Barak Gordon

Adolescent BMI trajectory and risk of diabetes versus coronary disease.

BACKGROUND The association of body-mass index (BMI) from adolescence to adulthood with obesity-related diseases in young adults has not been completely delineated. METHODS We conducted a prospective study in which we followed 37,674 apparently healthy young men for incident angiography-proven coronary heart disease and diabetes through the Staff Periodic Examination Center of the Israeli Army Medical Corps. The height and weight of participants were measured at regular intervals, with the first measurements taken when they were 17 years of age. RESULTS During approximately 650,000 person-years of follow-up (mean follow-up, 17.4 years), we documented 1173 incident cases of type 2 diabetes and 327 of coronary heart disease. In multivariate models adjusted for age, family history, blood pressure, lifestyle factors, and biomarkers in blood, elevated adolescent BMI (the weight in kilograms divided by the square of the height in meters; mean range for the first through last deciles, 17.3 to 27.6) was a significant predictor of both diabetes (hazard ratio for the highest vs. the lowest decile, 2.76; 95% confidence interval [CI], 2.11 to 3.58) and angiography-proven coronary heart disease (hazard ratio, 5.43; 95% CI, 2.77 to 10.62). Further adjustment for BMI at adulthood completely ablated the association of adolescent BMI with diabetes (hazard ratio, 1.01; 95% CI, 0.75 to 1.37) but not the association with coronary heart disease (hazard ratio, 6.85; 95% CI, 3.30 to 14.21). After adjustment of the BMI values as continuous variables in multivariate models, only elevated BMI in adulthood was significantly associated with diabetes (β=1.115, P=0.003; P=0.89 for interaction). In contrast, elevated BMI in both adolescence (β=1.355, P=0.004) and adulthood (β=1.207, P=0.03) were independently associated with angiography-proven coronary heart disease (P=0.048 for interaction). CONCLUSIONS An elevated BMI in adolescence--one that is well within the range currently considered to be normal--constitutes a substantial risk factor for obesity-related disorders in midlife. Although the risk of diabetes is mainly associated with increased BMI close to the time of diagnosis, the risk of coronary heart disease is associated with an elevated BMI both in adolescence and in adulthood, supporting the hypothesis that the processes causing incident coronary heart disease, particularly atherosclerosis, are more gradual than those resulting in incident diabetes. (Funded by the Chaim Sheba Medical Center and the Israel Defense Forces Medical Corps.).

Progression of Normotensive Adolescents to Hypertensive Adults. A Study of 26 980 Teenagers

Although prehypertension at adolescence is accepted to indicate increased future risk of hypertension, large-scale/long follow-up studies are required to better understand how adolescent blood pressure (BP) tracks into young adulthood. We studied 23 191 male and 3789 female adolescents from the Metabolic Lifestyle and Nutrition Assessment in Young Adults cohort (mean age: 17.4 years) with BP <140/90 mm Hg at enrollment or categorized by current criteria for pediatric BP and body mass index (BMI) values. Participants were prospectively followed up with repeated BP measurements between ages 25 and 42 years and retrospectively between ages 17 and 25 years for the incidence of hypertension. We identified 3810 new cases of hypertension between ages 17 and 42 years. In survival analyses, the cumulative risk of hypertension between ages 17 and 42 years was 3 to 4 times higher in men than in women. Using Cox regression models adjusted for age, BMI, and stratified by baseline BP, the hazard ratio of hypertension increased gradually across BP groups within the normotensive range at age 17 years, without a discernible threshold effect, reaching a hazard ratio of 2.50 (95% CI: 1.75 to 3.57) for boys and 2.31 (95% CI: 0.71 to 7.60) for girls in the group with BP at 130 to 139/85 to 89 mm Hg. BMI at age 17 years was strongly associated with future risk of hypertension even when adjusted to BP at age 17 years, particularly in boys. Yet, BMI at age 30 years attenuated this association, more evidently in girls. In conclusion, BP at adolescence, even in the low-normotensive range, linearly predicts progression to hypertension in young adulthood. This progression and the apparent interaction between BP at age 17 years and BMI at adolescence and at adulthood are sex dependent.

