Adolescent body mass index and cognitive performance: a nationwide study of 2.48 million Israeli adolescents.

IMPORTANCE: The increased incidence of adolescent obesity over recent decades may be associated with lower cognitive performance than the expected potential. OBJECTIVE: We aimed to assess the association between adolescent body mass index (BMI) and cognitive function. DESIGN: A nationwide, cross-sectional, population-based study. SETTING: Pre-recruitment evaluation for military service during 1967-2018. PARTICIPANTS: All Israeli-born adolescents, 1 459 522 males and 1 027 953 females aged 16 to ≤20 years. EXPOSURES: Weight and height were measured to calculate BMI. MAIN OUTCOME: Cognitive performance was assessed by using a validated intelligence-quotient-equivalent test and was standardized to the year- and sex-Z-score. For 445 385 persons, parental cognitive scores could be identified. Multinomial logistic regression models were applied. RESULTS: Among male adolescents with severe obesity, 29.4% achieved a cognitive score below the 25th percentile, compared with 17.7% among their normal-weight (50th-84th percentile) counterparts. A J-shaped relation was observed between BMI and the odds ratio (OR) for a low cognitive score among male adolescents: underweight, 1.45 (1.43-1.48); overweight, 1.13 (1.12-1.15); mild obesity, 1.36 (1.33-1.39); and severe obesity, 1.58 (1.52-1.64). Similar findings were observed in females. For both sexes, point estimates were overall consistent in models adjusted for sociodemographic confounders, coexisting morbidities, and parental cognitive scores. Examinees with abnormal BMI had higher ORs for a lower-than-expected cognitive score, based on their parents' data as adolescents, in a manner that depends on obesity severity. CONCLUSION AND RELEVANCE: Obesity, is associated with increased odds for a lower cognitive performance, and the inability to fully achieve cognitive potential, regardless of sociodemographic background.

Adolescent Hypertension Is Associated With Stroke in Young Adulthood: A Nationwide Cohort of 1.9 Million Adolescents.

BACKGROUND: Adult hypertension is a well-established risk factor for stroke in young adults (aged <55 years), and the effects are even more deleterious than at an older age. However, data are limited regarding the association between adolescent hypertension and the risk of stroke in young adulthood. METHODS: A nationwide, retrospective cohort study of adolescents (aged 16-19 years) who were medically evaluated before compulsory military service in Israel during 1985 to 2013. For each candidate for service, hypertension was designated after constructed screening, and the diagnosis was confirmed through a comprehensive workup process. The primary outcome was ischemic and hemorrhagic stroke incidence as registered at the national stroke registry. Cox proportional-hazards models were used. We conducted sensitivity analyses by excluding people with a diabetes diagnosis at adolescence or a new diabetes diagnosis during the follow-up period, analysis of adolescents with overweight, and adolescents with baseline unimpaired health status. RESULTS: The final sample included 1 900 384 adolescents (58% men; median age, 17.3 years). In total, 1474 (0.08%) incidences of stroke (1236 [84%] ischemic) were recorded, at a median age of 43 (interquartile range, 38-47) years. Of these, 18 (0.35%) occurred among the 5221 people with a history of adolescent hypertension. The latter population had a hazard ratio of 2.4 (95% CI, 1.5-3.9) for incident stroke after adjustment for body mass index and baseline sociodemographic factors. Further adjustment for diabetes status yielded a hazard ratio of 2.1 (1.3-3.5). We found similar results when the outcome was ischemic stroke with a hazard ratio of 2.0 (1.2-3.5). Sensitivity analyses for overall stroke, and ischemic stroke only, yielded consistent findings. CONCLUSIONS: Adolescent hypertension is associated with an increased risk of stroke, particularly ischemic stroke, in young adulthood.

Glucose intolerance in pregnancy and risk of early-onset type 2 diabetes: a population-based cohort study.

