Metabolomics signatures associated with an oral glucose challenge in pregnant women.

AIM: The oral glucose tolerance test (OGTT), widely used as a gold standard for gestational diabetes mellitus (GDM) diagnosis, provides a broad view of glucose pathophysiology in response to a glucose challenge. We conducted the present study to evaluate metabolite changes before and after an oral glucose challenge in pregnancy; and to examine the extent to which metabolites may serve to predict GDM diagnosis in pregnant women. METHODS: Peruvian pregnant women (n=100) attending prenatal clinics (mean gestation 25 weeks) participated in the study with 23% of them having GDM diagnosis. Serum samples were collected immediately prior to and 2-hours after administration of a 75-g OGTT. Targeted metabolic profiling was performed using a LC-MS based metabolomics platform. Changes in metabolite levels were evaluated using paired Student's t-tests and the change patterns were examined at the level of pathways. Multivariate regression procedures were used to examine metabolite pairwise differences associated with subsequent GDM diagnosis. RESULTS: Of the 306 metabolites detected, the relative concentration of 127 metabolites were statistically significantly increased or decreased 2-hours after the oral glucose load (false discovery rate [FDR] corrected P-value<0.001). We identified relative decreases in metabolites in acylcarnitines, fatty acids, and diacylglycerols while relative increases were noted among bile acids. In addition, we found that C58:10 triacylglycerol (ß=-0.08, SE=0.04), C58:9 triacylglycerol (ß=-0.07, SE=0.03), adenosine (ß=0.70, SE=0.32), methionine sulfoxide (ß=0.36, SE=0.13) were significantly associated with GDM diagnosis even after adjusting for age and body mass index. CONCLUSIONS: We identified alterations in maternal serum metabolites, representing distinct cellular and metabolic pathways including fatty acid metabolism, in response to an oral glucose challenge. These findings offer novel perspectives on the pathophysiological mechanisms underlying GDM.

Associations of socioeconomic position in childhood and young adulthood with cardiometabolic risk factors: the Jerusalem Perinatal Family Follow-Up Study.

BACKGROUND: Several stages in the life course have been identified as important to the development of cardiovascular disease. This study aimed to assess the associations of childhood and adulthood socioeconomic position (SEP) and social mobility with cardiometabolic risk factors (CMRs) later in life. METHODS: We conducted follow-up examinations of 1132 offspring, aged 32, within a population-based cohort of all births in Jerusalem from 1974 to 1976. SEP was indicated by parents' occupation and education, and adulthood SEP was based on offspring's occupation and education recorded at age 32. Linear regression models were used to investigate the associations of SEP and social mobility with CMRs. RESULTS: Childhood-occupational SEP was negatively associated with body mass index (BMI; ß=-0.29, p=0.031), fat percentage (fat%; ß=-0.58, p=0.005), insulin (ß=-0.01, p=0.031), triglycerides (ß=-0.02, p=0.024) and low-density lipoprotein cholesterol (LDL-C; ß=-1.91, p=0.015), independent of adulthood SEP. Adulthood-occupational SEP was negatively associated with waist-to-hip ratio (WHR; ß=-0.01, p=0.002), and positively with high-density lipoprotein cholesterol (HDL-C; ß=0.87, p=0.030). Results remained similar after adjustment for smoking and inactivity. Childhood-educational SEP was associated with decreased WHR and LDL-C level (p=0.0002), and adulthood-educational SEP was inversely associated with BMI (p=0.001), waist circumference (p=0.008), WHR (p=0.001) and fat% (p=0.0002) and positively associated with HDL-C (p=0.030). Additionally, social mobility (mainly upward) was shown to have adverse cardiometabolic outcomes. CONCLUSIONS: Both childhood and adulthood SEP contribute independently to CMR. The match-mismatch hypothesis may explain the elevated CMRs among participants experiencing social mobility. Identification of life-course SEP-related aspects that translate into social inequality in cardiovascular risk may facilitate efforts for improving health and for reducing disparities in cardiovascular disease.

Circulating microRNAs and sudden cardiac arrest outcomes.

