Ultra-processed foods and cardiovascular disease: analysis of three large US prospective cohorts and a systematic review and meta-analysis of prospective cohort studies.

Background: Prospective associations between total and groups of ultra-processed foods (UPF) and cardiovascular disease (CVD) remained to be characterised. Our aim was to assess the association of total and group-specific UPF intakes with CVD, coronary heart disease (CHD), and stroke in three large prospective cohorts of US adults. Additionally, we conducted a systematic review and meta-analyses on the existing evidence on the associations of total UPF intake with these outcomes. Methods: UPF intake was assessed through food frequency questionnaires in the Nurses' Health Study (NHS; n = 75,735), Nurses' Health Study II (NHSII; n = 90,813), and Health Professionals Follow-Up Study (HPFS; n = 40,409). Cox regression estimated cohort-specific associations of total and group-specific UPF intake with risk of CVD (cases = 16,800), CHD (cases = 10,401), and stroke (cases = 6758), subsequently pooled through fixed-effect models. Random-effects meta-analyses pooled existing prospective findings on the UPF-CVD association identified on Medline and Embase up to April 5, 2024, without language restrictions. Risk of bias was assessed with the Newcastle-Ottawa Scale, funnel plots, and Egger's tests, and meta-evidence was evaluated using NutriGrade. Findings: The baseline mean (SD) age was 50.8 years (7.2) for the NHS, 36.7 years (4.6) for the NHSII, and 53.4 years (9.6) for the HPFS. The proportion of participants of White race was 97.7% in the NHS, 96.4% in the NHSII, and 94.9% in the HPFS. Among the three cohorts, multivariable-adjusted hazard ratios [HRs (95% CIs)] for CVD, CHD, and stroke for the highest (vs. lowest) total UPF intake quintile were 1.11 (1.06-1.16), 1.16 (1.09-1.24), and 1.04 (0.96-1.12), respectively. UPF groups demonstrated divergent associations. Sugar-/artificially-sweetened drinks and processed meats were associated with higher CVD risk, whereas inverse associations were observed for bread/cold cereals, yoghurt/dairy desserts, and savoury snacks. Meta-analysing 22 prospective studies showed that total UPF intake at the highest category (vs. lowest) was associated with 17% (11%-24%), 23% (12%-34%), and 9% (3%-15%) higher CVD, CHD, and stroke risk. Meta-evidence quality was high for CHD, moderate for CVD, and low for stroke. Interpretation: Total UPF intake was adversely associated with CVD and CHD risk in US adults, corroborated by prospective studies from multiple countries, also suggesting a small excess stroke risk. Nutritional advice for cardiovascular health should consider differential consequences of group-specific UPF. Replication is needed in racially/ethnically-diverse populations. Funding: National Institutes of Health (NIH) grants supported the NHS, NHSII, and HPFS.

KECORT Study: An International e-Delphi Study on the Treatment of KEloids Using Intralesional CORTicosteroids in Clinical Practice.

BACKGROUND: Intralesional corticosteroid administration (ICA) is a first-line keloid treatment. However, it faces significant variability in current clinical and scientific practice, which hinders comparability of treatment results. OBJECTIVES: The aim of the study was to reach consensus on different aspects of ICA using hypodermic needles in keloids among an international group of dermatologists and plastic surgeons specialized in keloid treatment to provide consensus-based clinical treatment recommendations for all physicians treating keloids. METHODS: The keloid expert panel of 12 dermatologists and 11 plastic surgeons rated 30 statements. Two online e-Delphi rounds were held, both with a response rate of 100%. Fifteen (65%) keloid experts participated in the final consensus meetings. Consensus was defined as ≥ 75% of the participants choosing agree or strongly agree on a 7-point Likert scale. RESULTS: Consensus was reached on treatment goals, indication for ICA, triamcinolone acetonide (TAC) 40 mg/mL as the preferred corticosteroid administered at a maximum of 80 mg per month and at intervals of 4 weeks, minimizing pain during ICA, the use of 1 mL syringes and 25 or 27 Gauge needles, blanching as endpoint of successful infiltration, caution of not injecting subcutaneously, and the option of making multiple passes in very firm keloids prior to infiltration. Consensus could not be reached on TAC dosing, methods of prior local anesthesia, and location of injection. CONCLUSIONS: This e-Delphi study provides important clinical treatment recommendations on essential aspects of ICA in keloids. By implementing these recommendations, uniformity of ICA in keloid treatment will increase and better treatment results may be achieved.

