High Cardiometabolic Risk Research Articles

OR12-4 Metabolic Profiling in Adrenal Tumors Demonstrates Enhanced Chronic Inflammation, Branched Chain Amino Acids and Ketone Bodies, Biomarkers that Predict High Cardiometabolic Risk

Abstract Background Patients with adrenal hormone excess demonstrate an increased cardiovascular risk and mortality. We aimed to determine the impact of adrenal hormone excess on the metabolic profile that included plasma lipoproteins, total branched-chain amino acids (BCAA), ketone bodies, and GlycA (a proinflammatory glycoprotein biomarker). Method: We conducted a single-center cross-sectional study of consecutive patients with adrenal adenomas, Cushing syndrome (CS), and pheochromocytoma/paragangliomas (PPGL) between January 2015 and May 2021. Adrenal adenomas comprised nonfunctioning adenomas (NFA), adenomas with mild autonomous cortisol secretion (MACS), and primary aldosteronism (PA). Malignant and other benign tumors were excluded. Collected fasting plasma samples were measured using nuclear magnetic resonance spectroscopy for lipoproteins, BCCA, ketone bodies and GlycA. The results were compared to referent subjects from PREVEND (Prevention of Renal and Vascular End-stage Disease) study. Lipoprotein Insulin Resistance Index (LP-IR) which predicts incident diabetes was calculated based on 6 lipoprotein parameters. Results NFA (n=166, median age 60.1years, 63.3% women), MACS (n=158 (median age 61.8 years, 62. 0% women), CS (n=101, median age 43.8 years, 85.1% women), PA (n=71 (median age 55.8 years, 31. 0% women), PPGL (n=43, median age 55.5 years, 46.5% women) was diagnosed in 539 patients. Referent subjects (n=6540) were younger with a median age of 48.4, 50.2% women. When compared to referent subjects, and after age and sex-adjustment, GlycA was highest in patients with CS (OR 3.3, 95% CI 2.8-3.8), followed by PPGL (OR 2.3, 95%CI 1.8-2.9), MACS (OR 2, 95%CI 1.7-2.3), NFA (OR 1.9, 95%CI 1.7-2.2), and PA (OR 1.5, 95%CI 1.2-1.8). When compared to referent subjects, and after sex- and age adjustment, all patient groups demonstrated increase in BCAA: CS (OR 2.7 (95%CI 2.3-3.2), PPGL (OR 2.3, 95% CI 1.8-2.9), NFA (OR 2.4, 95% CI 2.1-2.7), PA (OR 2. 0, 95%CI 1.7-2.5), MACS (OR 2.2, 95% CI 1.7-2.6). Total ketone bodies were increased in patients with cortisol excess (OR of 1.4, 95%CI 1.2-1.5 in CS, and OR of 1.2, 95%CI 1-1.3 in MACS) and NFA (OR 1.2, 95%CI 1.1-1.3), but not in PA or PPGL. All patient groups except PPGL were more likely to have a higher LP-IR score. When compared to referent subjects, the highest sex- and age-adjusted LP-IR increase was in patients with CS (OR 1.9 (95%CI 1.5-2.2), followed by MACS (OR 1.4, 95% CI 1.2-1.7), PA (OR 1.4, 95%CI 1.1-1.8), and NFA (OR 1.4, 95% CI 1.2-1.7). Conclusion Patient with adrenal adenomas and PPGL demonstrate an increase in GlycA, BCAA, and ketone bodies - biomarkers associated with adverse cardiometabolic disorders and mortality. All patients except those with PPGL also demonstrated a higher LP-IR index that was reported to predict incident diabetes. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

Cardiometabolic Risk and Cardiovascular Disease in Young Women With Uterine Fibroids.

Uterine fibroids are associated with hypertension and cardiometabolic risk factors, yet the onset and severity of cardiovascular disease (CVD) in women with fibroids remain understudied. We used data from the National Health and Nutrition Examination Survey to assess the association between uterine fibroids, cardiometabolic risk, and CVD (ischemic heart disease, heart failure, and stroke). Among 5,552 women aged 20-54 years in our sample. Hypertension was more common in those diagnosed with fibroids (n=700; 33.4% vs. 15.3% in controls, p<0.001), but these women were also older (44 (SD=7) years vs. 35 (SD=10) years). When stratified by median age, women aged 35 or younger with fibroids (n=97) were more likely than controls (n=2771) to have hypertension (14.1% vs. 2.4%), obesity (51.5% vs. 32.5%), and diabetes mellitus (4.8% vs. 1.9%). Women older than 35 with fibroids also had higher cardiometabolic risk and rates of CVD than controls (8.5% vs. 4.5%). The odds ratio of CVD in women with fibroids, compared to the controls, was 3.10 with 95% confidence interval (CI) of 2.21 to 4.34. The odds ratio decreased to 1.63 (95%CI: 1.11 to 2.38) after adjusting for age, BMI, African ancestry, fasting plasma glucose, cholesterol, education, smoking history, and postmenopausal status and to 1.60 (95%CI: 1.08 to 2.37) after further adjusting for systolic blood pressure. These data indicate that uterine fibroids are associated with a worse cardiovascular risk profile, including hypertension, in relatively young women, leading to early CVD. A women-specific research agenda is urgently needed to study the nature of these associations and design preventive strategies to prevent cardiovascular events in young women with fibroids.