White Blood Cells Count and Incidence of Type 2 Diabetes in Young Men

OBJECTIVE Association between white blood cell (WBC) count and diabetes risk has been recently suggested. We assessed whether WBC count is an independent risk factor for diabetes incidence among young healthy adults. RESEARCH DESIGN AND METHODS WBC count was measured in 24,897 young (mean age 30.8 ± 5.36 years), normoglycemic men with WBC range of 3,000 to 12,000 cells/mm3. Participants were periodically screened for diabetes during a mean follow-up of 7.5 years. RESULTS During 185,354 person-years of follow-up, diabetes was diagnosed in 447 subjects. A multivariate model adjusted for age, BMI, family history of diabetes, physical activity, and fasting glucose and triglyceride levels revealed a 7.6% increase in incident diabetes for every increment of 1,000 cells/mm3 (P = 0.046). When grouped in quintiles, a baseline WBC count above 6,900 cells/mm3 had an independent 52% increase in diabetes risk (hazard ratio 1.52 [95% CI 1.06–2.18]) compared with the lowest quintile (WBC <5,400 cells/mm3). Men at the lowest WBC quintile were protected from diabetes incidence even in the presence of overweight, family history of diabetes, or elevated triglyceride levels. After simultaneous control for risk factors, BMI was the primary contributor of the variation in multivariate models (P < 0.001), followed by age and WBC count (P < 0.001), and family history of diabetes and triglyceride levels (P = 0.12). CONCLUSIONS WBC count, a commonly used and widely available test, is an independent risk factor for diabetes in young men at values well within the normal range.

Measured Body Mass Index in Adolescence and the Incidence of Colorectal Cancer in a Cohort of 1.1 Million Males

Background and Aims: The increasing prevalence of adolescent obesity affects adult health. We investigated the association of adolescent overweight with colorectal cancer incidence in a large cohort of males. Methods: Body mass index (BMI) was measured in 1.1 million Jewish Israeli males who underwent a general health examination at ages 16 to 19 between 1967 and 2005. Overweight was defined as BMI ≥ 85th percentile of the standard U.S. distribution in adolescence. Colorectal cancer was identified by linkage with the Israel National Cancer Registry up to 2006. The mean follow-up period was 17.6 ± 10.9 years, reflecting 19.5 million person-years. Cox proportional hazards modeling was used. Results: The prevalence of adolescent overweight increased from 9.9% to 16.8% in the first 10 and last 10 annual examination cohorts. Colon (n = 445) and rectal cancer (n = 193) cases were detected. Overweight predicted an increased risk of colon cancer [HR = 1.53; 95% confidence interval (CI), 1.17–2.02, P = 0.002] but not of rectal cancer (HR = 1.09; 95% CI, 0.38–1.73, P = 0.72). The risk was greatest for nonmucinous adenocarcinoma of the colon (HR = 1.68, 95% CI, 1.26–2.23, P = 0.001). The association of BMI ≥ 85th percentile with colon cancer was even more pronounced in analyses that were restricted to men followed until at least 40 years of age [N = 367,478; HR = 1.75 (95% CI, 1.33–2.3, P < 0.001)]. Conclusions: Adolescent overweight is substantially associated with colon cancer incidence in young to middle-aged adults. Impact: These long-term sequelae add to the urgency to seriously address increasing childhood and adolescent obesity with its attendant increasing population impact. Cancer Epidemiol Biomarkers Prev; 20(12); 2524–31. ©2011 AACR.

Population-based trends in male adolescent obesity in Israel 1967-2003.

Obesity increased monotonically from 1.2% to 3.8% of males age 17 (1967-2003). Low socioeconomic status had an independent positive effect on obesity. The likelihood of obesity had risen more steeply over time among the low socioeconomic status group than among other adolescents. Rise in obesity, standard of living, and income inequality (as measured by the Gini index) increased concomitantly.