Planetary health diet and cardiovascular disease: results from three large prospective cohort studies in the USA.

BACKGROUND: In 2019, the EAT-Lancet Commission on healthy diets from sustainable food systems proposed a Planetary Health Diet that seeks to optimise both chronic disease prevention as well as global environmental health. In this study, we aimed to examine the association between a dietary index based on the Planetary Health Diet and risk of cardiovascular disease. METHODS: We included women from the Nurses' Health Study (NHS I; 1986-2016), women from the Nurses' Health Study II (NHS II; 1991-2017), and men from the Health Professionals Follow-up Study (HPFS; 1986-2016) who were free of cardiovascular disease, cancer, and diabetes at baseline. Dietary data were collected every 4 years using a validated, semi-quantitative food frequency questionnaire. The Planetary Health Diet Index (PHDI) was based on 15 food groups: whole grains, vegetables, fruit, fish and shellfish, nuts and seeds, non-soy legumes, soy foods, and unsaturated oils were scored positively; starchy vegetables, dairy, red or processed meat, poultry, eggs, saturated fats and trans fat, and added sugar received negative scores. Scores for each food group were summed to get a total score of 0-140. Higher scores indicated greater adherence to the PHDI. We used Cox proportional hazards regression with time-varying covariates to evaluate the association between PHDI score, cumulatively averaged, and incident cardiovascular disease (defined as fatal and non-fatal myocardial infarction and stroke), adjusting for demographic, health, and lifestyle confounders in all participants with available data. Cohort-specific estimates were combined using inverse variance-weighted fixed effects meta-analyses. FINDINGS: Of the 62 919 women included from the NHS I, 88 535 women included from the NHS II, and 42 164 men included from the HPFS, a total of 9831 cases of cardiovascular disease were confirmed over 4 541 980 person-years of follow-up. Mean PHDI scores ranged from 60·7 (SD 5·1) to 90·6 (5·3) in the lowest versus highest quintile in NHS I, 55·6 (4·9) to 86·3 (6·3) in NHS II, and 59·6 (5·9) to 94 (5·9) in HPFS. In the multivariable-adjusted meta-analysis, participants in the highest quintile of PHDI score had a lower risk of incident cardiovascular disease than did those in the lowest quintile (hazard ratio [HR] 0·83 [95% CI 0·78-0·89]; p-trend <0·0001). When we examined cardiovascular disease subtypes, the highest quintile of PHDI was also associated with a lower risk of coronary heart disease (HR 0·81 [95% CI 0·74-0·88]; p-trend <0·0001) and total stroke (HR 0·86 [0·78-0·95]; p-trend=0·0004) compared with the lowest quintile. INTERPRETATION: We found that adherence to the Planetary Health Diet, designed to be a more environmentally sustainable dietary pattern, was associated with a lower risk of cardiovascular disease in three large cohorts of men and women in the USA. These observations support the Planetary Health Diet as a promising strategy to promote both human and planetary health. FUNDING: National Institutes of Health.

Glycemic Control Contributes to the Neuroprotective Effects of Mediterranean and Green-Mediterranean Diets on Brain Age; The DIRECT PLUS Brain-MRI Randomized Controlled Trial.