BACKGROUND: The risk of type 2 diabetes among women with glucose intolerance during pregnancy that does not meet gestational diabetes criteria requires further investigation. We aimed to explore the associations between various degrees of gestational glucose intolerance and the risk of type 2 diabetes in young adulthood. METHODS: For this population-based cohort study, the national Israeli conscription database was linked to Maccabi Healthcare Services (MHS), the second-largest state-mandated health provider in Israel. We included 177 241 women who underwent a pre-recruitment evaluation at adolescence (age 16-20 years), 1 year before mandatory military service, and later underwent, from Jan 1, 2001, to Dec 31, 2019, two-step gestational diabetes screening with a 50 g glucose challenge test (GCT) based on a threshold of 140 mg/dL (7·8 mmol/L), followed as needed by a 100 g oral glucose tolerance test (OGTT). Abnormal OGTT values were defined according to the Carpenter-Coustan thresholds: 95 mg/dL (5·3 mmol/L) or higher in the fasting state; 180 mg/dL (10·0 mmol/L) or higher at 1 h; 155 mg/dL (8·6 mmol/L) or higher at 2 h; and 140 mg/dL (7·8 mmol/L) or higher at 3 h. The primary outcome was incident type 2 diabetes in the MHS diabetes registry. Cox proportional hazards models were applied to estimate adjusted hazard ratios (HRs) with 95% CIs for incident type 2 diabetes. FINDINGS: During a cumulative follow-up of 1 882 647 person-years, and with a median follow-up of 10·8 (IQR 5·2-16·4) years, 1262 women were diagnosed with type 2 diabetes. Crude incidence rates of type 2 diabetes were 2·6 (95% CI 2·4-2·9) per 10 000 person-years in women with gestational normoglycaemia, 8·9 (7·4-10·6) per 10 000 person-years in women with an abnormal GCT and normal OGTT, 26·1 (22·4-30·1) per 10 000 person-years in women with one abnormal OGTT value (in the fasting state or 1 h, 2 h, or 3 h post-challenge), and 71·9 (66·0-78·3) per 10 000 person-years in women with gestational diabetes. After adjustment for sociodemographic characteristics, adolescent BMI, and age at gestational screening, the risk of type 2 diabetes was higher, compared to the gestational normoglycaemia group, in women with an abnormal GCT and normal OGTT (adjusted hazard ratio [HR] 3·39 [95% CI 2·77-4·16]; p<0·0001), in women with one abnormal OGTT value (9·11 [7·64-10·86]; p<0·0001), and in women with gestational diabetes (24·84 [21·78-28·34]; p<0·0001). The risk of type 2 diabetes was modestly increased in women with isolated elevated fasting glucose (adjusted HR 11·81 [95% CI 8·58-16·25]; p<0·0001), and in women with gestational diabetes and an abnormal fasting glucose (38·02 [32·41-44·61]; p<0·0001). INTERPRETATION: Gestational glucose intolerance, including conditions not meeting gestational diabetes criteria of the two-step strategy, confers a high risk of type 2 diabetes in young adulthood. These conditions should be recognised as risk factors for type 2 diabetes, especially among women with abnormal fasting glucose concentrations during pregnancy. FUNDING: None.

Obesity in late adolescence and incident type 1 diabetes in young adulthood.

AIMS/HYPOTHESIS: Studies in children have reported an association between increased BMI and risk for developing type 1 diabetes, but evidence in late adolescence is limited. We studied the association between BMI in late adolescence and incident type 1 diabetes in young adulthood. METHODS: All Israeli adolescents, ages 16-19 years, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycaemia. Data were linked with information about adult onset of type 1 diabetes in the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied, with BMI being analysed both as a categorical and as a continuous variable. RESULTS: There were 777 incident cases of type 1 diabetes during 15,819,750 person-years (mean age at diagnosis 25.2±3.9 years). BMI was associated with incident type 1 diabetes. In a multivariable model adjusted for age, sex and sociodemographic variables, the HRs for type 1 diabetes were 1.05 (95% CI 0.87, 1.27) for the 50th-74th BMI percentiles, 1.41 (95% CI 1.11, 1.78) for the 75th-84th BMI percentiles, 1.54 (95% CI 1.23, 1.94) for adolescents who were overweight (85th-94th percentiles), and 2.05 (95% CI 1.58, 2.66) for adolescents with obesity (≥95th percentile) (reference group: 5th-49th BMI percentiles). One increment in BMI SD was associated with a 25% greater risk for incidence of type 1 diabetes (HR 1.25, 95% CI 1.17, 1.32). CONCLUSIONS: Excessively high BMI in otherwise healthy adolescents is associated with increased risk for incident type 1 diabetes in early adulthood.

