Associations of the BDNF Val66Met Polymorphism With Body Composition, Cardiometabolic Risk Factors, and Energy Intake in Youth With Obesity: Findings From the HEARTY Study

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is functionally related to BDNF, and is associated with obesity and metabolic complications in adults, but limited research exists among adolescents. This study comparatively examined carriers and non-carriers of the BDNF Val66Met polymorphism on body composition, energy intake, and cardiometabolic profile among adolescents with obesity. The sample consisted of 187 adolescents with obesity; 99 were carriers of the homozygous Val (G/G) alleles and 88 were carriers of the Val/Met (G/A) or Met (A/A) alleles. Cardiometabolic profile and DNA were quantified from fasted blood samples. Body composition was assessed by magnetic resonance imaging (MRI). Compared to carriers of the homozygous Val (G/G) allele, carriers of the Val/Met (G/A) or Met/Met (A/A) variants exhibited significantly higher protein (p = 0.01) and fat (p = 0.05) intake, C-Reactive protein (p = 0.05), and a trend toward higher overall energy intake (p = 0.07), fat-free mass (p = 0.07), and lower HDL-C (p = 0.07) Results showed for the first time that among youth with obesity, carriers of the Val66Met BDNF Met-alleles exhibited significantly higher C-reactive protein and energy intake in the form of fat and protein compared to Val-allele carriers, thereby providing support for the possible role of BDNF in appetite, weight, and metabolic regulation during adolescence.Clinical Trial Registration:http://clinicaltrials.gov/, identifier NCT00195858.

Resolving early obesity leads to a cardiometabolic profile within normal ranges at 23 years old in a two-decade prospective follow-up study

Obesity is the most important predisposing factor for cardiovascular disease and type-2 diabetes. We explored the relationship between the age at onset of obesity and selected cardiometabolic parameters in young adults. Longitudinal study of n = 1,039 participants (48% males) in their early twenties. BMI was measured at birth, 1–5–10–12–14–16–23 years. BMI trajectories were interpolated. Five groups were identified: never obese (never-OB); early childhood obesity transitioning to non-obesity before adolescence (former-OB); obesity starting in preadolescence transitioning to non-obesity as adolescents (transient-OB); obesity from adolescence into early adulthood (recent-onset-OB); participants who were obese in early childhood and remained obese into adulthood (persistent-OB). Waist circumference (WC), blood pressure, lipids, glucose, and insulin were measured at 23 years. HOMA-IR and the Metabolic Syndrome Risk Z-Score were estimated. In the sample, 47% were obese during at least one time-point. Mean obesity duration was 20.7 years, 8.5 years, 6.2 years, and 3.3 years in persistent-OBs, recent-onset-OBs, former-OBs, and transient-OBs, respectively. The cardiometabolic profile was more adverse in recent-onset-OBs (12%) and persistent-OBs (15%) compared to never-OB participants (53%). Although former-OBs (15%) and transient-OBs (4%) had higher WC values than never-OBs, no differences were seen in other biomarkers. Both persistent and recent-onset obesity led to a cardiometabolic profile of risk in early adulthood, as suggested by values of WC, HOMA-IR, and hs-CRP above normal limits and HDL-chol values below normal limits. Participants who had obesity in early childhood or preadolescence but transitioned to a non-obesity status had a cardiometabolic profile similar to participants who were never obese and within normal limits. Obesity leads to risky values in a number of cardiometabolic biomarkers in young adulthood independent of age at obesity onset. Likewise, overcoming obesity during the pediatric age leads to a cardiometabolic profile within normal ranges at 23 years of age.