BACKGROUND: We recently reported that Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by ∼50% within 18 months. OBJECTIVE: To explore the contribution of specific diet-induced parameters to brain volume deviation from chronological age. METHODS: A post-hoc analysis of the 18-month DIRECT-PLUS trial, where participants were randomly assigned to: (1)-healthy-dietary-guidelines (HDG); (2)-MED diet; or (3)-green-MED diet, high in polyphenols and low in red meat. Both MED groups consumed 28g walnuts/day (+440mg/day polyphenols). The green-MED group further consumed green-tea (3-4 cups/day) and Mankai green shake (Wolffia-globosa aquatic plant) (+800mg/day polyphenols). We collected blood samples through the intervention and followed brain structure volumes by magnetic-resonance-imaging (MRI). We used hippocampal-occupancy (HOC) score (hippocampal and inferior-lateral-ventricle volumes ratio) as a neurodegeneration marker and brain age proxy. We applied multivariate-linear-regression models. RESULTS: Of 284 participants (88% male; age=51.1years; BMI=31.2kg/m2; HbA1c=5.48%; APOE-ε4 genotype=15.7%), 224 completed the trial with eligible whole-brain MRIs. Individuals with higher HOC-deviations (i.e., younger brain age) presented lower body weight (r=-0.204;95%CI[-0.298,-0.101]), waist-circumference (r=-0.207;95%CI[-0.310,-0.103]), diastolic (r=-0.186;95%CI[-0.304,-0.072]), and systolic blood pressure (r=-0.189;95%CI[-0.308,-0.061]), insulin (r=-0.099;95%CI[-0.194,-0.004]) and HbA1c (r=-0.164;95%CI[-0.337,-0.006]) levels. After 18 months, greater changes in HOC-deviations (i.e., brain-age decline attenuation) were independently associated with improved HbA1c (ß=-0.254;95%CI[-0.392,-0.117]), HOMA-IR (ß=-0.200;95%CI[-0.346,-0.055]) fasting glucose (ß=-0.155;95%[CI -0.293,-0.016]), and s-CRP (ß=-0.153;95%[CI -0.296,-0.010]). Improvement in diabetes status was associated with greater HOC-deviation changes compared to either no change in diabetes status (0.010;95%CI]0.002,0.019[) or with an unfavorable change (0.012;95%CI]0.002,0.023]). A decline in HbA1c is further associated with greater deviation changes in the Thalamus, Caudate nucleus, and Cerebellum (p<0.05). Greater consumption of Mankai and green-tea (green-MED diet components) were associated with greater HOC-deviation changes beyond weight loss. CONCLUSIONS: Glycemic control contributes to the neuroprotective effects of the MED and green-MED diets on brain age. Polyphenols-rich diet components as Mankai and green-tea may contribute to a more youthful brain age. TRIAL-REGISTRATION-CLINICAL-TRIALS-IDENTIFIER: NCT03020186 URL OF REGISTRATION: https://clinicaltrials.gov/study/NCT03020186.

Newborn DNA methylation age differentiates long-term weight trajectories: the Boston Birth Cohort.

BACKGROUND: Gestational age (GEAA) estimated by newborn DNA methylation (GAmAge) is associated with maternal prenatal exposures and immediate birth outcomes. However, the association of GAmAge with long-term overweight or obesity (OWO) trajectories is yet to be determined. METHODS: GAmAge was calculated for 831 children from a US predominantly urban, low-income, multi-ethnic birth cohort based on cord blood DNA methylation profile using Illumina EPIC array. Repeated anthropometric measurements aligned with pediatric primary care schedule allowed us to calculate body-mass-index percentiles (BMIPCT) at specific age and to define long-term weight trajectories from birth to 18 years. RESULTS: GAmAge was associated with BMIPCT trajectories, defined by 4 groups: stable (consistent OWO: "early OWO"; constant normal weight: "NW") or non-stable (OWO by year 1 of follow-up: "late OWO"; OWO by year 6 of follow-up: "NW to very late OWO"). GAmAge differentiated between the group with consistently normal BMIPCT pattern and the non-stable groups with late and very late OWO development. Such differentiation was observed in the age periods of birth to 1year, 3years, 6years, 10years, and 14years (p < 0.05 for all). The findings persisted after adjusting for GEAA, maternal smoking, delivery method, and child's sex in multivariate models. Birth weight was a mediator for the GAmAge effect on OWO status for specific groups at multiple age periods. CONCLUSIONS: GAmAge is associated with BMIPCT trajectories from birth to age 18 years, independent of GEAA and birth weight. If further confirmed, GAmAge may serve as an early biomarker for predicting BMI trajectory to inform early risk assessment and prevention of OWO. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03228875).