Glucose Intolerance in Pregnancy and Offspring Obesity in Late Adolescence.

OBJECTIVE: Gestational hyperglycemia is associated with deleterious neonatal outcomes, but long-term risks for offspring obesity are less clear. We estimated the odds for offspring adolescent overweight and obesity among mothers with gestational glucose intolerance. RESEARCH DESIGN AND METHODS: In a mother-offspring historical cohort, the Israel military conscription data set was linked to a large health maintenance organization. Included were women who were evaluated at adolescence and underwent two-step gestational diabetes screening (mean age, 31 years) with a 50-g glucose challenge test (GCT), followed by a 100-g oral glucose tolerance test (OGTT) if the result was abnormal. Glucose tolerance categories included gestational normoglycemia, abnormal GCT with normal OGTT, impaired glucose tolerance (IGT; one abnormal OGTT value), and gestational diabetes. The primary outcome was offspring overweight/obesity (BMI ≥85th percentile) at adolescence, measured prior to military conscription. Logistic regression models were applied. RESULTS: Of 33,482 mother-offspring pairs, overweight and obesity were observed in 6,516 offspring. Across increasing categories of pregnancy glycemia, the proportions of offspring with adolescent overweight/obesity increased: normoglycemia, 19%; abnormal GCT with normal OGTT, 22%; gestational IGT, 24%; and gestational diabetes, 25% (P < 0.0001). Corresponding odds ratios after adjustment for the mother's late adolescent characteristics (sociodemographic confounders and BMI) and pregnancy age were 1.2 (95% CI 1.1-1.4), 1.3 (1.2-1.5), and 1.4 (1.3-1.6), respectively. Further adjustment for offspring birth weight percentile and sociodemographic variables did not materially change results. Associations were more pronounced with increasing obesity severity. CONCLUSIONS: Gestational glucose intolerance, including categories not meeting the gestational diabetes threshold, was associated with increased odds for offspring overweight/obesity at late adolescence.

The Global Spread of Severe Obesity in Toddlers, Children, and Adolescents: A Systematic Review and Meta-Analysis.

INTRODUCTION: Severe obesity among children and adolescents has emerged as a public health concern in multiple places around the world. METHODS: We searched the Medline database for articles on severe obesity rates in children published between January 1960 and January 2020. For studies with available prevalence rates for an early and a more recent time period, the relative increase in prevalence was imputed. RESULTS: In total, 874 publications were identified, of which 38 contained relevant epidemiological data. Rates of severe obesity varied significantly according to age, gender, geographic area, and the definition of severe obesity. The highest rates of class II and III obesity in the USA according to the Centers of Disease Control cut-off were 9.5% and 4.5%, respectively. Seventeen studies reported prevalence rates in at least two time periods. Data for 9,190,718 individuals showed a 1.71 (95% CI, 1.53-1.90) greater odds for severe obesity in 2006-2017 (N = 5,029,584) versus 1967-2007 (N = 4,161,134). In an analysis limited to studies from 1980s with a minimum follow-up of 20 years, a 9.16 (95% CI, 7.76-10.80) greater odds for severe obesity in recent versus earlier time was found. An analysis limited to studies from 2000, with a follow-up of 5-15 years, a 1.09 (95% CI, 0.99-1.20) greater odds was noted when comparing (2011-2017; N = 4,991,831) versus (2000-2011; N = 4,134,340). CONCLUSION: Severe pediatric obesity is escalating with a marked increase from the 1980s and a slower rate from 2000.

