Large Population-based Cohort Research Articles

Sex and age significantly modulate cardiovascular disease presentation in type 2 diabetes: a large population-based cohort study

Sex and age significantly modulate cardiovascular disease presentation in type 2 diabetes: a large population-based cohort study

Long-Term Risk of Type 2 Diabetes After Preterm Delivery or Hypertensive Disorders of Pregnancy.

To examine long-term diabetes risk after preterm delivery or hypertensive disorders of pregnancy in a large population-based cohort. This retrospective cohort study included all women with a singleton delivery in Sweden during 1973-2015 and no preexisting diabetes mellitus. Participants were followed up for development of type 2 diabetes identified from nationwide outpatient and inpatient diagnoses through 2018. Cox regression was used to compute hazard ratios (HRs) for the association between preterm delivery or hypertensive disorders of pregnancy and type 2 diabetes with adjustment for gestational diabetes and other maternal factors. Co-sibling analyses assessed for confounding by shared familial (genetic or environmental) factors. Overall, 2,184,417 women were included. Within 10 years after delivery, adjusted HRs for type 2 diabetes associated with specific pregnancy outcomes were as follows: any preterm delivery (before 37 weeks of gestation), 1.96 (95% CI, 1.83-2.09); extremely preterm delivery (22-27 weeks), 2.53 (95% CI, 2.03-3.16); and hypertensive disorders of pregnancy, 1.52 (95% CI, 1.43-1.63). All HRs remained significantly elevated (1.1-1.7-fold) 30-46 years after delivery. These findings were largely unexplained by shared familial factors. In this large national cohort, preterm delivery and hypertensive disorders of pregnancy were associated with increased risk for type 2 diabetes up to 46 years later. Women with these pregnancy complications are candidates for early preventive actions and long-term monitoring for type 2 diabetes.

Associations of accelerometer-estimated free-living daily activity impact intensities with 10-year probability of osteoporotic fractures in adults

PurposeAccelerometers are used to objectively measure physical activity; however, the relationship between accelerometer-based activity parameters and bone health is not well understood. This study examines the association between accelerometer-estimated daily activity impact intensities and future risk estimates of major osteoporotic fractures in a large population-based cohort. MethodsParticipants were 3165 adults 46 years of age from the Northern Finland Birth Cohort 1966 who agreed to wear a hip-worn accelerometer during all waking hours for 14 consecutive days. Raw accelerometer data were converted to resultant acceleration. Impact magnitude peaks were extracted and divided into 32 intensity bands, and the osteogenic index (OI) was calculated to assess the osteogenic effectiveness of various activities. Additionally, the impact peaks were categorized into three separate impact intensity categories (low, medium, and high). The 10-year probabilities of hip and all major osteoporotic fractures were estimated with FRAX-tool using clinical and questionnaire data in combination with body mass index collected at the age of 46 years. The associations of daily activity impact intensities with 10-year fracture probabilities were examined using three statistical approaches: multiple linear regression, partial correlation, and partial least squares (PLS) regression. ResultsOn average, participants’ various levels of impact were 8331 (SD = 3478) low; 2032 (1248) medium; and 1295 (1468) high impacts per day. All three statistical approaches found a significant positive association between the daily number of low-intensity impacts and 10-year probability of hip and all major osteoporotic fractures. In contrast, increased number of moderate to very high daily activity impacts was associated with a lower probability of future osteoporotic fractures. A higher OI was also associated with a lower probability of future major osteoporotic fractures. ConclusionLow-intensity impacts might not be sufficient for reducing fracture risk in middle-aged adults, while high-intensity impacts could be beneficial for preventing major osteoporotic fractures.

Abstract PO1-02-14: Breast cancer in older women - long-term prognosis by age and subtype in a large population-based cohort

Abstract Background Compared to middle-aged women, older women have a higher risk of breast cancer death. Whether the increased risk of breast cancer death is present in all subgroups of older adults with breast cancer, or negligible in the subgroups receiving adequate surgical and oncological treatment, has been debated. We studied long-term prognosis by age and subtype, adjusting for stage, treatment, socioeconomic status and comorbidity, clarifying which subgroups of older patients that are at increased risk of breast cancer death. Methods In a nation-wide cohort of 45,949 women aged ≥60 years at diagnosis of breast cancer 1997-2014, we estimated crude probabilities of breast cancer death and from other causes using competing risk methods. Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) with 95% confidence intervals (CI. Results In this large population-based cohort study of older women with breast cancer, we found an increasing risk of breast cancer death with increasing age at diagnosis, both at 5- and 10-year follow up. The strong association between age and breast cancer death was found for all breast cancer subtypes, being most prominent in Her2-positive breast cancer. The age effect was also significant in Luminal A breast cancer where treatment opportunities are not necessarily affected by age. High-risk tumors were equally common in all age groups above 60 years. In multivariable analysis, stage, subtype, grade and treatment were important explanatory variables to the age-related differences in survival, while comorbidity and socioeconomic status contributed minorly. After adjustments, older age remained an independent risk factor for both overall and breast cancer survival. Older women with triple-negative (60-79 years) or Her2-positive (60-84 years) tumors had a 5-year risk of breast cancer death exceeding the risk of death by other causes. Conclusions Older women had a significantly higher risk of breast cancer death irrespective of breast cancer subtype, also in Luminal A disease where treatment opportunities are not necessarily affected by age. Table 3. Crude probabilities of breast cancer specific death and death by other cause (competing cause of death) at 5, 10 and 15 years. Table 4. Multivariable analysis of prognostic factors affecting 15-year overall (OS) and breast cancer- specific survival (BCSS) Table 5. Multivariable analysis of prognostic factors affecting 15-year overall (OS) and breast cancer- specific survival (BCSS) by age at diagnosis and subtype. Citation Format: Amelia Chiorescu, Anna L V Johansson, Antonis Valachis, Alexios Matikas, Jan Frisell, Lars Holmberg, Irma Fredriksson. Breast cancer in older women - long-term prognosis by age and subtype in a large population-based cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-14.

