Increased innate immune responses in adolescents with obesity and its relation to subclinical cardiovascular measures: An exploratory study.

Cardiometabolic risk accrues across the life course and childhood and adolescence are key periods for effective prevention. Obesity is associated with inflammation in adults, but pediatric data are scarce. In a cross-sectional and longitudinal study, we investigated immune cell composition and activation in 31 adolescents with obesity (41.9% male, BMIz>2.5, 14.4 years) and 22 controls with healthy weight (45.1% male, -1.5

Change in adiposity is associated with change in glycoprotein acetyls but not hsCRP in adolescents with severe obesity.

BACKGROUND: Obesity-associated chronic inflammation mediates the development of adverse cardiometabolic outcomes. There are sparse data on associations between severe obesity and inflammatory biomarkers in adolescence; most are cross-sectional and limited to acute phase reactants. Here, we investigate associations between adiposity measures and inflammatory biomarkers in children and adolescents with severe obesity both cross-sectionally and longitudinally. METHODS: From the Childhood Overweight Biorepository of Australia (COBRA) study, a total of n = 262 participants, mean age 11.5 years (SD 3.5) with obesity had measures of adiposity (body mass index, BMI; % above the 95th BMI-centile, %>95th BMI-centile; waist circumference, WC; waist/height ratio, WtH; % total body fat, %BF; % truncal body fat, %TF) and inflammation biomarkers (glycoprotein acetyls, GlycA; high-sensitivity C-Reactive Protein, hsCRP; white blood cell count, WBC; and neutrophil/lymphocyte ratio, NLR) assessed at baseline. Ninety-eight individuals at mean age of 15.9 years (3.7) participated in a follow-up study 5.6 (2.1) years later. Sixty-two individuals had longitudinal data. Linear regression models, adjusted for age and sex for cross-sectional analyses were applied. To estimate longitudinal associations between change in adiposity measures with inflammation biomarkers, models were adjusted for baseline measures of adiposity and inflammation. RESULTS: All adiposity measures were cross-sectionally associated with GlycA, hsCRP and WBC at both time points. Change in BMI, %>95th BMI-centile, WC, WtH and %TF were associated with concomitant change in GlycA and WBC, but not in hsCRP and NLR. CONCLUSION: GlycA and WBC but not hsCRP and NLR may be useful in assessing adiposity-related severity of chronic inflammation over time.

Nano-chromium picolinate and heat stress enhance insulin sensitivity in cross-bred sheep.

This study evaluated the effects of heat stress (HS) and dietary nano chromium picolinate (nCrPic) on metabolic responses of sheep to an intravenous glucose tolerance test (IVGTT), an intravenous insulin tolerance test (ITT) and an intramuscular adrenocorticotropin hormone (ACTH) challenge in sheep. Thirty-six sheep housed in metabolic cages were randomly allocated within 3 dietary groups (0, 400 and 800 µg/kg supplemental nCrPic) to either thermoneutral (22 °C) or cyclic HS (22 to 40 °C) conditions for 3 wk. Basal plasma glucose tended to be increased during HS (P = 0.052) and decreased by dietary nCrPic (P = 0.013) while plasma non-esterified fatty acid concentrations were decreased (P = 0.010) by HS. Dietary nCrPic reduced the plasma glucose area under the curve (P = 0.012) while there were no significant effects of HS on plasma glucose area under the curve in response to the IVGTT. The plasma insulin response over the first 60 min after the IVGTT was decreased by HS (P = 0.013) and dietary nCrPic (P = 0.022) with the effects being additive. In response to the ITT plasma glucose reached a nadir sooner (P = 0.005) in sheep exposed to HS, although there was no effect on the depth of the nadir. Dietary nCrPic decreased (P = 0.007) the plasma glucose nadir after ITT. Over the duration of the ITT plasma insulin concentrations were lower in sheep exposed to HS (P = 0.013) whereas there was no significant effect of supplemental nCrPic. There was no effect of either HS or nCrPic on cortisol response to ACTH. Dietary nCrPic supplementation decreased (P = 0.013) mitogen-activated protein kinase-8 (JNK) and increased (P = 0.050) carnitine palmitoyltransferase 1B (CPT1B) mRNA expression in skeletal muscle. Results of this experiment demonstrated that animals under HS and supplemented with nCrPic had greater insulin sensitivity.

Genetic Variants in SRD5A2 in a Spectrum of DSD Patients from Australian Clinics Highlight Importance of Genetic Testing alongside Typical First-Line Investigations.