Attention-Deficit/Hyperactivity Disorder and Obesity: A National Study of 1.1 Million Israeli Adolescents.

PURPOSE: The incidences of obesity and attention-deficit/hyperactivity disorder (ADHD) have increased in parallel over recent decades. We assessed the association between obesity and ADHD in a national sample of adolescents. METHOD: In a nationwide population-based study of 1 118 315 adolescents (57% males; mean age 17 years), risks of obesity were compared between individuals with severe and mild ADHD and those without ADHD. Diagnoses of ADHD were confirmed by specialists in either neurology or psychiatry. Adolescents requiring regular and continuous treatment with stimulants with no improvement of symptoms under treatment were classified as having severe ADHD; data were available from 2004 to 2019. During 2015 to 2019, the diagnosis of ADHD was defined, and 65 118 (16.76%) of 388 543 adolescents with mild symptoms who required medications only for learning or who used stimulants irregularly were defined as having mild ADHD. RESULTS: The prevalence of severe and mild ADHD was 0.3% and 20.1%, respectively. Obesity was more prevalent among adolescents with severe ADHD than among those without ADHD (13.5% vs 7.5%). In the mild ADHD group 12.6% of males and 8.4% of females were diagnosed with obesity compared to 9.7% and 6.4%, respectively, in the non-ADHD group. The adjusted odds of severe ADHD for males and females with obesity were 1.77 (1.56-2.02) and 2.09 (1.63-2.66) times the odds for males and females with low-normal body mass index, respectively, and 1.42 (1.37-1.48) and 1.42 (1.34-1.50) for males and females with mild ADHD, respectively. The elevated risk persisted in several sensitivity analyses. CONCLUSIONS: Both adolescents with severe and mild ADHD are at increased risk for obesity.

[ADOLESCENT OBESITY IN ISRAEL].

INTRODUCTION: Childhood and adolescent obesity are significant global public health concerns. In recent decades, the Israel Medical Corps, in collaboration with other health organizations, initiated studies regarding the obesity epidemic in Israel, characterized specific groups that are at-risk for obesity and analyzed the short- and the long- term risks for associated medical conditions among those with obesity. According to these data, adolescent obesity and severe obesity prevalence have increased by 4- and 20-fold in the last decades in Israel, respectively. Low socioeconomic status, low level of education and low cognitive function were associated with a higher risk for obesity. Adolescents with obesity are at greater risk than those with normal weight for hyperhidrosis, asthma, different orthopedic abnormalities, hypertension and type 2 diabetes. A longitudinal study that followed the adolescents for 11 years has demonstrated a significant risk for adolescents with obesity for type 2 diabetes with hazard ratios (HRs) of 13 to 45, depending on sex and obesity degree. Longitudinal studies reported hazard ratios of 7 for end-stage chronic kidney disease, 1.3 for cancer, 3 for ischemic stroke and 7 for coronary heart disease in adulthood for adolescents with obesity compared to those with normal weight. Adolescents with overweight and obesity had greater risk for all-cause mortality in adulthood. Given the alarming increase in the prevalence of obesity and the significant short- and long- term consequences of adolescent obesity, the burden of the economic and clinical services on the healthcare system is expected to rise.

Adolescent cognitive function and incident early-onset type 2 diabetes.