Racial and Ethnic Cardiometabolic Risk Disparities in the Type 1 Diabetes Exchange Clinic Registry Cohort

ObjectiveTo determine whether individuals from a historically underrepresented racial group have a higher cardiometabolic risk than historically represented individuals with type 1 diabetes (T1D) considering socioeconomic deprivation. MethodsWe used the multivariable logistic and linear regression models to examine socioeconomic deprivation (upper 10th percentile) by race/ethnicity interaction for each cardiometabolic risk factor and cardiometabolic risk burden score, respectively, across 6320 zip code tabulation areas. We also determined the age-adjusted prevalence of low, moderate, and high cardiometabolic risks defined as 0, 1 to 2, and 3 or more risk factors for hypertension, obesity, dyslipidemia, and off-target glycemia for non-Hispanic White (n = 15 746), non-Hispanic Black (n = 1019), Hispanic (n = 1115), and other (n = 887), respectively. ResultsThe sample comprised 18 767 adolescents and adults with T1D. Those identifying as non-Hispanic Black were more likely to have a high cardiometabolic risk profile, including a 4.5-fold increase in the odds of off-target glycemia, a twofold increase in the odds of systolic hypertension, and 0.29 (unadjusted) and 0.46 (adjusted) increases in a higher cardiometabolic risk burden compared with non-Hispanic White individuals (P < .01). Those identifying as Hispanic had a 3.4-fold increase in the odds of off-target glycemia but were less likely to be overweight/obese or have systolic hypertension compared with non-Hispanic White. However, the lower likelihood of overweight/obesity and hypertension did not persist after considering covariates. ConclusionThere is a need to investigate additional determinants of racially/ethnically underrepresented cardiometabolic health, including structural racism and implicit bias in cardiometabolic care for individuals with T1D.

Acanthosis Nigricans: Pointer of Endocrine Entities.

Acanthosis nigricans (AN) has been reported in relation to insulin resistance (IR). We aim to review AN through an endocrine and metabolic perspective focusing on IR in association with metabolic complications such as obesity, diabetes mellitus (DM), and metabolic syndrome (MS) with/without polycystic ovary syndrome (PCOS). We revised English papers on PubMed covering publications from the last 5 years. The current prevalence of AN varies from 4.5 to 74% (or even 100%, depending on the studied population), with equal distribution among females and males. Despite higher incidence with an age-dependent pattern, an alarming escalation of cases has been noted for obesity and MS in younger populations. Most frequent IR-associated sites are the neck, axilla, and knuckles, but unusual locations such as the face have also been reported. Quantitative scales such as Burke have been used to describe the severity of the dermatosis, particularly in correlation with IR elements. Dermoscopic examination are required, for instance, in cases with sulcus cutis, hyperpigmented spots, crista cutis, and papillary projections. A skin biopsy may be necessary, but it is not the rule. Both IR that clinically manifests with or without obesity/MS correlates with AN; most studies are cross-sectional, with only a few longitudinal. The approach varied from screening during school periodic checkups/protocols/programs to subgroups of individuals who were already known to be at high cardio-metabolic risk. AN was associated with type2DM, as well as type 1DM. Females with PCOS may already display metabolic complications in 60–80% of cases, with AN belonging to the associated skin spectrum. AN management depends on underlying conditions, and specific dermatological therapy is not generally required, unless the patient achieves metabolic control, has severe skin lesions, or desires cosmetic improvement. In IR cases, lifestyle interventions can help, including weight control up to bariatric surgery. In addition, metformin is a key player in the field of oral medication against DM type 2, a drug whose indication is extended to PCOS and even to AN itself, outside the specific panel of glucose anomalies. In terms of cosmetic intervention, limited data have been published on melatonin, urea cream, topical retinoids, vitamin D analogs, or alexandrite laser. In conclusion, awareness of IR and its associated clinical features is essential to provide prompt recognition of underlying conditions. AN represents a useful non-invasive surrogate marker of this spectrum in both children and adults. The pivotal role of this dermatosis could massively improve endocrine and metabolic assessments.

