Branched-Chain and Aromatic Amino Acids, Type 2 Diabetes, and Cardiometabolic Risk Factors among Puerto Rican Adults.

(1) Background: Branched-chain and aromatic amino acids (BCAAs/AAAs) have been considered as markers of type 2 diabetes (T2D); however, studies on associations between these metabolites and T2D and cardiometabolic traits in Hispanic populations are limited. The aim of this study was to examine the associations between baseline BCAAs (isoleucine, leucine, valine)/AAAs (phenylalanine, tyrosine) and prevalent and incident T2D, as well as baseline and longitudinal (2 year) changes in cardiometabolic traits (measures of glycemia, dyslipidemia, inflammation, and obesity) in two large cohorts of adults of Puerto Rican descent. (2) Methods: We included participants of the Boston Puerto Rican Health Study (BPRHS, n = 670) and San Juan Overweight Adult Longitudinal study (SOALS, n = 999) with available baseline metabolite and covariate data. T2D diagnosis was defined based on American Diabetes Association criteria. Multivariable logistic (for baseline T2D), Poisson (for incident T2D), and linear (for cardiometabolic traits) regression models were used; cohort-specific results were combined in the meta-analysis and adjusted for multiple comparisons. (3) Results: Higher baseline BCAAs were associated with higher odds of prevalent T2D (OR1SD BCAA score = 1.46, 95% CI: 1.34-1.59, p < 0.0001) and higher risk of incident T2D (IRR1SD BCAA score = 1.24, 95% CI: 1.13-1.37, p < 0.0001). In multivariable longitudinal analysis, higher leucine and valine concentrations were associated with 2-year increase in insulin (beta 1SD leucine = 0.37 mcU/mL, 95% CI: 0.11-0.63, p < 0.05; beta 1SD valine = 0.43 mcU/mL, 95% CI: 0.17-0.68, p < 0.01). Tyrosine was a significant predictor of incident T2D (IRR = 1.31, 95% CI: 1.09-1.58, p < 0.05), as well as 2 year increases in HOMA-IR (beta 1SD tyrosine = 0.13, 95% CI: 0.04-0.22, p < 0.05) and insulin concentrations (beta 1SD tyrosine = 0.37 mcU/mL, 95% CI: 0.12-0.61, p < 0.05). (4) Conclusions: Our results confirmed the associations between BCAAs and prevalent and incident T2D, as well as concurrent measures of glycemia, dyslipidemia, and obesity, previously reported in predominantly White and Asian populations. Baseline leucine, valine, and tyrosine were predictors of 2 year increases in insulin, whereas tyrosine was a significant predictor of deteriorating insulin resistance over time. Our study suggests that BCAAs and tyrosine could serve as early markers of future glycemic changes in Puerto Ricans.

Saliva, Plasma, and Multifluid Metabolomic Signatures of Periodontal Disease, Type 2 Diabetes Progression, and Markers of Glycemia and Dyslipidemia Among Puerto Rican Adults With Overweight and Obesity.

BACKGROUND: Evidence from cohort studies indicates a bidirectional relationship between periodontal disease and type 2 diabetes (T2D), but the underlying mechanisms remain unknown. In this study, we aimed to (1) identify saliva, plasma, and multifluid metabolomic signatures associated with periodontal disease and (2) determine if these signatures predict T2D progression and cardiometabolic biomarkers at year 3. METHODS AND RESULTS: We included participants from the SOALS (San Juan Overweight Adult Longitudinal Study) (n=911). Metabolites from saliva (k=635) and plasma (k=1051) were quantified using liquid chromatography-mass spectrometry. We applied elastic net regression with 10-fold cross-validation to identify baseline metabolomic signatures of periodontal disease. Multivariable Cox proportional hazards regression and linear regression were used to evaluate the association with T2D progression and biomarker concentrations. Metabolomic profiles included highly weighted metabolites related to lysine and pyrimidine metabolism. Periodontal disease or its 3 metabolomic signatures were not associated with T2D progression in 3 years. Prospectively, 1-SD increments in the multifluid and saliva metabolomic signatures were associated with higher low-density lipoprotein (multifluid: 12.9±5.70, P=0.02; saliva: 13.3±5.11, P=0.009). A 1-SD increment in the plasma metabolomic signature was also associated with Homeostatic Model Assessment for Insulin Resistance (2.67±1.14, P=0.02) and triglyceride (0.52±0.18, P=0.002). CONCLUSIONS: Although metabolomic signatures of periodontal disease could not predict T2D progression, they were associated with low-density lipoprotein, triglyceride, and Homeostatic Model Assessment for Insulin Resistance levels at year 3.

