circumference was measured around the widest portion of the buttocks, with the tape parallel to the floor [18].WC and HC measurements were expressed in centimeters and Waist / Hip ratio (WHR) was calculated.

Subjects and Methods
BMI was calculated by dividing the body weight (in kilograms) by square of height (in meters).
WHO STEPS states that abdominal obesity is defined as a WHR above 0.90 for males and above 0.86 for females, or BMI above 30.0[18].As regards ACR, early morning urine samples were obtained, the amount of albumin in the sample was compared against its concentration of creatinine, to compensate for variations in urine concentration in spot-check samples [19].Micro-albuminuria is defined as ACR ≥ 3.5 mg/mmol (female) or ≥ 2.5 mg/mmol (male) [20].NICE recommends that ACR should be used in preference to other tests of proteinuria, because it offers greater sensitivity for the detection of lower, but clinically significant, levels of proteinuria [21].
As regards Co-morbidities among subjects, renal insufficiency was defined as admission values for creatinine > 1.4 mg/dl, Diabetes Milletus was defined by fasting blood glucose level ≥ 126 mg/dl or 2hours postprandial plasma glucose ≥ 200mg/dl and Hypertension as systolic blood pressure ≥ 140 or diastolic blood pressure ≥ 90 .
The collected data were coded, tabulated, revised and statistical analyzed using SPSS program (version 20).Descriptive statistics were done using mean and standard deviation for numerical parametric data and by number and percentage for categorical data.Statistical analysis was done for quantitative variables by using independent t-test in case of two independent groups, paired t-test in related samples with parametric data.Stepwise linear regression analysis used for significant clinical variables.The level of significance was taken at P value < 0.05.

Results
Analysis of baseline socio-demographic characters of subjects showed that mean age of participants was 74.9 ± 5.6 years, males represented 52% of subjects and females represented 48%.
Distributions of co-morbidities showed that hypertension followed by diabetes were the most common present co-morbidities among participants (Table 1 Significant clinical variables (Diabetes Milletus, Hypertension, renal disease, ischemic heart disease, sex, systolic blood pressure, fasting blood sugar, serum triglycerides, renal functions, WC and WHR) were all entered in a multivariate stepwise regression model which showed in the final step of analysis that abdominal obesity as presented by WHR is the most correlated variable with presence of micro-albuminuria (Table 5).