Atherogenic lipoprotein profile associated with anthropometric indices of obesity and their association with cardiometabolic risk markers: a cross-sectional study in community

Abstract Background Obesity, especially abdominal fat accumulation, is strongly associated with various metabolic comorbidities. Whether simple anthropometric measures are independently associated with atherogenic lipoproteins is not completely clear. Methods We randomly recruited 505 participants (51.5% women; mean age: 48.8 years) from the Flemish community, who had undergone lipoprotein particle measurements by nuclear magnetic resonance spectroscopy and conventional lipid measurements. Each lipoprotein fraction was subgrouped into large, medium, and small subclass. Anthropometric measures included body mass index (BMI) and waist-to-hip ratio (WHR), and defined BMI obesity as BMI ≥30 kg/m2, and WHR obesity as WHR ≥0.85 (women) or 0.9 (men). Results In the multivariable logistic regression analysis, total very-low-density lipoprotein (VLDL) particle and its subclasses were positively associated with BMI obesity (adjusted odds ratio [OR] for total VLDL: 2.37; 95% confidence interval [CI]: 1.70–3.31) and WHR obesity (OR for total VLDL: 2.06 [95% CI: 1.55–2.73]). The level of total high-density lipoprotein (HDL) particle and its subclass was negatively associated with BMI (OR for total HDL: 0.63 [95% CI: 0.45–0.90), but not with WHR (P≥0.11). None of the low-density lipoprotein (LDL) particles was associated with the two types of obesity (P≥0.092). BMI was inversely associated with the size of LDL and HDL particles, whereas high WHR was significantly associated with smaller VLDL and HDL sizes. For conventional lipid measures, both BMI and WHR were independently associated with high triglyceride and remnant cholesterol, both mainly driven from VLDL particles, and low HDL cholesterol (P≤0.008). These associations were confirmed in multivariable linear regression analysis, except the association of BMI with HDL number and the association of WHR with HDL size. With partial least squares analysis, the lipoprotein profiles of BMI and WHR were significantly associated with a high 10-year cardiovascular disease risk score, the homeostasis model assessment-estimated insulin resistance (HOMA-IR), and C-reactive protein. Conclusion BMI and WHR were independently associated with high triglyceride-rich lipoproteins, decreased HDL cholesterol. The size of LDL and HDL was more consistently associated with BMI than WHR. The lipoprotein alterations may link obesity with high cardiometabolic risk. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): The European Research Council; the European Research Area Net for Cardiovascular Diseases

Adolescent sleep duration and cardiometabolic risk in adulthood: Evidence from sibling comparison designs with biomarker data.

Despite the well-established link between sleep patterns and physical health, less is known about whether sleep duration during adolescence is related to physical health in adulthood. This study examines: (a) whether there is an association between sleep duration in adolescence and cardiometabolic risk in adulthood, and (b) whether this association differs by sex. Using data from the National Longitudinal study of Adolescent to Adult Health, this study estimates sibling fixed effects models to account for unobservable family-specific heterogeneity. This study investigates whether sleep duration in adolescence is associated with cardiometabolic risk in adulthood, independently of sleep duration in adulthood. Conventional OLS regression models showed that, compared with individuals who slept 8-9 hr per night during adolescence, those who slept 6 or fewer hours had higher cardiometabolic risk in adulthood (about 13 years later). This was the case for both females and males. Controlling for unobserved family heterogeneity, however, substantially attenuated the association among females, rendering it statistically insignificant. The association for males was robust to controlling for sibling fixed effects. This study also found that the observed association for males is not explained by sleep duration in adulthood. Adolescent sleep duration is associated with cardiometabolic risk in adulthood among males, but not females. A life course approach should be adopted in interventions aiming to reduce cardiovascular disease and diabetes. In particular, this study suggests that a fruitful approach to preventing cardiovascular issues in adulthood includes public health interventions that promote healthy sleeping patterns during adolescence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Early Signs of Autonomic Nervous System Imbalance in Children with High Cardiometabolic Risk

