Jacobs, David R

ABSTRACT Aims To investigate whether the association between the nitrite‐generating capacity of the subgingival microbiome and early cardiometabolic risk biomarkers varies by dietary nitrate intake. Materials and Methods Cross‐sectional data from 668 participants (mean age 31 ± 9 years, 73% women) were analysed. Dietary nitrate intake was calculated from food frequency questionnaires. Subgingival 16S rRNA sequencing (Illumina, MiSeq) and PICRUSt2 estimated microbial genes. The Microbiome‐Induced Nitric Oxide Enrichment Score (MINES) was calculated as a ratio of microbial gene abundances representing enhanced net capacity for NO generation. Adjusted multivariable linear models regressed cardiometabolic risk biomarkers (HbA1c, glucose, insulin, insulin resistance (HOMA‐IR), blood pressure) on nitrate intake and MINES together with a MINES × nitrate intake interaction term. Results Mean nitrate intake was 190 ± 171 mg/day. Significant interactions of MINES and nitrate intake were observed for insulin and HOMA‐IR ( p < 0.05). Among participants with a low MINES, higher nitrate intake was associated with lower HOMA‐IR (1.2 [1.1–1.4] vs. 1.5 [1.3–1.6]; p = 0.002), but levels were similar in those with high MINES ( p = 0.84). Conclusions A biomarker of higher microbial NO‐generating capacity in subgingival plaque is associated with lower insulin and insulin resistance among individuals with lower dietary nitrate intake. Future trials evaluating the cardiometabolic benefits of nitrate‐rich diets should incorporate measures of the entire oral microbiome.

ABSTRACTObjectiveTo study the association between dietary patterns and subgingival microbiota.MethodsParticipants (n = 651) who were enrolled in the Oral Infections, Glucose Intolerance, and Insulin Resistance Study (ORIGINS) with subgingival plaque sampling (n = 890 plaques) and a dietary assessment were included. 16S rRNA gene amplicon sequences of subgingival plaque from sites with either probing depth <4 or ≥4 mm were processed separately and used to obtain α‐diversity metrics (Faith, Shannon, Simpson, Observed) and taxa ratios (Red Complex to Corynebacterium [RCLR], Treponema to Corynebacterium [TCLR], and Treponema to Neisseria [TNLR]). Food frequency questionnaires (FFQs) were processed to calculate Alternate Healthy Eating Index (AHEI) and A Priori Diet Quality Score (APDQS) scores. Mixed regression models examined the mean levels of microbial metrics across quartiles of diet quality. Means ± standard errors are reported along with p‐values.ResultsIn multivariable models assessing the association between diet scores and α‐diversity metrics, higher AHEI values were significantly associated with lower Faith (p‐value = 0.01) and Observed (p‐value = 0.04) diversity values; similar findings were observed for APDQS (p‐value = 0.01, p‐value = 0.04). In multivariable models assessing the association between diet scores (AHEI and APDQS) and taxa ratios (RCLR, TCLR and TNLR), as the AHEI quartile increased, all taxa ratios decreased significantly as follows: −1.06 ± 0.093 in Q1 to −1.34 ± 0.099 in Q4 (RCLR), −0.43 ± 0.077 in Q1 to −0.64 ± 0.083 in Q4 (TCLR) and −0.09 ± 0.083 in Q1 to −0.38 ± 0.089 in Q4 (TNLR), respectively. In contrast, as the APDQS quartiles increased, only TNLR decreased significantly from −0.08 ± 0.085 in Q1 to −0.34 ± 0.091 in Q4.ConclusionDiets rich in fruits, vegetables, whole grains and other nutritionally rich plant foods are associated with lower oral microbial diversity and favourable ratios of pathogenic to commensal microbiota.

Abstract Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objectives By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate genome-wide association study and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n = 1,278) and adults from the UKBiobank (n = 369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP (hedgehog interacting protein), DSP, and NPNT as potential molecular targets based on colocalization of their expression. A higher dysanapsis genetic risk score was associated with obstructive spirometry among 5-year-old children and among adults in the fifth, sixth, and seventh decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development, and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endophenotype link between the genetic variations associated with lung function and COPD.

