Longitudinal associations between ambient PM2.5 exposure and lipid levels in two Indian cities.

Background: Exposure to ambient PM2.5 is known to affect lipid metabolism through systemic inflammation and oxidative stress. Evidence from developing countries, such as India with high levels of ambient PM2.5 and distinct lipid profiles, is sparse. Methods: Longitudinal nonlinear mixed-effects analysis was conducted on >10,000 participants of Centre for cArdiometabolic Risk Reduction in South Asia (CARRS) cohort in Chennai and Delhi, India. We examined associations between 1-month and 1-year average ambient PM2.5 exposure derived from the spatiotemporal model and lipid levels (total cholesterol [TC], triglycerides [TRIG], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]) measured longitudinally, adjusting for residential and neighborhood-level confounders. Results: The mean annual exposure in Chennai and Delhi was 40 and 102 µg/m3 respectively. Elevated ambient PM2.5 levels were associated with an increase in LDL-C and TC at levels up to 100 µg/m3 in both cities and beyond 125 µg/m3 in Delhi. TRIG levels in Chennai increased until 40 µg/m3 for both short- and long-term exposures, then stabilized or declined, while in Delhi, there was a consistent rise with increasing annual exposures. HDL-C showed an increase in both cities against monthly average exposure. HDL-C decreased slightly in Chennai with an increase in long-term exposure, whereas it decreased beyond 130 µg/m3 in Delhi. Conclusion: These findings demonstrate diverse associations between a wide range of ambient PM2.5 and lipid levels in an understudied South Asian population. Further research is needed to establish causality and develop targeted interventions to mitigate the impact of air pollution on lipid metabolism and cardiovascular health.

Diabetes disparities in the United States: Trends by educational attainment from 2001 to 2020.

INTRODUCTION: Tracking changes in socioeconomic disparities in diabetes in the US is important to evaluate progress in health equity and guide prevention efforts. Disparities in diabetes prevalence by educational attainment from 2001 to 2020 were investigated. METHODS: Using a serial cross-sectional design, data from 33,220 adults aged 30 to 79 assessed in nine rounds of the National Health and Nutrition Examination Surveys between 2001 to 2020 were analyzed in 2023-4. Diabetes was defined as self-reported prior diagnosis, elevated glycated hemoglobin (HbA1c≥6.5%), or use of diabetes medications. Marginalized age- and covariate-adjusted prevalence differences (PD) and prevalence ratios (PR) of diabetes by educational attainment (less than high school graduation, high school graduation, some college education or associate degree, or college graduation [reference]) by calendar period (2001-04, 2005-08, 2009-12, 2013-16, 2017-20) were derived from logistic regression models. RESULTS: From 2001 to 2020, age-adjusted diabetes prevalence was consistently higher among adults without a college degree. Adults without a high school diploma exhibited the largest disparities in both 2001-04 (PD 8.0%; 95%CI 5.6-10.5 and PR 2.1; 95%CI 1.5-2.6) and 2017-20 (PD 11.0%; 95%CI 6.7-15.2 and PR 2.1; 95%CI 1.5-2.7). Between 2001-04 and 2017-20, the absolute disparity in diabetes increased only among adults with a high school diploma (PD 1.7% 95%CI -0.5-3.9 vs PD 8.8%; 4.1-13.4, respectively), while the PR did not change in any group. Education-related disparities in diabetes were attenuated after accounting for socio-demographic factors and BMI. CONCLUSIONS: From 2001 to 2020, national education-related disparities in diabetes prevalence have shown no signs of narrowing.

Access to essential medicines for diabetes care: availability, price, and affordability in central Ethiopia.