Discussion
The relation between abdominal obesity and micro-albuminuria has been investigated in this cross sectional study.Mean age of participants was 74.96 ± 5.603 years, males represented 52% of sample and females represented 48%.
As per our results central obesity as measured by WHR has been significantly associated with MA among subjects in the whole sample, also there has been a significant relation between MA, some comorbidities and some laboratorial measurements, meanwhile on multivariate regression analysis, abdominal obesity as measured by WHR was the most significantly correlated variable with MA.
Reviewing literature, several studies suggested that abdominal obesity is independently associated with MA [22][23][24][25], also some studies described the correlations among central obesity, insulin resistance and micro-albuminuria, an early sign of kidney disease and an important risk factor for overt nephropathy suggesting that abdominal obesity, may be independently associated with micro-albuminuria [26][27][28].On the contrary, other studies showed that abdominal obesity is not related to the albuminuria level [29,30].The latter studies may have been biased by factors such as a small sample size.The association between abdominal obesity and MA is attributed to elevated insulin levels, peripheral tissue resistance to the insulin-sensitizing action of leptin and increased macrophage infiltration in fat tissues with concomitant release of pro-inflammatory cytokines [15,16], which in turn decreases the functional integrity of the renal endothelial wall and lead to micro-albuminuria [9].
In the current study, Diabetes was among the co-morbidities that showed significant relation with MA among studied subjects, which agreed with results of number of studies conducted on patients with diabetes [31][32][33] reporting micro-albuminuria as an independent predictor of progressive renal disease.
Although Diabetes was significantly related to MA in this study, WHR was the most significantly correlated variable with MA, which agreed with studies signifying the role of anthropometric measurements in the identification of non-diabetic individuals at risk of developing MA [34] and also, agreed with several studies reporting that endothelial dysfunction precedes and predicts the onset of micro-albuminuria in individuals with and without diabetes [35,36].
Hypertension was also one of the co-morbidities that showed significant relation with MA among studied subjects, which agreed with results of number of studies reporting MA as an independent predictor of progressive renal disease in patients with hypertension [37].
On the other hand, Scaglione et al reported that both in normotensive and hypertensive individuals, only those with centrally located obesity but not those with peripheral obesity had elevated urinary albumin excretion rates [38].Also Chang et al study showed that systolic blood pressure was an independent predictors of MA in Asian normotensive, euglycemic male population, which signifies the importance of observing systolic blood pressure even in men without hypertension and diabetes [39].
In the current study, a significant relation between MA and ischemic heart disease was found which agreed with studies reporting proteinuria as a risk factor for cardiovascular and total mortality [4,5].
The relation between renal disease and presence of MA is well-established and is evident in our study as well as other studies which reported that micro-albuminuria is associated with renal functional abnormalities in non-diabetic subjects [8] and is a predictor of nephropathy in diabetic patients [7].
WC and WHR (measures of abdominal obesity) showed a significant association with MA in the current study whereas BMI had not, supporting that body mass index does not account for the wide variations in body fat distribution, and has limitations in prediction of intra-abdominal fat accumulation [12].Of the three measurements, only the waist-hip ratio takes account of the differences in body structure.Waist hip ratio is reported to be a better predictor of cardiovascular disease than waist circumference [14].If obesity is defined using WHR, the proportion of people categorized as at risk of heart attack worldwide increases threefold [40].
On stepwise regression analysis, significant relation between WHR, Systolic blood pressure, fasting blood sugar, serum triglycerides level and MA among subjects is being observed, suggesting a possible association between metabolic syndrome and MA and that agreed with the Third National Health and Nutrition Examination Survey (NHANES III: 1988-1994) which recommended considering MA a component of the metabolic syndrome [25].The precise pathogenetic basis of MA in metabolic syndrome is not known; it is, however, possible that microalbuminuria in metabolic syndrome reflects renin-angiotensin system activation and resultant oxidant stress and inflammation.Several investigators have shown that hypertension, dyslipidemia, and insulin resistance are associated with renin-angiotensin system activation and generation of large amounts of angiotensin II [41,42].
We did not find a significant relation between age and MA, which may be attributed to the narrow range of age in our study unlike the results of that cross sectional study conducted on Korean men in which age ranged from 20-78 years and found a significant relation with MA [39].On the other hand, sex difference showed a significant correlation with MA in the present study and that agreed with what was reported by Bhaktha et al [9].
Thus we can conclude through the present study results that Abdominal obesity is strongly associated with micro-albuminuria in Egyptian elderly which signifies the importance of weight control to prevent micro-albuminuria and renal damage.

Conclusion
Our study has some limitations.First, we undertook only a single blood pressure measurement that does not take into account day-to-day variability and white coat blood pressure effect.Second, lack of data regarding dietary habits of participants as diet represent an important risk factor for kidney diseases.

Study limitations
We are grateful to all residents, staff and participating patients.Informed consent was taken from elderly participating in this study; also an approval was taken from the head of participating departments.The study methodology was reviewed and approved by the Research Review Board of the Geriatrics and Gerontology Department, Faculty of medicine, Ain Shams University, cairo, Egypt.

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Table 3 :
Relation between co-morbidities among subjects and albumin/creatinine ratioSex difference showed a significant correlation with MA as shown in (Table4).

Table 4 :
Relation between gender and albumin/creatinine ratio

Table 5 :
The final step of multivariate stepwise regression model for significant clinical variables