Medicine

OBSERVATIONAL STUDY

Adolescent BMI at Northern Israel: From Trends, to

Associated Variables and Comorbidities, and to
Medical Signatures
Yossy Machluf, PhD, Daniel Fink, MD, Rivka Farkash, BSc, MPH, Ron Rotkopf, PhD,
Avinoam Pirogovsky, MD, MHA, Orna Tal, MD, MHA, Tamar Shohat, MD, MPH,
Giora Weisz, MD, Erez Ringler, MD, David Dagan, MD, MHA, and Yoram Chaiter, MD, MSc

Abstract: The increasing prevalence of abnormal body mass index females). Underweight, exclusively in males, was associated with
(BMI), mainly obesity, is becoming a significant public health problem. increased risk for endocrine disorders, proteinuria, and cardiac dis-
This cross-sectional study aimed to provide a comprehensive view of orders. Hierarchical clustering analysis revealed the intricate relations
secular trends of BMI, and the associated socio-demographic variables between gender, BMI, and medical signatures. It brought to light novel
and comorbidities among adolescents with abnormal BMI. Individuals clusters of diseases that were abundant among populations having
of the study population were born mainly between 1970 and 1993, and above-normal BMI or underweight males. Furthermore, above-normal
were examined at 16 to 19 years of age during the years 1987 to 2010, at BMI was associated with a lower rate of cardiac anomalies and
1 conscription center in the northern district of Israel. scoliosis/kyphosis, whereas being underweight was associated with a
The study population included 113,694 adolescents. Univariate and lower risk for hypertension and flat foot.
multivariable logistic regression models were used to investigate the This study provides a reliable and in-depth view of secular trends in
associations between BMI categories, socio-demographic variables, and height, weight, and BMI of male and female adolescents. It supports
medical conditions. previous associations between abnormal BMI and demographic vari-
A downward trend in the prevalence of normal BMI among both ables and comorbidities, while uncovering novel associations, mainly
male and female adolescents was obtained, while trends of overweight regarding medical signatures of each gender–BMI group. This might
and obesity (in both genders) and underweight (only among females) lead to better monitoring, early detection, prevention, and treatment of
rose. Socio-demographic variables such as religion, education, family- various conditions associated to abnormal BMI categories and gender
related parameters, residential environment, country of birth, and origin groups.
were all associated with different risks for abnormal BMI. Obesity was (Medicine 95(12):e3022)
associated with higher risk for hyperlipidemia, endocrine disorders
(only in males), knee disorders, and hypertension type I þ II (in both Abbreviations: ADHD = attention deficit hyperactivity disorder,
genders). Overweight was associated with knee disorders (only in ANOVA = analysis of variance, BMI = body mass index, BP =
blood pressure, CI = confidence interval, FCC = Functional
Editor: Claudio Chiesa. Classification Code, FUSSR = former Union of Soviet Socialist
Received: October 26, 2015; revised: February 11, 2016; accepted: Republics, HMO = Health Maintenance Organization, ICD =
February 12, 2016. International Classification of Diseases, IDF = Israel Defense
From the Medical Corps, Israel Defense Forces (IDF) (YM, DF, AP, ER,
DD, YC), Tel HaShomer; The Weizmann Institute of Science (YM, RR), Forces, OR = odds ratio, SD = standard deviation, SE = standard
Rehovot; Shaare Zedek Medical Center (DF, RF, GW), Jerusalem; error, SES = socio-economic status.
Schneider Children Medical Center (AP), Petach Tikvah; Assaf Harofeh
Medical Center (OT), Zerifin; Israel Center for Disease Control (TS),
Ministry of Health, Tel Aviv; Sackler School of Medicine (TS), Tel Aviv
University, Tel Aviv, Israel. INTRODUCTION
Correspondence: Yoram Chaiter, Israel Defense Forces, Pinsker 72 Street, besity in the young population is a worldwide epidemic,1
Haifa 3271214, Israel (e-mail: chaiter@bezeqint.net).
YM and YC conceived the conception and design of this study, as well as
have full access to all the data in the study and take responsibility for the
O threatening the long-term health and wellbeing of children
and adolescents,2 and warranting further evaluation and treat-
integrity of the data and the accuracy of the data analysis. YM, YC, and ment.3,4 Children5– 8 and adolescents9 with obesity have a
RF were involved in acquisition/collection and assembly of data. YC, greater likelihood of becoming adults with obesity. Over the
YM, and DD were involved in critical revision for important intellectual
content. RF, YC, YM, RR, and DF performed the statistical analysis. past 30 years, the prevalence of overweight or obesity among
YM, YC, RF, GW, and DD provided administrative, technical, or logistic American children and adolescents has increased dramatically,
support. All authors were involved in analysis and interpretation of the as evidenced by diverse studies, such as the National Health and
data, drafting of the article, and final approval of the article. In addition, Nutrition Examination Survey (NHANES),10,11 Bogalusa12 and
all authors agree to be accountable for all aspects of the work in ensuring
that questions related to the accuracy or integrity of any part of the work others.13 If past obesity trends continue unimpeded, a dramatic
are appropriately investigated and resolved. negative effect on US population life expectancy is fore-
The authors have no funding and conflicts of interest to disclose. casted.14 Data on the prevalence and long-time trends of obesity
Supplemental Digital Content is available for this article. among adolescents worldwide are scant.15 Although current
Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved.
This is an open access article distributed under the Creative Commons trends in obesity prevalence among US adolescents are under
Attribution-NonCommercial-NoDerivatives License 4.0, where it is debate, there is wide agreement that the prevalence of obesity is
permissible to download, share and reproduce the work in any medium, too high,16 and greater than that in European countries.17 High
provided it is properly cited. The work cannot be changed in any way or and increasing prevalence of overweight and/or obesity among
used commercially.
ISSN: 0025-7974 adolescents has also been found across European countries such
DOI: 10.1097/MD.0000000000003022 as Italy,18 Scotland,19 Sweden,20 Portugal,21 Spain,22 and

Medicine  Volume 95, Number 12, March 2016 www.md-journal.com | 1

Machluf et al Medicine  Volume 95, Number 12, March 2016

Israel23–25 (and the list continues to grow). Other studies have 1987 until 2010 (24 years), were included in the initial study
indicated that in some countries, the prevalence rates of obesity population. The study population consisted of conscripts who
and overweight have reached a plateau, but a very high one.26,27 were born mainly between 1970 and 1993. To ensure a uniform
An elevated body mass index (BMI) in childhood or medical baseline, we focused on conscripts who completed the
adolescence has been associated with diverse socio-demo- medical profiling process at the age of 16 to 19 years, and had
graphic characteristics, such as gender, ethnicity, socio- valid height and weight measures. To analyze trends (over years
economic status (SES), education, and geographical of birth) of the medical parameters, a minimum cutoff of 1,000
parameters, as well as family functioning and weight-related conscripts per gender per year was determined.
attributes and behaviors,23,24,28–32 with an increased risk of
diverse psychological and physical diseases (or even death) in Definitions
concurrent or later life.25,30,33– 43 Previous studies of Israeli BMI categories were defined according to gender-related
adolescents25,37,44 –48 established the higher risks of prehyper- percentiles for 17-year-old BMI on growth charts of the Israeli
tension, hypertension, diabetes, hyperlipidemia, joint con- Ministry of Health, similarly to the approach of the US Centers
ditions of the lower extremities (hip, ankle, and knee for Disease Control and Prevention.57 As opposed to the
disorders), and coronary heart disease among overweight and International Obesity Task Force definitions,58,59 these also
obese recruits, whereas underweight was associated with bron- include the underweight group, which is of high interest in this
chial and lung conditions (including asthma), scoliosis, intes- study. The actual definitions were as follows: obesity—above
tinal conditions, and emotional disorders. Morbidity and the 95th percentile (>28.2 and >29.6 kg/m2 for males and
mortality rates from diseases attributable to obesity are expected females, respectively); overweight—the 85th to 95th percentiles
to rise in the near future.11,42,49– 51 (25.0–28.2 and 25.2–29.6 kg/m2, respectively); and under-
Less attention has been focused on being underweight. The weight—below the 5th percentile (<17.6 and <17.2 kg/m2,
prevalence of underweight BMI among children and adoles- respectively). The median age (and interquartile range; mean
cents in the United States is declining, especially among:  standard deviation [SD]) of males and females was 17.36
children, females, and mainly until 2006.52 Whereas in Italy (17.08–17.91; 17.57  0.74) and 17.24 (17.02–17.64;
the prevalence of thinness among adolescents has declined 17.39  0.62), respectively (see Supplemental Content 3,
(although it increases with age in females),18 in Israel it is http://links.lww.com/MD/A755, which demonstrates the age
steadily increasing.23,25 Underweight is also associated with and BMI distributions of the study population).
functional limitations, though these are less likely to affect an The detailed definitions and examples of the medical
individual’s general health.30 Underweight adolescents may conditions used in this study have been described in detail
also suffer from negative body image and/or psychiatric dis- elsewhere56,60 (see also Supplemental Content 4, http://
orders, which lead to disturbed eating behavior53,54 and/or links.lww.com/MD/A755, which describes the criteria for the
neuroendocrine dysfunction. diagnosis of each medical condition). Briefly, 26 medical
Despite the abundance of research on diverse weight- conditions, representing approximately 90% of all FCCs com-
related associations among adolescents, there is a need for monly assigned to Israeli adolescents,56 were analyzed in
further studies in such pediatric population over a long period. relation to BMI groups. Most of these conditions were also
Such studies should look systematically, comprehensively, and previously described as being associated with BMI in other
in depth at all BMI categories, and analyze possible associations studies, mostly in separate, but not group analyses (see ‘‘Intro-
with a wide range of familial and socio-demographic variables, duction’’ and ‘‘Discussion’’ sections). Nevertheless, the selec-
as well as medical conditions. Here, we analyzed trends in tion of medical conditions was not limited to previously studied
weight, height, and BMI categories, the associated socio-demo- ones, but to those with a possibly sound hypothesis (at the
graphic variables, and coexisting comorbidities among Israeli epidemiological, cellular, or molecular level). We wished to
adolescents, who were mainly born between the years 1970 and investigate whether such established associations also exist in
1993 and were examined by the Israel Defense Forces (IDF) our study population, whether novel associations might be
medical committee at 1 conscription center in northern Israel. uncovered, and how such associations are related to each other.