BACKGROUND: Diabetes is a major global public health burden. Effective diabetes management is highly dependent on the availability of affordable and quality-assured essential medicines (EMs) which is a challenge especially in low-and-middle-income countries such as Ethiopia. This study aimed to assess the accessibility of EMs used for diabetes care in central Ethiopia's public and private medicine outlets with respect to availability and affordability parameters. METHODS: A cross-sectional study was conducted in 60 selected public and private medicine outlets in central Ethiopia from January to February 2022 using the World Health Organization/Health Action International (WHO/HAI) standard tool to assess access to EMs. We included EMs that lower glucose, blood pressure, and cholesterol as these are all critical for diabetes care. Availability was determined as the percentage of surveyed outlets per sector in which the selected lowest-priced generic (LPG) and originator brand (OB) products were found. The number of days' wages required by the lowest paid government worker (LPGW) to purchase a one month's supply of medicines was used to measure affordability while median price was determined to assess patient price and price markup difference between public procurement and retail prices. RESULTS: Across all facilities, availability of LPG and OB medicines were 34.6% and 2.5% respectively. Only two glucose-lowering (glibenclamide 5 mg and metformin 500 mg) and two blood pressure-lowering medications (nifedipine 20 mg and hydrochlorothiazide 25 mg) surpassed the WHO's target of 80% availability. The median price based on the least measurable unit of LPG diabetes EMs was 1.6 ETB (0.033 USD) in public and 4.65 ETB (0.095 USD) in private outlets. The cost of one month's supply of diabetes EMs was equivalent to 0.3 to 3.1 days wages in public and 1.0 to 11.0 days wages in private outlets, respectively, for a typical LPGW. Thus, 58.8% and 84.6% of LPG diabetes EMs included in the price analysis were unaffordable in private and public outlets, respectively. CONCLUSIONS: There are big gaps in availability and affordability of EMs used for diabetes in central Ethiopia. Policy makers should work to improve access to diabetes EMs. It is recommended to increase government attention to availing affordable EMs for diabetes care including at the primary healthcare levels which are more accessible to the majority of the population. Similar studies are also recommended to be conducted in different parts of Ethiopia.

Multiple cardiovascular risk factor care in 55 low- and middle-income countries: A cross-sectional analysis of nationally-representative, individual-level data from 280,783 adults.

The prevalence of multiple age-related cardiovascular disease (CVD) risk factors is high among individuals living in low- and middle-income countries. We described receipt of healthcare services for and management of hypertension and diabetes among individuals living with these conditions using individual-level data from 55 nationally representative population-based surveys (2009-2019) with measured blood pressure (BP) and diabetes biomarker. We restricted our analysis to non-pregnant individuals aged 40-69 years and defined three mutually exclusive groups (i.e., hypertension only, diabetes only, and both hypertension-diabetes) to compare individuals living with concurrent hypertension and diabetes to individuals with each condition separately. We included 90,086 individuals who lived with hypertension only, 11,975 with diabetes only, and 16,228 with hypertension-diabetes. We estimated the percentage of individuals who were aware of their diagnosis, used pharmacological therapy, or achieved appropriate hypertension and diabetes management. A greater percentage of individuals with hypertension-diabetes were fully diagnosed (64.1% [95% CI: 61.8-66.4]) than those with hypertension only (47.4% [45.3-49.6]) or diabetes only (46.7% [44.1-49.2]). Among the hypertension-diabetes group, pharmacological treatment was higher for individual conditions (38.3% [95% CI: 34.8-41.8] using antihypertensive and 42.3% [95% CI: 39.4-45.2] using glucose-lowering medications) than for both conditions jointly (24.6% [95% CI: 22.1-27.2]).The percentage of individuals achieving appropriate management was highest in the hypertension group (17.6% [16.4-18.8]), followed by diabetes (13.3% [10.7-15.8]) and hypertension-diabetes (6.6% [5.4-7.8]) groups. Although health systems in LMICs are reaching a larger share of individuals living with both hypertension and diabetes than those living with just one of these conditions, only seven percent achieved both BP and blood glucose treatment targets. Implementation of cost-effective population-level interventions that shift clinical care paradigm from disease-specific to comprehensive CVD care are urgently needed for all three groups, especially for those with multiple CVD risk factors.

