Association of Gut Microbiota-Related Metabolites and Type 2 Diabetes in Two Puerto Rican Cohorts.

(1) Aims: Gut microbiota metabolites may play integral roles in human metabolism and disease progression. However, evidence for associations between metabolites and cardiometabolic risk factors is sparse, especially in high-risk Hispanic populations. We aimed to evaluate the cross-sectional and longitudinal relationships between gut microbiota related metabolites and measures of glycemia, dyslipidemia, adiposity, and incident type 2 diabetes in two Hispanic observational cohorts. (2) Methods: We included data from 670 participants of the Boston Puerto Rican Health Study (BPRHS) and 999 participants of the San Juan Overweight Adult Longitudinal Study (SOALS). Questionnaires and clinical examinations were conducted over 3 years of follow-up for SOALS and 6 years of follow-up for BPRHS. Plasma metabolites, including L-carnitine, betaine, choline, and trimethylamine N-oxide (TMAO), were measured at baseline in both studies. We used multivariable linear models to evaluate the associations between metabolites and cardiometabolic risk factors and multivariable logistic and Poisson regressions to assess associations with prevalent and incident type 2 diabetes, adjusted for potential confounding factors. Cohort-specific analyses were combined using a fixed-effects meta-analysis. (3) Results: Higher plasma betaine was prospectively associated with lower fasting glucose [-0.97 mg/dL (95% CI: -1.59, -0.34), p = 0.002], lower HbA1c [-0.02% (95% CI: -0.04, -0.01), p = 0.01], lower HOMA-IR [-0.14 (95% CI: -0.23, -0.05), p = 0.003], and lower fasting insulin [-0.27 mcU/mL (95% CI: -0.51, -0.03), p = 0.02]. Betaine was also associated with a 22% lower incidence of type 2 diabetes (IRR: 0.78, 95% CI: 0.65, 0.95). L-carnitine was associated with lower fasting glucose [-0.68 mg/dL (95% CI: -1.29, -0.07), p = 0.03] and lower HbA1c at follow-up [-0.03% (95% CI: -0.05, -0.01), p < 0.001], while TMAO was associated with higher fasting glucose [0.83 mg/dL (95% CI: 0.22, 1.44), p = 0.01] and higher triglycerides [3.52 mg/dL (95% CI: 1.83, 5.20), p < 0.0001]. Neither choline nor TMAO were associated with incident type 2 diabetes. (4) Conclusions: Higher plasma betaine showed consistent associations with a lower risk of glycemia, insulinemia, and type 2 diabetes. However, TMAO, a metabolite of betaine, was associated with higher glucose and lipid concentrations. These observations demonstrate the importance of gut microbiota metabolites for human cardiometabolic health.

Multidisciplinary approach combining food metabolomics and epidemiology identifies meglutol as an important bioactive metabolite in tempe, an Indonesian fermented food.

This study introduces a multidisciplinary approach to investigate bioactive food metabolites often overlooked due to their low concentrations. We integrated an in-house food metabolite library (n = 494), a human metabolite library (n = 891) from epidemiological studies, and metabolite pharmacological databases to screen for food metabolites with potential bioactivity. We identified six potential metabolites, including meglutol (3-hydroxy-3-methylglutarate), an understudied low-density lipoprotein (LDL)-lowering compound. We further focused on meglutol as a case study to showcase the range of characterizations achievable with this approach. Green pea tempe was identified to contain the highest meglutol concentration (21.8 ± 4.6 mg/100 g). Furthermore, we identified a significant cross-sectional association between plasma meglutol (per 1-standard deviation) and lower LDL cholesterol in two Hispanic adult cohorts (n = 1,628) (ß [standard error]: -5.5 (1.6) mg/dl, P = 0.0005). These findings highlight how multidisciplinary metabolomics can serve as a systematic tool for discovering and enhancing bioactive metabolites in food, such as meglutol, with potential applications in personalized dietary approaches for disease prevention.

Impact of Hurricanes Irma and Maria on Asthma, Hypertension, and Depression in a Sample of the Puerto Rico Population.