INTRODUCTION: Steroid 5-alpha reductase deficiency (5α-R2D) is a rare condition caused by genetic variants that reduce the activity of the enzyme that converts testosterone into dihydrotestosterone. The clinical spectrum of 5α-R2D is known to overlap with other 46,XY differences of sex development (DSD) such as androgen insensitivity or gonadal dysgenesis. However, the clinical trajectories of the aetiologies can differ, with 5α-R2D presenting its own challenges. METHODS: In this study, we have collated clinical information for five individuals with variants in SRD5A2 identified using research genetic testing in an Australian paediatric setting. RESULTS: We describe how a genetic finding resolved or confirmed a diagnosis for these individuals and how it guided clinical management and family counselling. CONCLUSION: This work highlights the importance of early genetic testing in children born with 46,XY DSD where it complements traditional first-line testing.

Evidence for protein leverage in a general population sample of children and adolescents.

BACKGROUND/OBJECTIVES: The strong regulation of protein intake can lead to overconsumption of total energy on diets with a low proportion of energy from protein, a process referred to as protein leverage. The protein leverage hypothesis posits that protein leverage explains variation in energy intake and potentially obesity in ecological settings. Here, we tested for protein leverage and the protein leverage hypothesis in children and adolescents. SUBJECTS/METHODS: A population sample of children, mean (SD) age 7.6 (0.4) years (n = 422), followed up at age 9.8 (0.4) years (n = 387) and at age 15.8 (0.4) years (n = 229), participating for the Physical Activity and Nutrition in Children (PANIC) study. EXPOSURES: 4-day food records-related proportional energy intake of proteins, fats, and carbohydrates. OUTCOMES: energy intake, body mass index (BMI) z-score and dual-energy X-ray absorptiometry-related energy expenditure. RESULTS: Proportional energy intake of proteins was inversely associated with energy intake following power functions at all 3 ages (mean [95%CI] strength of leverage of L = -0.36 [-0.47 to -0.25]; L = -0.26 [-0.37 to -0.15]; L = -0.25 [-0.38 to -0.13]; all P < 0.001). Mixture analysis indicated that variance in energy intake was associated primarily with the proportional intake of energy from proteins, not with either fats or carbohydrates. At all 3 ages, energy intake was not associated with BMI z-score but positively associated with energy expenditure (all P < 0.001). CONCLUSIONS: This study provides evidence consistent with protein leverage in a population sample of children and adolescents. Increased energy intake on diets with lower protein content was counterbalanced by increased energy expenditure and therefore did not translate into increased adiposity.

Use of antibiotics and risk of type 2 diabetes, overweight and obesity: the Cardiovascular Risk in Young Finns Study and the national FINRISK study.

PURPOSE: To investigate whether exposure to systemic antibiotics influences the risk of developing type 2 diabetes and overweight/obesity. METHODS: The study sample comprised 2209 (110 with incident diabetes) participants from the population-based Cardiovascular Risk in Young Finns Study (YFS) aged 24-39 years in 2001. The exposure was national linked register data on purchased antibiotic courses between 1993 and 2001. Clinical examinations including BMI were conducted in 2001, 2007 and 2011. Participants with prevalent diabetes in 2001 were excluded. Data on type 2 diabetes was also obtained from two national registers until 2017. Data from four population-based National FINRISK studies were used for replication (N = 24,674, 1866 with incident diabetes). RESULTS: Prior antibiotic exposure (> 5 versus 0-1 antibiotic courses) was associated with subsequent type 2 diabetes in both YFS (OR 2.29; 95%CI 1.33-3.96) and FINRISK (HR 1.73; 95%CI 1.51-1.99). An increased risk for type 2 diabetes was observed in YFS (OR 1.043; 95%CI 1.013-1.074) and FINRISK (HR 1.022; 95%CI 1.016-1.029) per course. Exposure to antibiotics increased the risk of overweight/obesity (BMI > 25 kg/m2) after a 10-year follow-up in YFS (OR 1.043; 95%CI 1.019-1.068) and in FINRISK (OR 1.023; 95%CI 1.018-1.029) at baseline per antibiotic course. Adjustments for confounders from early life in YFS and at baseline in FINRISK, including BMI, socioeconomic status, smoking, insulin, blood pressure, and physical activity, did not appreciably alter the findings. CONCLUSION: Our results show that exposure to antibiotics was associated with increased risk for future type 2 diabetes and overweight/obesity and support judicious antibiotic prescribing.