Natural History of Type 2 Diabetes in Indians: Time to Progression.

OBJECTIVE: To describe the natural history of diabetes in Indians. RESEARCH DESIGN AND METHODS: Data are from participants older than 20 years in the Centre for Cardiometabolic Risk Reduction in South Asia longitudinal study. Glycemic states were defined per American Diabetes Association criteria. Markov models were used to estimate annual transition probabilities and sojourn time through states. RESULTS: Among 2,714 diabetes-free participants, 641 had isolated impaired fasting glucose (iIFG), and 341 had impaired glucose tolerance (IGT). The annual transition to diabetes for those with IGT was 13.9% (95% CI 12.0, 15.9) versus 8.6% (7.3, 9.8) for iIFG. In the normoglycemia ↔ iIFG → diabetes model, mean sojourn time in normoglycemia was 40.3 (34.6, 48.2) years, and sojourn time in iIFG was 9.7 (8.4, 11.4) years. For the normoglycemia ↔ IGT → diabetes model, mean sojourn time in normoglycemia was 34.5 (29.5, 40.8) years, and sojourn time in IGT was 6.1 (5.3, 7.1) years. CONCLUSIONS: Individuals reside in normoglycemia for 35-40 years; however, progression from prediabetes to diabetes is rapid.

Determinants of health and mortality in undiagnosed diabetes: A nationally representative US adult, 2011-2020.

AIM: This study examines the determinants of health and mortality associated with undiagnosed diabetes among a nationally representative sample of US adults. METHODS: Data are from the National Health and Nutrition Examination Survey between 2011 and 2012 and 2019-2020. Diabetes status is categorized into three groups: undiagnosed diabetes, diagnosed diabetes, and no diabetes. Multiple logistic regression is used to estimate the association between undiagnosed diabetes and three domains of risk factors, including sociodemographic and health behavioral and clinical factors. Cox proportional hazards models are performed to compare excess mortality risk between the three groups. RESULTS: Young adults, racial minorities, the foreign-born, and individuals with limited access to health care are more likely to be unaware of their diabetes. Moreover, adults without a family history of diabetes and chronic conditions have a higher chance of undiagnosed diabetes. No health behavioral factors are found to be associated with undiagnosed diabetes. Adults with undiagnosed diabetes have a lower risk of all-cause and cardiovascular disease mortality compared to those with diagnosed diabetes, but a higher risk of all-cause mortality than those with no diabetes. CONCLUSION: Targeted public health approaches should address sociodemographic and clinical factors to reduce the burden of undiagnosed diabetes.

Impact of electronic information exchange on repeat imaging during 30-day readmissions among Medicare beneficiaries.

OBJECTIVES: We examined the association between electronic health information sharing and repeat imaging in readmissions among older adults with and without Alzheimer disease (AD). STUDY DESIGN: Cohort study using national Medicare data. METHODS: Among Medicare beneficiaries with 30-day readmissions in 2018, we examined repeat imaging on the same body system during the readmission. This was evaluated between fragmented and nonfragmented (same-hospital) readmissions and across categories of electronic information sharing via health information exchanges (HIEs) in fragmented readmissions: admission and readmission hospitals share the same HIE, admission and readmission hospitals participate in different HIEs, one or both do not participate in HIE, or HIE data missing. This relationship was evaluated using unadjusted and adjusted logistic regression. RESULTS: Overall, 14.3% of beneficiaries experienced repeat imaging during their readmission. Compared with nonfragmented readmissions, fragmented readmissions were associated with 5% higher odds of repeat imaging on the same body system in older adults without AD. This was not mitigated by the presence of electronic information sharing: Fragmented readmissions to hospitals that shared an HIE had 6% higher odds of repeat imaging (adjusted OR, 1.06; 95% CI, 1.00-1.13). There was no difference seen in the odds of repeat imaging for older adults with AD. CONCLUSIONS: Despite substantial investment, HIEs as currently deployed and used are not associated with decreased odds of repeat imaging in readmissions.