Objective:Autonomic nervous system is involved in many disorders, and changes in its modulation are the known risk factors for cardiovascular diseases. Its role in metabolic disarrangements in children at high cardio-metabolic risk is not known. Aim of the study is to analyze the relation between clinical-metabolic parameters and autonomic nervous system in children.Materials and Methods:Children affected by type 1 diabetes (group 1), obesity (group 2), and control group (group 3) were enrolled. Autonomic nervous system functionality was assessed with dynamic tests (The Expiration to Inspiration indexes—E/I delta and ratio, 30:15 Ratio Test, Systolic blood pressure response to standing—deltaPA), and ultrasonography was performed to evaluate Intima Media Thickness (cIMT). Clinical parameters were recorded.Results:The study popultaion had a total of 75 children with mean age of 12.5 ± 2.8 years: 26 in group 1, 28 in group 2, 21 in group 3. Obese children had higher cIMT z-score (P < .001). Diabetic patients had lower EI delta values (P < .001) and 30:15 ratio test (P = .01). There was an inverse correlation between E/I delta and microalbuminuria levels (rho −0.955, P < .001) and 30:15 ratio test and microalbuminuria (rho −0.936, P < .001) in group 1, even after adjustment for age. DeltaPA was higher in obese (P = .032) and correlated with BMI z-score and homeostatic model assessment.Conclusion:Our results highlight imbalances in sutonomic nervous system function in children at high metabolic risk, in particular with involvement of parasympathetic function in type 1 Diabetes Mellitus and sympathetic one in obesity. An early screening could lead to a prompt identification of these alterations and could have a predictive role on cardio-metabolic risk.

Screening for primary aldosteronism in the diabetic population: a cohort study.

Primary aldosteronism (PA) is the most common endocrine cause of hypertension. It is associated with higher cardio-metabolic risk than essential hypertension. Hypertension is common in patients with type 2 diabetes who carry increased cardiovascular risk; however, it is unknown how frequently they are tested for PA. To assess the extent to which the Endocrine Society's 2016 PA screening guidelines have been applied in a tertiary diabetes care setting and evaluate the demographic, clinical and biochemical characteristics of patients who met screening criteria compared with those who did not. This is a retrospective cohort study. Data were collected from 272 patients who attended tertiary diabetes clinics and had two or more blood pressure measurements from January to December 2018. Of 272 patients, 60 (22.1%) had indication(s) for PA screening, but only 14 (23.3%) of 60 were screened using the aldosterone-to-renin ratio (ARR). Five patients who did not meet screening criteria were screened. Only one of 19 patients screened had an abnormal ARR; however, 16 were taking medications known to affect aldosterone and/or renin production. In a tertiary diabetes outpatient setting, only a minority of patients who fulfilled the Endocrine Society criteria for PA screening were actually screened. Appropriate screening for PA in the diabetic hypertensive population is necessary for the diagnosis and targeted treatment of a highly modifiable cardiovascular risk factor. Further studies are needed to develop feasible strategies to identify patients with PA in this population.

Early Signs of Autonomic Nervous System Imbalance in Children with High Cardiometabolic Risk.

Autonomic nervous system is involved in many disorders, and changes in its modulation are the known risk factors for cardiovascular diseases. Its role in metabolic disarrangements in children at high cardio-metabolic risk is not known. Aim of the study is to analyze the relation between clinical-metabolic parameters and autonomic nervous system in children. Children affected by type 1 diabetes (group 1), obesity (group 2), and control group (group 3) were enrolled. Autonomic nervous system functionality was assessed with dynamic tests (The Expiration to Inspiration indexes-E/I delta and ratio, 30:15 Ratio Test, Systolic blood pressure response to standing-deltaPA), and ultrasonography was performed to evaluate Intima Media Thickness (cIMT). Clinical parameters were recorded. The study popultaion had a total of 75 children with mean age of 12.5 ± 2.8 years: 26 in group 1, 28 in group 2, 21 in group 3. Obese children had higher cIMT z-score (P < .001). Diabetic patients had lower EI delta values (P < .001) and 30:15 ratio test (P = .01). There was an inverse correlation between E/I delta and microalbuminuria levels (rho -0.955, P < .001) and 30:15 ratio test and microalbuminuria (rho -0.936, P < .001) in group 1, even after adjustment for age. DeltaPA was higher in obese (P = .032) and correlated with BMI z-score and homeostatic model assessment. Our results highlight imbalances in sutonomic nervous system function in children at high metabolic risk, in particular with involvement of parasympathetic function in type 1 Diabetes Mellitus and sympathetic one in obesity. An early screening could lead to a prompt identification of these alterations and could have a predictive role on cardio-metabolic risk.

Retinol and Retinol Binding Protein 4 Levels and Cardiometabolic Disease Risk.