METHODS Statistical Methods

Characteristics, such as weight, height, and BMI, were
Study Population evaluated by prevalence rates (proportions), means  SD/errors,
Adolescents in Israel are obliged to service by law. The and medians with interquartile ranges, for males and females.
National Military Service Act requires all 17-year-old Israelis to Univariate analyses included chi-squared tests to compare
present themselves to a local recruitment center (see Supple- categorical variables between BMI categories. Continuous vari-
mental Content 1, http://links.lww.com/MD/A755, which ables were compared using 1-way analysis of variance
describes the law and the populations that are exempt from (ANOVA) or Kruskal–Wallis test. Stratification by variables
service). At the end of the medical process, a medical profile was also conducted in light of criteria of the Israeli National
and appropriate Functional Classification Codes (FCCs) are Bureau of Statistics. Trends over the years of mean height,
assigned for each recruit (see Supplemental Content 2, http:// weight, and BMI were assessed by Spearman correlation, and
links.lww.com/MD/A755, which describes in detail the medical further confirmed by linear models. Temporal trends of BMI
process resulting in data acquisition and its recording to the categories prevalence rates were examined by linear-by-linear
computerized database). association tests. The choice of a parametric or nonparametric
Only the northern recruitment center of Israel was chosen test depended on the distribution of a continuous variable. A P
due to its stringent assessment and the reliability of the medical value below 0.05 was considered statistically significant.
data.55,56 All subjects who had an electronic record in the Multivariable logistic regression models were run to inves-
computerized medical database, from its establishment in tigate the associations between BMI categories and each of the

2 | www.md-journal.com Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved.
Medicine  Volume 95, Number 12, March 2016 Adolescent BMI: From Trends to Medical Signatures

medical conditions tested in the study. For each medical RESULTS

condition (outcome), a separate model was run. Each model
was performed in 2 blocks. Block 1 included BMI categories Study Population
(underweight, overweight, and obesity using normal BMI as The initial study population consisted of 158,255 con-
reference group), considered as main effects in this study, scripts. Inclusion criteria were completion of the medical
which were forced into the models using the ‘‘enter’’ method. evaluation process, as evidenced by valid medical profile;
In block 2, a further adjustment was performed for potential completion of the medical process at the age of 16 to 19
clinical and socio-demographic characteristics, which were (inclusive) years; and available data on both weight and height
associated with BMI (Table 1), using ‘‘LR forward stepwise’’ measures. Thus, 29,227 subjects who had not completed their
method. Candidate variables for entrance to the model were medical evaluation at all, as well as 12,049 subjects who had
country of birth (reference group: born in Israel), country of completed their medical evaluation, but not at 16 to 19 years of
origin (Israeli origin), year of birth (1986–1990), religion age, and 3,285 who answered the first 2 criteria but lacked
(Jewish), level of education (12 years), intelligence score readings of height and/or weight, were all excluded (see
(median score), residential environment (urban), family size Supplemental Content 5, http://links.lww.com/MD/A755,
(2–3 children), and blood pressure (BP) index (normal BP). which portrays the socio-demographic characteristics of the
Only those variables for which most of the population had a excluded and included populations) leaving a total of 113,694
valid value were tested. Therefore, SES (the 10 SES adolescents who formed the final study population (71.85% of
categories, based on the Israeli Central Bureau of Statistics’ the initial population): 66,569 (58.6%) males and 47,125
classification, were grouped into low, medium, and high SES (41.4%) females. Of these, 99.8% were born between 1970
as described previously)23 was omitted, but education, resi- and 1994, and more specifically, 97.4% were born between
dential environment, and family size, which may be viewed 1972 and 1993 (the period selected for the trends analysis, in
as mediator variables related to SES, were included. To deal light of the criteria described in the ‘‘Methods’’ section).
with characteristics that included more than 2 categories,
dummy variables were created for all categories except the General Trends
reference group and were added to the model as covariates. For clarity, ‘‘increase’’ and ‘‘decrease’’ are used in the
For example, 2 BP-related dummy variables were created: following to describe trends or changes in average (Figure 1) or
prehypertension and hypertension I þ II, and were added to prevalence-rated (Figure 2) height, weight, BMI (Figure 1), and
the model, where the ‘‘normal BP’’ was the reference group. BMI categories (Figure 2) in males and females.
The criterion for entrance into the model was a univariate The males’ average height did not change dramatically
probability value of P < 0.05, and P > 0.10 for removal over the period of 22 years, whereas a slight though significant
from the model. All analyses were performed separately decrease in females’ average height was observed (Figure 1A).
for males and females. Calibration of the model was assessed A significant increase in average weight was observed in both
with a Hosmer–Lemeshow goodness-of-fit statistic.61 Odds genders, being more pronounced among males (Figure 1B).
ratios (OR) and 95% confidence intervals (95% CIs) were Consequently, a significant increase in average BMI was
calculated. obtained in both genders, mainly among males, in terms of
The discriminatory power of the models was examined trend size and duration (Figure 1C). The year of birth 1981 was
using C statistics, whereas C value ranges from 0.5 (indicating the first year in which the average BMI of males was higher than
that the model’s predictions are not better than chance) to 1.0 that of females (Figure 1C). All these trends are particularly
(the model always assigns higher probabilities to correct cases evident since early and mid-1980s among males and females,
than to incorrect ones). C values of 0.7 to 0.8 are considered to respectively. Independent analysis by separate linear models for
show acceptable discrimination, values of 0.8 to 0.9 to indicate each of these 3 variables and year of birth further support these
excellent discrimination, and values of 0.9 to show outstand- findings (data not shown).
ing discrimination.61 A 2-sided P value below 0.05 was con-
sidered statistically significant. All analyses were performed BMI Category Trends
separately for males and females, using the SPSS version 20.0
A significant downward trend in the prevalence of normal
statistical package (SPSS, Inc., Chicago, IL).
BMI was observed in both male (P < 0.0001) and female
(P < 0.0001) adolescents (Figure 2A). A significant upward
Hierarchical Clustering trend in the prevalence of underweight BMI was observed
ORs, presented in Table 2, were transformed following among females (P < 0.0001), with 2 peaks: at years of birth
these conditions: statistically nonsignificant (P > 0.05) ORs 1975 (5.9%) and 1984 (8.5%) (Figure 2B). Significant upward
were transformed into 0; statistically significant ORs smaller trends (P < 0.0001) in the prevalence of overweight (Figure 2C)
than 1 were transformed into 1/OR whereas those bigger than and obese (Figure 2D) BMI were observed in both genders.
1 were not transformed. Hierarchical clustering of the ORs of Whereas the prevalence of overweight increased gradually from
the different medical conditions (only those comprising over the early 1980s, that of obesity increased mainly from the mid to
0.1% were taken into account) and gender–BMI groups was late 1970s, in both genders. The prevalence of underweight and
performed in Partek1 Genomics Suite1 software, version 6.6# overweight BMI was higher among females, while that of
2014 (Partek Inc., St. Louis, MO) with Pearson dissimilarity and obesity (and normal BMI) was higher among males.
complete linkage.
Association With Socio-Demographic
Institutional Review Board Approval Parameters
The IDF Institutional Board and Helsinki Committee The relationships between prevalence of BMI categories
approved the study on the basis of preservation of participants’ and familial/socio-demographic parameters were examined
anonymity. (Table 1).

Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. www.md-journal.com | 3
Machluf et al Medicine  Volume 95, Number 12, March 2016

FIGURE 1. Trends of height (A), weight (B), and body mass index (C) among adolescent males (black square) and females (gray square)
who were born between the years 1972 and 1993. Data are shown as mean values, I bars indicate standard errors (SE), while spearman
correlation parameters (R and P value) are also indicated. A moving average trendline of 3 y period is presented.