Association of pro-inflammatory cytokines, adipokines and hepatokine with incident diabetes in India: a nested case-control study within CARRS cohort.

AIMS: To study the association of pro-inflammatory markers with incident diabetes in India. METHODS: We did a nested case-control study within the CARRS (Centre for Ardiometabolic Risk Reduction in South Asia) cohort. Of the 5739 diabetes-free individuals at the baseline, 216 participants with incident diabetes and 432 age-, gender- and city-matched controls at 2-year follow-up were included. We measured high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 ( MCP-1), adiponectin, leptin and fetuin-A in the stored baseline blood samples. We did multivariate conditional logistic regression to estimate association of inflammatory markers (as quartiles) and incident diabetes. Covariates were baseline fasting plasma glucose (FPG) and lipids, body mass index (BMI), family history of diabetes, smoking and alcohol use. RESULTS: Baseline hsCRP and TNF-α were higher, and IL-6 and adiponectin were lower among cases vs. controls. In multivariate conditional logistic regression models, only quartile-3 (odds ratio [OR]: 2.96 [95% CI:1.39, 6.30]) and quartile-4 (OR: 2.58 [95% CI: 1.15, 5.79]) of TNF-α and quartile-4 of MCP-1 (OR: 2.55 [95% CI: 1.06, 6.16]) were positively associated with diabetes after adjusting for baseline FPG and BMI. These associations did not remain after adjusting for family history. High level (quartile-4) of IL-6 was negatively associated with diabetes after adjusting for all factors (OR: 0.18 [95% CI: 0.06, 0.55]). CONCLUSIONS: Higher TNF-α and MCP-1 levels and lower IL-6 were associated with higher risk of developing diabetes. Better understanding and potential methods of addressing these biomarkers, especially in relation to family history, are needed to address diabetes in South Asians.

Association of collaborative care intervention features with depression and metabolic outcomes in the INDEPENDENT study: A mixed methods study.

AIMS: The INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) trial tested a collaborative care model including electronic clinical decision support (CDS) for treating diabetes and depression in India. We aimed to assess which features of this clinically and cost-effective intervention were associated with improvements in diabetes and depression measures. METHODS: Post-hoc analysis of the INDEPENDENT trial data (189 intervention participants) was conducted to determine each intervention feature's effect: 1. Collaborative case reviews between expert psychiatrists and the care team; 2. Patient care-coordinator contacts; and 3. Clinicians' CDS prompt modifications. Primary outcome was baseline-to-12-months improvements in diabetes control, blood pressure, cholesterol, and depression. Implementer interviews revealed barriers and facilitators of intervention success. Joint displays integrated mixed methods' results. RESULTS: High baseline HbA1c≥ 74.9 mmol/mol (9%) was associated with 5.72 fewer care-coordinator contacts than those with better baseline HbA1c (76.8 mmol/mol, 9.18%, p < 0.001). Prompt modification proportions varied from 38.3% (diabetes) to 1.3% (LDL). Interviews found that providers' and participants' visit frequencies were preference dependent. Qualitative data elucidated patient-level factors that influenced number of clinical contacts and prompt modifications explaining their lack of association with clinical outcomes. CONCLUSION: Our mixed methods approach underlines the importance of the complementarity of different intervention features. Qualitative findings further illuminate reasons for variations in fidelity from the core model.

Understanding Barriers and Facilitators to Integrated HIV and Hypertension Care in South Africa.