Childhood overeating is associated with adverse cardiometabolic and inflammatory profiles in adolescence

Childhood eating behaviour contributes to the rise of obesity and related noncommunicable disease worldwide. However, we lack a deep understanding of biochemical alterations that can arise from aberrant eating behaviour. In this study, we prospectively associate longitudinal trajectories of childhood overeating, undereating, and fussy eating with metabolic markers at age 16 years to explore adolescent metabolic alterations related to specific eating patterns in the first 10 years of life. Data are from the Avon Longitudinal Study of Parents and Children (n = 3104). We measure 158 metabolic markers with a high-throughput (1H) NMR metabolomics platform. Increasing childhood overeating is prospectively associated with an adverse cardiometabolic profile (i.e., hyperlipidemia, hypercholesterolemia, hyperlipoproteinemia) in adolescence; whereas undereating and fussy eating are associated with lower concentrations of the amino acids glutamine and valine, suggesting a potential lack of micronutrients. Here, we show associations between early behavioural indicators of eating and metabolic markers.

Impact of sex and APOE ε4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study

Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer’s disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40—89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13—8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (β=−1.43), hippocampus (−1.25), superior frontal gyrus (−1.70), middle frontal gyrus (−1.99), posterior cingulate (−2.46), and precuneus (−2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.

Nutrients Intakes From Complementary Foods Are Associated With the Cardiometabolic Profile of 3-5-Year-Old Peruvian Amazonian Children

Objectives Characterize relationships between dietary patterns and the cardiometabolic profile of Peruvian children at risk of undernutrition. Methods The study was nested in the Peru site of the ‘MAL-ED’ study, a longitudinal birth cohort to evaluate relationships between diet, enteric exposures and child growth and development. Dietary recalls were collected from 9–24 months of age. At 3–5 years, we conducted a follow-up. Three additional dietary recalls were collected, and blood pressure, height, weight, subscapular skinfolds, and fasting plasma glucose, insulin, and lipid profiles were assessed. Nutrient intakes were expressed as average density per 100 kcals i) from 9–24 months, and ii) at follow-up. Reduced rank regression (RRR) was used to identify the combination of nutrient intakes explaining the greatest variation in the outcome variables. Multiple linear regression models adjusting for subscapular skinfold-for-age Z-scores (SSFZ) were used to test whether observed relationships were mediated by body composition. Results Of the 153 children included, 26% were stunted at follow-up. RRR extracted 2 factors explaining 7% of the variation in infant nutrient intakes and 12% of the variation in response variables. The first factor had higher loadings for vitamin D, calcium, and cholesterol, while the second had higher loadings for non-animal source protein and iron. RRR also extracted 2 factors from the child intake data. These factors had higher loadings for sugar and fats, and sugar and protein, respectively. The first infant RRR factor was associated with lower plasma triglycerides and higher high-density lipoprotein, whereas the second was associated with higher homeostatic model assessment-insulin resistance (HOMA-IR) and weight-for-height Z-scores (WHZ). The first child RRR factor was associated with higher triglycerides, HOMA-IR, and WHZ, and the second was related to higher blood pressure. Associations with glucose and insulin, but not blood pressure or cholesterol, were attenuated after adjusting for SSFZ. Conclusions Nutrient densities of the diet in each childhood are associated with cardiometabolic profile in a chronically undernourished population. Funding Sources The project was supported by the Thrasher Foundation and the BMGF.

Differential Phenotype of Primary Bilateral Macronodular Adrenal Hyperplasia and Other Bilateral Adrenal Lesions With Associated Subclinical Hypercortisolism. Study of 98 Patients.