Deimplementation of Routine Maternal Oxygen Supplementation for Intrauterine Fetal Resuscitation: A Retrospective Cohort Study.

OBJECTIVE: Current practice guidelines for laboring patients with category II intrapartum tracings recommend maternal oxygen supplementation despite emerging randomized data challenging its benefit and utility. We aim to validate that de-implementing maternal oxygen supplementation for fetal resuscitation did not increase the risk of neonatal acidemia in a real-world setting. STUDY DESIGN: This is a retrospective observational study conducted at a single tertiary care center from January 2019 to June 2021. All laboring deliveries during the study period were reviewed and eligible participants included singleton or twin pregnancies between 23 and 42 weeks gestational age with persistent category II tracings. Known major fetal anomalies, contraindications to labor, and maternal indication for O2 supplementation, including active coronavirus disease 2019, were excluded. Cohorts were allocated based on the time of delivery. Those occurring prior to our hospital policy change were identified as historical controls and deliveries after April 1, 2020, as the postdeimplementation cohort. The primary outcome was fetal acidemia, defined as umbilical cord pH < 7.2. Secondary outcomes included severe acidemia (pH < 7.0), 5-minute Apgar score <4, and neonatal intensive care admission. Regression analyses controlling for known variables associated with neonatal acidemia generated adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: Among 9,088 deliveries during the study period, 1,162 tracings were flagged as persistent category II, including 681 (59%) in the postintervention group. The two cohorts had comparable baseline and obstetric characteristics. No difference in neonatal acidemia was observed between the postdeimplementation group and historical controls (13.8 vs. 15.4%, aOR = 0.87, 95% CI: 0.62, 1.22). Severe acidemia, 5-minute Apgar <4, and neonatal intensive care admission were not increased in the postdeimplementation group. CONCLUSION: De-implementation of routine maternal oxygen supplementation for fetal resuscitation did not increase the likelihood of neonatal acidemia in a real-world setting, validating guidelines recommending against the intervention. KEY POINTS: · De-implementation of maternal O2 supplementation for fetal resuscitation did not increase acidemia.. · Real-world experience validates experimental findings regarding maternal oxygenation.. · Other perinatal outcomes reflected no difference in fetal acidemia..

Epigenetic Clock at Birth and Childhood Blood Pressure Trajectory: A Prospective Birth Cohort Study.

BACKGROUND: The impact of methylation gestational age (GAmAge; a biomarker of fetal maturity) at birth on childhood blood pressure (BP) trajectories is unknown. METHODS: This cohort study included 500 boys and 440 girls with data on cord blood DNA methylation and BP at 3 to 15 years of age. Systolic BP (SBP) and diastolic BP percentiles were calculated based on clinical guidelines. Time-series K-means clustering identified 4 distinct SBP and diastolic BP percentile trajectories: high-steady, high-decrease, normal-increase, and normal-steady. GAmAge was estimated using an existing pediatric epigenetic clock. Extrinsic age acceleration was calculated as residuals of associations between GAmAge and chronological gestational age. Intrinsic age acceleration was calculated using the same method adjusting for cord blood cell compositions. RESULTS: Extrinsic age acceleration and intrinsic age acceleration were inversely associated with repeated measures of BP percentiles. Significant inverse associations were observed between extrinsic age acceleration and SBP percentiles in boys (ß=-2.02; P=0.02) but not in girls (ß=-0.49; P=0.58). Both extrinsic age acceleration and intrinsic age acceleration were inversely associated with SBP percentiles in girls born preterm (<37 weeks; ßEAA=-2.95; ßIAA=-3.00; P<0.05). Compared with the normal-steady SBP trajectory, significant inverse associations were observed between intrinsic age acceleration and high-steady, high-decrease, and normal-increase SBP trajectories in boys (odds ratio, 0.73-0.81; P<0.03), and significant positive associations were observed for high-decrease and normal-increase SBP trajectories in girls (odds ratio, 1.26-1.38; P<0.01). Significant sex differences were observed (Psex-interaction<2×10-16). CONCLUSIONS: GAmAge acceleration at birth was inversely associated with child BP, and such association was more pronounced in boys than in girls. Our findings may shed new light on the developmental origins of high BP and sex differences in cardiovascular risk.