BACKGROUND: Cognitive function among apparently healthy adolescents has been associated with cardiovascular morbidity and mortality. We examined the relationship between global and subdomain cognitive scores in adolescence and early-onset type 2 diabetes (T2D) in men and women. METHODS: A nationwide, population-based study of 971,677 Israeli born adolescents (56% men; mean age 17.4 years) who were medically examined and their cognitive performance was assessed before compulsory military service during 1992-2010. Data included global and subdomain cognitive Z-scores (problem-solving, verbal abstraction and categorization, verbal comprehension, and mathematical abilities). Data were linked to the Israeli National Diabetes Registry. The relations between global and subdomain scores and incident T2D was determined using Cox proportional hazard models and logistic regression models. Analyses were conducted separately for men and women. FINDINGS: During 16,095,122 person-years, 3,570 individuals developed T2D. After adjustment, those in the low compared to the high quintile of global cognitive Z-score had the highest risk for T2D; HR 2.46, (95% CI 2.10-2.88) for men and 2.33 (95% CI 1.88-2.89) for women. A one-unit lower global cognitive Z-score was associated with 1.41 (95% CI 1.34-1.48) and 1.46 (95% CI 1.36-1.56) increased risks for men and women, respectively. The relationship was noted for the cognitive subdomains scores as well as for the global cognitive score, with no heterogeneity across cognitive subdomains. INTERPRETATION: This large nationally representative cohort suggests relationship between global, as well as subdomain cognitive scores in late adolescence, and incident early onset T2D in both sexes, which was independent of socioeconomic status.

Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight Loss.

Bariatric operations induce weight loss, which is associated with an improvement in hepatic steatosis and a reduction in hepatic glucose production. It is not clear whether these outcomes are entirely due to weight loss, or whether the new anatomy imposed by the surgery contributes to the improvement in the metabolic function of the liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided with a high-fat high-sucrose diet and compared them to diet and weight-matched sham-operated mice (WMS). At 40 days after surgery, VSG-operated mice displayed less hepatic steatosis compared with WMS. By measuring the fasting glucose and insulin levels in the blood vessels feeding and draining the liver, we showed directly that hepatic glucose production was suppressed after VSG. Insulin levels were elevated in the portal vein, and hepatic insulin clearance was elevated in VSG-operated mice. The hepatic expression of genes associated with insulin clearance was upregulated. We repeated the experiment in lean mice and observed that portal insulin and glucagon are elevated, but only insulin clearance is increased in VSG-operated mice. In conclusion, direct measurement of glucose and insulin in the blood entering and leaving the liver shows that VSG affects glucose and insulin metabolism through mechanisms independent of weight loss and diet.

Adolescent Thyroid Disorders and Risk for Type 2 Diabetes in Young Adulthood.

CONTEXT: Thyroid hormones play a key role in systemic metabolism, yet the relationship between thyroid dysfunction and risk for type 2 diabetes is unclear. OBJECTIVE: To assess type 2 diabetes risk in adulthood among adolescents with thyroid disorders. DESIGN AND SETTING: A nationwide, population-based study of Israeli adolescents who were examined before military recruitment during 1988 to 2007 and were followed until December 31, 2016. PARTICIPANTS: 1 382 560 adolescents (mean age 17.3 years). INTERVENTIONS: The diagnosis of thyroid disorders was based on recent thyroid function tests. Data were linked to the Israeli National Diabetes Registry. Cox proportional hazard models were applied. MAIN OUTCOME MEASURES: Type 2 diabetes incidence. RESULTS: During a mean follow-up of 18.5 years, 1.12% (69 of 6,152) of adolescents with thyroid disorders were diagnosed with type 2 diabetes vs 0.77% of adolescents without thyroid disorders. The hazard ratio (HR) for type 2 diabetes was 2.3 (95% CI, 1.8-2.9) among those with thyroid disorders, after adjustment for sex, birth-year, body mass index, and sociodemographic confounders. The increased diabetes risk was observed in both men and women, with the presence or absence of obesity, and in the absence of other health conditions and was associated with different types of thyroid disorders. It was also similar when the outcome was defined as type 2 diabetes diagnosed at or before the age of 30 years (HR 2.3, 95% CI, 1.5-3.5). CONCLUSIONS: Thyroid disorders diagnosed in adolescence are a risk factor for early-onset type 2 diabetes in both men and women.

Body Mass Index in 1.9 Million Adolescents and Stroke in Young Adulthood.