Decreasing severity of obesity from early to late adolescence and young adulthood associates with longitudinal metabolomic changes implicated in lower cardiometabolic disease risk.

BACKGROUND: Obesity in childhood is associated with metabolic dysfunction, adverse subclinical cardiovascular phenotypes and adult cardiovascular disease. Longitudinal studies of youth with obesity investigating changes in severity of obesity with metabolomic profiles are sparse. We investigated associations between (i) baseline body mass index (BMI) and follow-up metabolomic profiles; (ii) change in BMI with follow-up metabolomic profiles; and (iii) change in BMI with change in metabolomic profiles (mean interval 5.5 years). METHODS: Participants (n = 98, 52% males) were recruited from the Childhood Overweight Biorepository of Australia study. At baseline and follow-up, BMI and the % >95th BMI-centile (percentage above the age-, and sex-specific 95th BMI-centile) indicate severity of obesity, and nuclear magnetic resonance spectroscopy profiling of 72 metabolites/ratios, log-transformed and scaled to standard deviations (SD), was performed in fasting serum. Fully adjusted linear regression analyses were performed. RESULTS: Mean (SD) age and % >95th BMI-centile were 10.3 (SD 3.5) years and 134.6% (19.0) at baseline, 15.8 (3.7) years and 130.7% (26.2) at follow-up. Change in BMI over time, but not baseline BMI, was associated with metabolites at follow-up. Each unit (kg/m2) decrease in sex- and age-adjusted BMI was associated with change (SD; 95% CI; p value) in metabolites of: alanine (-0.07; -0.11 to -0.04; p < 0.001), phenylalanine (-0.07; -0.10 to -0.04; p < 0.001), tyrosine (-0.07; -0.10 to -0.04; p < 0.001), glycoprotein acetyls (-0.06; -0.09 to -0.04; p < 0.001), degree of fatty acid unsaturation (0.06; 0.02 to 0.10; p = 0.003), monounsaturated fatty acids (-0.04; -0.07 to -0.01; p = 0.004), ratio of ApoB/ApoA1 (-0.05; -0.07 to -0.02; p = 0.001), VLDL-cholesterol (-0.04; -0.06 to -0.01; p = 0.01), HDL cholesterol (0.05; 0.08 to 0.1; p = 0.01), pyruvate (-0.08; -0.11 to -0.04; p < 0.001), acetoacetate (0.07; 0.02 to 0.11; p = 0.005) and 3-hydroxybuturate (0.07; 0.02 to 0.11; p = 0.01). Results using the % >95th BMI-centile were largely consistent with age- and sex-adjusted BMI measures. CONCLUSIONS: In children and young adults with obesity, decreasing the severity of obesity was associated with changes in metabolomic profiles consistent with lower cardiovascular and metabolic disease risk in adults.

Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium.

BACKGROUND: In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce. METHODS: We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3-19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries. RESULTS: 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03-1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01-1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03-1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12-1.63). CONCLUSIONS: Higher childhood BMI was independently associated with increased overall cancer mortality.

Modest decrease in severity of obesity in adolescence associates with low arterial stiffness.

BACKGROUND AND AIMS: Childhood obesity is associated with cardiovascular risk factors (CVRF), subclinical cardiovascular phenotypes (carotid intima-media thickness, cIMT; pulse-wave velocity, PWV; and carotid elasticity), and adult cardiovascular disease (CVD) mortality. In youth with obesity (body mass index, BMI ≥95th centile), we investigated associations between changes in adiposity and CVRF in early adolescence and subclinical cardiovascular phenotypes in late adolescence. METHODS: Participants had adiposity measures (the severity of obesity in percentage >95th BMI-centile (%>95th BMI-centile)), waist circumference (WC), percentage total body fat (%BF) and CVRF (systolic blood pressure, SBP; glycoprotein acetyls, GlycA; and low-density lipoprotein cholesterol) assessed in early (mean age 10.2 ± 3.5y) and late (15.7 ± 3.7y) adolescence. Subclinical cardiovascular phenotypes were assessed in late adolescence. Multivariable regression analysis was performed. RESULTS: Decreasing the %>95th BMI-centile was associated with carotid elasticity (0.945%/10 mmHg, p = 0.002) in females, and with PWV in males (-0.75 m/s, p < 0.001). Changes in all adiposity measures (per 1-unit increase) were associated with carotid elasticity (-0.020 to -0.063%/10 mmHg, p < 0.005), and PWV (0.011-0.045 m/s, p < 0.005). Changes in GlycA (per 50µmol-increase) were associated with elasticity (-0.162%/10 mmHg, p = 0.042), and changes in SBP (per 10 mmHg-increase) were associated with PWV (0.260 m/s, p < 0.001). Adjusted for change in BMI, the coefficient for GlycA was reduced by 46% and for SBP by 12%. Only male sex was associated with cIMT (+34 µm, p = 0.006). CONCLUSIONS: In youth with obesity, decreasing or maintaining the severity of obesity, and decreasing the levels of SBP and GlycA from early to late adolescence was associated with low arterial stiffness.