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.

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.

Hispanic adults with type 2 diabetes mellitus using lipid-lowering agents have better periodontal health than non-users.

Background: Recent studies suggest that lipid-lowering agents (LLA) may reduce chronic periodontitis, but it is unknown whether this benefit extends to people with type 2 diabetes (T2D). Objective: We assessed the association between LLA use and periodontitis in Hispanic adults with T2D. Design: This was a cross-sectional observational study. Methods: We assessed the association of LLA use and periodontal parameters in 253 Puerto Ricans 40-65 years with T2D who participated in the Lipid-Lowering agents use in Periodontitis and Diabetes Study study. Participants were classified as (a) none- or <1 year, (b) 1-4 years, or (c) >4 years. The primary outcome consists of a tertile percent of sites with probing pocket depth (PPD) ⩾ 4 mm and the secondary outcome includes tertiles of percent sites with clinical attachment loss (CAL) ⩾ 4 mm. Multinomial logistic regression models adjusted for age, gender, smoking status, education, waist circumference, glycosylated hemoglobin A1C (HbA1c), bleeding on probing, examiner, and anti-inflammatory agents were used to estimate the association. Results: LLA (92.5%, statins) was used by 52% of participants. LLA use 1-4 years was associated with lower odds of PPD ⩾ 4 mm (OR: 0.22, p = 0.005; high versus low tertile) or lower odds of CAL ⩾ 4 mm (OR: 0.33, p = 0.02, middle versus low tertile), compared to those with LLA minimal or no use. This association was lost for participants who used LLA for >4 years. LLA users for >4 years with periodontal disease had elevated HbA1c (OR: 1.36, p = 0.05). Conclusion: The use of LLA for 1-4 years was associated with lower values of periodontal parameters versus minimal LLA use. This association was not present among people using LLA > 4 years users, but these participants had poorer glycemic control compared to other participants. In this cross-sectional study, the finding that LLA use 1- 4 years is associated with lower values of periodontal parameters of severity in T2D individuals may help clarify some of the controversies regarding the benefit of these medications in this population.

Lipid-lowering agents and lower values of periodontal parameters in individuals with type 2 diabetes • Lipid-lowering agents (LLA), such as statins, are reported to reduce chronic periodontitis, making individuals with diabetes ideal candidates for this treatment due to their high prevalence of oral disease.• The association between LLA use and periodontitis was assessed among Hispanic adults with type 2 diabetes (T2D).• Short-term LLA use (but not long-term use) was associated with lower values of periodontal parameters in individuals with T2D.• For long-term LLA use, high glycemic level was associated with high values of periodontitis.• Thus, under the study design limitations, the finding may provide clinical implications and may help clarify some of the controversies regarding the benefits of LLA use in humans.• Furthermore, the higher glycemic levels for periodontal patients with long-term LLA use points to the need to monitor these patients carefully.

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.

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 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.

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.

The associations between major dietary patterns and risk of periodontitis.

AIM: To prospectively investigate the associations between major dietary patterns and incidence of periodontitis. METHODS: We included 34,940 men from the Health Professionals Follow-Up Study, free of periodontal disease and major illnesses at baseline. Detailed medical and dental history was collected through biennial mailed questionnaires, and dietary information was provided through quadrennial food frequency questionnaires. Using principal component analysis, we identified two major dietary patterns ("prudent" and "Western"). We used Cox proportional hazard models to examine the associations between the two dietary patterns and self-reported incidence of periodontitis over a 24-year follow-up period. We investigated each pattern separately. RESULTS: There was no overall association between Western or prudent dietary patterns and periodontitis. Among obese, however, the Western dietary pattern was significantly associated with incident periodontitis. The hazard ratio for those in the highest quintile of Western diet versus those in the lowest (reference) was 1.83 (95% confidence interval: 1.21-2.76). CONCLUSIONS: There was no overall association between Western or prudent dietary patterns and periodontitis; however, in subgroups analysis, the Western diet was significantly associated with higher periodontitis risk only among obese men, a finding that requires replication and biological explication.

Dietary flavonoid intake and risk of periodontitis.