OBJECTIVE: To evaluate the impact of Hurricanes Irma and Maria on 3 major chronic diseases in Puerto Rico. METHODS: San Juan Overweight Adults Longitudinal study participants were re-evaluated after Hurricanes Irma and Maria (May 2019-July 2020) for the Preparedness to Reduce Exposures and Diseases Post-hurricanes and Augment Resilience study. This study compared the prevalence and incidence of asthma, depression, and hypertension within the same 364 individuals over time. RESULTS: Asthma and depression prevalence and incidence did not change significantly after the hurricanes. The prevalence of hypertension increased significantly after the hurricanes (OR = 2.2, 95% CI: 1.2, 3.9). The incidence of hypertension after the hurricanes (IR = 9.0, 95% CI: 6.5, 12.4) increased significantly compared to before the hurricanes (IR = 6.1, 95% CI: 4.5, 8.0) (age-adjusted incidence rate ratio [aIRR] = 1.4, 95% CI: 4.5, 8.0) for similar time periods. CONCLUSION: Hurricanes Irma and Maria were associated with a significant increase in the prevalence and incidence of hypertension in this study population. Contrary to expectations, no significant increases were observed in depression and asthma prevalence after the hurricanes. Results from this study can inform better strategies to prevent and manage hypertension in the population affected by a hurricane.

Longitudinal Association between Periodontitis and the Risk of Hypertension.

Objectives: Hypertension poses a major public health challenge due to its association with increased risk of heart disease, chronic kidney disease, and death. The objective of this study is to evaluate the longitudinal association between periodontitis and the risk of hypertension. Methods: Using a cohort study design, 540 participants free of diagnosed hypertension/prehypertension in the San Juan Overweight Adults Longitudinal Study and with complete 3-year follow-up data were included. Periodontitis was classified according to the 2012 Centers for Disease Control and Prevention/American Academy of Periodontology definition. Participants were considered to have developed hypertension if they reported physician-diagnosed hypertension over the follow-up period or had average systolic blood pressure (SBP) ≥140 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg at follow-up. Participants free of diagnosed hypertension or prehypertension and with normal BP at baseline (SBP < 120 mm Hg and DBP < 80 mm Hg) were considered to develop prehypertension if they had SBP between 120 and 139 mm Hg or DBP between 80 and 89 mm Hg at follow-up. An additional (secondary) outcome was defined as the development of prehypertension/hypertension over the follow-up period among participants who had normal BP at baseline. We used Poisson regression, adjusting for age, sex, smoking status, physical activity, alcohol intake, diabetes, waist circumference, and family history of hypertension. Results: One hundred and six (19.6%) participants developed hypertension, and 58 of the 221 with normal BP (26%) developed prehypertension/hypertension. There was no consistent association between periodontitis and the risk of developing hypertension. However, people with severe periodontitis had an increased incidence of prehypertension/hypertension (multivariate incidence rate ratios: 1.47; 95% confidence interval: 1.01, 2.17) than people without periodontitis after adjusting for confounders. Conclusion: There was no association between periodontitis and hypertension in this cohort study. However, severe periodontitis was associated with an increased risk of prehypertension/hypertension.

Systemic Inflammation, Endothelial Function, and Risk of Periodontitis in Overweight/Obese Adults.

The network interaction between systemic inflammatory mediators, endothelial cell adhesion function, and adiponectin as mediators of the association between metabolic diseases and periodontitis has not been evaluated. The objective of this study is to assess whether the interaction of baseline serum levels of TNF-α, hs-CRP, ICAM-1, VCAM-1, and adiponectin leads to periodontitis. Five hundred and ninety-seven overweight/obese (overweight: BMI 25 to <30 kg/m2; obese: >30 kg/m2) adults, aged 40-65 years, with complete 3-year follow-up data were included. Generalized structural equation models with negative binomial regression were used to estimate the regression coefficient (ß) for the outcome number of teeth with probing pocket depth (PPD) ≥ 4 mm and bleeding on probing (BOP) at 3-year follow-up for a 1 standard deviation unit increase (Δ = +1SD) in each biomarker. After adjusting for multiple covariates, baseline ICAM-1 and VCAM-1 had significant direct effects on increased log-transformed number of teeth with PPD ≥ 4 mm and BOP (ß: 0.16; 95% CI: 0.02-0.30; ß: 0.15; 95% CI: 0.02-0.30, respectively). Baseline hs-CRP showed a significant indirect effect via ICAM-1 on the log-transformed number of teeth with PPD ≥ 4 mm and BOP (ß: 4.84; 95% CI: 0.27-9.42). Thus, elevated serum ICAM-1 and VCAM-1 have a significant direct effect and increased hs-CRP has a significant indirect effect on the predicted level of periodontitis at the 3-year follow-up among overweight/obese Hispanic adults.