The effect of Mankai plant consumption on postprandial glycaemic response among patients with type 2 diabetes: A randomized crossover trial.

AIM: To explore the effect of Mankai, a cultivated aquatic duckweed green plant, on postprandial glucose (PG) excursions in type 2 diabetes (T2D). METHODS: In a 4-week, randomized crossover-controlled trial, we enrolled 45 adults with T2D (HbA1c range: 6.5%-8.5%) from two sites in Israel. Participants were randomized to drink Mankai (200 mL of raw-fresh-aquatic plant + 100 mL of water, 40 kcal, ~10 g of dry matter equivalent) or water (300 mL) following dinner, for 2 weeks each, with a 4-day washout interval, without dietary, physical activity or pharmacotherapy alterations. We used continuous glucose monitoring (CGM) devices. RESULTS: Forty patients (adherence rate = 88.5%; 743 person-intervention-days, 68.9% men, age = 64 years, HbA1c = 6.8%) completed the study with a consistent diet and complete CGM reads. Only two-thirds of the individuals responded beneficially to Mankai. Overall, Mankai significantly lowered the PG peak by 19.3% (∆peak = 24.3 ± 16.8 vs. 30.1 ± 18.5 mg/dL; P < .001) and delayed the time-to-peak by 20.0% (112.5 [interquartile range: 75-135] vs. 90 [60-105] min; P < .001) compared with water. The PG incline and decline slopes were shallower following postdinner Mankai (incline slope: 16.8 vs. water: 29.9 mg/[dL h]; P < .001; decline slope: -6.1 vs. water: -7.9 mg/[dL h]; P < .01). Mean postprandial net incremental area-under-the-glucose-curve was lowered by 20.1% with Mankai compared with water (P = .03). Results were consistent across several sensitivity and subgroup analyses, including across antidiabetic pharmacotherapy treatment groups. Within 2 weeks, the triglycerides/high-density lipoprotein cholesterol ratio in the Mankai group (-0.5 ± 1.3) decreased versus water (+0.3 ± 1.5, P = .05). CONCLUSIONS: Mankai consumption may mitigate the PG response in people with T2D with an ~20% improvement in glycaemic values. These findings provide case-study evidence for plant-based treatments in T2D to complement a healthy lifestyle and pharmacotherapy.

The MIND diet, brain transcriptomic alterations, and dementia.

INTRODUCTION: Dietary patterns are associated with dementia risk, but the underlying molecular mechanisms are largely unknown. METHODS: We used RNA sequencing data from post mortem prefrontal cortex tissue and annual cognitive evaluations from 1204 participants in the Religious Orders Study and Memory and Aging Project. We identified a transcriptomic profile correlated with the MIND diet (Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay) among 482 individuals who completed ante mortem food frequency questionnaires; and examined its associations with cognitive health in the remaining 722 participants. RESULTS: We identified a transcriptomic profile, consisting of 50 genes, correlated with the MIND diet score (p = 0.001). Each standard deviation increase in the transcriptomic profile score was associated with a slower annual rate of decline in global cognition (ß = 0.011, p = 0.003) and lower odds of dementia (odds ratio = 0.76, p = 0.0002). Expressions of several genes (including TCIM and IGSF5) appeared to mediate the association between MIND diet and dementia. DISCUSSION: A brain transcriptomic profile for healthy diets revealed novel genes potentially associated with cognitive health. HIGHLIGHTS: Why healthy dietary patterns are associated with lower dementia risk are unknown. We integrated dietary, brain transcriptomic, and cognitive data in older adults. Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet intake is correlated with a specific brain transcriptomic profile. This brain transcriptomic profile score is associated with better cognitive health. More data are needed to elucidate the causality and functionality of identified genes.