Associations of Body Mass Index and Body Height With Low Back Pain in 829,791 Adolescents

Body mass index (BMI) (calculated as weight (kg)/height (m)²) and height are linked to the pathogenesis of low back pain, but evidence-based confirmation is lacking. We examined the prevalence of low back pain in adolescents and its association with BMI and height. Disability clauses (official military limitations related to a persons health status) indicating low back pain severity were divided according to symptoms of low back pain alone and symptoms of low back pain with objective corroborating findings. All 829,791 males and females undergoing mandatory premilitary recruitment examinations since 1998 were included. Logistic regression models assessed the relationships of BMI and height with low back pain. Prevalence of low back pain was 0.2% for both males and females with objective findings and 5.2% for males and 2.7% for females without objective findings. Higher BMI was significantly associated with low back pain in males (for overweight, odds ratio = 1.097, P < 0.001; for obese, odds ratio = 1.163, P < 0.001) and in females (for overweight, odds ratio = 1.174, P < 0.001; for obese, odds ratio = 1.211, P < 0.001). Height was associated with increased risk of low back pain in both genders. Odds ratios for low back pain in the tallest group compared with the shortest group were 1.438 (P < 0.001) for males and 1.224 (P < 0.001) for females. Low back pain with or without objective findings was associated with overweight and obesity as well as with height.

White Blood Cell Count and the Risk for Coronary Artery Disease in Young Adults

Background The association between white blood cell (WBC) count and coronary artery disease (CAD) is unknown in young adults. Our objective was to assess the association between WBC count and its changes over time with CAD incidence in the Metabolic, Life-style and Nutrition Assessment in Young adults (MELANY) study, a cohort of Israeli army personnel. Methods and Findings 29,120 apparently healthy young men (mean age; 31.2±5.5 years) with a normal baseline WBC count (3,000–12,000 cells/mm3) were followed during a mean follow up of 7.5±3.8 years for incidence of CAD. Participants were screened every 3–5 years using a stress test, and CAD was confirmed by coronary angiography. In a multivariate model adjusted for age, body mass index (BMI), LDL- and HDL-cholesterol, blood pressure, family history of CAD, physical activity, diabetes, triglycerides and smoking status, WBC levels (divided to quintiles) above 6,900 cells/mm3 (quintile 4) were associated with a 2.17-fold increase (95%CI = 1.18–3.97) in the risk for CAD as compared with men in quintile 1 (WBC≤5,400 cells/mm3). When modeled as a continuous variable, a WBC increment of 1000 cells/mm3 was associated with a 17.4% increase in CAD risk (HR 1.174; 95%CI = 1.067–1.290, p = 0.001). A decrease in the WBC level (within the normal range) during the follow-up period was associated with increased physical activity and decreased triglyceride levels as well as with reduced incidence of CAD. Conclusions WBC count is an independent risk factor for CAD in young adults at values well within the normal range. WBC count may assist in detecting subgroups of young men at either low or high risk for progression to CAD.

Inter-Arm Blood Pressure Differences in Young, Healthy Patients

The prevalence and magnitude of inter‐arm BP difference (IAD) in young healthy patients is not well characterized. Flight academy applicants and designated aviators undergo annual evaluation that includes blood pressure (BP) measurement on both arms. All BP measurements performed from January 1, 2012, to April 30, 2012, were recorded and IAD was calculated. Results were compared between patients in whom BP was initially measured in the right arm (group 1), those in whom BP was initially measured in the left arm (group 2), and those in whom the arm in which BP was initially measured was not recorded (group 3). A total of 877 healthy patients had BP measured during the study period. In the entire group, mean systolic BP was the same in both arms. Absolute IAD was 5.6±5.5 mm Hg for systolic and 4.7±4.5 mm Hg for diastolic BP. IAD >10 mm Hg was recorded in 111 (12.6%) and 77 (8.8%) patients for systolic and diastolic BP, respectively. IAD was the same in the 3 groups and was unrelated to age, body mass index, and heart rate, but was related to systolic BP. IAD is common in young healthy patients, is not dependent on which arm was measured first, and unrelated to age, body mass index, and heart rate.