Background and Purpose: There is a continuous rise in the prevalence of adolescent obesity and incidence of stroke among young adults in many Western countries, but the association between them is unclear. Methods: A nationwide population-based study of 1 900 384 Israeli adolescents (58% men; mean age, 17.3 years) who were evaluated before mandatory military service during 1985 and 2013. Body mass index was classified according to the US Center for Disease Control and Prevention percentiles. Primary outcome was a first stroke event as recorded by the Israeli National Stroke Registry between 2014 and 2018. Cox proportional hazard models were applied. Results: There were 1088 first stroke events (921 ischemic and 167 hemorrhagic; mean diagnosis age, 41.0 years). Adolescent body mass index was significantly associated with a graded increase in the risk for any stroke, ischemic stroke, but less so with hemorrhagic stroke. The hazard ratios for the first ischemic stroke event were 1.4 (95% CI, 1.2­1.6), 2.0 (95% CI, 1.6­2.4), and 3.4 (95% CI, 2.7­4.3) for the 50th to 84th percentile, overweight and obese groups, respectively, after adjustment for sex, age, and sociodemographic confounders with the 5th to 49th body mass index percentile group as the reference. The respective hazard ratios after further adjustment for diabetes status were 1.3 (1.1­1.5), 1.6 (1.3­2.0), and 2.4 (1.9­3.1). Results persisted when the cohort was divided by diabetes status and when ischemic stroke before age 30 was the outcome. Conclusions: High adolescent body mass index was associated with ischemic stroke in young adults with or without diabetes. The rising prevalence of adolescent obesity may increase the future burden of stroke in young adults.

Adolescent and Childhood Obesity and Excess Morbidity and Mortality in Young Adulthood-a Systematic Review.

PURPOSE OF REVIEW: Rates of childhood obesity have been soaring in recent decades. The association between obesity in adulthood and excess morbidity and mortality has been readily established, whereas the association of childhood and adolescent obesity has not. The purpose of this review is to summarize existing data regarding the association of the presence of obesity in childhood/adolescence and early-onset adverse outcomes in adulthood, with specific focus on young adults under the age of 45 years. RECENT FINDINGS: Diabetes, cancer, and cardiometabolic outcomes in midlife are closely linked to childhood and adolescent obesity. Childhood and adolescent obesity confer major risks of excess and premature morbidity and mortality, which may be evident before age 30 years in both sexes. The scientific literature is mixed regarding the independent risk of illness, which may be attributed to childhood BMI regardless of adult BMI, and additional data is required to establish causality between the two. Nonetheless, the increasing prevalence of childhood and adolescent obesity may impose an increase of disease burden in midlife, emphasizing the need for effective interventions to be implemented at a young age.

Adolescent Nonalcoholic Fatty Liver Disease and Type 2 Diabetes in Young Adulthood.

CONTEXT: The long-term risk of type 2 diabetes in adolescents with nonalcoholic fatty liver disease (NAFLD) is unclear. OBJECTIVE: To assess type 2 diabetes risk among adolescents with NAFLD. DESIGN AND SETTING: A nationwide, population-based study of Israeli adolescents who were examined before military service during 1997-2011 and were followed until December 31, 2016. PARTICIPANTS: A total of 1 025 796 normoglycemic adolescents were included. INTERVENTIONS: Biopsy or radiographic tests were prerequisite for NAFLD diagnosis. Data were linked to the Israeli National Diabetes Registry. MAIN OUTCOME MEASURES: Type 2 diabetes incidence. RESULTS: During a mean follow-up of 13.3 years, 12 of 633 adolescents with NAFLD (1.9%; all with high body mass index [BMI] at baseline) were diagnosed with type 2 diabetes compared with 2917 (0.3%) adolescents without NAFLD. The hazard ratio (HR) for type 2 diabetes was 2.59 (95% confidence interval [CI], 1.47-4.58) for the NAFLD vs. the non-NAFLD group after adjustment for BMI and sociodemographic confounders. The elevated risk persisted in several sensitivity analyses. These included an analysis of persons without other metabolic comorbidities (adjusted HR, 2.75 [95% CI, 1.48-5.14]) and of persons with high BMI; and an analysis whose outcome was type 2 diabetes by age 30 years (adjusted HR, 2.14 [95% CI, 1.02-4.52]). The results remained significant when a sex-, birth year-, and BMI-matched control group was the reference (adjusted HR, 2.98 [95% CI, 1.54-5.74]). CONCLUSIONS: Among normoglycemic adolescents, NAFLD was associated with an increased adjusted risk for type 2 diabetes, which may be apparent before age 30 years.