Background:Despite mechanistic studies linking retinol and RBP4 (retinol binding protein 4) to the pathogenesis of cardiovascular diseases (CVD) and type 2 diabetes (T2D), epidemiological evidence is still conflicting. We investigated whether conflicting results of previous studies may be explained by differences in the association of retinol and RBP4 with cardiometabolic risk across subgroups with distinct sex, hypertension state, liver, or kidney function.Methods:We used case-cohorts nested in the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Potsdam cohort (N=27 548) comprising a random sample of participants (n=2500) and all physician-verified cases of incident CVD (n=508, median follow-up time 8.2 years) and T2D (n=820, median follow-up time 6.3 years). We estimated nonlinear and linear multivariable-adjusted associations between the biomarkers and cardiometabolic diseases by restricted cubic splines and Cox regression, respectively, testing potential interactions with hypertension, liver, and kidney function. Additionally, we performed 2-sample Mendelian Randomization analyses in publicly available data.Results:The association of retinol with cardiometabolic risk was modified by hypertension state (P interaction CVD<0.001; P interaction T2D<0.001). Retinol was associated with lower cardiometabolic risk in participants with treated hypertension (hazard ratioper SD [95% CI]: CVD, 0.71 [0.56–0.90]; T2D, 0.81 [0.70–0.94]) but with higher cardiometabolic risk in normotensive participants (CVD, 1.32 [1.06–1.64]; T2D, 1.15 [0.98–1.36]). Our analyses also indicated a significant interaction between RBP4 and hypertension on CVD risk (P interaction=0.04). Regarding T2D risk, we observed a u-shaped association with RBP4 in women (P nonlinearity=0.01, P effect=0.02) and no statistically significant association in men. The biomarkers’ interactions with liver or kidney function were not statistically significant. Hypertension state-specific associations for retinol concentrations with cardiovascular mortality risk were replicated in National Health and Nutrition Examination Survey III.Conclusions:Our findings suggest a hypertension-dependent relationship between plasma retinol and cardiometabolic risk and complex interactions of RBP4 with sex and hypertension on cardiometabolic risk.

Prevalence and associated factors of metabolic body size phenotype in children and adolescents: A national cross-sectional analysis in China.

BackgroundMetabolically healthy obesity (MHO) is a group of subjects with overweight/obesity who present a metabolically healthy profile; however, associated factors are complex and are far from completely understood. The aim of the current study was to estimate the prevalence of different metabolic body size phenotypes and investigate the associated factors in Chinese children and adolescents.MethodsA cross-sectional survey was conducted of 12,346 children and adolescents aged 7–18 years from seven provinces in China in 2013. Anthropometric, blood pressure, and biochemical measurements were obtained. A multi-component questionnaire covering demographic, neonatal, and lifestyle characteristics was administered. The classification of metabolic body size phenotype based on three definitions was compared. With metabolically healthy with normal weight (MHNW) as a reference group, logistic regression analyses were used to estimate the potential effects of associated risk factors, with adjustment for age, sex, single-child status, and residence area.ResultsThe prevalence of MHNW, MHO, metabolically unhealthy with normal weight (MUNW), and metabolically unhealthy overweight/obesity (MUO) phenotype was 68.6%, 2.0%, 26.4%, and 3.0%, respectively. There were 39.3% MHO and 60.7% MUO among obese participants and 72.2% MHNW and 27.8% MUNW among those with normal weight. Compared to cardiometabolic risk factor (CMRF) criteria and metabolic syndrome (MetS) component definition, the application of the 2018 consensus-based definition may identify more children with abnormal cardiovascular risks, independent of weight status. Compared to younger children, older-aged adolescents were positively associated with higher risks of MUNW (odds ratio (OR) = 1.38, 95% CI = 1.27–1.50) and MUO (OR = 1.29, 95% CI = 1.04–1.60), while factors positively associated with MHO were younger age, single-child status, urban residence, high birth weight, prolonged breastfeeding duration, parental overweight/obesity status, long screen time, and less physical activity.ConclusionThere were still a high proportion of children and adolescents at high cardiometabolic risk in China. Our findings reinforce the need for cardiometabolic risk prevention in children and adolescents irrespective of their weight statuses, such as parental educational programs and healthy lifestyle interventions.

Adherence to Combined Healthy Movement Behavior Guidelines among Adolescents: Effects on Cardiometabolic Health Markers.