Stratification by 5 years of birth revealed a significant males), and by a negative trend in the prevalence of normal BMI
increase in the average BMI in both male and female subjects (both genders). The prevalence of being underweight initially
(from 1976 to 1980), accompanied by trends of increasing rose—in males until 1976 to 1980 and in females until 1981 to
prevalence of both obesity (both genders) and overweight (only 1985, and then declined. Stratification by season of birth

4 | www.md-journal.com Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved.
Medicine  Volume 95, Number 12, March 2016 Adolescent BMI: From Trends to Medical Signatures

FIGURE 2. Trends of normal (A), underweight (B), overweight (C), and obesity (D) body mass index among adolescent males (black
square) and females (gray square) who were born between the years 1972 and 1993. Data are shown as prevalence, I bars indicate 95%
confidence intervals (CIs), while P value for trend is also indicated. A moving average trendline of 3 y period is presented.

revealed significant differences in average BMI among both prevalence of normal BMI and underweight increased and that
genders. Differences were mainly evident in the females’ of overweight and obesity decreased. Single-offspring status
prevalence rates of underweight, which were higher among was associated with higher BMI and higher prevalence of
those born during the spring and summer. obesity and overweight. Younger and elder offspring in the
Most male (84%) and female (95%) conscripts were family were associated with a higher prevalence of obesity and
Jewish. In males, the prevalence of overweight and obesity was overweight and a lower prevalence of underweight.
lowest in the Druze recruits and highest in the Arab ones, The prevalence of normal BMI was almost identical
whereas the prevalence of underweight was almost 10 times among native Israelis and immigrants. Nevertheless, male
higher in the former compared to Arabs and Christians. A higher immigrants were less likely to be underweight and more likely
prevalence of obesity and overweight was observed among to be overweight or obese—a mirror image of female immi-
Jewish females (compared to all non-Jewish females). It should grants. Males of Asian and African origin and females of Asian
be noted that only a small proportion of the Arab and Bedouin and former Union of Soviet Socialist Republics (FUSSR) origin
populations was represented in the study population, since their had lower mean BMI, mainly due to a lower prevalence of
draft into the IDF is voluntary (see Supplemental Content 1, obesity and overweight (only in the males) and higher preva-
http://links.lww.com/MD/A755, which describes the IDF’s ser- lence of underweight. The reverse was true among males and
vice law and the populations that are exempt from service). females of American origin.
The higher mean BMI of both male and female rural To analyze the environmental effect, we focused on con-
conscripts stem mainly from a lower prevalence of being scripts of either FUSSR or Ethiopian origin, representing the
underweight in the rural population. Low SES in females most recent main immigration waves to Israel. The population
(and to a lesser extent, medium SES in males) is characterized was divided into 3 groups based on origin, place of birth, and
by a higher prevalence of all abnormal BMI categories. A strong age of immigration (Table 2). Among both genders, a longer
association between BMI and education was evident. A higher period spent in Ethiopia (immigration age, compared to Israeli
education score was associated with increased prevalence of origin) was associated with a lower mean BMI, and a decreasing
normal BMI in both genders. A lower education score was prevalence of all abnormal BMI categories, mainly in males. A
associated with a higher prevalence of obesity, underweight (in much higher prevalence of abnormal BMI was observed in
both genders), and overweight (only in females). males and females of Ethiopian origin born in Israel compared
An association between parent- and family-related to those born in Ethiopia. Among conscripts born in Israel, the
parameters and BMI, especially in males, was also noted. In prevalence of below- and above-normal BMI was higher and
general, as the number of children in the family increased, the lower, respectively, in ethnic Ethiopians compared to native

Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. www.md-journal.com | 5
6
Machluf et al

TABLE 1. Mean Body Mass Index and Prevalence of Body Mass Index Categories Among Adolescent Males and Females Stratified by Diverse Socio-Demographic Variables

Males Females

| www.md-journal.com
Prevalence (%) of BMI categories Prevalence (%) of BMI categories
Parameter Categories
n Mean (SD) 95 of CI Normal Under Over n Mean (SD) 95 of CI Normal Under Over
Obesity Obesity
weight weight weight weight weight weight
Year of birth <=1975 14,085 21.68 (3.12) 21.63-21.73 85.2 2.4 8.3 4.1 8,977 21.90 (3.24) 21.84-21.97 82.2 4.1 10.7 3.0
1976-1980 15,644 21.57 (3.26) 21.52-21.62 83.5 3.7 8.1 4.7 11,022 21.70 (3.32) 21.64-21.76 81.7 5.2 9.9 3.2
1981-1985 12,225 21.96 (3.59) 21.90-22.03 80.8 3.2 9.4 6.6 8,790 21.79 (3.68) 21.72-21.87 78.4 6.9 10.5 4.2
1986-1990 16,069 22.44 (3.96) 22.38-22.50 77.8 2.8 11.2 8.2 11,649 22.15 (3.90) 22.08-22.22 77.4 5.7 11.7 5.1
=>1991 8,546 22.81 (4.21) 22.73-22.91 74.7 2.5 12.5 10.3 6,687 22.50 (4.19) 22.40-22.60 73.9 5.6 14.3 6.2
P value for trend (Linear-by-Linear Associaon): <0.0001 0.247 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001
Season of birth Autumn 16,581 22.11 (3.63) 22.05-22.16 80.8 2.8 10.0 6.4 11,659 22.05 (3.64) 21.99-22.12 79.2 5.1 11.3 4.4
Winter 16,603 21.99 (3.58) 21.94-22.05 80.8 3.1 9.7 6.4 11,646 22.05 (3.61) 21.99-22.12 79.4 5.0 11.4 4.2
Spring 16,344 22.07 (3.67) 22.01-22.12 80.8 2.8 9.7 6.7 11,680 21.91 (3.68) 21.85-21.98 78.6 5.9 11.2 4.2
Summer 17,041 21.98 (3.61) 21.93-22.04 81.0 3.1 9.4 6.4 12,140 21.91 (3.69) 21.84-21.97 78.9 5.9 11.0 4.2
Religion Jews 55,311 22.04 (3.62) 22.01-22.07 80.9 3.0 9.7 6.4 44,337 22.00 (3.66) 21.96-22.03 78.9 5.5 11.3 4.3
Druze 3,374 21.22 (3.40) 21.11-21.34 83.0 5.4 6.9 4.7 2 22.18 (2.16) 2.78-41.59 100.0 0.0 0.0 0.0
Bedouins 2,787 22.00 (3.61) 21.87-22.14 81.7 2.1 9.4 6.7 12 22.06 (3.39) 19.91-24.22 75.0 0.0 25.0 0.0
Muslims 968 22.86 (3.75) 22.62-23.10 76.1 1.1 13.2 9.5 17 22.98 (5.76) 20.02-25.95 52.9 11.8 17.6 17.6
Circassians 505 22.55 (3.62) 22.23-22.87 77.4 1.6 14.5 6.5 0
Chrisans 488 22.98 (3.36) 22.68-23.28 76.6 0.6 15.0 7.8 70 22.38 (3.22) 21.61-23.15 77.1 4.3 15.7 2.9
Arabs 364 24.37 (4.68) 23.89-24.85 63.2 0.5 19.5 16.8 27 25.49 (5.46) 23.33-27.65 59.3 0.0 14.8 25.9
Others 238 21.43 (3.05) 21.04-21.82 88.7 2.5 5.0 3.8 218 21.02 (2.58) 20.68-21.37 86.2 6.9 6.4 0.5
Unknown 2,017 22.27 (3.66) 22.11-22.43 81.0 2.1 9.9 7.1 1,865 21.61 (3.60) 21.45-21.78 81.3 6.2 9.3 3.2
Residenal Urban 32,378 21.97 (3.68) 21.93-22.01 80.5 3.5 9.5 6.6 24,352 21.92 (3.72) 21.87-21.96 78.3 6.1 11.3 4.3
environment Rural 34,191 22.10 (3.57) 22.06-22.14 81.2 2.5 9.9 6.4 22,773 22.05 (3.58) 22.00-22.10 79.9 4.8 11.1 4.2

Copyright
Socio-economic Low 5,508 22.33 (3.95) 22.23-22.44 77.9 2.8 11.1 8.1 1,918 22.30 (4.12) 22.11-22.48 73.0 7.1 14.0 5.8

#
status (SES) Medium 16,395 22.32 (4.00) 22.25-22.38 77.3 3.4 10.8 8.5 13,213 22.07 (4.02) 22.00-22.14 76.0 6.8 11.9 5.3
High 561 22.36 (3.88) 22.04-22.68 80.4 2.3 9.4 7.8 623 22.04 (3.67) 21.75-22.33 76.6 6.3 13.2 4.0
Educaon 1-6 2,000 22.19 (4.20) 22.00-22.37 77.7 4.4 8.8 9.1 284 23.15 (4.59) 22.61-23.69 70.4 4.2 16.5 8.8
7-9 3,514 21.95 (3.62) 21.83-22.07 80.4 3.2 9.8 6.6 539 22.04 (4.20) 22.05-22.76 74.2 5.8 13.2 6.9
Medicine

10-11 16,679 22.06 (3.81) 22.00-22.12 79.5 3.3 9.6 7.6 6,179 22.27 (4.02) 22.17-22.37 75.1 6.0 13.2 5.7


12 42,351 22.03 (3.52) 22.00-22.06 81.5 2.7 9.8 5.9 39,096 21.91 (3.57) 21.88-21.95 79.8 5.4 10.8 3.9
≥13 2,004 21.99 (3.46) 21.84-22.15 81.0 3.0 9.6 6.3 1,019 22.20 (3.70) 21.98-22.43 77.4 5.4 12.2 5.0
Number of 1 2,629 22.61 (3.86) 22.46-22.76 77.4 2.2 11.8 8.5 2,423 22.02 (3.79) 21.87-22.17 77.9 6.0 12.3 3.8
children in 2-3 25,257 22.29 (3.72) 22.24-22.33 79.3 2.7 10.7 7.3 21,718 22.09 (3.74) 22.04-22.14 78.2 5.4 11.6 4.8
family 4-5 24,901 21.99 (3.58) 21.94-22.03 81.2 2.9 9.5 6.4 18,456 21.91 (3.58) 21.86-21.96 79.8 5.3 10.9 4.0
≥6 13,656 21.56 (3.40) 21.50-21.62 83.6 3.8 7.9 4.8 4,525 21.72 (3.44) 21.62-21.82 80.3 6.3 10.3 3.2