Adolescence BMI and Trends in Adulthood Mortality: A Study of 2.16 Million Adolescents

CONTEXT The consequence of elevated body mass index (BMI) at adolescence on early adulthood mortality rate and on predicted life expectancy is unclear. OBJECTIVE The objective of the investigation was to study the relationship between BMI at adolescence and mortality rate as well as the mortality trend over the past 4 decades across the entire BMI range. DESIGN AND SETTING The study included a nationwide longitudinal cohort. PARTICIPANTS A total of 2 159 327 adolescents (59.1% males) born between 1950 and 1993, who were medically evaluated for compulsory military service in Israel, participated in the study. INTERVENTIONS Height and weight were measured at age 17 years, and BMI was stratified based on the Centers for Disease Control and Prevention-established percentiles for age and sex. MAIN OUTCOME MEASURE Incident cases of all-cause mortality before age 50 years were recorded. Cox-proportional hazard models were used to assess mortality rates and its trend overtime. RESULTS During 43 126 211 person-years of follow-up, 18 530 deaths were recorded. As compared with rates observed in the 25th to 50th BMI percentiles, all-cause mortality continuously increased across BMI range, reaching rates of 8.90/10(4) and 2.90/10(4) person-years for men and women with BMI greater than the 97th percentile, respectively. A multivariate analysis adjusted for age, socioeconomic status, education, and ethnicity demonstrated a significant increase in mortality at BMI greater than the 50th percentile (BMI > 20.55 kg/m(2)) for men and the 85th percentile or greater in women (BMI > 24.78 kg/m(2)). During the last 4 decades, a significant decrease in mortality rates was documented in normal-weight participants born between 1970 and 1980 vs those born between 1950 and 1960 (3.60/104 vs 4.99/10(4) person-years, P < .001). However, no improvement in the survival rate was observed among overweight and obese adolescents during the same time interval. Significant interaction between BMI and birth year was observed (P = .007). CONCLUSIONS BMI at adolescence, within the normal range, is associated with all-cause mortality in adulthood. Mortality rates among overweight and obese adolescents did not improve in the last 40 years, suggesting that preadulthood obesity may attenuate the progressive increase in life expectancy.

Flexible pes planus in adolescents: body mass index, body height, and gender--an epidemiological study.

Background: Most studies on the prevalence of flexible pes planus (FPP) have been conducted in pediatric populations and older adults. There is limited comparable information on these parameters for the adolescent age group. The purpose of this study was to report the prevalence of FPP and its association with body mass index (BMI), body height, and gender among healthy and fit adolescents. Methods: The data for this study were derived from a medical database containing records of 17-year-old males and females before their recruitment into mandatory military service. Information on the disability codes associated with FPP according to the Regulations of Medical Fitness Determination was retrieved. Logistic regression models were used to assess the association between BMI, body height, and gender to various grades of FPP severity. Results: The study cohort included 825 964 adolescents (467 412 males and 358 552 females). The prevalence was 12.4% for mild FPP and 3.8% for severe FPP among the males and 9.3% and 2.4%, respectively, for the females. An increased BMI was associated with FPP in both males (overweight: odds ratio [OR] 1.385, confidence interval [CI] 1.352-1.419, P < .001; obese: OR 1.765, CI 1.718-1.813, P < .001) and females (overweight: OR 1.408, CI 1.365-1.620, P < .001; obese: OR 1.549, CI 1.481-1.620, P < .001). Body height was associated with a decreased risk of FPP when the highest height quintile was compared with the lowest height quintile in both males (OR 0.782, CI 0.762-0.802, P < .001) and females (OR 0.730, CI 0.707-0.754, P < .001) for all FPP severity grades. Conclusions: There was a greater prevalence of FPP among males compared with females in a general healthy adolescent age group. FPP was associated with increased BMI and shorter body height for all grades of FPP severity. Level of Evidence: Level II, diagnostic study.