Background: The combined movement behavior guidelines for adolescents recommend ≥60 min of moderate to vigorous physical activity, ≤2 h of screen time, and 8–10 h of sleep. Considering that the information available on this topic in the young Latin American population is rare, this study aimed to identify the proportion of a sample of Brazilian adolescents meeting individual guidelines as well as the combination of the three healthy movement behavior guidelines. In addition, another objective of the study was to examine the effects of compliance with these guidelines on cardiometabolic health markers. Methods: This is a cross-sectional school-based study, with the participation of 306 adolescents aged 14 to 18 years. A questionnaire with structured questions was applied to collect data on physical activity, screen time, and sleep duration. Cardiometabolic health was assessed by the calculation of a continuous risk score, including twelve markers related to body fat, blood pressure, plasma lipids and lipoproteins, glycemia, and insulin. Results: Only 4.8% (4.3–5.4) of the adolescents met the three healthy movement behavior guidelines, while 9.3% (8.4–10.4) of the sample did not meet any of the guidelines. No significant difference between sexes was found in the simultaneous compliance of the three movement guidelines. Adolescents who did not meet any of the movement guidelines were twice as likely to have higher cardiometabolic risk (OR = 2.05 (1.41–3.17)) than their peers who met all three guidelines. Conclusions: Considering the high proportion of adolescents who did not meet the movement behavior guidelines and the negative effects on cardiometabolic health, it is suggested that future policies and interventions should consider an integrated and holistic approach aimed at simultaneous actions of maximizing physical activity, minimizing screen time, and ensuring sufficient sleep duration.

Uric acid and cardiometabolic risk by gender in youth with type 1 diabetes

The aim of this study was to investigate the association between uric acid (UA) and cardiometabolic risk factors (CMRFs) by sex in youth with type 1 diabetes (T1D). Retrospective data collected from 1323 children and adolescents (5–18 years; 716 boys) with T1D recruited in 9 Italian Pediatric Diabetes Centers were analyzed. CMRFs included UA, HbA1c, blood pressure (BP), cholesterol (TC), HDL, triglycerides (TG), neutrophils (N) and lymphocytes (L) count, glomerular filtration rate (eGFR) (calculated using Schwartz-Lyon equation). In boys, we found a higher age, daily insulin dose, TG, TG/HDL ratio, TC/HDL ratio, systolic BP, N/L ratio and lower HDL, and eGFR across UA tertiles (p = 0.01–0.0001). Similar results were found in girls but not for TG and systolic BP. In boys, the odds ratio (OR) of high levels of TG/HDL ratio, TC/HDL ratio, BP and mildly reduced eGFR (MRGFR) increased for 0.5 mg/dL of UA. Instead, in girls an increased levels of 0.5 mg/dL of UA were associated with high OR of TC/HDL ratio, N/L ratio and MRGFR. Uric acid may represent a useful marker for identifying youth with T1D at high cardiometabolic risk, and this association appears to vary by sex.

Cross-sectional association between physical fitness and cardiometabolic risk in Chilean schoolchildren: the fat but fit paradox.

BackgroundPrevious studies have examined the “fat but fit” paradox, revealing that greater levels of physical fitness may diminish the harmful consequences of excess weight on cardiometabolic risk. Despite the above, specific information about the “fat but fit” paradox in prepuberal population is scarce. The aim of this study was to determine the relationship between cardiometabolic risk across (individual and combined) physical fitness and excess weight status and whether the “fat but fit” paradox is met in the sample of schoolchildren analyzed.MethodsA cross-sectional study was conducted including 452 children (59.1% girls), aged 7–9 years from Santiago (Chile). Physical fitness was assessed as cardiorespiratory fitness and muscular fitness. Cardiorespiratory fitness was determined by the 6-minute-walk-test and muscle strength was assessed by the handgrip and standing long jump tests. Excess weight (overweight and obesity) was computed through body mass index (z-score). Cardiometabolic risk was established by summing the z-score of the serum glucose, triglycerides, high-density lipoprotein, insulin and waist-to-height ratio.ResultsSchoolchildren with high physical fitness (individual or combined) showed the lowest cardiometabolic risk mean scores (P for trend <0.001 for all physical fitness groups). Conversely, schoolchildren with low physical fitness (individual or combined) showed the highest cardiometabolic risk mean scores (P for trend <0.001 for all categories). Additionally, schoolchildren without excess weight and with high individual or combined physical fitness status exhibits lower cardiometabolic risk mean scores compared to schoolchildren with excess weight and low physical fitness status (individual or combined) (P for trend <0.001 for all physical fitness groups). A lower odd of having high cardiometabolic risk was found in schoolchildren without excess weight and with both high physical fitness (both cardiorespiratory fitness and muscular fitness) [odds ratio (OR) =0.08; 95% confidence interval (CI): 0.04 to 0.16] in comparison to those with excess weight and low physical fitness.ConclusionsOur results suggest that improvements in both fatness and aerobic fitness could be associated with lower cardiometabolic risk.