Background The burden of hypertension among people with HIV is high, particularly in low-and middle-income countries, yet gaps in hypertension screening and care in these settings persist. The objective of this study was to identify facilitators of and barriers to hypertension screening, treatment, and management among people with HIV seeking treatment in primary care clinics in Johannesburg, South Africa. Methods Using a cross-sectional study design, data were collected via interviews (n = 53) with people with HIV and hypertension and clinic managers and focus group discussions (n = 9) with clinic staff. A qualitative framework analysis approach guided by the Theoretical Domains Framework was used to identify and compare determinants of hypertension care across different stakeholder groups. Results Data from clinic staff and managers generated three themes characterizing facilitators of and barriers to the adoption and implementation of hypertension screening and treatment: 1) clinics have limited structural and operational capacity to support the implementation of integrated care models, 2) education and training on chronic care guidelines is inconsistent and often lacking across clinics, and 3) clinicians have the goal of enhancing chronic care within their clinics but first need to advocate for health system characteristics that will sustainably support integrated care. Patient data generated three themes characterizing existing facilitators of and barriers to clinic attendance and chronic disease self-management: 1) the threat of hypertension-related morbidity and mortality as a motivator for lifestyle change, 2) the emotional toll of clinic's logistical, staff, and resource challenges, and 3) hypertension self-management as a patchwork of informational and support sources. The main barriers to hypertension screening, treatment, and management were related to environmental resources and context (i.e., lack of enabling resources and siloed flow of clinic operations) the patients' knowledge and emotions (i.e., lack of awareness about hypertension risk, fear, and frustration). Clinical actors and patients differed in perceived need to prioritize HIV versus hypertension care. Conclusions The convergence of multi-stakeholder data regarding barriers to hypertension screening, treatment, and management highlight key areas for improvement, where tailored implementation strategies may address challenges recognized by each stakeholder group.

Changes in Diabetes Care and Management Practices during the COVID-19 Pandemic.

Background: Evidence suggests diabetes management was negatively impacted early in the pandemic. However, the impact of the pandemic on key healthcare services for diabetes control and diabetes self-management practices is less known. We examined changes in diabetes care and management practices before and during the COVID-19 pandemic. Methods: Population-based data regarding 4 diabetes-related healthcare engagement and 4 self-management indicators were obtained from adults with diabetes surveyed in 19 US States and Washington DC through the Behavioral Risk Factor Surveillance System. Using logistic regression, we estimated changes in the prevalence of each indicator, overall and by sociodemographic subgroups, before (2019; n = 15,307) and during (2021; n = 13,994) the COVID-19 pandemic. Results: Between 2019 and 2021, the prevalence of biannual HbA1c tests reduced by 2.6 percentage points (pp, 95% CI :-4.8, -0.4), from 75.4-73.1%, and prevalence of annual eye exams fell by 4.0 pp (-6.2, -2.8), from 72.2-68.7%. The composite indicator of engagement with healthcare for diabetes control fell by 3.5 pp (-5.9, -1.1), from 44.9-41.9%. Reductions in engagement with healthcare were largely seen across sex, age, education, employment status, marital status, insurance status, and urbanicity; and were more pronounced among those aged 18-34 and the uninsured. Reductions in engagement with healthcare were seen in several states, with Delaware and Washington DC reporting the largest decrease. Of self-management behaviors, we only observed change in avoidance of smoking, an increase of 2.0 pp (0.4, 3.6) from 84.7-87.1%. Conclusions: The pandemic had mixed impacts on diabetes care and self-management. The findings suggest a deterioration of the uptake of evidence-based, preventive health services requiring laboratory services and clinical examination for diabetes control during the pandemic. On the other hand, smoking rates decreased, suggesting potential positive impacts of the pandemic on health behaviors in people with diabetes.

Body mass index changes and their association with SARS-CoV-2 infection: a real-world analysis.