Meat consumption and incident type 2 diabetes: an individual-participant federated meta-analysis of 1·97 million adults with 100 000 incident cases from 31 cohorts in 20 countries.

BACKGROUND: Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and harmonised analytical approaches. METHODS: This individual-participant federated meta-analysis involved data from 31 cohorts participating in the InterConnect project. Cohorts were from the region of the Americas (n=12) and the Eastern Mediterranean (n=2), European (n=9), South-East Asia (n=1), and Western Pacific (n=7) regions. Access to individual-participant data was provided by each cohort; participants were eligible for inclusion if they were aged 18 years or older and had available data on dietary consumption and incident type 2 diabetes and were excluded if they had a diagnosis of any type of diabetes at baseline or missing data. Cohort-specific hazard ratios (HRs) and 95% CIs were estimated for each meat type, adjusted for potential confounders (including BMI), and pooled using a random-effects meta-analysis, with meta-regression to investigate potential sources of heterogeneity. FINDINGS: Among 1 966 444 adults eligible for participation, 107 271 incident cases of type 2 diabetes were identified during a median follow-up of 10 (IQR 7-15) years. Median meat consumption across cohorts was 0-110 g/day for unprocessed red meat, 0-49 g/day for processed meat, and 0-72 g/day for poultry. Greater consumption of each of the three types of meat was associated with increased incidence of type 2 diabetes, with HRs of 1·10 (95% CI 1·06-1·15) per 100 g/day of unprocessed red meat (I2=61%), 1·15 (1·11-1·20) per 50 g/day of processed meat (I2=59%), and 1·08 (1·02-1·14) per 100 g/day of poultry (I2=68%). Positive associations between meat consumption and type 2 diabetes were observed in North America and in the European and Western Pacific regions; the CIs were wide in other regions. We found no evidence that the heterogeneity was explained by age, sex, or BMI. The findings for poultry consumption were weaker under alternative modelling assumptions. Replacing processed meat with unprocessed red meat or poultry was associated with a lower incidence of type 2 diabetes. INTERPRETATION: The consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations. These findings highlight the importance of reducing meat consumption for public health and should inform dietary guidelines. FUNDING: The EU, the Medical Research Council, and the National Institute of Health Research Cambridge Biomedical Research Centre.

Impact of a school-based food assistance program on household food insecurity in Greece, 2012-2019: a multi-year evaluation of the DIATROFI program.

Background: Childhood food insecurity can persist among low socioeconomic areas in high-income countries. Universal Free School Meal (UFSM) programs are designed to respond to this pressing issue. This study aimed to conduct a multi-year evaluation of the DIATROFI Program's impact on household food insecurity in Greece. Methods: This study utilized data from 18,716 students (618 kindergarten to high schools), from low socioeconomic areas participating in the school-level UFSM Program DIATROFI between 2012 and 2019. Parents of students completed annual baseline and follow-up paper-based self-completed questionnaires. The primary outcome was household food insecurity, measured using the Food Security Survey Module (FSSM) at both questionnaires, and evaluated through mixed linear and logistic regression models with repeated measurements. Findings: Students' median age was 9 years old (Interquartile range (IQR): 6.5, 12.0), 51.6% (n = 9658) were girls, and 82.2% (n = 15,382) lived in low/medium socioeconomic affluence households. Households with food insecurity reduced from 51.5% (n = 9630) to 47.6% (n = 8901) after one school year. Food insecurity score declined steadily for four years of consecutive participation, compared to baseline score (one-year b:-0.26; 95% Confidence Interval (CI):-0.30, -0.22, and four-year -1.28; -1.53, -1.03). The likelihood of retaining food insecure status reduced from 17% after one-year participation (Odds Ratio (OR): 0.83; 95% CI: 0.79, 0.87) to 36% after four-year participation (0.64; 0.49, 0.82). The Program's impact on household food insecurity alleviation was greater among households with low parental education and low socioeconomic affluence. Interpretation: The DIATROFI Program effectively improved household food security during and after the Greek socioeconomic crisis. School-level UFSM programs targeting underprivileged students can improve household food insecurity, with a more pronounced effect with increased years of participation, and among economically disadvantaged households. Funding: The DIATROFI Program was funded through various national and private organizations, including national prefecture authorities, Greek payment authorities, philanthropic/charitable organizations, and private companies.

