Metabolite Signatures of Metabolic Risk Factors and their Longitudinal Changes

Abstract Context: Metabolic dysregulation underlies key metabolic risk factors—obesity, dyslipidemia, and dysglycemia. Objective: To uncover mechanistic links between metabolomic dysregulation and metabolic risk by testing metabolite associations with risk factors cross-sectionally and with risk factor changes over time. Design: Cross-sectional—discovery samples (n = 650; age, 36–69 years) from the Framingham Heart Study (FHS) and replication samples (n = 670; age, 61–76 years) from the BioImage Study, both following a factorial design sampled from high vs low strata of body mass index, lipids, and glucose. Longitudinal—FHS participants (n = 554) with 5–7 years of follow-up for risk factor changes. Setting: Observational studies. Participants: Cross-sectional samples with or without obesity, dysglycemia, and dyslipidemia, excluding prevalent cardiovascular disease and diabetes or dyslipidemia treatment. Age- and sex-matched by group. Interventions: None. Main Outcome Measure(s): Gas chromatography-mass spectrometry detected 119 plasma metabolites. Cross-sectional associations with obesity, dyslipidemia, and dysglycemia were tested in discovery, with external replication of 37 metabolites. Single- and multi-metabolite markers were tested for association with longitudinal changes in risk factors. Results: Cross-sectional metabolite associations were identified with obesity (n = 26), dyslipidemia (n = 21), and dysglycemia (n = 11) in discovery. Glutamic acid, lactic acid, and sitosterol associated with all three risk factors in meta-analysis (P < 4.5 × 10−4). Metabolites associated with longitudinal risk factor changes were enriched for bioactive lipids. Multi-metabolite panels explained 2.5–15.3% of longitudinal changes in metabolic traits. Conclusions: Cross-sectional results implicated dysregulated glutamate cycling and amino acid metabolism in metabolic risk. Certain bioactive lipids were associated with risk factors cross-sectionally and over time, suggesting their upstream role in risk factor progression. Functional studies are needed to validate findings and facilitate translation into treatments or preventive measures.

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Different Risk for Hypertension, Diabetes, Dyslipidemia, and Hyperuricemia According to Level of Body Mass Index in Japanese and American Subjects

Nutrients ◽

10.3390/nu10081011 ◽

2018 ◽

Vol 10 (8) ◽

pp. 1011 ◽

Cited By ~ 20

Author(s):

Masanari Kuwabara ◽

Remi Kuwabara ◽

Koichiro Niwa ◽

Ichiro Hisatome ◽

Gerard Smits ◽

...

Keyword(s):

Risk Factors ◽

Body Mass Index ◽

Risk Factor ◽

Body Mass ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Cross Sectional ◽

Drinking Habits ◽

Definition Of ◽

The U.S

Obesity is a risk factor for hypertension, diabetes mellitus (DM), dyslipidemia, and hyperuricemia. Here, we evaluated whether the same body mass index (BMI) for the U.S. population conferred similar metabolic risk in Japan. This was a cross-sectional analysis involving 90,047 Japanese adults (18–85 years) from St. Luke’s International Hospital, Tokyo, Japan and 14,734 adults from National Health and Nutrition Examination Survey (NHANES) collected in the U.S. We compared the prevalence of hypertension, DM, dyslipidemia, and hyperuricemia according to BMI in Japan and the U.S. The prevalence of hypertension, DM, and dyslipidemia were significantly higher in the U.S. than Japan, whereas the prevalence of hyperuricemia did not differ between countries. Higher BMI was an independent risk factor for hypertension, DM, dyslipidemia, and hyperuricemia both in Japan and in the U.S. after adjusting for age, sex, smoking and drinking habits, chronic kidney disease, and other cardiovascular risk factors. The BMI cut-off above which the prevalence of these cardio-metabolic risk factors increased was significantly higher in the U.S. than in Japan (27 vs. 23 kg/m2 for hypertension, 29 vs. 23 kg/m2 for DM, 26 vs. 22 kg/m2 for dyslipidemia, and 27 vs. 23 kg/m2 for hyperuricemia). Higher BMI is associated with an increased prevalence of hypertension, DM, dyslipidemia, and hyperuricemia both in Japan and U.S. The BMI cut-off above which the prevalence of cardio-metabolic risk factors increases is significantly lower in Japan than the U.S., suggesting that the same definition of overweight/obesity may not be similarly applicable in both countries.