Abstract Background Non‐alcoholic fatty liver disease (NAFLD) is recognized as a prevalent determinant of cardiometabolic diseases. The association between NAFLD and obesity warrants further research on how NAFLD modifies associations between body mass index (BMI) and Waist circumference (WC) with cardiometabolic risk (CMR). Objective This study assessed whether NAFLD modifies associations between BMI and WC with 5‐year changes in CMR in 2366 CARDIA study participants. Methods Non‐contrast CT was used to quantify liver attenuation, with ≤51 Hounsfield Units (HU) used to define NAFLD in the absence of secondary causes of excess liver fat. The dependent variable was the average Z score of fasting glucose, insulin, triglycerides [log], (−) high‐density lipoprotein cholesterol (HDL‐C), and systolic blood pressure(SBP). Multivariable linear regression was used to estimate the associations between BMI and WC with CMR. Effect modification by NAFLD was assessed by an interaction term between NAFLD and BMI or WC. Results The final sample had 539 (23%) NAFLD cases. NAFLD modified the association of BMI and WC with CMR (interaction p < 0.0001 for both). BMI and WC were associated with CMR in participants without NAFLD ( p < 0.001), but not among those with NAFLD. Participants with NAFLD and normal BMI and WC had CMR estimates that were higher than those without NAFLD in the obese categories. Among those without NAFLD the 5 years CMR change estimate was 0.09 (95% CI: 0.062, 0.125) for BMI ≥30 kg/m 2 compared to −0.06 (−0.092, −0.018) for BMI < 25 kg/m 2 , and among those with NAFLD, these estimates were 0.15 (0.108, 0.193) and 0.16 (−0.035, 0.363). Conclusions NAFLD modifies associations of BMI and WC with CMR. Compared with BMI and WC, NAFLD was more strongly associated with CMR. In the presence of NAFLD, BMI and WC were not associated with CMR. These findings have implications for clinical screening guidelines.

AbstractAimWe investigated whether periodontal measures are cross‐sectionally associated with prediabetes and cardiometabolic biomarkers among non‐diabetic younger adults.Materials and MethodsOne thousand seventy‐one participants (mean age = 32.2 years [SE = 0.3]; 73% female) from the Oral Infections, Glucose Intolerance and Insulin Resistance Study were enrolled. Full‐mouth clinical attachment loss (fm‐CAL), probing depth (fm‐PD) and bleeding on probing were ascertained. Interproximal CAL (i‐CAL) and probing depths (i‐PD) served as our primary exposures. Glucose, HbA1c, insulin and insulin resistance (HOMA‐IR) outcomes were assessed from fasting blood. Prediabetes was defined per American Diabetes Association guidelines. Prediabetes prevalence ratios (PR [95% CI]) and mean [SE] cardiometabolic biomarkers were regressed on periodontal variables via multivariable robust variance Poisson regression or multivariable linear regression.ResultsPrevalence of prediabetes was 12.5%. Fully adjusted prediabetes PR in Tertiles 3 versus 1 of mean i‐CAL was 2.42 (1.77, 3.08). Fully adjusted fasting glucose estimates across i‐CAL tertiles were 83.29 [0.43], 84.31 [0.37], 86.48 [0.46]; p for trend <.01. Greater percent of sites with i‐PD ≥3 mm showed elevated natural‐log‐HOMA‐IR after adjustment (0%–12% of sites = 0.33 [0.03], 13%–26% of sites = 0.39 [0.03], ≥27% of sites = 0.42 [0.03]; p for trend = .04).Conclusionsi‐CAL (vs. fm‐CAL) was associated with elevated fasting glucose and prediabetes, whereas i‐PD (vs. fm‐PD) was associated with insulin resistance. Future studies are needed to examine periodontal disease and incident prediabetes.

#LGBTQ+ people with cancer are invisibilized: A call for #intersectional cancer research (link here) #healthequity