Objective: To study body mass index (BMI) changes among individuals aged 18-99 years with and without SARS-CoV-2 infection. Subjects/Methods: Using real-world data from the OneFlorida+ Clinical Research Network of the National Patient-Centered Clinical Research Network, we compared changes over time in BMI in an Exposed cohort (positive SARS-CoV-2 test between March 2020 - January 2022), to a contemporary Unexposed cohort (negative SARS-CoV-2 tests), and an age/sex-matched Historical control cohort (March 2018 - January 2020). Body mass index (kg/m2) was retrieved from objective measures of height and weight in electronic health records. We used target trial approaches to estimate BMI at baseline and change per 100 days of follow-up for Unexposed and Historical cohorts relative to the Exposed cohort by categories of sex, race-ethnicity, age, and hospitalization status. Results: The study sample consisted of 44,436 (Exposed cohort), 164,118 (Unexposed cohort), and 41,189 (Historical cohort). Cumulatively, 62% were women, 21.5% Non-Hispanic Black, 21.4% Hispanic and 5.6% Non-Hispanic Other. Patients had an average age of 51.9 years (SD: 18.9). At baseline, relative to the Exposed cohort (mean BMI: 29.3 kg/m2 [95%CI: 29.0, 29.7]), the Unexposed (-0.07 kg/m2 [95%CI; -0.12, -0.01]) and Historical controls (-0.27 kg/m2 [95%CI; -0.34, -0.20]) had lower BMI. Relative to no change in the Exposed over 100 days (0.00 kg/m2 [95%CI; -0.03,0.03]), the BMI of those Unexposed decreased (-0.04 kg/m2 [95%CI; -0.06, -0.01]) while the Historical cohort's BMI increased (+0.03 kg/m2 [95%CI;0.00,0.06]). BMI changes were consistent between Exposed and Unexposed cohorts for most population groups, except at start of follow-up period among Males and those 65 years or older, and in changes over 100 days among Males and Hispanics. Conclusions: In a diverse real-world cohort of adults, mean BMI of those with and without SARS-CoV2 infection varied in their trajectories. The mechanisms and implications of weight retention following SARS-CoV-2 infection remain unclear.

Access to telehealth and changes in diabetes care patterns during the pandemic: evidence from a large integrated health system in the Southeast USA.

INTRODUCTION: To examine the role of telehealth in diabetes care and management during versus pre-COVID-19 pandemic. RESEARCH DESIGN AND METHODS: We included adults (≥18 years) with prevalent diabetes as of January 1, 2018, and continuously enrolled at Kaiser Permanente Georgia through December 31, 2021 (n=22,854). We defined pre (2018-2019) and during COVID-19 (2020-2021) periods. Logistic generalized estimating equations (GEEs) assessed the within-subject change in adherence to seven annual routine care processes (blood pressure (BP), hemoglobin A1C (HbA1c), cholesterol, creatinine, urine-albumin-creatinine ratio (UACR), eye and foot examinations) pre versus during COVID-19 among telehealth users (ie, more than one telehealth visit per year per period) and non-telehealth users. Linear GEE compared mean laboratory measurements pre versus during COVID-19 by telehealth use. RESULTS: The proportion of telehealth users increased from 38.7% (2018-2019) to 91.5% (2020-2021). During (vs pre) the pandemic, adherence to all care processes declined in telehealth (range: 1.6% for foot examinations to 12.4% for BP) and non-telehealth users (range: 1.9% for foot examinations to 40.7% for BP). In telehealth users, average HbA1c (mean difference: 0.4% (95% CI 0.2% to 0.6%), systolic BP (1.62 mm Hg (1.44 to 1.81)), and creatinine (0.03 mg/dL (0.02 to 0.04)), worsened during (vs pre) COVID-19, while low density lipoprotein (LDL) cholesterol improved (-9.08 mg/dL (-9.77 to -8.39)). For UACR, odds of elevated risk of kidney disease increased by 48% (OR 1.48 (1.36-1.62)). Patterns were similar in non-telehealth users. CONCLUSIONS: Telehealth use increased during the pandemic and alleviated some of the observed declines in routine diabetes care and management.

Evaluating bias with loss to follow-up in a community-based cohort: empirical investigation from the CARRS Study.