AIM: MicroRNAs (miRNAs) have regulatory functions in organs critical in resuscitation from sudden cardiac arrest due to ventricular fibrillation (VF-SCA); therefore, circulating miRNAs may be markers of VF-SCA outcome. METHODS: We measured candidate miRNAs (N=45) in plasma using qRT-PCR among participants of a population-based VF-SCA study. Participants were randomly selected cases who died in the field (DF, n=15), died in hospital (DH, n=15), or survived to discharge (DC, n=15), and, age-, sex-, and race-matched controls (n=15). MiRNA levels were compared using ANOVA, t-tests, and fold-changes. RESULTS: Mean age of groups ranged from 66.9 to 69.7. Most participants were male (53-67%) and white (67%). Comparing cases to controls, plasma levels of 17 miRNAs expressed in heart, brain, liver, and other tissues (including miR-29c, -34a, -122, -145, -200a, -210, -499-5p, and -663b) were higher and three non-specific miRNAs lower (miR-221, -330-3p, and -9-5p). Among DH or DC compared with DF cases, levels of two miRNAs (liver-specific miR-122 and non-specific miR-205) were higher and two heart-specific miRNAs (miR-208b and -499-5p) lower. Among DC vs. DF cases, levels of three miRNAs (miR-122, and non-specific miR-200a and -205) were higher and four heart-specific miRNAs (miR-133a, -133b, -208b, and -499-5p) lower. Among DC vs. DH cases, levels of two non-specific miRNAs (miR-135a and -9-3p) were lower. CONCLUSIONS: Circulating miRNAs expressed in heart, brain, and other tissues differ between VF-SCA cases and controls and are related to resuscitation outcomes. Measurement of miRNAs may clarify mechanisms underlying resuscitation, improve prognostication, and guide development of therapies. Results require replication.

Associations of Maternal Urinary Cadmium with Trimester-Specific Blood Pressure in Pregnancy: Role of Dietary Intake of Micronutrients.

Previous studies revealed associations of urinary Cd (U-Cd), a chronic Cd exposure biomarker, with blood pressure (BP) in non-pregnant adults. However, the evidence regarding trimester-specific blood pressure in pregnancy and U-Cd and effect modification by dietary intake of micronutrients is scarce. We randomly selected 653 women from the Omega Study cohort. U-Cd was quantified by inductively coupled plasma mass spectrometry. Trimester-specific, systolic (SBP) and diastolic blood pressure (DBP) were determined employing standard protocols and mean arterial pressure (MAP) was also calculated. Associations of SBP, DBP, and MAP with U-Cd tertiles (≤0.21; 0.22-0.41; ≥0.42 µg/g Cr) were assessed using multivariable linear regression models. We also explored effect modification by pre-pregnancy BMI (≤25 or >25 kg/m2) or low/high micronutrients intake. After adjusting confounders in women with elevated (upper tertile) as compared with those with low (lowest tertile) U-Cd (≥0.42 vs. ≤0.21 µg/g Cr, respectively) had reduced third trimester MAP (-1.8; 95 % confidence interval (CI) = -3.1, -0.5 mmHg) and second trimester MAP (-1.1; 95 % CI = -2.3, -0.03 mmHg). A significant decrease in third-trimester MAP associated with increased U-Cd was observed only among normal/underweight women (BMI ≤ 25 kg/m2) and women with high dietary intake of micronutrients (calcium, magnesium, zinc, and selenium). Notably, U-Cd concentrations increased with the increased consumption of zinc and non-heme iron food sources. No significant differences in U-Cd concentrations were found in preeclamptic women compared with non-preeclamptic women. Our study provides evidence that dietary intake of micronutrients should be taken into account when assessing the health effects of Cd in pregnant women.

Prevalence and correlates of hypertension: a cross-sectional study among rural populations in sub-Saharan Africa.

Substantial evidence suggests an increasing burden of hypertension (HTN) in urban sub-Saharan Africa (SSA). However, data on HTN prevalence in rural SSA are sparse. In a cross-sectional study, we investigated magnitude and correlates of HTN in rural SSA. Study participants (N=1485), 18 years and above, were selected using a stratified random sampling technique from three villages (in Malawi, Rwanda and Tanzania) that participated in the Millennium Villages Project. Information on socio-demographic characteristics, risk factors and blood pressure measures was collected using standardized protocols. Prevalence of HTN and pre-HTN were 22 and 44%, respectively. Older age (P<0.001), higher body mass index (BMI) (P=0.07), television ownership (P=0.01) and less work-related vigorous physical activity (P=0.02) were associated with higher prevalence of HTN and higher blood pressure measures (all P<0.05). Frequent meat and fat intake were associated with higher HTN prevalence (trend P=0.02 and 0.07, respectively). Frequent fruit and vegetable intake was significantly associated with lower blood pressure measures (all P<0.05). HTN and pre-HTN are common in rural SSA. Modifiable risk factors (such as BMI, dietary intake and physical activity) are associated with HTN prevalence in this population, indicating potential opportunities for prevention measures.