Fatty liver index predicts incident risk of prediabetes, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).

AIMS: To investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up. METHODS: At baseline (in 2001) 2020 participants, males and females, aged 24-39 years, were stratified according to body mass index (BMI), normal weight (<25 kg/m2), overweight (≥25-<30 kg/m2), or obese (≥30 kg/m2) and FLI (as high FLI ≥60 or low FLI <60). We examined the incidence of prediabetes/type 2 diabetes and NAFLD (ultrasound assessed) over 10 years to 2011 to determine the relative impact of FLI and BMI. RESULTS: 514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes (n = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9-10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups. CONCLUSIONS: An increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.Key messagesObesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes.Additionally, NAFLD is more prevalent in people with prediabetes and type 2 diabetes when compared to age- and BMI-matched individuals.The presence of a raised fatty liver index (FLI) confers a significantly increased risk of developing prediabetes, type 2 diabetes and NAFLD above that conferred by being overweight/obese.The degree of elevation of FLI can risk stratify for incident prediabetes and type 2 diabetes in people with obesity.

Dietary nano chromium picolinate can ameliorate some of the impacts of heat stress in cross-bred sheep.

Two studies were conducted to evaluate the effect of nano chromium picolinate (nCrPic) during heat stress (HS) in sheep. In the initial study, 36 Merino × Poll cross-bred sheep were individually penned and allocated to 3 dietary treatments (0, 400 and 800 µg/kg nCrPic) for 8 wk. Body composition was determined at the beginning and end of the experiment using dual energy X-ray absorptiometry. The sheep remained in their dietary groups but were then placed in metabolic cages and randomly allocated within the dietary group to differing ambient temperature regimes, i.e., thermo-neutral (TN) (n = 18) and HS (n = 18), for 3 wk. Dietary nCrPic had no effect on growth performance and body composition during the initial study conducted under TN conditions. Heat stress decreased average daily feed intake (ADFI) (P = 0.002) whereas sheep under HS had reduced average daily gain (ADG) and indeed lost weight (P < 0.001). Dietary nCrPic increased both ADFI (P = 0.041) and ADG (P = 0.049) under both TH and HS conditions such that the performance of sheep receiving supplemental nCrPic and exposed to HS was similar to that of control sheep maintained under TN conditions. Heat stress increased rectal temperature (P < 0.001) and respiration rate (P < 0.001), particularly during the hottest parts of the day as indicated by interactions (P < 0.001) between time of day and thermal treatment. Rectal temperature was lower in sheep fed nCrPic (P = 0.050), particularly under peak HS conditions during the afternoon as indicated by the interactions between dietary nCrPic and time of day (P < 0.001) and dietary nCrPic, thermal treatment and time of day (P = 0.010). Similarly, respiration rate was lower in sheep fed nCrPic under peak HS conditions during the afternoon as indicated by the interactions between dietary nCrPic and thermal treatment (P < 0.001) and dietary nCrPic and time of day (P = 0.030). In conclusion, dietary nCrPic can partially ameliorate the negative effects of HS as indicated by the maintenance of ADFI and decreased physiological responses, such as elevations in rectal temperature and respiration rate.

Dietary Pattern Trajectories from Youth to Adulthood and Adult Risk of Impaired Fasting Glucose: A 31-year Cohort Study.