History of infertility and long-term weight, body composition, and blood pressure among women in Project Viva

To evaluate the association of a history of infertility with long-term weight, body composition, and blood pressure. We studied 1581 women from the prospective cohort Project Viva. History of infertility was based on self-reported time to pregnancy ≥12 months or use of medical treatment to conceive for the index or any prior pregnancy; a diagnosis of infertility; claims for infertility treatments/prescriptions abstracted from medical records. The outcomes were weight, waist circumference, and body fat assessed through 12 years postpartum; and blood pressure assessed through 3 years postpartum. We used linear mixed-effect models adjusted for age, race/ethnicity, income, education, marital status, parity, and age at menarche. Three hundred forty-two women (21.6%) had a history of infertility. In adjusted models, women with versus without infertility, had higher average weight (3.29 kg, 95% confidence interval [CI]: 1.35-5.24), waist circumference (2.46 cm, 95% CI: 0.78-4.13) and body fat (1.76 kg, 95% CI: 0.09-3.43). Among younger (18-29 years), but not older (≥30 years) women, infertility was associated with higher systolic (4.08 mmHg, 95% CI: 0.93, 7.23) and diastolic blood pressure (2.16 mmHg, 95% CI: 0.11-4.20). A history of infertility may serve as a marker to identify women at higher cardiometabolic risk.

Acculturation and Cardiometabolic Abnormalities Among Chinese and Korean Americans.

BackgroundStudies generally show that higher acculturation is associated with greater cardiovascular disease (CVD) risk among immigrants in the United States (US). However, few studies have compared how proxies of acculturation are differentially associated with metabolic abnormalities measured using objective biomarkers, self-reported diagnosis, and medication use, particularly among East Asian Americans.MethodsSurvey data and biomarker measurements collected from random (non-fasting) blood samples of Chinese and Korean immigrants in the US (n = 328) were used to examine the associations between two proxies for acculturation (years living in the US and English speaking proficiency) with three cardiometabolic abnormalities (high triglyceride levels, diabetes, and hypercholesterolemia). Poisson regression models estimated prevalence ratios adjusted for demographic characteristics, socioeconomic factors, and body mass index. Gender, Asian subgroup, and household income were tested as potential effect modifiers.ResultsLiving longer in the US was associated with greater likelihood of having high triglycerides. In addition, living longer in the US was associated with greater likelihood of diabetes for people with lower household income and greater likelihood of hypercholesterolemia for people with higher household income. Higher level of English proficiency was less consistently associated with higher cardiometabolic risk, although there was a significant association with greater likelihood of hypercholesterolemia.ConclusionsLonger time lived in the US is associated with higher risk of cardiometabolic abnormalities among Chinese and Korean Americans. Future studies of acculturation and cardiometabolic risk should carefully consider potential mechanisms and what proxy measures of acculturation capture.Trial Registration NumberNCT03481296, date of registration: 3/29/2018.

Breakfast Consumption May Improve Fasting Insulin, HOMA-IR, and HbA1c Levels in Predominately Low-Income, Hispanic Children 7-12 Years of Age.

Children from low-income households and minority families have high cardiometabolic risk. Although breakfast consumption is known to improve cardiometabolic health in children, limited randomized control trials (RCT) have explored this association in low-income and racial/ethnic U.S. minority families. This study conducted secondary analyses from TX Sprouts, a school-based gardening, cooking, and nutrition education RCT, to examine the intervention effect on breakfast consumption and how changes in breakfast consumption impact cardiometabolic risk in predominately low-income, multi-ethnic children. TX Sprouts consisted of 16 schools (8 intervention; 8 control) in greater Austin, TX. A total of 18 lessons were taught, including topics on breakfast consumption benefits and choosing healthy food options at school. Children completed clinical measures (e.g., anthropometrics, body composition via bioelectrical impedance), and the number of breakfast occasions (BO) per week (at home and school) was captured via validated survey at baseline and post-intervention. Post-study—Baseline changes in breakfast consumption were used to categorize students as: maintainers (BO −1 to 1 day/week), decreasers (BO ≤−2 day/week), and increasers (BO ≥2 day/week). Optional fasting blood draws were performed on a subsample. Generalized weighted linear mixed modeling tested differences between intervention and control, with schools as random clusters. Analysis of covariance and linear regression examined changes in breakfast consumption on cardiometabolic outcomes, controlling for age, sex, race/ethnicity, free and reduced-price school meal participation (FRL), school site, breakfast location, physical activity, baseline cardiometabolic measures, and BMI z-score. This study included 1417 children (mean age 9 years; 53% male; 58% Hispanic, 63% FRL; breakfast consumption patterns: 63% maintainers, 16% decreasers, and 21% increasers). There was no intervention effect on changes in breakfast consumption. Compared to decreasers, increasers had an increase in insulin (−0.3 µIU/mL vs. +4.1 µIU/mL; p = 0.01) and a larger increase in HOMA-IR (+0.4 vs. +1.5; p < 0.01). Every one-day increase in breakfast consumption decreased fasting insulin by 0.44 µIU/mL, HOMA-IR by 0.11, and hemoglobin A1c by 0.01% (p ≤ 0.03). Increased breakfast consumption was linked to improved glucose control, suggesting breakfast can mitigate risk in a high-risk population. To better understand underlying mechanisms linking breakfast consumption to improved metabolic health, RCTs focusing on breakfast quality and timing are warranted.

Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS.

BackgroundThe enterosalivary nitrate–nitrite–nitric oxide (NO3–NO2–NO) pathway generates NO following oral microbiota‐mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross‐sectionally.Methods and ResultsThis study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO2, NO, or ammonia [NH3]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation‐to‐depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic Z score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic Z score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH3 summary ratio was inversely associated with a −0.10 (false discovery rate q=0.003) lower composite cardiometabolic Z score in simple adjusted models. Higher NH3 summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate q=0.04) higher composite cardiometabolic Z score.ConclusionsIncreased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.

A clinical update on the molecular pathogenesis of gestational diabetes mellitus and its consequences

Gestational diabetes mellitus (GDM) is becoming more common all over the world, mainly to an increase in maternal obesity. There have been a number of approaches to screening for and diagnosing GDM described, however there is no consensus on which methods are the most effective. For the mother, developing fetus, and children born to mothers with GDM, GDM poses severe short and long-term health hazards. Macrosomia, shoulder dystocia, delivery trauma, and hypoglycemia in the immediate postpartum period are all short-term dangers for the fetus. Increased rates of childhood and adulthood obesity, as well as a higher cardio metabolic risk, are long-term hazards for offspring born to women with GDM. More investigations on the aetiology and underlying mechanisms of gestational diabetes and its complications on the long-term health of offspring are needed to offer a foundation for creating effective therapies during this important period with the goal of promoting lifelong health and well-being.

Abstract 180: South Asian Nativity And Cardiometabolic Risk Factors In Pregnant Women In The United States

Introduction: Women of South Asian (SA) descent have high cardiometabolic risk which may impact obstetric and long-term morbidity and mortality. Data regarding contemporary epidemiology of cardiometabolic risk factors in pregnant women are scarce. Therefore, we sought to investigate contemporary epidemiology of cardiometabolic risk factors in pregnant women in the US with a focus on SA-born women in comparison with United States (US)-born and women born in the rest of the world (ROW). Methods: We used the natality database 2016-2020 to investigate the incidence/prevalence of cardiometabolic risk factors (pre-pregnancy diabetes [pre-DM], gestational diabetes [GDM], pre-pregnancy hypertension [pre-HTN], gestational hypertension [GHTN], smoking, and obesity) in the US, by country of nativity. SA women were defined as women born in Bangladesh, India, Nepal, Pakistan, and Sri Lanka. US women were those born in the US (including US Virgin Islands) and ROW refers to women born in other countries. Results: A total of 18,916,536 pregnancies were studied (370,619 SA; 14,745,134 US; and 3,800,783 ROW). SA women had higher risk of pre-DM compared with US and ROW (1.2% vs 0.9% vs 1.0%), GDM (15.7% vs 5.9% vs 8.8%), but lower rates of pre-HTN (0.9% vs 2.3% vs 1.3%), GHTN (4.2% vs 7.8% vs 4.9%), obesity (11.2% vs 29.6% vs 20.2%), and smoking (0.1% vs 8.1% vs 0.6%). Between 2016 and 2020, there was a significant increase in cardiometabolic risk factors in SA women: pre-DM (1.2% to 1.5%), GDM (14% to 17.7%), pre-HTN (0.8% to 1.0%), GHTN (3.7% to 5.0%), obesity (10% to 12.4%). Conclusions: In this contemporary analysis of pregnant women in the US, SA women had higher risk of pre-DM and GDM compared with US and ROW women. Between 2016 and 2020, there was a significant increase in the rates of all cardiometabolic risk factors in SA women. Intensive preventive strategies should be implemented in high-risk SA pregnant women in the US.