Purpose: To evaluate the prevalence of primary bilateral macronodular adrenal hyperplasia (PBMAH) in patients with adrenal incidentalomas (AIs) with subclinical hypercortisolism. Also to analyse the differential phenotype of patients with PBMAH compared to other bilateral adrenal lesions which do not meet PBMAH definition.Methods: Retrospective study of patients with AIs diagnosed in our centre between 2013 and 2019 (n=730). Patients with bilateral disease and associated subclinical hypercortisolism (possible ACS or ACS) were included (n=98). Possible ACS and ACS were defined as a cortisol post-1mg-dexamethasone suppression test (DST)>1.8µg/dl but ≤5.0µg/dl and >5.0µg/dl. without specific clinical signs of Cushing´s syndrome, respectively. PBMAH diagnosis was established in patients with subclinical hypercortisolism, hyperplasia and bilateral adrenal nodules >1cm.Results: PBMAH was confirmed in 31.6% of bilateral AIs with subclinical hypercortisolism. Patients with PBMAH presented a higher prevalence of ACS than non-PBMHA (OR 4.1, 95%CI 1.38-12.09, P=0.010), but differences disappeared after adjusting by tumour size and total adenomatous mass (adjusted OR 2.3, 95%CI=0.65-8.27 and 2.3, 95%CI 0.47-11.21, respectively). However, no significant differences in the cardiometabolic profile of both groups were observed. Tumour size and total adenomatous mass were significantly higher in PBMAH (30.2±12.16 vs 24.3±8.47, P=0.010 and 53.9±20.8 vs 43.3±14.62, P=0.023).Conclusion: PBMAH is common in patients with incidentally detected bilateral adrenals lesions with associated subclinical hypercortisolism. The higher prevalence of ACS in PBMAH compared to non-PBMAH is associated with a higher tumour size and total adenomatous mass in PBMHA, but no differences in the cardiometabolic profile were observed between both groups.

Abstract P179: Cardiometabolic Profile Of A Young Adult Population Assisted By A Primary Health Care Unit In Brazil- LAPARC Cohort Study

Introduction: Dyslipidemia, Glucose Intolerance (GI), Diabetes Mellitus (DM), and Metabolic Syndrome (MS) are metabolic conditions often asymptomatic and related to high cardiovascular (CV) morbidity and mortality. Nonetheless, these conditions are not commonly screened in younger adults. The LapARC cohort Study is a population-based study to assess CV risk profile in a young adult population. Objective: To evaluate the prevalence of dyslipidemia, DM, GI, and MS in a young adult population enrolled in the Family Health Strategy (FHS) in the center of Rio de Janeiro, Brazil. Methods: Cross-sectional population study that enrolled individuals aged 20-50 years registered in an FHS unit in Rio de Janeiro. Sociodemographic, anthropometric characteristics, and CV risk factors were recorded. Office blood pressure (BP) was obtained by the average of 2 measurements obtained on two different occasions. All participants underwent laboratory evaluation (lipid and glycemic profile) and home blood pressure monitoring (HBPM). Two screening questionnaires for obstructive sleep apnea (OSA): STOP-BANG (SBQ) and Epworth Sleepiness Scale (ESS) were applied. Results: We evaluated 575 individuals [39% male gender; average age: 39.9 ± 8.7 years old]. The most common modifiable CV risk factors were physical inactivity (43.0%), and obesity (25.0%). The prevalence of dyslipidemia was 57.6%. These individuals had a higher prevalence of male gender (42.0% vs 34.0%), MS (25.0% vs 4.0%), and high risk for OSA by ESS (35.0% vs 27%). A total of 91 individuals (15.8%) were diagnosed with MS, being predominantly males (52.0% vs 36.0%), older and obese (46.0% vs 21.0%), with a higher prevalence of dyslipidemia (90.0% vs 52.0%), GI (20.0% vs 5.0%), hypertension (63.0% vs 18.0%) with uncontrolled office and Home BP. They also had a high risk for OSA by SBQ and ESS (25.0% vs 8.0%). Moreover, a total of 55 (9.6%) subjects presented an altered glycemic profile. These individuals were older with a higher prevalence of obesity (38.0% vs 24.0%), hypertension (36.0% vs 23.0%), uncontrolled HBPM (22.0% vs 12.0%) and MS (29.0% vs 13.0%) when compared to normoglycemic patients. Conclusion: This young and apparently healthy population has an adverse cardiometabolic profile, indicating the importance of precocious CV risk stratification. Thus, efficient primary preventive strategies can be implemented to reduce the probability of CV disease development in the future.