Cardiovascular morbidity, diabetes and cancer risk among children and adolescents with severe obesity.

Severe obesity among children and adolescents is a significant global public health concern. The prevalence has markedly increased over the last decades, becoming common in many countries. Overwhelming rates of obesity among youth have prompted efforts to identify an evidence-based immediate- and long-term cardiometabolic risk factor profile in childhood-onset severe obesity, and to highlight gaps that require further investigation. The PubMed database was systematically searched in accordance with PRISMA guidelines. The search yielded 831 results, of which 60 fulfilled stringent criteria and were summarized in this review. The definition of severe obesity was variable, with only one half the publications using the definition BMI > 120% of the 95th percentile. Point estimates of the prevalence of at least one cardiometabolic risk factor in children with severe obesity reportedly range from 67 to 86%. Cross-sectional studies indicate that children and adolescents with severe obesity are at greater risk than those with mild obesity for type 2 diabetes, hypertension, fatty liver disease and dyslipidemia, already at childhood and adolescence. Robust epidemiological data on the long-term risk and actual point estimates in adulthood are lacking for these diseases as well as for other diseases (coronary heart disease, stroke, chronic kidney disease and cancer). Recent longitudinal studies indicate an increased risk for cardiomyopathy, heart failure, cardiovascular mortality and all-cause mortality in adulthood for adolescents with severe obesity compared to those with mild obesity. Given the alarming increase in the prevalence of severe obesity, the persistence of adiposity from childhood to adulthood and the precarious course of young adults with chronic comorbidities, the economic and clinical services burden on the healthcare system is expected to rise.

Childhood Pancreatitis and Risk for Incident Diabetes in Adulthood.

OBJECTIVE: The relationship between acute pancreatitis and incident diabetes is unclear. We assessed whether a resolved single event of acute pancreatitis in childhood was associated with incident diabetes in adulthood. RESEARCH DESIGN AND METHODS: A nationwide, population-based study of 1,802,110 Israeli adolescents (mean age 17.4 years [range 16-20]) who were examined before compulsory military service between 1979 and 2008 and whose data were linked to the Israeli National Diabetes Registry (INDR). Resolved pancreatitis was defined as a history of a single event of acute pancreatitis with normal pancreatic function at enrollment. Logistic regression analysis was applied. RESULTS: Incident diabetes developed in 4.6% of subjects with resolved pancreatitis (13 of 281; none of these cases were identified as type 1 diabetes) and 2.5% among the unexposed group (44,463 of 1,801,716). Resolved acute pancreatitis was associated with incident diabetes with an odds ratio (OR) of 2.23 (95% CI 1.25-3.98) with adjustment for age, sex, and birth year. Findings persisted after further adjustments for baseline BMI and sociodemographic confounders (OR 2.10 [95% CI 1.15-3.84]). Childhood pancreatitis was associated with a diagnosis of diabetes at a younger age, with 92% of diabetes case subjects diagnosed before 40 years of age compared with 47% in the unexposed group (P = 0.002). The association accentuated when the study sample was limited to individuals of unimpaired health or normal BMI at baseline. CONCLUSIONS: A history of acute pancreatitis in childhood with normal pancreatic function in late adolescence is a risk factor for incident type 2 diabetes, especially at young adulthood.

Impact of Immigration on Body Mass Index and Blood Pressure Among Adolescent Males and Females: A Nationwide Study.