2016 Wolters Kluwer Health, Inc. All rights reserved.

Volume 95, Number 12, March 2016
 Medicine

Copyright


#
Males Females
Prevalence (%) of BMI categories Prevalence (%) of BMI categories
Parameter Categories
n Mean (SD) 95 of CI Normal Under Over n Mean (SD) 95 of CI Normal Under Over
Obesity Obesity
weight weight weight weight weight weight
Birth's order A single
2,629 22.61 (3.86) 22.46-22.76 77.4 2.2 11.8 8.5 2,423 22.02 (3.79) 21.87-22.17 77.9 6.0 12.3 3.8
offspring
Mulple
63,938 22.01 (3.61) 21.99-22.05 81.0 3.0 9.6 6.4 44,702 21.98 (3.65) 21.94-22.01 79.1 5.4 11.2 4.3
offspring
Youngest
18,991 22.29 (3.80) 22.24-22.34 78.9 2.7 10.8 7.6 15,204 22.06 (3.77) 22.00-22.12 78.7 5.4 11.3 4.7
offspring
Non-youngest
47,452 21.94 (3.55) 21.91-21.97 81.6 3.1 9.3 6.0 31,918 21.94 (3.60) 21.90-21.98 79.2 5.5 11.2 4.1
offspring
Elder offspring 21,333 22.23 (3.70) 22.18-22.28 79.8 2.7 10.3 7.3 16,495 22.04 (3.69) 21.98-22.09 78.6 5.4 11.6 4.4
Volume 95, Number 12, March 2016

Non-elder
45,236 21.95 (3.58) 21.91-21.98 81.3 3.1 9.4 6.1 30,630 21.95 (3.64) 21.91-21.99 79.3 5.5 11.1 4.2
offspring
Blood pressure Normal 16,629 20.96 (2.98) 20.92-21.01 86.4 5.1 5.8 2.7 23,108 21.24 (3.08) 21.20-21-28 83.7 6.9 7.7 1.8
Hypotension 118 21.25 (3.39) 20.64-21.87 83.1 5.9 6.8 4.2 125 21.50 (4.30) 20.73-22.26 78.4 10.4 6.4 4.8
Pre-
32,721 22.02 (3.50) 21.98-22.06 81.9 2.6 9.7 5.9 13,893 22.20 (3.61) 22.14-22-26 78.5 4.6 12.6 4.3
hypertension

2016 Wolters Kluwer Health, Inc. All rights reserved.

Hypertension
16,856 23.11 (4.07) 23.05-23.18 73.5 1.7 13.6 11.2 9,858 23.41 (4.40) 23.32-23.49 69.1 3.3 17.6 9.9
type I-II
Country of Sabra 56,739 22.01 (3.61) 21.98-22.04 80.9 3.1 9.6 6.4 38,923 22.01 (3.66) 21.97-22.04 79.0 5.3 11.3 4.4
origin Immigrants 9,830 22.18 (3.69) 22.11-22.26 80.8 2.5 10.0 6.8 8,202 21.85 (3.62) 21.77-21.93 79.2 6.3 10.8 3.6
Connent of Israel 12,183 22.02 (3.63) 21.95-22.08 80.8 3.0 9.6 6.6 3,509 22.07 (3.75) 21.95-22.20 79.1 4.9 10.9 5.1
origin Former USSR 9,967 22.31 (3.71) 22.24-22.38 80.0 2.2 10.7 7.1 8,649 21.84 (3.53) 21.77-21.92 79.6 6.0 10.9 3.5
Europe 12,275 22.11 (3.58) 22.05-22.18 81.3 2.4 9.8 6.5 10,676 22.10 (3.63) 22.03-22.17 79.9 4.5 11.1 4.6
Asia 9,362 21.87 (3.63) 21.80-21.95 80.9 3.8 9.0 6.2 7,327 21.78 (3.60) 21.70-21.87 78.7 6.4 11.2 3.6
Africa 19,911 21.89 (3.60) 21.84-21.94 81.0 3.5 9.3 6.2 14,589 21.98 (3.74) 21.92-22.04 78.3 5.9 11.3 4.4
America 2,352 22.41 (3.56) 22.27-22.56 80.2 1.7 10.9 7.2 1,989 22.42 (3.70) 22.26-22.58 78.5 3.2 13.2 5.1
Oceania 59 21.90 (2.93) 21.13-22.66 76.3 5.1 16.9 1.7 55 22.39 (3.43) 21.46-23.32 80.0 3.6 10.9 5.5
Unknown 460 22.14 (3.36) 21.83-22.44 82.2 2.0 11.5 4.3 331 22.19 (3.67) 21-79-22.59 78.9 3.3 14.2 3.6

Univariate analysis: 1-way ANOVA or Kruskal–Wallis tests were used to compare means of categories within each variable. Chi-squared test was used to compare prevalence rates of categorical
variables between BMI categories.
ANOVA ¼ analysis of variance, BMI ¼ body mass index, CI ¼ confidence intervals, SD ¼ standard deviation, USSR ¼ Union of Soviet Socialist Republics.
Significance code: all significant differences marked in bold, and level of significance is color coded: P < 0.05; P < 0.01; P < 0.0001.

www.md-journal.com |
7
Adolescent BMI: From Trends to Medical Signatures
8
Machluf et al

TABLE 2. Mean Body Mass Index and Prevalence of Body-Mass Index Categories Among Adolescent Males and Females Stratified by Origin Place of Birth and Age of
Immigration

| www.md-journal.com
Males Females
Prevalence (%) of BMI categories Prevalence (%) of BMI categories
Categories
n Mean (SD) 95% of CI Normal Under Over n Mean (SD) 95% of CI Normal Under Over
Obesity Obesity
weight weight weight weight weight weight
Birth: Israel AND Origin: Israel 12,064 22.01 (3.63) 21.95-22.08 80.7% 3.0% 9.7% 6.6% 3,414 22.05 (3.74) 21.93-22.18 79.0% 5.0% 10.9% 5.1%
Ethiopia Birth: Israel (AND
366 20.28 (3.64) 19.91-20.66 73.5% 17.5% 5.7% 3.3% 324 21.20 (4.15) 20.75-21.65 68.8% 16.7% 9.9% 4.6%
Origin: Ethiopia
Birth: Ethiopia
(Immigrated at the 327 20.03 (2.57) 19.75-20.30 86.9% 8.3% 4.3% 0.6% 222 20.59 (3.64) 20.11-21.07 77.0% 14.9% 5.4% 2.7%
age of 0-7 years old
Birth: Ethiopia
(Immigrated at the 372 19.84 (1.93) 19.65-20.04 92.5% 6.2% 1.1% 0.3% 124 20.38 (2.88) 19.86-20.89 79.8% 12.9% 6.5% 0.8%
age of >7 years old
Total Ethiopia 1,065 20.05 (2.81) 19.88-20.22 84.2% 10.7% 3.7% 1.4% 670 20.85 (3.78) 20.56-21.13 73.6% 15.4% 7.8% 3.3%
Former Birth: Israel AND
2,734 22.41 (3.76) 22.27-22.55 79.3% 1.7% 11.7% 7.4% 2,416 22.11 (3.57) 21.97-22.26 78.8% 4.4% 12.6% 4.2%
USSR Origin: FUSSR
(FUSSR) Birth: FUSSR
(Immigrated at the 2,520 22.52 (4.04) 22.36-22.67 78.8% 2.4% 10.3% 8.6% 2,284 21.90 (3.88) 21.74-22.06 77.5% 7.0% 11.3% 4.3%
age of 0-7 years old
Birth: FUSSR
(Immigrated at the 4,880 22.14 (3.48) 22.05-22.24 81.3% 2.3% 10.5% 5.9% 4,091 21.63 (3.29) 21.53-21.73 81.3% 6.4% 9.7% 2.7%
age of >7 years old
Total FUSSR 10,134 22.31 (3.71) 22.24-22.38 80.1% 2.2% 10.7% 7.0% 8,791 21.83 (3.53) 21.76-21.91 79.6% 6.0% 10.9% 3.5%

Copyright
Univariate analysis: One way ANOVA or Kruskal-Wallis tests were used to compare means of categories within each variable. Chi-square test was used to compare prevalence rates of categorical

#
variables between BMI categories.
ANOVA ¼ analysis of variance, BMI ¼ body mass index, CI ¼ confidence intervals, OR ¼ odds ratio, SD ¼ standard deviation, USSR ¼ union of soviet socialist republics.
Significance code: all significant differences marked in bold, and level of significance is color coded: P < 0.05; P < 0.01; P < 0.0001.
Medicine


2016 Wolters Kluwer Health, Inc. All rights reserved.

Volume 95, Number 12, March 2016
 Medicine

Copyright


#
TABLE 3. Odds-Ratios for Diverse Medical Conditions in the Males and Females Stratified by Body Mass Index Categories

Males Females
Medical condion OR (95% of CI) OR (95% of CI)
n (%) n (%)
Under weight Over weight Obesity Under weight Over weight Obesity
Pre-hypertension 32,721 (49.2) 0.74 (0.68-0.81) 0.98 (0.93-1.03) 0.84 (0.79-0.90) 13,893 (29.5) 0.81 (0.74-0.89) 1.20 (1.13-1.28) 1.03 (0.93-1.14)
Scoliosis/Kyphosis 19,720 (29.6) 1.67 (1.52-1.84) 0.67 (0.63-0.71) 0.50 (0.46-0.55) 11,949 (25.4) 1.68 (1.54-1.83) 0.68 (0.63-0.74) 0.49 (0.43-0.56)
Volume 95, Number 12, March 2016