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Abstract P035: Association Between Caregiver and Child Metabolic Risk Factors: Hispanic Community Health Study/Study of Latino (SOL) Youth

Circulation ◽

10.1161/circ.133.suppl_1.p035 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Mercedes R Carnethon ◽

Srikant I Bangdiwala ◽

A. Talavera ◽

Krista Perreira ◽

Samantha Reina ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Age Of Onset ◽

Normal Weight ◽

Metabolic Risk Factors ◽

Health Study ◽

Individual Risk ◽

Metabolic Risk ◽

Cross Sectional ◽

Adult Age

Background: There is limited prior research on the association of metabolic risk factors between youth and their caregivers within Latino families despite the high burden of obesity and the young age of onset of metabolic disorders. Hypothesis: Obesity and metabolic risk factors are correlated between youth and their caregivers. Methods: SOL Youth is a cross-sectional ancillary study of boys and girls ages 8 to 16 years old whose parents/caregivers participated in the HCHS/SOL. We studied 728 boys, 738 girls and 1,020 caregivers (86% women) who completed a clinical examination. Body mass index (BMI), waist circumference, systolic and diastolic blood pressure, fasting glucose, hemoglobin A1c (HbA1c) and lipids (total-, HDL-, and LDL- cholesterol and triglycerides) were measured. Obesity was determined as > 95 th age- and gender- specific percentile of BMI in youth and BMI > 30 kg/m 2 in adults. We used weighted logistic regression to determine the odds of obesity in youth when caregivers were obese and we tested the association of each individual risk factor in caregivers with the same risk factor among youth using weighted linear regression. All models were adjusted for field center, youth age and ancestry and adult age, gender and education levels. Results: On average, boys and girls were 12 years old and caregivers were 41 years old. When caregivers were obese (vs. normal weight), girls and boys were 1.5 (95% CI: 0.92, 2.43) and 3.9 (95% CI: 2.44, 6.29) times more likely to be obese, respectively. Among girls, measures of adiposity, HbA1c, SBP and lipids (except triglycerides) were each positively associated with those same measures among caregivers (Table). Among boys, all measures except glucose and HbA1c were positively associated with caregiver measures. Conclusions: There were notable differences by gender in the odds of obesity among youth when a caregiver was also obese. Strong correlations between caregiver and youth metabolic risk factors underscore the need for family based interventions.

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Eating behavior affects cardio-metabolic risk in high school teenagers in a developing country

Medical Journal of Indonesia ◽

10.13181/mji.oa.193494 ◽

2020 ◽

Vol 29 (1) ◽

pp. 71-81

Author(s):

Rita Suhadi ◽

Phebe Hendra ◽

Dita Maria Virginia ◽

Christianus Heru Setiawan

Keyword(s):

Risk Factors ◽

Heart Rate ◽

Waist Circumference ◽

Eating Behavior ◽

Eating Behaviors ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Cross Sectional ◽

Male Subjects ◽

Female Subjects

BACKGROUND Modernization negatively changes lifestyle, characterized by excessive eating and reduced energy consumption, and concurrently increases the cardiometabolic risk. This study was aimed to evaluate the association between eating behavior and cardio-metabolic risk factors including body mass index (BMI) in percentile, blood pressure (BP) in percentile, waist circumference, and heart rate in total subjects and gender sub-groups. METHODS This analytical cross-sectional study was done from July to November 2018. High schools in four provinces of Indonesia and students were selected using purposive sampling. Subjects’ profiles were collected from interview and cardio-metabolic parameters were measured at the study sites. Data were analyzed with chi-square and independent t-test. RESULTS Subjects who were overweight/obese and had high BP accounted for 27.1% and 9.3–12.0% of the total subjects (n = 768), respectively. Subjects who having breakfast tended to have lower BMI (p = 0.006), and the lower consumption of western meals had lower heart rate (p = 0.02). Male subjects had more meal frequency and had less quantity of snacks than female subjects (p<0.001). Male subjects with routine intake of vegetables had low heart rate (p = 0.03). Female subjects with routine breakfast had better BMI (p<0.001), and lower diastolic BP (p = 0.004) and waist circumference (p = 0.02), whereas those who consumed Western meals had higher heart rate (p = 0.046) and waist circumference (p = 0.001). CONCLUSIONS Eating behaviors are likely to affect cardio-metabolic risk factors, and the effects vary within gender groups.

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Vitamin D status and associated metabolic risk factors among North Korean refugees in South Korea: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2015-009140 ◽

2015 ◽

Vol 5 (11) ◽

pp. e009140 ◽

Cited By ~ 11

Author(s):

Kyeong Jin Kim ◽

Yoon Jung Kim ◽

Sun Hwa Kim ◽

Jee Hyun An ◽

Hye Jin Yoo ◽

...