Immigration from one cultural milieu to another has been associated with a greater risk for incident cardio-metabolic morbidity among adults. In this nationwide, population-based, cross-sectional study of data recorded from 1992 to 2016, we assessed the association between body mass index and blood pressure levels among adolescent immigrants, aged 16 to 19 years, of Ethiopian origin, and their secular trend of overweight and obesity. Adolescents of Ethiopian origin were classified as Israeli-born (n=16 153) or immigrants (N=23 487), with stratification by age at immigration. Adolescents whose fathers were at least 3 generations in Israel (n=277 789) served as a comparative group. Hypertensive-range blood pressure values adjusted for age, sex, and height served as outcome. Among adolescents of Ethiopian origin, overweight and obesity (body mass index ≥85th percentile), increased by 2.5 and 4-fold in males and females, respectively, during the study period, compared with a 1.5-fold increase among native Israeli-born males and females. The odds for hypertensive-range measurements increased with the length of residence in Israel: 7.3%, 10.6%, and 14.4% among males who immigrated at ages 12 to 19, 6 to 11.9, and 0 to 5.9 years, respectively; and 11.5%, 16.7%, and 19.3%, respectively, among females. Israeli-born Ethiopians had a significantly higher risk for hypertensive-range measurements at any body mass index level compared with native Israeli-born examinees, after adjusting for sociodemographic factors and health status. In conclusion, among Ethiopian Israeli adolescents, abnormal blood pressure correlates directly with the time-lapse since immigration. Immigrant populations require targeted surveillance and appropriate intervention.

Sleeve Gastrectomy Improves Glycemia Independent of Weight Loss by Restoring Hepatic Insulin Sensitivity.

Bariatric surgery dramatically improves glycemic control, yet the underlying molecular mechanisms remain controversial because of confounding weight loss. We performed sleeve gastrectomy (SG) on obese and diabetic leptin receptor-deficient mice (db/db). One week postsurgery, mice weighed 5% less and displayed improved glycemia compared with sham-operated controls, and islets from SG mice displayed reduced expression of diabetes markers. One month postsurgery SG mice weighed more than preoperatively but remained near-euglycemic and displayed reduced hepatic lipid droplets. Pair feeding of SG and sham db/db mice showed that surgery rather than weight loss was responsible for reduced glycemia after SG. Although insulin secretion profiles from islets of sham and SG mice were indistinguishable, clamp studies revealed that SG causes a dramatic improvement in muscle and hepatic insulin sensitivity accompanied by hepatic regulation of hepatocyte nuclear factor-α and peroxisome proliferator-activated receptor-α targets. We conclude that long-term weight loss after SG requires leptin signaling. Nevertheless, SG elicits a remarkable improvement in glycemia through insulin sensitization independent of reduced feeding and weight loss.

Plasma microRNA profiling: Exploring better biomarkers for lymphoma surveillance.

Early detection of relapsed lymphoma improves response and survival. Current tools lack power for detection of early relapse, while being cumbersome and expensive. We searched for sensitive biomarkers that precede clinical relapse, and serve for further studies on therapy response and relapse. We recruited 20 healthy adults, 14 diffuse large B-cell lymphoma (DLBCL) patients and 11 Hodgkin lymphoma (HL) patients at diagnosis. Using small-RNA sequencing we identified in DLBCL patients increased plasma levels of miR-124 and miR-532-5p, and decreased levels of miR-425, miR-141, miR-145, miR-197, miR-345, miR-424, miR-128 and miR-122. In the HL group, we identified miR-25, miR-30a/d, miR-26b, miR-182, miR-186, miR-140* and miR-125a to be up-regulated, while miR-23a, miR-122, miR-93 and miR-144 were down-regulated. Pathway analysis of potential mRNAs targets of these miRNA revealed in the DLBCL group potential up-regulation of STAT3, IL8, p13k/AKT and TGF-B signaling, and potential down-regulation of the PTEN and p53 pathways; while in the HL group we have found the cAMP-mediated pathway and p53 pathway to be potentially down-regulated. Survival analyses revealed that plasma levels of miR-20a/b, miR-93 and miR-106a/b were associated with higher mortality. In conclusion, we identified sets of dysregulated circulating miRNA that might serve as reliable biomarkers for relapsed lymphoma.