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) in U.S. adults is over 30%, yet the role of lifestyle factors in the etiology of NAFLD remains understudied. We examined the associations of physical activity, by intensity and type, and television viewing with prevalent NAFLD. Methods: Cross-sectional analysis of a population-based sample of 2726 Black (49%) and White (51%) adults (Mean (SD) age, 50 (3.6) years; 57.3% female) from the CARDIA study. Exposures were aerobic activity by intensity (moderate, vigorous; hours/week); activity type (aerobic, muscle-strengthening; hours/week); and television viewing (hours/week), examined concurrently in all models and assessed by validated questionnaires. Our outcome was NAFLD (liver attenuation < 51 Hounsfield Units), measured by non-contrast computed tomography, after exclusions for other causes of liver fat. Covariates were sex, age, race, study center, education, diet quality, smoking status, alcohol consumption, and body mass index or waist circumference. Results: 648 participants had NAFLD. In the fully adjusted modified Poisson regression model, the risk ratios per interquartile range of each exposure were moderate-intensity aerobic activity, 1.10 (95% CI, 0.97–1.26); vigorous-intensity aerobic activity, 0.72 (0.63–0.82); muscle-strengthening activity, 0.89 (0.80–1.01); and television viewing, 1.20 (1.10–1.32). Relative to less active participants with higher levels of television viewing, those who participated in ≥2 h/week of both vigorous-intensity aerobic and muscle-strengthening activity and <7 h/week of television viewing had 65% lower risk of NAFLD (risk ratio = 0.35, 95% CI = 0.23–0.51). Conclusion: Adults who follow public health recommendations for vigorous-aerobic and muscle-strengthening activity, as well as minimize television viewing, are considerably less likely to have NAFLD than those who do not follow the recommendations and who have relatively high levels of television viewing.

Abstract Objective: Controversy remains regarding the association between type 2 diabetes mellitus (DM) and colorectal cancer (CRC) risk. To clarify and extend the existing data, we prospectively evaluated the association between self-reported type 2 DM (onset at &gt;30 years of age) and incident CRC, overall and by anatomic subsite, among postmenopausal women in the Iowa Women's Health Study (n = 35,230). Methods: After 14 years of follow-up, a total of 870 incident CRC cases were identified through annual linkage to the Iowa Cancer Registry. DM was analyzed as reported at baseline and as a time-dependent variable using information obtained during follow-up. CRC risks were estimated using Cox proportional hazards regression models. Results: After adjusting for age, body mass index and other potential confounding variables, the relative risk (RR) for women with DM versus women without DM was modestly increased at 1.4 [95% confidence interval (95% CI), 1.1-1.8]. By anatomic subsite, the RR for proximal colon cancer was statistically significantly increased (RR, 1.9; 95% CI, 1.3-2.6), whereas the RRs for distal colon (RR, 1.1; 95% CI, 0.6-1.8) and rectal cancer (RR, 0.8; 95% CI, 0.4-1.6) were not statistically different from unity. Analyses that included DM ascertained at baseline and follow-up yielded similar results. Conclusion: In this large, prospective study of postmenopausal women, the association between DM and incident CRC was found to be subsite specific. If confirmed by others, this finding implies that CRC prevention strategies among type 2 DM patients should include examination of the proximal colon.

Objective: We aimed to investigate prospective associations between milk bioactives related to metabolic health (glucose, insulin, leptin, C reactive protein [CRP], and interleukin 6 [IL-6]) and incident formula initiation at 3 and 6 months postpartum. Design: This study included 363 mother–infant dyads who were fully breastfed at 1 month and participated in the prospective Mothers and Infants Linked for Healthy Growth study from pregnancy to 6 months postpartum. Associations between milk glucose, leptin, insulin, CRP, and IL-6 at 1 and 3 months and incident formula feeding (FF) at 3 and 6 months, respectively, were tested using multiple logistic regression, adjusting for numerous potential confounders such as maternal age and prepregnancy body mass index. Results: At 3 months postpartum, 1-month glucose (odds ratio [OR] 0.45 [95% confidence interval (CI): 0.27–0.75], p ≤ 0.01) and smaller decreases in glucose from 1 to 3 months (OR 0.51 [95% CI: 0.28–0.92], p = 0.03) were associated with lower odds of FF, whereas 1-month leptin (OR 2.30 [95% CI: 1.30–4.07], p < 0.01) and larger increase in insulin (OR 1.86 [95% CI: 1.23–2.81], p < 0.01) and leptin (OR 2.17 [95% CI: 1.29–3.68], p < 0.01) from 1 to 3 months were associated with increased odds of FF. At 6 months, insulin increases (OR 2.08 [95% CI: 1.03–4.17], p = 0.04) were associated with higher odds of FF. Conclusions: In a cohort of women with established lactation, 1-month milk glucose, insulin, and leptin predicted initiation of FF at 3 months. Early milk composition may provide a window into mammary gland function, allowing identification of women at risk of not meeting their breastfeeding goals.