Refracve errors 15,944 (24.0) 1.23 (1.11-1.37) 1.13 (1.06-1.20) 1.31 (1.22-1.41) 14,912 (31.6) 1.06 (0.97-1.16) 1.12 (1.05-1.19) 1.21 (1.10-1.33)
Hypertension type I+II 16,856 (25.3) 0.58 (0.51-0.66) 1.80 (1.70-1.90) 2.57 (2.41-2.74) 9,858 (20.9) 0.68 (0.60-0.76) 2.18 (2.05-2.32) 4.31 (3.93-4.73)
Flat foot 15,911 (23.9) 0.61 (0.54-0.70) 1.45 (1.37-1.54) 1.88 (1.76-2.02) 6,978 (14.8) 0.75 (0.66-0.85) 1.58 (1.46-1.71) 1.62 (1.44-1.83)
Mental disorders 3,652 (5.5) 1.37 (1.15-1.59) 1.02 (0.90-1.15) 1.19 (1.03-1.36) 1,058 (2.2) 1.49 (1.18-1.88) 1.00 (0.83-1.23) 1.06 (0.79-1.42)
Acve Asthma 2,921 (4.4) 1.43 (1.17-1.74) 1.04 (0.91-1.18) 1.69 (1.49-1.92) 1,661 (3.5) 1.09 (0.88-1.35) 1.18 (1.02-1.37) 1.56 (1.27-1.91)

2016 Wolters Kluwer Health, Inc. All rights reserved.

Knee disorders 2,751 (4.1) 1.28 (1.02-1.59) 1.34 (1.18-1.52) 3.75 (3.39-4.17) 1,391 (3.0) 0.99 (0.74-1.32) 2.75 (2.39-3.17) 9.45 (8.20-10.88)
Allergic rhinis 2,081 (3.1) 1.30 (1.02-1.67) 1.05 (0.91-1.22) 1.12 (0.95-1.32) 1,384 (2.9) 1.05 (0.83-1.32) 1.00 (0.84-1.18) 1.13 (0.88-1.44)
Learning disorders 1,478 (2.2) 1.39 (1.06 - 1.82) 1.39 (1.17-1.64) 1.99 (1.68-2.36) 1,035 (2.2) 1.25 (0.96-1.62) 1.32 (1.10-1.59) 2.13 (1.69-2.67)
Gastrointesnal disorders 1,282 (1.9) 1.37 (1.02-1.82) 0.89 (0.73-1.08) 1.21 (0.98-1.49) 1,080 (2.3) 1.10 (0.85-1.42) 1.02 (0.84-1.23) 1.30 (0.99-1.71)
Cardiac anomalies 999 (1.5) 2.58 (2.01-3.30) 0.72 (0.57-0.92) 0.65 (0.48-0.89) 510 (1.1) 1.48 (1.07-2.03) 0.51 (0.36-0.73) 0.30 (0.15-0.61)
Micro-hematuria 492 (0.7) 1.69 (1.11-2.59) 1.24 (0.93-1.65) 1.36 (0.98-1.89) 284 (0.6) 1.05 (0.62-1.77) 1.53 (1.11-2.11) 1.63 (1.00-2.64)
Endocrine disorders 344 (0.5) 6.70 (4.67-9.60) 1.32 (0.90-1.93) 5.86 (4.56-7.52) 263 (0.6) 1.32 (0.80-2.18) 1.58 (1.13-2.20) 2.08 (1.33-3.26)
ADHD - Ritalin 163 (0.2) 1.62 (0.71-3.71) 2.11 (1.40-3.17) 2.22 (1.42-3.48) 126 (0.3) 1.29 (0.62-2.69) 1.06 (.062-1.81) 2.53 (1.49-4.32)
Proteinuria 161 (0.2) 4.19 (2.55-6.90) 0.56 (0.29-1.11) 1.07 (0.59-1.94) 69 (0.1) 1.22 (0.49-3.06) 0.35 (0.11-1.13) 0.92 (0.29-2.94)
Hyperlipidemia 57 (0.1) 2.89 (0.88-9.51) 1.28 (0.49-3.30) 6.20 (3.37-11.41) 58 (0.1) 0.38 (0.05-2.76) 2.12 (1.11-4.06) 2.39 (0.94-6.07)
Diabetes mellitus 47 (0.1) 1.09 (0.15-8.02) 3.05 (1.52-6.15) 2.83 (1.23-6.51) 38 (0.1) 1.73 (0.52-5.78) 2.71 (1.26-5.87) 2.29 (0.69-7.65)
Sleeping disorder 55 (0.1) 1.22 (0.30-5.03) 0.57 (0.18-1.84) 1.71 (0.73-4.02) 12 (0.0) 2.43 (0.29-20.17) 3.40 (0.85-13.62) 5.78 (1.16-28.88)

Multivariable logistic regression models were conducted to investigate the associations between body mass index and each one of the medical conditions tested in the study (separate model for each
medical condition).
CI ¼ confidence intervals; OR ¼ odds ratio.
Significance code: all significant differences marked in bold, and level of significance is color coded: P < 0.05; P < 0.01; P < 0.0001.

www.md-journal.com |
9
Adolescent BMI: From Trends to Medical Signatures
Machluf et al Medicine  Volume 95, Number 12, March 2016

Israelis. Adolescents of FUSSR origin who were born in Israel were mainly observed among males. On the other hand, pro-
were more likely to be overweight and less likely to be under- tective effects were also uncovered: lower rates of cardiac
weight, compared to both adolescents of FUSSR origin who anomalies and scoliosis/kyphosis were obtained among males
were born in the FUSSR, and native Israeli conscripts. Strati- and females with above-normal BMI, whereas being under-
fication by age of immigration of FUSSR conscripts showed a weight was associated with reduced risks of developing pre-
lower prevalence of obesity (in both genders) and overweight hypertension, hypertension type I þ II, and flat foot.
(only among females) among those who came to Israel at 8 Hierarchical clustering analysis revealed the intricate
years of age or older. relationships between gender and BMI with regard to medical
signature. Two main clusters were obtained: one encompassed
Coexistence of Medical Conditions the underweight BMI categories of both genders, and the other,
An increase in BP was correlated with an increasing the above-normal BMI categories of both genders (Figure 3).
tendency toward overweight or obesity (Table 1). The latter cluster was further divided into 2 sub-clusters based
The association between BMI categories and the most on gender classification.
common medical conditions,56 where normal BMI category It also uncovered clusters of medical conditions with
served as a reference, was analyzed (Table 3). Obesity and distinctive associations to BMI categories and gender groups
overweight were associated with diverse risks for medical (Figure 3). In general, 2 main clusters were found in which a
conditions (11 and 7 conditions in males, 10 and 11 in females, higher risk of developing a medical condition was manifested
respectively). Many of these associations were common to both among either the underweight BMI category (Cluster #1) or the
BMI categories (in that case OR was usually higher in the obese above-normal BMI categories (Cluster #2). Among the con-
category than in the overweight category). Obesity among ditions in cluster #1 were cardiac anomalies, scoliosis/kyphosis
males was associated with higher risk (arbitrarily defined as and mental disorders (in both genders), allergic rhinitis, gastro-
OR > 2.5 and P < 0.0001) for hyperlipidemia (OR ¼ 6.20), intestinal disorders, proteinuria, micro-hematuria, asthma, and
endocrine disorders (5.86), knee disorders (3.75), and hyper- endocrine disorders (in males only, the last 3 conditions are also
tension type I þ II (2.57). Knee disorders (9.45) and hyperten- more prevalent among obese and overweight females). On the
sion type I þ II (4.31) were the only strong associations found in other hand, knee disorders, hypertension I þ II and flatfoot,
females with obesity. Being overweight was mainly associated refractive errors, and learning disorders were among the con-
with knee disorders (2.75) in females only. Being underweight ditions in cluster #2. These clusters were further divided into
was associated with higher risks for medical conditions, mainly sub-clusters where the higher risk of developing a group of
in males (12 conditions, compared to only 3 in females), among medical conditions was manifested among specific gender–
which were endocrine disorders (6.7), proteinuria (4.19), and BMI categories, solely or accompanied by increased risk or
cardiac disorders (2.58). Most of the significant associations of protective effect of developing these conditions by other gen-
higher risk for developing a medical condition (Table 3) der–BMI category/ies (see Supplemental Content 6, http://
observed in the above-normal BMI populations were found links.lww.com/MD/A755, which describes and discusses in
in both genders, whereas these in the underweight population details the clusters of diseases).

FIGURE 3. Hierarchical clustering of transformed odds rations of the different medical conditions and gender–body mass index groups.
Statistically significant increased risks are denoted by red shades, while statistically significant reduced risks are denoted by blue shades,
and white demarcates nonsignificant odds ratios.