Transgender and Gender Diverse Health Care in the US Military: What Dermatologists Need to Know.

The US Military has made considerable strides in providing quality health care to transgender and gender diverse service members (TSMs). Current policies ensure continued military readiness and allow TSMs to receive gender-affirming care while continuing to serve. Dermatologists play an important role in the multidisciplinary medical team required for medical gender transition; however, there is considerable discord between medically necessary procedures for dermatologic gender-affirming care and insurance-covered benefits. Within the scope of dermatology, many of the available procedures currently are not covered by insurance. This article seeks to discuss how military and civilian dermatologists can contribute to gender-affirming care. We also review existing disparities in health care and identify potential areas of improvement.

Integration of epidemiological and blood biomarker analysis links haem iron intake to increased type 2 diabetes risk.

Dietary haem iron intake is linked to an increased risk of type 2 diabetes (T2D), but the underlying plasma biomarkers are not well understood. We analysed data from 204,615 participants (79% females) in three large US cohorts over up to 36 years, examining the associations between iron intake and T2D risk. We also assessed plasma metabolic biomarkers and metabolomic profiles in subsets of 37,544 (82% females) and 9,024 (84% females) participants, respectively. Here we show that haem iron intake but not non-haem iron is associated with a higher T2D risk, with a multivariable-adjusted hazard ratio of 1.26 (95% confidence interval 1.20-1.33; P for trend <0.001) comparing the highest to the lowest quintiles. Haem iron accounts for significant proportions of the T2D risk linked to unprocessed red meat and specific dietary patterns. Increased haem iron intake correlates with unfavourable plasma profiles of insulinaemia, lipids, inflammation and T2D-linked metabolites. We also identify metabolites, including L-valine and uric acid, potentially mediating the haem iron-T2D relationship, highlighting their pivotal role in T2D pathogenesis.

All-cause and cause-specific mortality risk and loss in life expectancy associated with incident type 2 diabetes onset age and duration.

BACKGROUND: Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy. METHODS: We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses' Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), and kidney disease (8.55, 1.98-36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality. CONCLUSION: Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy.

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.

Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition.

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (-32%; 95% confidence interval (95% CI): -21% to -42%) and type 2 diabetes (-26%; 95% CI: -15% to -35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses' Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications.

Gut-Microbiota-Related Metabolite Phenylacetylglutamine and Risk of Incident Coronary Heart Disease among Women.

CONTEXT: Phenylacetylglutamine (PAGln) is a novel metabolite derived from gut microbial metabolism of dietary proteins, specifically phenylalanine, which may be linked to risks of adverse cardiovascular events. OBJECTIVE: We investigated whether higher plasma levels of PAGln were associated with a greater risk of incident coronary heart disease (CHD) and tested whether adherence to a plant-based diet, which characterizes habitual dietary patterns of animal and plant food intake, modified the associations. METHODS: We examined associations between plasma PAGln and risk of incident CHD over 11-16 years in a nested case-control study of 1520 women (760 incident cases and 760 controls) from the Nurses' Health Study. Separately, we analyzed relations between PAGln and dietary intakes measured through dietary records in the Women's Lifestyle Validation Study (n=725). RESULTS: Higher PAGln levels were related to a greater risk of CHD (p <0.05 for dose-response relationship). Higher PAGln was associated with greater red/processed meat intake and lower vegetable intake (p <0.05 for all). We found a significant interaction between PAGln and adherence to plant-based diet index (PDI) on CHD (Pinteraction=0.008); higher PAGln levels were associated with an increased risk of CHD (relative risk per 1 SD: 1.22 [95% CI: 1.05, 1.41]) among women with low PDI but not among those with high PDI. CONCLUSION: Higher PAGln was associated with higher risk of CHD, particularly in women with dietary patterns of eating more animal foods and fewer plant-based foods. Adherence to plant-based diets might attenuate unfavorable associations between a novel microbial metabolite and CHD risk.