Hurricanes Irma and Maria and Diabetes incidence in Puerto Rico.

OBJECTIVE: To evaluate the impact of Hurricanes Irma/Maria on diabetes incidence in Puerto Rico. Mortality increased substantially after the hurricanes, but morbidity was not assessed. METHODS: We recruited 364 participants from the San Juan Overweight Adults Longitudinal Study (SOALS) aged 40-65 years who completed a three-year follow-up and were free of diabetes. We conducted additional questionnaires 1.7-2.5 years after hurricanes. Glycosylated hemoglobin (HbA1c), fasting glucose and insulin were assessed at all three visits. We compared diabetes incidence between pre-hurricane visits and between visits spanning the hurricanes using Generalized Estimating Equation (GEE) adjusting for within person repeated measures, age, and body mass index (BMI). RESULTS: Diabetes incidence was significantly higher spanning the hurricanes than pre-hurricane (multivariate GEE model: IRR = 2.1; 95% CI: 1.4-3.1). There was a significantly higher increase spanning the hurricanes compared to pre-hurricanes for Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (median: 0.3 uIU/mL vs. 0.2 uIU/mL). HbA1c levels increased by 0.4% spanning the hurricanes. CONCLUSION: Increases in diabetes incidence, HOMA-IR and HbA1c were higher spanning the hurricanes compared to the pre-hurricanes period. The increase in diabetes incidence remains significant after adjusting for age and BMI.

Healthcare and Social Organizations' Disaster Preparedness, Response, and Recovery Experience: Lessons Learned From Hurricanes Irma and Maria.

BACKGROUND: Healthcare and social organizations (HSOs) are first respondents after natural disasters. Hence, their preparedness and resilience are critical components for addressing future disasters. However, little is known about HSOs' experiences prior to, during, and after hurricanes. OBJECTIVE: To describe preparedness, response, and recovery experiences from hurricanes Irma/ Maria among HSOs in Puerto Rico and the US Virgin Islands. METHODS: Using a convenience sample, semi-structured interviews were conducted with 52 key-informants. Content analysis for common and recurring themes and patterns was performed by HSO type. RESULTS: Most HSOs (80.8%) had a preparedness plan and 55.8% responded providing emergency supplies. HSOs' human resources (61.2%) was the main recovery facilitator/ enabler, while 36.5% identified the lack of economic resources and the lack of an integrated emergency plan as the top barriers. The main lesson learned include understanding the need to make improvements to their emergency preparedness plans (56.3%), and to establish an integrated/ centralized plan between relevant parties. CONCLUSION: Lessons learned after hurricanes allowed HSOs to identify gaps and opportunities to become more resilient. Infrastructure capacity, human resources, communication systems, and economic support, as well as training, partnerships, and new policies should be defined, revised, and/ or integrated into the HSOs' preparedness plans to mitigate the impact of future disasters.

Estimating COVID-19 cases in Puerto Rico using an automated surveillance system.

Due to concerns regarding limited testing and accuracy of estimation of COVID-19 cases, we created an automated surveillance system called "Puerto Rico Epidemiological Evaluation and Prevention of COVID-19 and Influenza" (PREPCOVI) to evaluate COVID-19 incidence and time trends across Puerto Rico. Automated text message invitations were sent to random phone numbers with Puerto Rican area codes. In addition to reported COVID-19 test results, we used a published model to classify cases from specific symptoms (loss of smell and taste, severe persistent cough, severe fatigue, and skipped meals). Between 18 November 2020, and 24 June 2021, we sent 1,427,241 messages, 26.8% were reached, and 6,975 participants answered questions about the last 30 days. Participants were aged 21-93 years and represented 97.4% of the municipalities. PREPCOVI total COVID-19 cases were higher among women and people aged between 21 and 40 years and in the Arecibo and Bayamón regions. COVID-19 was confirmed, and probable cases decreased over the study period. Confirmed COVID-19 cases ranged from 1.6 to 0.2% monthly, although testing rates only ranged from 30 to 42%. Test positivity decreased from 13.2% in November to 6.4% in March, increased in April (11.1%), and decreased in June (1.5%). PREPCOVI total cases (6.5%) were higher than cases reported by the Puerto Rico Department of Health (5.3%) for similar time periods, but time trends were similar. Automated surveillance systems and symptom-based models are useful in estimating COVID-19 cases and time trends, especially when testing is limited.