Abstract PO2-14-07: Association between expression of androgen receptor in tumor tissue and risk of breast cancer recurrence among premenopausal Danish women

Abstract Background: Breast cancer prognosis is influenced by tumor biomarker expression. For example, tumors that express the estrogen receptor (ER+) have a lower hazard of recurrence in the first five years following treatment than tumors that do not express the estrogen receptor. Identifying additional biomarkers that are prognostic of breast cancer recurrence may aid in risk stratification and the development of targeted therapies. The androgen receptor (AR) is one such candidate biomarker. While some previous studies have found lower breast cancer mortality associated with AR expression, others have shown no association. However, these studies were conducted in populations exclusively or primarily comprised of postmenopausal women. Since menopause is associated with an increased concentration of androgens relative to estrogens, the role of AR may differ in premenopausal women. Methods: Using the Predictors of Breast Cancer Recurrence cohort (N=5,959)—a prospective cohort study of premenopausal women diagnosed with stage I–III primary breast cancer between 2002 and 2011 and registered in the Danish Breast Cancer Cooperative Group (DBCG) clinical database—we measured the association between tumor AR expression and breast cancer recurrence. The majority of the cohort (77%) had ER+ tumors and were intended to be treated with tamoxifen. Primary paraffin-embedded tumors were collected from treating hospitals, and 2–3 cores were included in a tissue microarray for immunohistochemistry. AR staining of each core was automatically scored using a trained software application and quantified as the percent of tumor nuclei with positive staining. Patients were considered to have AR positive (AR+) tumors if the maximum score across replicate cores was >1% positive. Otherwise patients were classified as having AR negative (AR−) tumors. Patients were followed from breast cancer diagnosis until the first of recurrence, death, emigration, another malignancy, or 10 years. The DBCG defines breast cancer recurrence as any breast cancer diagnosed after the initial course of treatment, including contralateral breast cancers. The association between AR expression and breast cancer recurrence was computed as an unadjusted risk ratio and corresponding 95% confidence interval. Results: Among the 4,658 cohort members with available tumor tissue, 72% had AR+ tumors; 720 recurrences occurred over the 10-year follow-up. Patients with AR+ tumors were less likely to experience a recurrence than patients with AR− tumors [14% vs. 18% respectively; unadjusted risk ratio=0.80, 95% CI: (0.70, 0.92)]. Conclusion: AR expression in primary tumor tissue was associated with a lower risk of breast cancer recurrence in a large population-based cohort of premenopausal women. Additional analyses adjusting for clinical factors, examining the association by breast cancer subtype, and accounting for time to recurrence are forthcoming. Citation Format: Rebecca Nash, Anders Kjærsgaard, Kristina Christensen, Thomas Ahern, Lindsay Collin, Stephen Hamilton-Dutoit, Lauren McCullough, Joellen Schildkraut, Henrik Sørensen, Kevin Ward, Kirsten Woolpert, Timothy Lash, Deirdre Cronin-Fenton. Association between expression of androgen receptor in tumor tissue and risk of breast cancer recurrence among premenopausal Danish women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-14-07.

Arterial stiffness and incident glaucoma: a large population-based cohort study

To investigate whether arterial stiffness, assessed oscillometrically, is associated with incident glaucoma in the Vitamin D Assessment (ViDA) Study cohort, aged 50-84 years. Prospective, population-based cohort study METHODS: : Arterial stiffness was assessed in 4713 participants without known glaucoma (mean±SD age = 66±8 years) from 5 April 2011 to 6 November 2012 by way of aortic PWV (aPWV), estimated carotid-femoral PWV (ePWV) and aortic PP (aPP). Incident glaucoma was identified through linkage to national prescription and hospital discharge registers. Relative risks of glaucoma for each arterial stiffness measure were estimated by Cox proportional hazards regression, over the continuum of values and by quartiles. During a mean±SD follow-up of 10.5±0.4 years, 301 participants developed glaucoma. Arterial stiffness, as measured by aPWV (Hazard ratio (HR) per SD increase, 1.36, 95%CI 1.14-1.62) and ePWV (HR per SD increase, 1.40, 95%CI 1.14-1.71) but not aPP (HR per SD increase, 1.06, 95%CI 0.92-1.23) was associated with incident glaucoma. When arterial stiffness was analyzed as a categorical variable, the highest quartiles of aPWV (HR, 2.62, 95%CI 1.52-4.52; Ptrend=0.007), ePWV (HR, 2.42, 95%CI 1.37-4.27; Ptrend=0.03), and aPP (HR, 1.68, 95%CI 1.10-2.5; Ptrend=0.02) were associated with the development of glaucoma. Arterial stiffness measured with a simple oscillometric device predicted the development of glaucoma and could potentially be used in clinical practice to help identify people at risk of this condition. It may also present a new therapeutic research avenue, including in respect of systemic antihypertensives.