BACKGROUND: Retention of participants is a challenge in community-based longitudinal cohort studies. We aim to evaluate the factors associated with loss to follow-up and estimate attrition bias. METHODS: Data are from an ongoing cohort study, Center for cArdiometabolic Risk Reduction in South Asia (CARRS) in India (Delhi and Chennai). Multinomial logistic regression analysis was used to identify sociodemographic factors associated with partial (at least one follow-up) or no follow-up (loss to follow-up). We also examined the impact of participant attrition on the magnitude of observed associations using relative ORs (RORs) of hypertension and diabetes (prevalent cases) with baseline sociodemographic factors. RESULTS: There were 12 270 CARRS cohort members enrolled in Chennai and Delhi at baseline in 2010, and subsequently six follow-ups were conducted between 2011 and 2022. The median follow-up time was 9.5 years (IQR: 9.3-9.8) and 1048 deaths occurred. Approximately 3.1% of participants had no follow-up after the baseline visit. Younger (relative risk ratio (RRR): 1.14; 1.04 to 1.24), unmarried participants (RRR: 1.75; 1.45 to 2.11) and those with low household assets (RRR: 1.63; 1.44 to 1.85) had higher odds of being lost to follow-up. The RORs of sociodemographic factors with diabetes and hypertension did not statistically differ between baseline and sixth follow-up, suggesting minimal potential for bias in inference at follow-up. CONCLUSION: In this representative cohort of urban Indians, we found low attrition and minimal bias due to the loss to follow-up. Our cohort's inconsistent participation bias shows our retention strategies like open communication, providing health profiles, etc have potential benefits.

Perceived stress and progression of cardiometabolic risk factors among South Asians with prediabetes in a lifestyle intervention trial.

AIMS: To examine associations between perceived stress and cardiometabolic risk factors in South Asians with prediabetes and assess whether a diabetes prevention program mitigates the impact of stress on cardiometabolic health. METHODS: We conducted a secondary analysis of the Diabetes Community Lifestyle Improvement Program, a lifestyle modification trial for diabetes prevention in India (n = 564). Indicators for cardiometabolic health (weight, waist circumference, blood pressure, glucose, HbA1c, and lipids) were measured at each visit while perceived stress was assessed via questionnaire at baseline. Multivariable linear regression assessed associations between stress and cardiometabolic parameters at baseline and 3-year follow up. RESULTS: At baseline, perceived stress was associated with higher weight (b=0.16; 95% CI: 0.04, 0.29) and waist circumference (b=0.11; 95% CI: 0.01, 0.21) but lower 30-minute postload glucose (b=-0.44; 95% CI: -0.76, -0.14) and LDL cholesterol (b=-0.40; 95% CI: -0.76, -0.03). Over the study period, perceived stress was associated with weight gain (b=0.20; 95% CI: 0.07, 0.33) and increased waist circumference (b=0.14; 95% CI: 0.04, 0.24). Additionally, higher perceived stress was associated with lower HDL cholesterol among the control arm (pinteraction = 0.02). CONCLUSIONS: Baseline stress was associated with negative cardiometabolic risk factor outcomes over time in those with prediabetes.

Possible Role of Netrin-1/Deleted in Colorectal Cancer/Vascular Endothelial Growth Factor Signaling Pathway in the Pathogenesis of Placenta Accreta Spectrum: A Case-control Study.

SUMMARY: Netrin-1, an epithelial-secreted protein, plays a key role in placental formation through the promotion of cytotrophoblast proliferation and placental vascular development. These effects are mediated through several receptors, including the deleted in colorectal cancer (DCC) receptor. Placenta accreta spectrum (PAS) is an exaggerated trophoblastic invasion into the uterine myometrium. The exact etiology is unknown, but it is believed that increased trophoblastic invasion, defect decidualization, and/or abnormal angiogenesis might play a role. Our study aimed to investigate the suggested role of macrophage-induced netrin-1/DCC/vascular endothelial growth factor (VEGF) signaling in PAS pathogenesis. A total of 29 women with PAS (as cases) and 29 women with normal pregnancies (as controls) were enrolled in the study. At delivery, placental tissues of both groups were collected and processed for the evaluation of placental netrin-1 level by enzyme-linked immunoassay technique and immunohistochemical analysis of tissue DCC receptor. Placental tissue netrin-1 level of PAS cases showed a statistically significantly higher value than those in the normal group. Significant overexpression of DCC receptors, VEGF, and enhanced macrophage recruitment was noted in PAS cases in comparison to the normal placenta. Macrophage-induced netrin-1/DCC/VEGF signaling might be involved in PAS pathogenesis through the enhancement of trophoblastic angiogenesis.