CONTEXT: The influence of dietary pattern trajectories from youth to adulthood on adult glucose metabolism is unknown. OBJECTIVE: To identify dietary pattern trajectories from youth to adulthood and examine their associations with adult impaired fasting glucose (IFG). METHODS: Thirty-one-year population-based cohort study among 1007 youths aged 3-18 years at baseline in Finland. Diet intake was assessed in 1980, 1986, 2001, 2007, and 2011. Group-based trajectory modelling was used to identify dietary pattern (identified by factor analysis) trajectories. Adult IFG was measured by the latest available data from 2001, 2007, and 2011. RESULTS: Among 1007 participants, 202 (20.1%) developed IFG and 27 (2.7%) developed type 2 diabetes in adulthood (mean follow-up of 30.7 years; mean [SD] age 40.5 [5.0] years). Three dietary patterns were identified at baseline and were retained in 1986 and 2001: "Traditional Finnish," "High carbohydrate," and "Vegetables and dairy products." Three different patterns were identified in 2007, which remained similar in 2011: "Traditional Finnish and high carbohydrate," "Red meat," and "Healthy." Trajectories of increased or stably medium "red meat" pattern scores from youth to adulthood were detrimentally associated with IFG (relative risk 1.46, 95% CI 1.12-1.90 for Medium (M)-stable/M-large increase vs low-stable trajectory) after adjusting for confounders. This association was slightly reduced after further adjusting for long-term dietary fiber intake. CONCLUSION: Trajectories of an increased or stably moderate adherence to a "red meat" dietary pattern from youth to adulthood are associated with higher risk of adult IFG. This association is partly explained by low dietary fiber intake.

Childhood and Adulthood Passive Smoking and Nonalcoholic Fatty Liver in Midlife: A 31-year Cohort Study.

INTRODUCTION: Identifying early life risk factors remains key to the prevention of nonalcoholic fatty liver (hereinafter "fatty liver") in adulthood. However, the longitudinal association of childhood passive smoking with adult fatty liver is not studied. We examined the association of childhood and adulthood passive smoking with fatty liver in midlife. METHODS: This was a 31-year prospective cohort study of 1,315 participants. Information on childhood passive smoking (parental smoking) was collected in 1980 (aged 3-18 years) and 1983 and adulthood passive smoking in 2001, 2007, and 2011. Fatty liver was determined by ultrasound in 2011 (aged 34-49 years). RESULTS: The prevalence of fatty liver was 16.3%. Both childhood and adulthood passive smoking were associated with higher risk of fatty liver, adjusting for potential confounders such as age, sex, childhood socioeconomic status, and adulthood physical activity and alcohol consumption (relative risk = 1.41, 95% confidence interval: 1.01-1.97 for childhood; 1.35, 1.01-1.82 for adulthood). Individuals with persistent exposure to passive smoking between childhood and adulthood had the highest risk (relative risk = 1.99, 95% confidence interval: 1.14-3.45) compared with those without passive smoking in either childhood or adulthood. DISCUSSION: Passive smoking in both child and adult lives are associated with increased risk of adult fatty liver, suggesting that the prevention of passive smoking should start as early as possible and maintain throughout lifetime.

Childhood and long-term dietary calcium intake and adult cardiovascular risk in a population with high calcium intake.

BACKGROUND & AIMS: The influence of dietary calcium intake in childhood on adult cardiovascular health is unknown, particularly in those with long-term high intake. To examine both linear and non-linear associations of childhood and long-term (between childhood and adulthood) dietary calcium intake with adult cardiovascular risk outcomes. METHODS: A population-based prospective cohort study in Finland (n = 1029, aged 3-18 years at baseline). Dietary calcium intake was assessed in childhood (1980, baseline) and adulthood (mean of available data from 2001, 2007 and 2011). Long-term dietary calcium intake was calculated as the mean between childhood and adulthood. Outcomes were measured in 2001, 2007, and/or 2011, and the latest available data were used for analyses, including high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity (PWV), carotid artery compliance (CAC), Young's elastic modulus (YEM), and stiffness index (SI). RESULTS: There were no significant non-linear or linear associations between childhood or long-term dietary calcium intake with any adult cardiovascular outcomes, after adjustment for age, sex, and childhood and adulthood confounders (e.g., body mass index, systolic blood pressure, smoking, physical activity, fruit and vegetable consumption). CONCLUSIONS: Childhood or long-term dietary calcium intake that is higher than the recommended level is not associated with increased cardiovascular risk in adulthood.

Attainment of Targets of the 20-Year Infancy-Onset Dietary Intervention and Blood Pressure Across Childhood and Young Adulthood: The Special Turku Coronary Risk Factor Intervention Project (STRIP).