Planetary Health Diet Index and risk of total and cause-specific mortality in three prospective cohorts.

BACKGROUND: In 2019, the EAT-Lancet Commission proposed a healthy dietary pattern that, along with reductions in food waste and improved agricultural practices, could feed the increasing global population sustainably. We developed a Planetary Health Diet Index (PHDI) to quantify adherence to the EAT-Lancet reference diet. OBJECTIVES: We aimed to assess associations between PHDI and total and cause-specific mortality in 3 prospective cohorts of males and females in the United States. METHODS: We followed 66,692 females from the Nurses' Health Study (1986-2019), 92,438 females from the Nurses' Health Study II (1989-2019), and 47,274 males from the Health Professionals Follow-up Study (1986-2018) who were free of cancer, diabetes, and major cardiovascular diseases at baseline. The PHDI was calculated every 4 y using a semiquantitative food frequency questionnaire. Hazard ratios (HRs) were calculated using multivariable proportional-hazards models. RESULTS: During follow-up, we documented 31,330 deaths among females and 23,206 among males. When comparing the highest with the lowest quintile of PHDI, the pooled multivariable-adjusted HRs were 0.77 [95% confidence interval (CI): 0.75, 0.80] for all-cause mortality (P-trend < 0.0001). The PHDI was associated with lower risk of deaths from cardiovascular diseases (HR: 0.86; 95% CI: 0.81, 0.91), cancer (HR: 0.90; 95% CI: 0.85, 0.95), respiratory diseases (HR: 0.53; 95% CI: 0.48, 0.59), and neurodegenerative diseases (HR: 0.72; 95% CI: 0.67, 0.78). In females, but not males, the PHDI was also significantly associated with a lower risk of deaths from infectious diseases (HR: 0.62; 95% CI: 0.51, 0.76). PHDI scores were also associated inversely with greenhouse gas emissions and other environmental impacts. CONCLUSIONS: In 3 large United States-based prospective cohorts of males and females with up to 34 y of follow-up, a higher PHDI was associated with lower risk of total and cause-specific mortality and environment impacts.

Strain-specific gut microbial signatures in type 2 diabetes identified in a cross-cohort analysis of 8,117 metagenomes.

The association of gut microbial features with type 2 diabetes (T2D) has been inconsistent due in part to the complexity of this disease and variation in study design. Even in cases in which individual microbial species have been associated with T2D, mechanisms have been unable to be attributed to these associations based on specific microbial strains. We conducted a comprehensive study of the T2D microbiome, analyzing 8,117 shotgun metagenomes from 10 cohorts of individuals with T2D, prediabetes, and normoglycemic status in the United States, Europe, Israel and China. Dysbiosis in 19 phylogenetically diverse species was associated with T2D (false discovery rate < 0.10), for example, enriched Clostridium bolteae and depleted Butyrivibrio crossotus. These microorganisms also contributed to community-level functional changes potentially underlying T2D pathogenesis, for example, perturbations in glucose metabolism. Our study identifies within-species phylogenetic diversity for strains of 27 species that explain inter-individual differences in T2D risk, such as Eubacterium rectale. In some cases, these were explained by strain-specific gene carriage, including loci involved in various mechanisms of horizontal gene transfer and novel biological processes underlying metabolic risk, for example, quorum sensing. In summary, our study provides robust cross-cohort microbial signatures in a strain-resolved manner and offers new mechanistic insights into T2D.