Novel Plasma Metabolomic Markers Associated with Diabetes Progression in Older Puerto Ricans.

We assessed longitudinal associations between plasma metabolites, their network-derived clusters, and type 2 diabetes (T2D) progression in Puerto Rican adults, a high-risk Hispanic subgroup with established health disparities. We used data from 1221 participants free of T2D and aged 40-75 years at baseline in the Boston Puerto Rican Health and San Juan Overweight Adult Longitudinal Studies. We used multivariable Poisson regression models to examine associations between baseline concentrations of metabolites and incident T2D and prediabetes. Cohort-specific estimates were combined using inverse-variance weighted fixed-effects meta-analyses. A cluster of 13 metabolites of branched chain amino acids (BCAA), and aromatic amino acid metabolism (pooled IRR = 1.87, 95% CI: 1.28; 2.73), and a cell membrane component metabolite cluster (pooled IRR = 1.54, 95% CI: 1.04; 2.27) were associated with a higher risk of incident T2D. When the metabolites were tested individually, in combined analysis, 5 metabolites involved in BCAA metabolism were associated with incident T2D. These findings highlight potential prognostic biomarkers to identify Puerto Rican adults who may be at high risk for diabetes. Future studies should examine whether diet and lifestyle can modify the associations between these metabolites and progression to T2D.

Tooth count, untreated caries and mortality in US adults: a population-based cohort study.

BACKGROUND: The link between oral diseases and mortality remains under-explored. We aimed to evaluate the associations between tooth count, untreated caries and risk of all-cause and cause-specific mortality. METHODS: Data on 24 029 adults from the National Health and Nutrition Examination Survey 1988-94/1999-2010, with mortality linkage to the National Death Index to 31 December 2015, were analysed. Baseline total number of permanent teeth and any untreated caries were assessed by trained dental professionals. RESULTS: During up to 27 years of follow-up, 5270 deaths occurred. Fewer permanent teeth were associated with higher all-cause mortality, including heart disease and cancer mortality (all P <0.05 for trend) but not cerebrovascular disease mortality. For every 10 teeth missing, the multivariable-adjusted hazard ratios (HRs) were 1.13 (95% CI: 1.08 to 1.18) for all-cause, 1.16 (95% CI: 1.05, 1.29) for heart disease and 1.19 (95% CI: 1.09, 1.29) for cancer mortality. Untreated caries was associated with increased all-cause (HR: 1.26, 95% CI: 1.15, 1.39) and heart disease mortality (HR: 1.48, 95% CI: 1.17, 1.88) but not cerebrovascular disease/cancer mortality, after adjusting for tooth count, periodontitis and sociodemographic/lifestyle factors. Compared with those without untreated caries and with 25-28 teeth, individuals with untreated caries and 1-16 teeth had a 53% increased risk of all-cause mortality (HR: 1.53, 95% CI: 1.27, 1.85) and 96 % increased risk of heart disease mortality (HR: 1.96, 95% CI: 1.28, 3.01). CONCLUSIONS: In nationally representative cohorts, fewer permanent teeth and untreated caries were associated with all-cause and heart disease mortality. Fewer teeth were also associated with higher cancer mortality.

Impact of Impaired Glucose Metabolism on Periodontitis Progression over Three Years.