Keyword(s):

Risk Factors ◽

Vitamin D ◽

South Korea ◽

Cross Sectional Study ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Vitamin D Status ◽

Sectional Study ◽

Cross Sectional ◽

North Korean Refugees

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Metabolic Risk Factors and Associated Morbidities among Adult Urban People in Pyin Oo Lwin Township

Myanmar Health Sciences Research Journal ◽

10.34299/mhsrj.00931 ◽

2019 ◽

Vol 31 (2) ◽

pp. 105-110

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Age Distribution ◽

Metabolic Risk Factors ◽

P Value ◽

Metabolic Risk ◽

Cross Sectional ◽

Total Prevalence ◽

Significant Difference ◽

Urban People

Metabolic syndrome is a cluster of risk factors for type 2 diabetes and cardiovascular disease, with insulin resistance proposed as a linking factor. It is common and is increasing in prevalence worldwide, largely attributed to increasing obesity and sedentary lifestyles, and now is both a public health and clinical problem. This community-based, cross-sectional descriptive study was conducted during 2015 to identify metabolic risk factors and associated morbidities among adult urban people in Pyin Oo Lwin Township. A total of 355 participants, 94 men (26.5%) and 261 women (73.5%) were enrolled. Age distribution was from 18 to 85 years with mean of 49.98 (SD:15.22) years. Metabolic risk factors were identified according to National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) guideline. In this study, central obesity was the highest component with 145 subjects (40.8%) followed by elevated triglycerides 129(36. 3%), elevated blood pressure 104(29.3%), low HDL-cholesterols 85(23.9%), and elevated fasting glucose in only 48 individuals (13.5%). The total prevalence of metabolic syndrome was 35.2% with 26.6% in men and 38.3% in women, respectively. There were statistically significant associations above all five metabolic risk factors with metabolic syndrome (p value <0.001). Regarding its associated morbidities, ECG examinations showed normal 296 cases (83.4%) and abnormal in 59 cases (16.6%) but there was no significant difference between metabolic syndrome and abnormal ECG findings. In conclusion, this study recognizes the high prevalence rate of metabolic syndrome and can be depicted about the metabolic risks as the baseline data for implementation of further activities to reduce the incidence of non-communicable diseases.

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Impact of age, body weight and metabolic risk factors on steroid reference intervals in men

Acta Endocrinologica ◽

10.1530/eje-19-0928 ◽

2020 ◽

Vol 182 (5) ◽

pp. 459-471

Author(s):

Marco Mezzullo ◽

Guido Di Dalmazi ◽

Alessia Fazzini ◽

Margherita Baccini ◽

Andrea Repaci ◽

...

Keyword(s):

Risk Factors ◽

Reference Intervals ◽

Metabolic Risk Factors ◽

Specific Reference ◽

Metabolic Risk ◽

Cross Sectional ◽

Cholesterol Ratio ◽

Age Related ◽

Reference Limits ◽

17 Hydroxyprogesterone

Objective To evaluate the independent impact of age, obesity and metabolic risk factors on 13 circulating steroid levels; to generate reference intervals for adult men. Design Cross-sectional study. Methods Three hundred and fifteen adults, drug-free and apparently healthy men underwent clinical and biochemical evaluation. Thirteen steroids were measured by LC-MS/MS and compared among men with increasing BMI. Moreover, the independent impact of age, BMI and metabolic parameters on steroid levels was estimated. Upper and lower reference limits were generated in steroid-specific reference sub-cohorts and compared with dysmetabolic sub-cohorts. Results We observed lower steroid precursors and testosterone and increase in estrone levels in men with higher BMI ranges. By multivariate analysis, 17-hydroxyprogesterone and dihydrotestosterone decreased with BMI, while cortisol decreased with waist circumference. Estrone increased with BMI and systolic blood pressure. Testosterone decreased with worsening insulin resistance. 17-hydroxypregnenolone and corticosterone decreased with increasing total/HDL-cholesterol ratio. Age-related reference intervals were estimated for 17-hydroxypregnenolone, DHEA, 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol, cortisol and androstenedione, while age-independent reference intervals were estimated for progesterone, 11-deoxycorticosterone, testosterone, dihydrotestosterone, estrone and estradiol. Testosterone lower limit was 2.29 nmol/L lower (P = 0.007) in insulin resistant vs insulin sensitive men. Furthermore, the upper limits for dihydrotestosterone (−0.34 nmol/L, P = 0.045), cortisol (−87 nmol/L, P = 0.045–0.002) and corticosterone (−10.1 nmol/L, P = 0.048–0.016) were lower in overweight/obese, in abdominal obese and in dyslipidaemic subjects compared to reference sub-cohorts, respectively. Conclusions Obesity and mild unmedicated metabolic risk factors alter the circulating steroid profile and bias the estimation of reference limits for testosterone, dihydrotestosterone, cortisol and corticosterone. Applying age-dependent reference intervals is mandatory for steroid precursors and corticosteroids.