5-Year simulation of diabetes-related complications in people treated with tirzepatide or semaglutide versus insulin glargine.

AIM: This study compared the 5-year incidence rate of macrovascular and microvascular complications for tirzepatide, semaglutide and insulin glargine in individuals with type 2 diabetes, using the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes simulation model. RESEARCH DESIGN AND METHODS: This study was a 5-year SURPASS-2 trial extrapolation, with an insulin glargine arm added as an additional comparator. The 1-year treatment effects of tirzepatide (5, 10 or 15 mg), semaglutide (1 mg) and insulin glargine on glycated haemoglobin, systolic blood pressure, low-density lipoprotein and body weights were obtained from the SUSTAIN-4 and SURPASS-2 trials. We used the BRAVO model to predict 5-year complications for each study arm under two scenarios: the 1-year treatment effects persisted (optimistic) or diminished to none in 5 years (conservative). RESULTS: When compared with insulin glargine, we projected a 5-year risk reduction in cardiovascular adverse events [rate ratio (RR) 0.64, 95% confidence interval (CI) 0.61-0.67] and microvascular composite (RR 0.67, 95% CI 0.64-0.70) with 15 mg tirzepatide, and 5-year risk reduction in cardiovascular adverse events (RR 0.75, 95% CI 0.72-0.79) and microvascular composite (RR 0.79, 95% CI 0.76-0.82) with semaglutide (1 mg) under an optimistic scenario. Lower doses of tirzepatide also had similar, albeit smaller benefits. Treatment effects for tirzepatide and semaglutide were smaller but still significantly higher than insulin glargine under a conservative scenario. The 5-year risk reduction in diabetes-related complication events and mortality for the 15 mg tirzepatide compared with insulin glargine ranged from 49% to 10% under an optimistic scenario, which was reduced by 17%-33% when a conservative scenario was assumed. CONCLUSION: With the use of the BRAVO diabetes model, tirzepatide and semaglutide exhibited potential to reduce the risk of macrovascular and microvascular complications among individuals with type 2 diabetes, compared with insulin glargine in a 5-year window. Based on the current modelling assumptions, tirzepatide (15 mg) may potentially outperform semaglutide (1 mg). While the BRAVO model offered insights, the long-term cardiovascular benefit of tirzepatide should be further validated in a prospective clinical trial.

Weight Gain After HIV Therapy Initiation: Pathophysiology and Implications.

Rapid advances in the potency, safety, and availability of modern HIV antiretroviral therapy (ART) have yielded a near-normal life expectancy for most people living with HIV (PLWH). Ironically, considering the history of HIV/AIDS (initially called "slim disease" because of associated weight loss), the latest dilemma faced by many people starting HIV therapy is weight gain and obesity, particularly Black people, women, and those who commenced treatment with advanced immunodeficiency. We review the pathophysiology and implications of weight gain among PLWH on ART and discuss why this phenomenon was recognized only recently, despite the availability of effective therapy for nearly 30 years. We comprehensively explore the theories of the causes, from initial speculation that weight gain was simply a return to health for people recovering from wasting to comparative effects of newer regimens vs prior toxic agents, to direct effects of agents on mitochondrial function. We then discuss the implications of weight gain on modern ART, particularly concomitant effects on lipids, glucose metabolism, and inflammatory markers. Finally, we discuss intervention options for PLWH and obesity, from the limitations of switching ART regimens or specific agents within regimens, weight-gain mitigation strategies, and potential hope in access to emerging antiobesity agents, which are yet to be evaluated in this population.