Optimization and Application of Direct Infusion Nanoelectrospray HRMS Method for Large-Scale Urinary Metabolic Phenotyping in Molecular Epidemiology.

Large-scale metabolic profiling requires the development of novel economical high-throughput analytical methods to facilitate characterization of systemic metabolic variation in population phenotypes. We report a fit-for-purpose direct infusion nanoelectrospray high-resolution mass spectrometry (DI-nESI-HRMS) method with time-of-flight detection for rapid targeted parallel analysis of over 40 urinary metabolites. The newly developed 2 min infusion method requires <10 µL of urine sample and generates high-resolution MS profiles in both positive and negative polarities, enabling further data mining and relative quantification of hundreds of metabolites. Here we present optimization of the DI-nESI-HRMS method in a detailed step-by-step guide and provide a workflow with rigorous quality assessment for large-scale studies. We demonstrate for the first time the application of the method for urinary metabolic profiling in human epidemiological investigations. Implementation of the presented DI-nESI-HRMS method enabled cost-efficient analysis of >10 000 24 h urine samples from the INTERMAP study in 12 weeks and >2200 spot urine samples from the ARIC study in <3 weeks with the required sensitivity and accuracy. We illustrate the application of the technique by characterizing the differences in metabolic phenotypes of the USA and Japanese population from the INTERMAP study.

Linking social and built environmental factors to the health of public housing residents: a focus group study.

BACKGROUND: Public housing residents have a high risk of chronic disease, which may be related to neighborhood environmental factors. Our objective was to understand how public housing residents perceive that the social and built environments might influence their health and wellbeing. METHODS: We conducted focus groups of residents from a low-income public housing community in Baltimore, MD to assess their perceptions of health and neighborhood attributes, resources, and social structure. Focus groups were audio-recorded and transcribed verbatim. Two investigators independently coded transcripts for thematic content using editing style analysis technique. RESULTS: Twenty-eight residents participated in six focus groups. All were African American and the majority were women. Most had lived in public housing for more than 5 years. We identified four themes: public housing's unhealthy physical environment limits health and wellbeing, the city environment limits opportunities for healthy lifestyle choices, lack of trust in relationships contributes to social isolation, and increased neighborhood social capital could improve wellbeing. CONCLUSIONS: Changes in housing and city policies might lead to improved environmental health conditions for public housing residents. Policymakers and researchers may consider promoting community cohesiveness to attempt to empower residents in facilitating neighborhood change.

The Sex and Race Specific Relationship between Anthropometry and Body Fat Composition Determined from Computed Tomography: Evidence from the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Few studies have investigated the relationship of anthropometric measurements with computed tomography (CT) body fat composition, and even fewer determined if these relationships differ by sex and race. METHODS: CT scans from 1,851 participants in the population based Multi-Ethnic Study of Atherosclerosis were assessed for visceral and subcutaneous fat areas by semi-automated segmentation of body compartments. Regression models were used to investigate relationships for anthropometry with visceral and subcutaneous fat separately by sex and race/ethnicity. RESULTS: Participants were 50% female, 41% Caucasian, 13% Asian, 21% African American, and 25% Hispanic. For visceral fat, the positive relationship with weight (p = 0.028), waist circumference (p<0.001), waist to hip ratio (p<0.001), and waist to height ratio (p = 0.05) differed by sex, with a steeper slope for men. That is, across the range of these anthropometric measures the rise in visceral fat is faster for men than for women. Additionally, there were differences by race/ethnicity in the relationship with height (p<0.001), weight (p<0.001), waist circumference (p<0.001), hip circumference (p = 0.006), and waist to hip ratio (p = 0.001) with the Hispanic group having shallower slopes. For subcutaneous fat, interaction by sex was found for all anthropometric indices at p<0.05, but not for race/ethnicity. CONCLUSION: The relationship between anthropometry and underlying adiposity differs by sex and race/ethnicity. When anthropometry is used as a proxy for visceral fat in research, sex-specific models should be used.

Diabetes medication use and blood lactate level among participants with type 2 diabetes: the atherosclerosis risk in communities carotid MRI study.

BACKGROUND: The objective of this study is to compare lactate levels between users and non-users of diabetes medications under the hypothesis that the level of lactate is a marker of oxidative capacity. METHODS: The cross-sectional data of 493 participants aged 61-84 with type 2 diabetes who participated in the Atherosclerosis Risk in Communities Carotid MRI study were analyzed using survey weighted linear regression. RESULTS: Median plasma lactate level was 8.58 (95% CI: 8.23, 8.87) mg/dl. Comparing users of diabetic medications with non-users, thiazolidinedione use was significantly associated with lower lactate level (7.57 (6.95-8.25) mg/dL vs. 8.78 (8.43-9.14) mg/dL), metformin use with a slightly higher lactate level (9.02 (8.51-9.58) mg/dL vs. 8.36 (7.96-8.77) mg/dL), and sulfonylurea and insulin use were not associated with lactate level. After adjustment for demographic and lifestyle factors, the plasma lactate level for thiazolidinedione users was 15.78% lower than that for non-users (p<0.001). Considering use of each medication separately and in combination did not change the results. CONCLUSION: In conclusion, thiazolidinedione use was associated with lower plasma lactate level compared to non-use and metformin use was only marginally associated with a slightly higher lactate level. These results are consistent with the previously demonstrated effects of diabetes medications on oxidative metabolism. Further investigation of the role that diabetes medications play in improvement of oxidative metabolism is warranted.

Association of blood lactate with type 2 diabetes: the Atherosclerosis Risk in Communities Carotid MRI Study.

BACKGROUND: Accumulating evidence implicates insufficient oxidative capacity in the development of type 2 diabetes. This notion has not been well tested in large, population-based studies. METHODS: To test this hypothesis, we assessed the cross-sectional association of plasma lactate, an indicator of the gap between oxidative capacity and energy expenditure, with type 2 diabetes in 1709 older adults not taking metformin, who were participants in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study. RESULTS: The prevalence of type 2 diabetes rose across lactate quartiles (11, 14, 20 and 30%; P for trend <0.0001). Following adjustment for demographic factors, physical activity, body mass index and waist circumference, the relative odds of type 2 diabetes across lactate quartiles were 0.98 [95% confidence interval (CI) 0.59-1.64], 1.64 (95% CI 1.03-2.64) and 2.23 (95% CI 1.38-3.59), respectively. Furthermore, lactate was associated with higher fasting glucose among non-diabetic adults. CONCLUSIONS: Plasma lactate was strongly associated with type 2 diabetes in older adults. Plasma lactate deserves greater attention in studies of oxidative capacity and diabetes risk.