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Abstract 14615: The Preventable Causes of Cardiovascular Diseases in China: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors

Circulation ◽

10.1161/circ.132.suppl_3.14615 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Yanping Li ◽

Frank Hu

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Risk Factor ◽

High Blood Pressure ◽

Physical Inactivity ◽

Metabolic Risk Factors ◽

Morbidity And Mortality ◽

Metabolic Risk ◽

Rapid Urbanization ◽

Exposure Distribution

Background: fuelled by rapid urbanization and changes in dietary and lifestyle choices, cardiovascular disease (CVD) has emerged as the leading cause of death in China. Purposes: to estimate the CVD events that potentially contributed to 9 modifiable dietary, lifestyle, and metabolic risk factors in China. Methods: We used data on risk factor exposures in the Chinese population from nationally representative health surveys and CVD morbidity and mortality statistics from the China Health Statistical Yearbook and the National Population Census. We obtained the etiological effects of risk factors on CVD risk, by age, from systematic reviews and meta-analyses of epidemiological studies. We estimated the number of CVD events attributable to all non-optimal levels of each risk factor exposure, by urban/rural, age and sex. Results: Based on the exposure distribution estimated by 2009 China Health Nutrition Survey, the population attributable risk (PAR) on CVD events was 47.3% for high blood pressure, 23.2%, for physical inactivity, 18.5% for smoking, 13.5 for high BMI, 13.0% for high LDL cholesterol, 11.8% for high blood glucose, 11.1% for low dietary intakes of fruit and vegetable, 7.1% for high sodium intake and 3.5% for low PUFA intake, which was 78.0%, 18.8%, 20.9%, 21.9%, 8.2%, 16.1%, 12.0%, 20.3% and 2.0%, respectively, based on exposure distribution of 2002 China National Nutrition and Health Survey. In 2009, high blood pressure was responsible for 3.9 million CVD events, including 1.4 million CHD, 1.5 million ischemic strokes and 1 million hemorrhagic strokes. Large gender difference was found for PAR% of smoking (male 27.8%/female 6.5%). Conclusions: High blood pressure, smoking and physical inactivity, which all have effective interventions, are responsible for the largest number of CVD events in China. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of CVD morbidity and mortality in China.

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Increased Prevalence of Nephrolithiasis and Hyperoxaluria in Paget Disease of Bone

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa576 ◽

2020 ◽

Vol 105 (12) ◽

pp. e4430-e4438 ◽

Cited By ~ 1

Author(s):

Domenico Rendina ◽

Gianpaolo De Filippo ◽

Daniela Merlotti ◽

Marco Di Stefano ◽

Christian Mingiano ◽

...

Keyword(s):

Risk Factors ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Cross Sectional ◽

Metabolic Complications ◽

Multicentric Study ◽

Paget Disease Of Bone ◽

Paget Disease ◽

Metabolic Bone ◽

Metabolic Complication

Abstract Context Nephrolithiasis (NL) and primary hyperparathyroidism (HPTH) are metabolic complications of Paget disease of bone (PDB), but recent data regarding their prevalence in PDB patients are lacking. Objectives Study 1: To compare the prevalence of primary HPTH and NL in 708 patients with PDB and in 1803 controls. Study 2: To evaluate the prevalence of NL-metabolic risk factors in 97 patients with PDB and NL, 219 PDB patients without NL, 364 NL patients without PDB, and 219 controls, all of them without HPTH. Design Cross-sectional multicentric study. Setting Italian referral centers for metabolic bone disorders. Participants Patients with PDB from the Associazione Italiana malati di osteodistrofia di Paget registry. Participants in the Olivetti Heart and the Siena Osteoporosis studies. Main Outcome Measures HPTH; NL; NL-metabolic risk factors. Results Patients with PDB showed higher prevalence of primary HPTH and NL compared with controls (P < 0.01). The NL recurrence occurs more frequently in patients with polyostotic PDB. About one-half of patients with PDB but without NL showed 1 or more NL-related metabolic risk factors. The hyperoxaluria (HyperOx) prevalence was higher in patients with PDB and NL compared with patients with NL but without PDB and in patients with PDB without NL compared with controls (P = 0.01). Patients with PDB and HyperOx showed a longer lapse of time from the last aminobisphosphonate treatment. Conclusions NL and HPTH are frequent metabolic complication of PDB. The NL occurrence should be evaluated in patients with PDB, particularly in those with polyostotic disease and/or after aminobisphosphonate treatment to apply an adequate prevention strategy.

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