We evaluated the relationship between glucose abnormalities and periodontitis in overweight/obese individuals. Eight hundred and seventy (870) diabetes-free participants aged 40-65 years completed the three-year follow-up in the San Juan Overweight Adults Longitudinal Study. The ADA thresholds for fasting and 2-h post-load glucose and HbA1c were used to define prediabetes. The NHANES methods were used to assess periodontitis. Multivariable linear regression was used to evaluate the relationship between baseline glucose metabolism measures and periodontitis at follow-up, adjusting for potential confounders. There was no association between impaired glucose measures and mean pocket depth (PD), mean clinical attachment loss (CAL), or mean percent of sites ≥5 mm PD. Impaired glucose tolerance (IGT) was associated with a lower mean percent of sites ≥5 mm CAL (ß = -1.6, p = 0.037). Prediabetes and impaired fasting glucose (IFG) were associated with improvement in mean percent of sites ≥5 mm PD (ß = -1.4, p = 0.022; ß = -1.6, p = 0.032; respectively). IFG and IGT were associated with improvement in mean percent of sites with ≥5 mm CAL (ß = -1.6, p = 0.038; ß = -1.9, p = 0.020; respectively). In conclusion, there were no consistent associations between baseline prediabetes or insulin resistance and periodontitis progression over a three-year period.

Unpacking the behavioural components and delivery features of early childhood obesity prevention interventions in the TOPCHILD Collaboration: a systematic review and intervention coding protocol.

INTRODUCTION: Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity. METHODS AND ANALYSIS: Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components. ETHICS AND DISSEMINATION: The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study's findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders. PROSPERO REGISTRATION NUMBER: CRD42020177408.

Transforming Obesity Prevention for CHILDren (TOPCHILD) Collaboration: protocol for a systematic review with individual participant data meta-analysis of behavioural interventions for the prevention of early childhood obesity.

INTRODUCTION: Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of individual and trial-level subgroups. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups. METHODS AND ANALYSIS: Systematic searches of Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2021 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index z-score at age 24±6 months using WHO Growth Standards, and effect differences will be explored among prespecified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events. ETHICS AND DISSEMINATION: Approved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION NUMBER: CRD42020177408.

Associations between vitamin D levels and glucose metabolism markers among pregnant women and their infants in Puerto Rico / Asociaciones entre los niveles de vitamina D y los marcadores de glucosa en mujeres embarazadas y sus bebés en Puerto Rico

Objectives: low vitamin D during pregnancy is common and could adversely affect health outcomes. This study evaluated vitamin D status during pregnancy and early in life, and its association with glucose metabolism. Methods: maternal serum 25(OH)D, glucose, and insulin levels were measured longitudinally during pregnancy in Hispanic women with overweight/obesity (n = 31) and their infants at birth and 4 months. Results: insulin and HOMA-IR levels were higher among women with vitamin D below adequate levels compared to those with adequate levels in pregnancy (p < 0.05). Late in pregnancy, as vitamin D increased by one unit (ng/mL), insulin decreased by 0.44 units and HOMA-IR by 0.09 units. Maternal vitamin D late in pregnancy was correlated with infant vitamin D levels at birth (r = 0.89; p < 0.01) and 4 months (r = 0.9; p = 0.04), and with glucose (r = 0.79; p = 0.03) and insulin (r = 0.83; p = 0.04) at 4 months. Conclusion: maternal vitamin D status was associated with maternal and infant glucose metabolism in this sample. (AU)

Objetivos: un bajo nivel de vitamina D durante el embarazo es común y puede tener consecuencias adversas en la salud. Este estudio evaluó el nivel de vitamina D en mujeres embarazadas y sus bebés, así como su asociación con los marcadores de glucosa. Métodos: los niveles séricos de 25(OH)D, glucosa e insulina se midieron longitudinalmente en mujeres embarazadas hispanoamericanas con sobrepeso/obesidad (n = 31) y en sus bebés, desde el nacimiento hasta los 4 meses de edad, en Puerto Rico. Resultados: los niveles maternos de insulina y HOMA-IR eran mayores en las mujeres con niveles de vitamina D por debajo de lo considerado adecuado, comparado con aquellas con niveles adecuados durante todo el embarazo (p < 0,05). Al final del embarazo, a medida que los niveles de vitamina D aumentaron, por cada unidad (ng/mL) de aumento, la insulina disminuyo en 0,44 unidades y el HOMA-IR en 0,09 unidades. El nivel de vitamina D al final del embarazo se correlacionó con los niveles del bebé al nacer (r = 0,89; p < 0,01) y a los 4 meses (r = 0,9; p = 0,04), y con los niveles de glucosa (r = 0,79; p = 0,03) e insulina (r = 0,83; p = 0,04) a los 4 meses. Conclusión: el nivel materno de vitamina D se asoció con los marcadores maternos e infantiles de glucosa en esta muestra. (AU)

Longitudinal association between adiposity measures and regression of prediabetes/diabetes.