10 | www.md-journal.com Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved.
Medicine  Volume 95, Number 12, March 2016 Adolescent BMI: From Trends to Medical Signatures

DISCUSSION may be associated with younger age of menarche.74,75 Both

BMI and early puberty were associated with socio-economic
Secular Trends factors and may reflect the combined effect of genetics and
This study not only provides further support for the environment.
previously established upward trends in the prevalence of Low SES and low education level were both associated
overweight and obesity among male and female adolescents with lower prevalence of normal BMI and a higher prevalence
but also uncovered downward trends in the prevalence of of obesity and also overweight, mainly in females. These
normal BMI and mainly increasing trend of underweight (the findings further support previous studies.23,25,32,44 Low SES
latter among females), mainly since the early to mid-1980s. has been associated with reduced physical activity,76 poorer
This represents an increase in BMI extremes at the expense of education, and a less healthy diet. The more unfavorable effect
normal BMI, resulting in an increase in the average BMI. The of low SES on females might be explained by a gender-specific
underlying mechanisms (such as lifestyle changes, historic decrease in height combined with increased weight which is
events, etc.) that might explain these trends were not assessed common among adults of this SES sector.70
in this study and require further investigation. Stratification by country of origin and age of immigration
The rising prevalence of underweight among females may allowed examination of environmental effects. Among individ-
be explained, at least in part, by recently highlighted body uals of Ethiopian origin, the effect on BMI was correlated with
image issues resulting in a tendency toward the ‘‘ideal image’’ the time spent in Ethiopia. This can be explained, at least in part,
of the thinner female,62–64 coupled with a possible increase in by altered growth patterns due to nutritional and dietary habits
dieting behavior and eating disorders, as implied here (Table 3, and cultural differences in childhood.77 As noted previously,
see mental disorders) and by others.65 Preliminary analysis of even in the Israeli-born Ethiopian population, which generally
the prevalence of eating disorders among females in our study belongs to lower education and SES, there was a decline in the
population demonstrated a clear upward trend (from 0.00% to prevalence of underweight. These findings are intriguing and
0.10%, 0.23%, and 0.21% among females who were born before deserve further investigation. In contrast to Ethiopian origin, no
1981, during 1981–1985, 1986–1990, and 1991 and later, age of immigration dependency was found among FUSSR
respectively). However, the prevalence rate is low and thus immigrants, which might imply difference in adaptation to
can only partly explain the observed increase in underweight Israel due to differences in either cultural or genetic back-
females. A milder spectrum of eating behaviors that are not ground. Nevertheless, the prevalence of obesity (in both gen-
diagnosed as overt eating disorders might further affect this ders) was lower among those who came to Israel at 8 years of
trend. Since our study did not include dietary questionnaires, we age or older, from either Ethiopia or FUSSR, compared to those
cannot substantiate this hypothesis. of the corresponding origins (and also those of Israeli origin)
Interestingly, and somewhat speculatively, the 2 peaks who were born in Israel. This strongly points to a possible effect
observed in the underweight prevalence coincided with histori- of lifestyle in Israel.
cal events: the Yom Kippur War (1973–1974) and the First
Lebanon War (1982–1984), further compounded by the tense Coexistence of Medical Conditions
periods surrounding these wars. Children born during these It is not uncommon today to encounter chronic diseases
periods were subjected to considerable stress or dietary factors among adolescents that were once considered diseases of the
(of pregnant mothers or babies) which affected their neonate fifth decade, such as type 2 diabetes mellitus, essential hyper-
length/weight measures or developmental process, which cor- tension, hyperlipidemia, and others.1 This study only provides a
relates to their 17-year-old anthropometric indices.66 Further- comprehensive analysis of the medical signatures of each of the
more, waves of immigrations to Israel might have influenced BMI–gender groups, looking separately at a wide array of
BMI measurements, as immigrants—depending on their medical conditions and at the same time, the broader medical
country of origin—had different patterns of weight and disease picture. The analysis further supported known associations and
prevalence.67 uncovered novel (and surprising) ones (see further on).
As demonstrated in our study, obesity in both genders was
Socio-Demographic Parameters positively associated with hyperlipidemia, diabetes mellitus,
Genetics, cultural habits, traditional/natural versus ‘‘mod- endocrine disorders, hypertension, and active asthma. These
ern’’ diet, physically active versus sedentary lifestyle, familial associations can be explained by the more pro-inflammatory
characteristics and parental education, exposure to fashion environment in obesity, as well as hormonal changes.78–81
trends, belonging to SES, and even smoking habits68 might These associations might also pinpoint the work-up required
be among the causes for differences between religious groups, for the obese patient to determine the presence of metabolic
rural versus urban residents, and different ethnic ori- syndrome early on and treat subjects in that sub-group accord-
gins.23,32,69,70 Such background and environmental factors, as ingly.82 This and other medical signatures are discussed in detail
well as lifestyle habits, are interrelated, but each may affect in Supplementary Content 6, http://links.lww.com/MD/A755.
BMI independently, as they affect mortality.71 This study As most research on BMI has tended to focus on obesity,
further supports and extends our knowledge on socio-demo- we characterized the medical signature of all BMI categories,
graphic variables and environmental effects related to BMI including underweight, in male and female adolescents. While
among adolescents. Not only were diverse variables tested (year this study provided further support for the previously estab-
and season of birth, religious and residential environments, lished associations, with the exception of cardiac anomalies, it
education, family size, birth order, country, and continent of also uncovered novel ones. Surprisingly, in both genders,
origin were all associated with BMI), but also gender sim- obesity and overweight BMI were independently associated
ilarities and differences were obtained. with lower rates of spinal deformities and cardiac anomalies.
The downward trend of females’ average height correlates This could be related to either diagnostic issues, as these
with a similar trend of mean age of menarche in Israeli females conditions are more apparent when examining thinner individ-
born after 1970.72,73 Increased childhood and adolescent BMI uals, or medical implications, as underweight BMI may be more

Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. www.md-journal.com | 11
Machluf et al Medicine  Volume 95, Number 12, March 2016

prevalent among those suffering from cardiac anomalies due to physician has been established to address the abnormal BMI
developmental implications. Further research, in the form of epidemic and its short- and long-term morbidity.92 The aims of
noncross-sectional studies, is needed to substantiate the findings the information exchange are education, prevention, and early
and address the direction of this association and its underlying intervention in target populations. Bidirectional information
medical basis. Underweight habitus is associated with chronic exchange between the recruitment center medical committee
(systemic) illnesses and disabling conditions including genetic and the primary-care physician at the Health Maintenance
syndromes and a spectrum of connective tissue abnormalities, Organizations leads to further and deeper investigation, while
such as Marfan syndrome83 and homocystinuria, which are special attention is drawn to subjects at risk for current/future
characterized by spinal deformities, cardiac anomalies (such morbidity and mortality, for example, adolescents suffering
as mitral valve prolapse, aortic valve abnormalities, and from micro-hematuria, hypertension, or cardiac anomalies that
abnormalities of aortic root and arch), and findings in the are associated with an above- or below-normal BMI, as revealed
urine.83–88 Reduced fat mass and lower BMI are common in by this study. This project has already proved fruitful as
patients with classical homocystinuria, and in addition cysteine identification of subjects at risk has enabled further investi-
concentrations showed a positive correlation with BMI, while gation, monitoring, appropriate intervention, and prevention. In
homocysteine and methionine levels were negatively correlated the near future, educational activities will be undertaken to
with BMI.86,89 highlight the emerging significance and risks of an abnormal
On the other hand, in both genders, underweight BMI was BMI. These activities will be held at schools and community
associated with a reduced risk for flat foot, hypertension I þ II, centers in collaboration with the medical authorities and
and prehypertension, whereas above-normal BMI was associ- relevant Israeli medical associations (diabetes, cancer, and
ated with an increased risk for the 2 former medical conditions. others), targeting both the general adolescent population and
The associations to flat foot may be explained by the higher populations at risk.
burden applied to the lower extremities in the overweight and
obese categories, while lower burden is applied to the lower ACKNOWLEDGMENTS
extremities among the thinner population.90 Differences in flat
foot and hypertension frequencies may also be a result of tissue We wish to thank Prof Samuel Menahem for a fruitful
thickness, which may affect diagnosis91: flat feet might be less discussion of the manuscript, Camille Vainstein for professional
and more apparent due to thinner and thicker tissue, respect- linguistic and scientific editing services, and Ziv Ariely for
ively. Similarly, measuring BP of thin and obese subjects might graphic design.
lead to lower and higher values due to cuffs that are too wide or
too tight, respectively. While a higher risk for hypertension REFERENCES
among overweight and obese adolescents has already been 1. Ludwig DS. Childhood obesity—the shape of things to come. N
widely observed, the reduced risk for prehypertension among Engl J Med. 2007;357:2325–2327.
males with obesity is surprising. As BMI increased from normal 2. Ebbeling CB, Pawlak DB, Ludwig DS. Childhood obesity: public-
to overweight and obesity, the prevalence within the BMI health crisis, common sense cure. Lancet. 2002;360:473–482.
category of hypertension I þ II also increased (23.1%, 3. Barlow SE, Dietz WH. Obesity evaluation and treatment: expert
35.7%, and 44.1%, respectively), while the prevalence of pre- committee recommendations. The Maternal and Child Health
hypertension decreased (49.9%, 49.2%, and 45.3%, respect- Bureau, Health Resources and Services Administration and the
ively). Namely, compared to normal BMI, both overweight and Department of Health and Human Services. Pediatrics.
obese males tend to have higher BP, yet there is a higher shift 1998;102:E29.
toward hypertension I þ II at the expense of prehypertension in 4. Kohn M, Rees JM, Brill S, et al. Preventing and treating adolescent
males with obesity. obesity: a position paper of the Society for Adolescent Medicine. J
Despite the large sample size of the study population, of Adolesc Health. 2006;38:784–787.
the study’s limitations is that it was restricted to 1 recruitment 5. Freedman DS, Khan LK, Serdula MK, et al. The relation of
center, with an under-representation of certain populations (see childhood BMI to adult adiposity: the Bogalusa Heart Study.
Supplemental Content 1, http://links.lww.com/MD/A755, Pediatrics. 2005;115:22–27.
which describes the IDF’s service law and populations that
6. Deshmukh-Taskar P, Nicklas TA, Morales M, et al. Tracking of
are exempt from service). Moreover, additional information,
overweight status from childhood to young adulthood: the Bogalusa
such as waist circumference, physical activity, and other life- Heart Study. Eur J Clin Nutr. 2006;60:48–57.
style factors, such as habits and dietary intake, were not
available for analysis. We also lacked birth parameter records 7. Serdula MK, Ivery D, Coates RJ, et al. Do obese children become
obese adults? A review of the literature. Prev Med. 1993;22:
and genetic information of those born during the mentioned
167–177.
periods.
Nevertheless, the current findings of a very large nonse- 8. Whitaker RC, Wright JA, Pepe MS, et al. Predicting obesity in
lective study population of adolescents bring to light the young adulthood from childhood and parental obesity. N Engl J
importance of addressing not only the medical conditions Med. 1997;337:869–873.
associated with the obesity epidemic but also those related to 9. The NS, Suchindran C, North KE, et al. Association of adolescent
an underweight BMI, mainly among young males. Moreover, obesity with risk of severe obesity in adulthood. JAMA.
the intricate interplay of BMI and gender further strengthens the 2010;304:2042–2047.
value of gender- and weight-based approaches for research, 10. Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of overweight
diagnosis, intervention, and understanding the molecular, ana- and obesity in the United States, 1999–2004. JAMA.
tomical, behavioral, and sociological basis underlying the 2006;295:1549–1555.
commonalities and differences. 11. Ogden CL, Flegal KM, Carroll MD, et al. Prevalence and trends in
A pilot project of information sharing between the recruit- overweight among US children and adolescents, 1999–2000. JAMA.
ment center medical committee and the recruits’ primary-care 2002;288:1728–1732.