BACKGROUND: The anti-inflammatory effect associated with flavonoid-containing foods and beverages could potentially impact the risk of periodontal disease. We prospectively investigate the associations between habitual flavonoid intake and incidence of periodontitis. METHODS: The study population was 34,940 men from the Health Professionals Follow-Up Study, who were healthy and free of periodontal disease at baseline (1986). Participants in the study provided medical and dental history through mailed questionnaires biennially, and provided dietary data through semi-quantitative food frequency questionnaires every 4 years. We examined the associations between total flavonoids and six flavonoid subclasses (flavonoid polymers, anthocyanins, flavan-3-ols, flavanones, flavones, and flavonols) and incidence of periodontitis using Cox proportional hazard models. We adjusted for age, smoking, body mass index, physical activity, alcohol consumption, Alternative Healthy Eating Index, and diabetes. RESULTS: There was no association between total flavonoids and the risk of periodontitis. The hazard ratio comparing the highest quintile of total flavonoid to the lowest quintile was 0.97 (95% confidence interval: 0.87 to 1.08, P-value for trend = 0.61). Similar comparisons for flavonoids subclasses also did not show significant associations. CONCLUSION: No association was detected between habitual flavonoid intake and risk of periodontitis in the study population.

Longitudinal association between adiposity and inter-arm blood pressure difference.

This is the first longitudinal study evaluating whether adiposity is associated with inter-arm blood pressure difference. We evaluated 714 overweight/obese individuals aged 40-65 years over a 3-year follow-up. Systolic and diastolic blood pressures were measured in both arms simultaneously using an automated machine. Linear regression assessed the associations of body mass index, fat %, waist, neck, thigh, and arm circumferences (cm), with absolute inter-arm differences in systolic (IAS) and diastolic (IAD) blood pressure (mm Hg). Poisson regression was used for binary outcomes (IAS and IAD ≥ 10 mm Hg). All models were adjusted for age, gender, smoking, physical activity, and HOMA-IR. Adiposity measures were associated with increased IAS and IAD (ß range: 0.09-0.20 and 0.09-0.30). Neck circumference showed the strongest association with IAS (ß = 0.20, 95% CI: 0.03, 0.37) and IAD (ß = 0.30, 95% CI: 0.12, 0.47); arm circumference showed a similar association with IAS, but lower with IAD. Highest quartiles of BMI, thigh, and arm showed significant associations with IAS (IRR: 2.21, 2.46 and 2.70). Highest quartiles of BMI, waist, neck, and arm circumferences were significantly associated with IAD (IRR: 2.38, 2.68, 4.50 and 2.24). If the associations are corroborated in other populations, adiposity may be an important modifiable risk factor for inter-arm blood pressure difference with a large potential public health impact.

Longitudinal association between periodontitis and development of diabetes.

BACKGROUND: Clinical trials have shown very modest short-term improvements in glycemic control among participants with diabetes after periodontitis treatment. Few longitudinal studies suggest that periodontitis may be related to prediabetes/diabetes risk. METHODS: We evaluated 1206 diabetes free participants in the San Juan Overweight Adults Longitudinal Study (SOALS) and 941 with complete 3-year follow-up data were included. The National Health and Nutrition Examination Survey (NHANES) methods were used to assess periodontitis. Diabetes and prediabetes were classified using American Diabetes Association cutoffs for fasting and 2-hour post-load glucose and HbA1c. We used Poisson regression adjusting for baseline age, gender, smoking, education, family history of diabetes, physical activity, waist circumference, and alcohol intake. RESULTS: Over the 3-year follow-up, 69 (7.3%) of the 941 individuals developed type 2 diabetes, and 142 (34.9%) of the 407 with normal glycemia at baseline developed prediabetes. In multivariable models, greater mean pocket depth and mean attachment loss at baseline were associated with lower risk of developing prediabetes/diabetes over the follow-up (IRR = 0.81; 95% CI: 0.67-0.99, and IRR = 0.86; 95% CI: 0.74-0.99, respectively). Increase in periodontal attachment loss from baseline to follow-up was associated with higher prediabetes/diabetes risk (multivariate IRR = 1.25; 95% CI: 1.09-1.42), and increase in pocket depth was associated with >20% fasting glucose increase (multivariate IRR = 1.43; 95% CI: 1.14-1.79). The inverse associations persisted after additionally adjusting for baseline income, sugar-sweetened beverages, number of teeth, oral hygiene, glycemia, or previous periodontal therapy. CONCLUSIONS: There is no association between periodontitis and risk of prediabetes/diabetes in this longitudinal study.

Over-the-counter mouthwash use and risk of pre-diabetes/diabetes.