We examined whether success in achieving the key targets of an infancy-onset 20-year dietary intervention was associated with blood pressure (BP) from infancy to young adulthood. In the prospective randomized STRIP (Special Turku Coronary Risk Factor Intervention Project; n=877 children), dietary counseling was provided biannually based on the Nordic Nutrition Recommendations primarily to improve the quality of dietary fat in children's diets and secondarily to promote intake of vegetables, fruits, and whole grains. Dietary data and BP were accrued annually from the age of 13 months to 20 years. The dietary targets for fat quality were defined as the ratio of saturated fatty acids to monounsaturated and polyunsaturated fatty acids <1:2 and intake of saturated fatty acids <10 E%, dietary fiber intake in the top age-specific quintile, and dietary sucrose intake as being in the lowest age-specific quintile. Attaining a higher number of the dietary targets was associated with lower systolic BP (mean [SE] systolic BP, 107.3 [0.3], 107.6 [0.3], 106.8 [0.3], and 106.7 [0.5] mm Hg in participants meeting 0, 1, 2, and 3 to 4 targets, respectively; P=0.03) and diastolic BP (mean [SE] diastolic BP, 60.4 [0.2], 60.5 [0.2], 59.9 [0.2], and 59.9 [0.3] mm Hg; P=0.02). When the lowest age-specific quintile of dietary cholesterol was added as an additional target, the association with systolic BP remained significant (P=0.047), but the association with diastolic BP attenuated (P=0.13). Achieving the key targets of an infancy-onset 20-year dietary intervention, reflecting dietary guidelines, was favorably albeit modestly associated with systolic and diastolic BP from infancy to young adulthood. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00223600.

Nano Chromium Picolinate Improves Gene Expression Associated with Insulin Signaling in Porcine Skeletal Muscle and Adipose Tissue.

The aim of this study was to investigate the interactive effects of dietary nano chromium picolinate (nCrPic) and dietary fat on genes involved in insulin signaling in skeletal muscle and subcutaneous adipose tissue of pigs. Forty-eight gilts were stratified on body weight into four blocks of four pens of three pigs and then within each block each pen was randomly allocated to four treatment groups in a 2 × 2 factorial design. The respective factors were dietary fat (22 or 57 g/kg) and dietary nCrPic (0 or 400 ppb nCrPic) fed for six weeks. Skeletal muscle samples were collected from the Longissimus thoracis and subcutaneous adipose tissue collected from above this muscle. Dietary nCrPic increased adiponectin, uncoupling protein 3 (UCP3) and serine/threonine protein kinase (AKT) mRNA expression, whereas dietary fat decreased adiponectin and increased leptin, tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptors γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) mRNA expression in adipose tissue. In skeletal muscle, dietary nCrPic increased phosphatidylinositol 3 kinase (PI3K), AKT, UCP3 and interleukin-15 (IL-15), as well as decreased suppressor of cytokine signaling 3 (SOCS3) mRNA expression. The improvement in insulin signaling and muscle mass and the reduction in carcass fatness by dietary nCrPic may be via decreased SOCS3 and increased UCP3 and IL-15 in skeletal muscle and increased adiponectin in subcutaneous adipose tissue.

Association of Body Mass Index in Youth With Adult Cardiometabolic Risk.

Background Whether long-term exposure to overweight or obesity from early life to adulthood has a detrimental influence on health outcomes is unknown. We aimed to investigate whether duration of overweight or obesity from youth to adulthood is associated with adult cardiometabolic risk. Methods and Results A population-based cohort study was performed of 1268 youths, aged 3 to 18 years, with follow-ups at 3, 6, 9, 12, 21, 27, and 31 years. Duration of overweight or obesity over 31-year follow-up was calculated. Adulthood outcomes included type 2 diabetes mellitus, impaired fasting glucose, high insulin levels, high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity, carotid artery compliance, Young elastic modulus, and stiffness index. Rates of overweight/obesity were 7.9% at baseline and 55.9% after 31 years. After adjustment for confounders, longer duration of overweight or obesity was associated with increased risk of all outcomes (relative risk ranged from 1.45-9.06 for type 2 diabetes mellitus, impaired fasting glucose, carotid intima-media thickness, hypertension, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides; ß from 0.370-0.543 m/s for pulse wave velocity; -0.193 to -0.237 %/10 mm Hg for carotid artery compliance; 52.1-136.8 mm Hg·mm for Young elastic modulus; and 0.554-0.882 for stiffness index). When body mass index was further adjusted, these associations disappeared or were substantially reduced. Detrimental associations of adult body mass index with all outcomes were robust to adjustment for confounders and duration of overweight or obesity. Conclusions Overweight or obesity in adulthood rather than childhood appears to be more important for adult cardiometabolic health.