BACKGROUND AND AIMS: The recent COVID-19 pandemic has further increased the importance of reducing obesity and prediabetes/diabetes. We aimed to evaluate the association between adiposity and regression of prediabetes/diabetes. METHODS AND RESULTS: The San Juan Overweight Adults Longitudinal Study (SOALS) included 1351 individuals with overweight/obesity, aged 40-65, free of major cardiovascular diseases and physician diagnosed diabetes. From the 1012 participants with baseline prediabetes/diabetes, 598 who completed the follow-up were included. Over the follow-up, 25% regressed from prediabetes to normoglycemia or from diabetes to prediabetes or normoglycemia. Poisson regression with robust standard error was used to estimate the relative risk (RR) adjusting for major confounders. Higher neck circumference (NC) was associated with regression of prediabetes/diabetes (RR = 0.45 comparing extreme tertiles; 95% CI:0.30-0.66); RR was 0.49 (95% CI:0.34-0.73) for waist circumference (WC) and 0.64 (95% CI:0.44-0.92) for BMI. Significant associations were found using median cut-offs or continuous measures for weight and BMI. Greater reduction in BMI (comparing extreme tertiles) was significantly associated with regression of prediabetes/diabetes (RR = 1.44; 95% CI:1.02-2.02). Continuous measures of change in adiposity (except for NC) were also associated with regression of prediabetes/diabetes for BMI and weight. Participants who reduced BMI (>5%) increased prediabetes/diabetes regression (RR = 1.61; 95% CI:1.15-2.25) compared to those who did not; similarly for weight (RR = 1.55; 95% CI: 1.10-2.19). Additional analysis for body fat percentage showing slightly weaker results than BMI/weight further supported our findings. CONCLUSION: Lower baseline adiposity and higher reduction in adiposity were associated with regression of prediabetes/diabetes among individuals with overweight/obesity.

Associations between vitamin D levels and glucose metabolism markers among pregnant women and their infants in Puerto Rico.

INTRODUCTION: Objectives: low vitamin D during pregnancy is common and could adversely affect health outcomes. This study evaluated vitamin D status during pregnancy and early in life, and its association with glucose metabolism. Methods: maternal serum 25(OH)D, glucose, and insulin levels were measured longitudinally during pregnancy in Hispanic women with overweight/obesity (n = 31) and their infants at birth and 4 months. Results: insulin and HOMA-IR levels were higher among women with vitamin D below adequate levels compared to those with adequate levels in pregnancy (p < 0.05). Late in pregnancy, as vitamin D increased by one unit (ng/mL), insulin decreased by 0.44 units and HOMA-IR by 0.09 units. Maternal vitamin D late in pregnancy was correlated with infant vitamin D levels at birth (r = 0.89; p < 0.01) and 4 months (r = 0.9; p = 0.04), and with glucose (r = 0.79; p = 0.03) and insulin (r = 0.83; p = 0.04) at 4 months. Conclusion: maternal vitamin D status was associated with maternal and infant glucose metabolism in this sample.

INTRODUCCIÓN: Objetivos: un bajo nivel de vitamina D durante el embarazo es común y puede tener consecuencias adversas en la salud. Este estudio evaluó el nivel de vitamina D en mujeres embarazadas y sus bebés, así como su asociación con los marcadores de glucosa. Métodos: los niveles séricos de 25(OH)D, glucosa e insulina se midieron longitudinalmente en mujeres embarazadas hispanoamericanas con sobrepeso/obesidad (n = 31) y en sus bebés, desde el nacimiento hasta los 4 meses de edad, en Puerto Rico. Resultados: los niveles maternos de insulina y HOMA-IR eran mayores en las mujeres con niveles de vitamina D por debajo de lo considerado adecuado, comparado con aquellas con niveles adecuados durante todo el embarazo (p < 0,05). Al final del embarazo, a medida que los niveles de vitamina D aumentaron, por cada unidad (ng/mL) de aumento, la insulina disminuyo en 0,44 unidades y el HOMA-IR en 0,09 unidades. El nivel de vitamina D al final del embarazo se correlacionó con los niveles del bebé al nacer (r = 0,89; p < 0,01) y a los 4 meses (r = 0,9; p = 0,04), y con los niveles de glucosa (r = 0,79; p = 0,03) e insulina (r = 0,83; p = 0,04) a los 4 meses. Conclusión: el nivel materno de vitamina D se asoció con los marcadores maternos e infantiles de glucosa en esta muestra.

Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent.

INTRODUCTION: We investigated whether network analysis revealed clusters of coregulated metabolites associated with prevalent type 2 diabetes (T2D) among Puerto Rican adults. RESEARCH DESIGN AND METHODS: We used liquid chromatography-mass spectrometry to measure fasting plasma metabolites (>600) among participants aged 40-75 years in the Boston Puerto Rican Health Study (BPRHS; discovery) and San Juan Overweight Adult Longitudinal Study (SOALS; replication), with (n=357; n=77) and without (n=322; n=934) T2D, respectively. Among BPRHS participants, we used unsupervised partial correlation network-based methods to identify and calculate metabolite cluster scores. Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D at the baseline blood draw in the BPRHS, and significant associations were replicated in SOALS. Inverse-variance weighted random-effect meta-analysis was used to combine cohort-specific estimates. RESULTS: Six metabolite clusters were significantly associated with prevalent T2D in the BPRHS and replicated in SOALS (false discovery rate (FDR) <0.05). In a meta-analysis of the two cohorts, the OR and 95% CI (per 1 SD increase in cluster score) for prevalent T2D were as follows for clusters characterized primarily by glucose transport (0.21 (0.16 to 0.30); FDR <0.0001), sphingolipids (0.40 (0.29 to 0.53); FDR <0.0001), acyl cholines (0.35 (0.22 to 0.56); FDR <0.0001), sugar metabolism (2.28 (1.68 to 3.09); FDR <0.0001), branched-chain and aromatic amino acids (2.22 (1.60 to 3.08); FDR <0.0001), and fatty acid biosynthesis (1.54 (1.29 to 1.85); FDR <0.0001). Three additional clusters characterized by amino acid metabolism, cell membrane components, and aromatic amino acid metabolism displayed significant associations with prevalent T2D in the BPRHS, but these associations were not replicated in SOALS. CONCLUSIONS: Among Puerto Rican adults, we identified several known and novel metabolite clusters that associated with prevalent T2D.

Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics.

Stroke constitutes the second leading cause of death and a major cause of disability worldwide. Stroke is normally classified as either ischemic or hemorrhagic stroke (HS) although 87% of cases belong to ischemic nature. Approximately 700,000 individuals suffer an ischemic stroke (IS) in the US each year. Recent evidence has denoted a rather pivotal role for defective macroautophagy/autophagy in the pathogenesis of IS. Cellular response to stroke includes autophagy as an adaptive mechanism that alleviates cellular stresses by removing long-lived or damaged organelles, protein aggregates, and surplus cellular components via the autophagosome-lysosomal degradation process. In this context, autophagy functions as an essential cellular process to maintain cellular homeostasis and organismal survival. However, unchecked or excessive induction of autophagy has been perceived to be detrimental and its contribution to neuronal cell death remains largely unknown. In this review, we will summarize the role of autophagy in IS, and discuss potential strategies, particularly, employment of natural compounds for IS treatment through manipulation of autophagy.

The relationship between inflammatory dietary pattern and incidence of periodontitis.

The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food-based, reduced rank regression (RRR)-derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34 940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years and dietary data through validated semi-quantitative FFQ every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) with the lowest quintile was 0·99 (95 % CI 0·89, 1·10, P-value for trend = 0·97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile with the lowest was 1·39 (95 % CI 0·98, 1·96, P-value for trend = 0·03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated, EDIP was significantly associated with increased risk of periodontitis only among non-smokers who were obese. Hence, this association must be interpreted with caution.