AIMS: Over-the-counter mouthwash comprises part of routine oral care for many; however, potential adverse effects of the long-term daily use have not been evaluated. Most mouthwash contain antibacterial ingredients, which could impact oral microbes critical for nitric oxide formation, and in turn predispose to metabolic disorders including diabetes. Our aim was to evaluate longitudinally the association between baseline over-the-counter mouthwash use and development of pre-diabetes/diabetes over a 3-year follow-up. MATERIALS AND METHODS: The San Juan Overweight Adults Longitudinal Study (SOALS) recruited 1206 overweight/obese individuals, aged 40-65, and free of diabetes and major cardiovascular diseases; 945 with complete follow-up data were included in the analyses. We used Poisson regression models adjusting for baseline age, sex, smoking, physical activity, waist circumference, alcohol consumption, pre-hypertension/hypertension status; time between visits was included in the models as an offset. RESULTS: Many participants (43%) used mouthwash at least once daily and 22% at least twice daily. Participants using mouthwash ≥ twice daily at baseline, had a significantly elevated risk of pre-diabetes/diabetes compared to less frequent users (multivariate IRR = 1.55, 95% CI: 1.21-1.99), or non-users of mouthwash (multivariate IRR = 1.49; 95% CI: 1.13-1.95). The effect estimates were similar after adding income, education, oral hygiene, oral conditions, sleep breathing disorders, diet (processed meat, fruit, and vegetable intake), medications, HOMA-IR, fasting glucose, 2hr post load glucose or CRP to the multivariate models. Both associations were also significant among never-smokers and obese individuals. Mouthwash use lower than twice daily showed no association, suggesting a threshold effect at twice or more daily. CONCLUSIONS: Frequent regular use of over-the-counter mouthwash was associated with increased risk of developing pre-diabetes/diabetes in this population.

Relationship between tooth loss and peripheral arterial disease among women.

AIM: We assessed the longitudinal association between tooth loss and peripheral arterial disease (PAD) within the Nurses' Health Study. MATERIALS AND METHODS: After excluding participants with prior cardiovascular diseases, 277 of 79,663 women were confirmed as PAD cases during 16 years of follow-up. Number of teeth and recent tooth loss were reported initially in 1992. Subsequent tooth loss was recorded in 1996 and in 2000. We evaluated the associations of baseline number of teeth and recent tooth loss with risk of PAD, adjusting for age, smoking, diabetes, hypertension, high cholesterol, aspirin use, family history of myocardial infarction, BMI, alcohol consumption, physical activity, postmenopausal hormone use, and use of vitamin E, vitamin D, multivitamin and calcium. RESULTS: Incident tooth loss during follow-up was significantly associated with higher hazard of PAD (HR = 1.31 95% CI: 1.00-1.71). However, the association appeared inverse among never smokers. There was no dose-response relationship between baseline number of teeth and PAD. CONCLUSIONS: Tooth loss showed a modest association with PAD, but no dose-response relationship was observed.

Salivary extracellular RNA biomarkers for insulin resistance detection in hispanics.

AIMS: Insulin resistance (IR) detection is challenging and no test is currently used in clinical practice. We developed salivary biomarkers that could be used for IR detection. METHODS: We collected saliva from 186 healthy and 276 pre-diabetic participants, divided them into high and low IR groups based on a HOMA cutoff of 2.5. We profiled extracellular transcriptome by microarray in saliva supernatant from 23 high IR and 15 low IR participants, and pre-validated the top ten extracellular mRNA (exRNA) markers in a new cohort of 40 high and 40 low IR participants. A prediction panel was then built and validated in an independent cohort of 149 high and 195 low IR participants. RESULTS: Transcriptomic analyses identified 42 exRNA candidates differentially present in saliva of high and low IR participants. From the top ten candidates, six were individually validated (PRKCB, S100A12, IL1R2, CAMP, VPS4B, CAP1) (p<0.01) and yielded AUC values ranging from 0.66 to 0.76. Body mass index (BMI) was significant higher in high compared to low IR group with AUC of 0.66, and showed no correlation with any of candidate biomarkers. The combination of four exRNA markers (IL1R2, VPS4B, CAP1, LUZP6) with BMI achieved excellent results in the prediction panel building dataset (AUC=0.79, sensitivity=79%, specificity=64%). The prediction model was validated in an independent cohort (AUC=0.82, sensitivity=63%, specificity=92%). CONCLUSIONS: A panel of four salivary exRNA biomarkers (IL1R2, VPS4B, CAP1, LUZP6) and BMI was validated that can distinguish high and low IR participants, overall and in subgroups of healthy and pre-diabetic participants.