12 | www.md-journal.com Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved.
Medicine  Volume 95, Number 12, March 2016 Adolescent BMI: From Trends to Medical Signatures

12. Broyles S, Katzmarzyk PT, Srinivasan SR, et al. The pediatric 31. Wang Y, Beydoun MA. The obesity epidemic in the United States—
obesity epidemic continues unabated in Bogalusa, Louisiana. Pedia- gender, age, socioeconomic, racial/ethnic, and geographic character-
trics. 2010;125:900–905. istics: a systematic review and meta-regression analysis. Epidemiol
13. Institute of Medicine. Progress in Preventing Childhood Obesity: How Rev. 2007;29:6–28.
Do We Measure Up?The National Academies Press; 2007: http:// 32. Gross R, Brammli-Greenberg S, Rabinowitz J, et al. Disparities in
www.nap.edu/catalog/11722/progress-in-preventing-childhood-obesity- obesity temporal trends of Israeli adolescents by ethnic origin. Int J
how-do-we-measure-up. Pediatr Obes. 2011;6:e154–e161.
14. Stewart ST, Cutler DM, Rosen AB. Forecasting the effects of 33. Eriksson JG, Forsen T, Tuomilehto J, et al. Early growth and
obesity and smoking on U.S. life expectancy. N Engl J Med. coronary heart disease in later life: longitudinal study. BMJ (Clin
2009;361:2252–2260. Res ed). 2001;322:949–953.
15. Wardle J, Brodersen NH, Cole TJ, et al. Development of adiposity 34. Forsen T, Eriksson JG, Tuomilehto J, et al. Growth in utero and
in adolescence: five year longitudinal study of an ethnically and during childhood among women who develop coronary heart
socioeconomically diverse sample of young people in Britain. BMJ disease: longitudinal study. BMJ (Clin Res ed). 1999;319:1403–
(Clin Res ed). 2006;332:1130–1135. 1407.
16. Yanovski SZ, Yanovski JA. Obesity prevalence in the United 35. Lawlor DA, Leon DA. Association of body mass index and
States—up, down, or sideways? N Engl J Med. 2011;364:987–989. obesity measured in early childhood with risk of coronary heart
17. Lissau I, Overpeck MD, Ruan WJ, et al. Body mass index and disease and stroke in middle age: findings from the Aberdeen
overweight in adolescents in 13 European countries, Israel, and the children of the 1950s prospective cohort study. Circulation.
United States. Arch Pediatr Adolesc Med. 2004;158:27–33. 2005;111:1891–1896.
18. Lazzeri G, Rossi S, Pammolli A, et al. Underweight and overweight 36. Lawlor DA, Martin RM, Gunnell D, et al. Association of body mass
among children and adolescents in Tuscany (Italy). Prevalence and index measured in childhood, adolescence, and young adulthood
short-term trends. J Prev Med Hyg. 2008;49:13–21. with risk of ischemic heart disease and stroke: findings from 3
historical cohort studies. Am J Clin Nutr. 2006;83:767–773.
19. Sweeting H, West P, Young R. Obesity among Scottish 15 year olds
1987–2006: prevalence and associations with socio-economic status, 37. Tirosh A, Shai I, Afek A, et al. Adolescent BMI trajectory and risk
well-being and worries about weight. BMC Public Health. of diabetes versus coronary disease. N Engl J Med. 2011;364:
2008;8:404. 1315–1325.
20. Rasmussen F, Johansson M, Hansen HO. Trends in overweight and 38. Bibbins-Domingo K, Coxson P, Pletcher MJ, et al. Adolescent
obesity among 18-year-old males in Sweden between 1971 and overweight and future adult coronary heart disease. N Engl J Med.
1995. Acta Paediatr (Oslo, Norway: 1992). 1999;88:431–437. 2007;357:2371–2379.
21. Padez C. Trends in overweight and obesity in Portuguese conscripts 39. Freedman DS, Khan LK, Dietz WH, et al. Relationship of childhood
from 1986 to 2000 in relation to place of residence and educational obesity to coronary heart disease risk factors in adulthood: the
level. Public Health. 2006;120:946–952. Bogalusa Heart Study. Pediatrics. 2001;108:712–718.
22. Moreno LA, Mesana MI, Fleta J, et al. Overweight, obesity and 40. Freedman DS, Dietz WH, Srinivasan SR, et al. The relation of
body fat composition in Spanish adolescents. The AVENA Study. overweight to cardiovascular risk factors among children and
Ann Nutr Metab. 2005;49:71–76. adolescents: the Bogalusa Heart Study. Pediatrics. 1999;103:
1175–1182.
23. Gross R, Brammli-Greenberg S, Gordon B, et al. Population-based
trends in male adolescent obesity in Israel 1967–2003. J Aolesc 41. Andersen LG, Angquist L, Eriksson JG, et al. Birth weight,
Health. 2009;44:195–198. childhood body mass index and risk of coronary heart disease in
adults: combined historical cohort studies. PLoS ONE.
24. Meydan C, Afek A, Derazne E, et al. Population-based trends in
2010;5:e14126.
overweight and obesity: a comparative study of 2,148,342 Israeli
male and female adolescents born 1950–1993. Pediatr Obes. 42. Baker JL, Olsen LW, Sorensen TI. Childhood body-mass index and
2013;8:98–111. the risk of coronary heart disease in adulthood. N Engl J Med.
2007;357:2329–2337.
25. Levin A, Morad Y, Grotto I, et al. Weight disorders and associated
morbidity among young adults in Israel 1990–2003. Pediatr Int. 43. Steinberger J, Daniels SR, Eckel RH, et al. Progress and challenges
2010;52:347–352. in metabolic syndrome in children and adolescents: a scientific
statement from the American Heart Association Atherosclerosis,
26. Marques A, de Matos MG. Trends in prevalence of overweight and
Hypertension, and Obesity in the Young Committee of the Council
obesity: are Portuguese adolescents still increasing weight? Int J
on Cardiovascular Disease in the Young; Council on Cardiovascular
Public Health. 2016;61:49–56.
Nursing; and Council on Nutrition, Physical Activity, and Metabo-
27. van Jaarsveld CH, Gulliford MC. Childhood obesity trends from lism. Circulation. 2009;119:628–647.
primary care electronic health records in England between 1994
44. Bar Dayan Y, Elishkevits K, Grotto I, et al. The prevalence of
and 2013: population-based cohort study. Arch Dis Child. 2015;100:
obesity and associated morbidity among 17-year-old Israeli con-
214–219.
scripts. Public Health. 2005;119:385–389.
28. Neumark-Sztainer D, Wall MM, Larson N, et al. Secular trends in
45. Lusky A, Barell V, Lubin F, et al. Relationship between morbidity
weight status and weight-related attitudes and behaviors in adoles-
and extreme values of body mass index in adolescents. Int J
cents from 1999 to 2010. Prev Med. 2012;54:77–81.
Epidemiol. 1996;25:829–834.
29. Berge JM, Wall M, Larson N, et al. Family functioning: associations
46. Tirosh A, Afek A, Rudich A, et al. Progression of normotensive
with weight status, eating behaviors, and physical activity in
adolescents to hypertensive adults: a study of 26,980 teenagers.
adolescents. J Adolesc Health. 2013;52:351–357.
Hypertension. 2010;56:203–209.
30. Swallen KC, Reither EN, Haas SA, et al. Overweight, obesity, and
47. Israeli E, Schochat T, Korzets Z, et al. Prehypertension and
health-related quality of life among adolescents: the National
obesity in adolescents: a population study. Am J Hypertens. 2006;19:
Longitudinal Study of Adolescent Health. Pediatrics. 2005;115:
708–712.
340–347.

Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. www.md-journal.com | 13
Machluf et al Medicine  Volume 95, Number 12, March 2016

48. Israeli E, Korzets Z, Tekes-Manova D, et al. Blood-pressure the impact of recent immigration. Israel Med Assoc J. 2007;9:
categories in adolescence predict development of hypertension in 149–152.
accordance with the European guidelines. Am J Hypertens. 68. Grotto I, Zarka S, Balicer RD, et al. Risk factors for overweight and
2007;20:705–709. obesity in young healthy adults during compulsory military service.
49. Ogden CL, Carroll MD, Kit BK, et al. Prevalence of obesity and Israel Med Assoc J. 2008;10:607–612.
trends in body mass index among US children and adolescents, 69. Lusky A, Lubin F, Barell V, et al. Body mass index in 17-year-old
1999–2010. JAMA. 2012;307:483–490. Israeli males of different ethnic backgrounds; national or ethnic-
50. Flegal KM, Kit BK, Orpana H, et al. Association of all-cause specific references? Int J Obes Relat Metab Disord. 2000;24:88–92.
mortality with overweight and obesity using standard body mass 70. Kaluski DN, Keinan-Boker L, Stern F, et al. BMI may overestimate
index categories: a systematic review and meta-analysis. JAMA. the prevalence of obesity among women of lower socioeconomic
2013;309:71–82. status. Obesity (Silver Spring, MD). 2007;15:1808–1815.
51. Mitka M. AHA: severe obesity in US youth is increasing and 71. Lubin F, Lusky A, Chetrit A, et al. Lifestyle and ethnicity play a
difficult to treat. JAMA. 2013;310:1436. role in all-cause mortality. J Nutr. 2003;133:1180–1185.
52. Fryar CD, Ogden CL. Health E-Stat from NHANES: prevalence of 72. Flash-Luzzatti S, Weil C, Shalev V, et al. Long-term secular trends
underweight among children and adolescents aged 2–19 years: in the age at menarche in Israel: a systematic literature review and
United States, 1963–1965 through 2007–2010. 2012; http:// pooled analysis. Horm Res Paediatr. 2014;81:266–271.
www.cdc.gov/nchs/data/hestat/underweight_child_07_10/under-
73. Chodick G, Huerta M, Balicer RD, et al. Secular trends in age at
weight_child_07_10.htm (accessed June 3, 2015).
menarche, smoking, and oral contraceptive use among Israeli girls.
53. Henninghausen K, Rischmuller B, Heseker H, et al. Low body mass Prev Chronic Dis. 2005;2:A12.
indices in adolescents with obsessive-compulsive disorder. Acta
74. Currie C, Ahluwalia N, Godeau E, et al. Is obesity at individual and
Psychiatr Scand. 1999;99:267–273.
national level associated with lower age at menarche? Evidence from
54. Hebebrand J, Henninghausen K, Nau S, et al. Low body weight in 34 countries in the Health Behaviour in School-aged Children Study.
male children and adolescents with schizoid personality disorder or J Adolesc Health. 2012;50:621–626.
Asperger’s disorder. Acta Psychiatr Scand. 1997;96:64–67.
75. Mandel D, Zimlichman E, Mimouni FB, et al. Age at menarche and
55. Chaiter Y, Pirogovsky A, Palma E, et al. Medical quality control in body mass index: a population study. J Pediatr Endocrinol Metab.
conscription centers—ten years of activity. J Israeli Mil Med. 2004;17:1507–1510.
2008;5:75–79.
76. Kaluski DN, Demem Mazengia G, Shimony T, et al. Prevalence and
56. Chaiter Y, Machluf Y, Pirogovsky A, et al. Quality control and determinants of physical activity and lifestyle in relation to obesity
quality assurance of medical committee performance in the Israel among schoolchildren in Israel. Public Health Nutr. 2009;12:
Defense Forces. Int J Health Care Qual Assur. 2010;23:507–515. 774–782.
57. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, et al. CDC 77. Reifen R, Haftel L, Manor G, et al. Ethiopian-born and native Israeli
growth charts: United States. Adv Data. 2000:1–27. school children have different growth patterns. Nutrition (Burbank,
58. Cole TJ, Bellizzi MC, Flegal KM, et al. Establishing a standard Los Angeles County, CA). 2003;19:427–431.
definition for child overweight and obesity worldwide: international 78. Lu KD, Manoukian K, Radom-Aizik S, et al. Obesity, asthma, and
survey. BMJ (Clin Res ed). 2000;320:1240–1243. exercise in child and adolescent health. Pediatr Exer Sci. 2015.
59. Cole TJ, Lobstein T. Extended international (IOTF) body mass index Epub ahead of print.
cut-offs for thinness, overweight and obesity. Pediatr Obes. 79. Boutagy NE, McMillan RP, Frisard MI, et al. Metabolic endotox-
2012;7:284–294. emia with obesity: is it real and is it relevant? Biochimie. 2015.
60. Vivante A, Afek A, Frenkel-Nir Y, et al. Persistent asymptomatic Epub ahead of print.
isolated microscopic hematuria in Israeli adolescents and young 80. Fuentes E, Fuentes F, Vilahur G, et al. Mechanisms of chronic state
adults and risk for end-stage renal disease. JAMA. 2011;306: of inflammation as mediators that link obese adipose tissue and
729–736. metabolic syndrome. Mediators Inflamm. 2013;2013:136584.
61. Hosmer DW, Lemeshow S. Applied Logistic Regression. New York, 81. Ye J, Gimble JM. Regulation of stem cell differentiation in adipose
NY: John Wiley & Sons Inc; 2000. tissue by chronic inflammation. Clin Exp Pharmacol Physiol.
62. Mendonca KL, Sousa AL, Carneiro CS, et al. Does nutritional status 2011;38:872–878.
interfere with adolescents’ body image perception? Eat Behav. 82. Sun SS, Liang R, Huang TTK, et al. Childhood obesity predicts
2014;15:509–512. adult metabolic syndrome: the Fels Longitudinal Study. J Pediatr.
63. Kim S, So WY. Prevalence and sociodemographic trends of weight 2008;152:191–200e191.
misperception in Korean adolescents. BMC Public Health. 83. Chiu HH, Wu MH, Chen HC, et al. Epidemiological profile of
2014;14:452. Marfan syndrome in a general population: a national database study.
64. Neumark-Sztainer D, Palti H, Butler R. Weight concerns and dieting Mayo Clin Proc. 2014;89:34–42.
behaviors among high school girls in Israel. J Adolesc Health. 84. Rybczynski M, Mir TS, Sheikhzadeh S, et al. Frequency and age-
1995;16:53–59. related course of mitral valve dysfunction in the Marfan syndrome.
65. von Soest T, Wichstrom L. Secular trends in eating problems among Am J Cardiol. 2010;106:1048–1053.
Norwegian adolescents from 1992 to 2010. Int J Eat Disord. 85. Pearson GD, Devereux R, Loeys B, et al. Report of the National
2014;47:448–457. Heart, Lung, and Blood Institute and National Marfan Foundation
66. Farfel A, Afek A, Derazne E, et al. Anthropometric indices at age Working Group on research in Marfan syndrome and related
17 years of full-term neonates born short. Arch Dis Child. disorders. Circulation. 2008;118:785–791.
2009;94:959–961. 86. Poloni S, Leistner-Segal S, Bandeira IC, et al. Body composition in
67. Farfel A, Green MS, Shochat T, et al. Trends in specific morbidity patients with classical homocystinuria: body mass relates to homo-
prevalence in male adolescents in Israel over a 50 year period and cysteine and choline metabolism. Gene. 2014;546:443–447.

14 | www.md-journal.com Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved.
Medicine  Volume 95, Number 12, March 2016 Adolescent BMI: From Trends to Medical Signatures

87. Profitlich LE, Kirmse B, Wasserstein MP, et al. High prevalence of 90. Tenenbaum S, Hershkovich O, Gordon B, et al. Flexible pes planus
structural heart disease in children with cblC-type methylmalonic in adolescents: body mass index, body height, and gender—an
aciduria and homocystinuria. Mol Genet Metab. 2009;98:344–348. epidemiological study. Foot Ankle Int. 2013;34:811–817.
88. van Karnebeek CD, Naeff MS, Mulder BJ, et al. Natural history of 91. Riddiford-Harland DL, Steele JR, Baur LA. Are the feet of obese
cardiovascular manifestations in Marfan syndrome. Arch Dis Child. children fat or flat? Revisiting the debate. Int J Obes. 2011;35:115–120.
2001;84:129–137. 92. Machluf Y, Navon N, Yona A, et al. From a quality assurance and
89. Elshorbagy AK, Nurk E, Gjesdal CG, et al. Homocysteine, cysteine, control system for medical processes, through epidemiological trends
and body composition in the Hordaland Homocysteine Study: does of medical conditions, to a Nationwide Health Project. In: Eldin AB,
cysteine link amino acid and lipid metabolism? Am J Clin Nutr. ed. Modern Approaches to Quality Control, InTech 1. 2011:p. –282.
2008;88:738–746. ISBN: 978-953-307-971-4.

Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. www.md-journal.com | 15