Body Mass Index From Early to Late Childhood and Cardiometabolic Measurements at 11 to 12 Years.

OBJECTIVES: To examine how overweight and obesity at specific ages and overall BMI growth patterns throughout childhood predict cardiometabolic phenotypes at 11 to 12 years. METHODS: In a population-based sample of 5107 infants, BMI was measured every 2 years between ages 2 to 3 and 10 to 11 years. We identified 5 BMI trajectories using growth curve models. At ages 11 to 12 years, 1811 children completed assessments for metabolic syndrome risk scores, carotid-femoral pulse wave velocity, and carotid intima-media thickness. Multivariable regression models were used to estimate associations, adjusted for potential confounders (eg, age, sex, smoking exposure, and small for gestational age). RESULTS: Overweight and obesity from early childhood onward were strongly associated with higher cardiometabolic risk at 11 to 12 years of age. At age 6 to 7 years, compared with those with a healthy weight, children with overweight had higher metabolic syndrome risk scores by 0.23 SD units (95% confidence interval 0.05 to 0.41) and with obesity by 0.76 SD units (0.51-1.01), with associations almost doubling by age 10 to 11 years. Obese (but not overweight) children had higher outcome pulse wave velocity (0.64-0.73 SD units) from ages 6 to 7 years and slightly higher outcome carotid intima-media thickness (0.20-0.30 SD units) at all ages. Cumulative exposure to high BMI from 2 to 3 years of age carried the greatest cardiometabolic risk, with a gradient of risk across trajectories. CONCLUSIONS: High early-childhood BMI is already silently associated with the development of cardiometabolic risk by 11 to 12 years, highlighting the urgent need for effective action to reduce overweight and obesity in early childhood.

Longitudinal association of a body mass index (BMI) genetic risk score with growth and BMI changes across the life course: The Cardiovascular Risk in Young Finns Study.

BACKGROUND: The role of genetic risk scores associated with adult body mass index (BMI) on BMI levels across the life course is unclear. We examined if a 97 single nucleotide polymorphism weighted genetic risk score (wGRS97) associated with age-related progression in BMI at different life stages and distinct developmental trajectories of BMI across the early life course. METHODS: 2188 Cardiovascular Risk in Young Finns Study participants born pre-1980 who had genotype data and objective measurements of height and weight collected up to 8 times from age 6 to 49 years. Associations were examined using Individual Growth Curve analysis, Latent Class Growth Mixture Modelling, and Poisson modified regression. RESULTS: The wGRS97 associated with BMI from age 6 years with peak effect sizes observed at age 30 years (females: 1.14 kg/m2; males: 1.09 kg/m2 higher BMI per standard deviation increase in wGRS97). The association between wGRS97 and BMI became stronger with age in childhood but slowed in adolescence, especially in females, and weakened at age 35-40 years. A higher wGRS97 associated with an increased BMI velocity in childhood and adulthood, but not with BMI change in adulthood. Compared with belonging to a 'normal stable' life-course trajectory group (normal BMI from childhood to adulthood), a one standard deviation higher wGRS97 associated with a 13-127% increased risk of belonging to a less favourable life-course BMI trajectory group. CONCLUSIONS: Individuals with genetic susceptibility to higher adult BMI have higher levels and accelerated rates of increase in BMI in childhood/adolescence, and are at increased risk of having a less favourable life-course BMI trajectory.

Lower grip strength in youth with obesity identifies those with increased cardiometabolic risk.

BACKGROUND: We examined whether grip strength differentiates youth with obesity with increased cardiometabolic risk. METHODS: The sample comprised 43 youth with severe obesity (mean age 14.8, standard deviation 3.0 years) enrolled in the Childhood Overweight BioRepository of Australia. Grip strength was normalized to body mass and categorized as low and moderate/high. RESULTS: Youth with low grip strength had higher systolic blood pressure (mean difference 13mmHg), low-density lipoprotein cholesterol (0.26mmol/l), continuous metabolic syndrome score (0.36), and carotid intima-media thickness (0.05mm) compared with those with moderate/high grip strength. CONCLUSIONS: Low grip strength may differentiate youth with obesity with increased cardiometabolic risk.