Factors Associated With the Prevalence of Irritable Bowel Syndrome: The Miyagi Part of the Tohoku Medical Megabank Project Community-based Cohort Study.

The objective of this research is to examine factors related to irritable bowel syndrome (IBS) prevalence in a large population-based study. A cross-sectional study was conducted with participants in the Miyagi part of the Tohoku Medical Megabank Project Community-Based cohort study who completed the Rome II Modular Questionnaire. Multivariate odds ratios (ORs) for the presence of IBS and 95% confidence intervals (95% CIs) for the reference group were calculated for each factor. Additionally, a stratified analysis was performed by sex and age group (20-49 years, 50-64 years, and ≥ 65 years). Among 16 252 participants, 3025 (18.6%) had IBS, comprising 750 men (15.5%) and 2275 women (19.9%). Multivariate ORs for the presence of IBS decreased significantly with each year of age (OR, 0.98; 95% CI, 0.98-0.99). Moreover, compared with the reference group, ORs for the presence of IBS were significantly higher in individuals whose home was partially damaged by the Great East Japan Earthquake, those with < 16 years of education, those who spent less time walking, those with high perceived stress (1.77, 1.57-2.01), those with high psychological distress (1.58, 1.36-1.82), and those with high symptoms of depression (1.76, 1.60-1.94). In stratified analyses, a significant relationship was found between psychological factors and IBS prevalence in all sex and age groups. This large cross-sectional population-based cohort study identified several factors associated with IBS prevalence. Psychological factors were significantly associated with IBS prevalence across all age groups and sexes.

Chronic kidney disease and risk of bloodstream infections and sepsis: a 17-year follow-up of the population-based Trøndelag Health Study in Norway.

Bloodstream infections (BSI) and sepsis are important causes of hospitalization, loss of health, and death globally. Targetable risk factors need to be identified to improve prevention and treatment. In this study, we aimed to evaluate the association of chronic kidney disease (CKD) and risk of and mortality from BSI and sepsis in the general population during a 22-year period. We conducted a prospective cohort study among participants in the population-based Norwegian HUNT Study, where 68,438 participated. The median follow-up time was 17.4 years. The exposures were estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in urine. The outcomes were hazard ratios (HR) of hospital admission or death due to BSI or sepsis. The associations were adjusted for age, sex, diabetes, obesity, systolic blood pressure, smoking status, and cardiovascular disease. Participants with eGFR < 30 ml/min/1.732 had HR 3.35 for BSI (95% confidence intervals (CI) 2.12-5.3) and HR 2.94 for sepsis (95% CI 1.82-4.8) compared to normal eGFR (≥ 90 ml/min/1.732). HRs of death from BSI and sepsis were 4.2 (95% CI 1.71-10.4) and 4.1 (95% CI 1.88-8.9), respectively. Participants with severely increased albuminuria (ACR > 30 mg/mmol) had HR 3.60 for BSI (95% CI 2.30-5.6) and 3.14 for sepsis (95% CI 1.94-5.1) compared to normal albumin excretion (ACR < 3 mg/mmol). HRs of death were 2.67 (95% CI 0.82-8.7) and 2.16 (95% CI 0.78-6.0), respectively. In this large population-based cohort study, CKD was clearly associated with an increased risk of BSI and sepsis and related death.

P043 The different roles of FRAX risk factors as predictors of fragility fractures in peri-menopausal vs post-menopausal patients: results from a large population-based cohort study

Abstract Background/Aims The marked rise in the prevalence of fragility fractures affecting both women undergoing the transition to menopause (i.e. peri-menopause), and post-menopausal women, confers a significant burden on patients’ health and quality of life. The risk factors for fractures in post-menopausal women have been previously well-explored, and tend to align with the FRAX variables. However, there is less consensus regarding the fracture risk factors in peri-menopausal women. We compare the association between FRAX risk factors and fractures across peri-menopausal and post-menopausal women, selected from the same large population-based cohort. Methods Female patients referred for a DXA scan at the Royal Lancaster Infirmary between 2004-2011 provided information relating to any previous fragility fracture(s), FRAX risk factors, and menopause status (i.e. not post-menopausal vs post-menopausal) through a questionnaire. Patients aged 41 to 51 (median menopause age in UK) who had not undergone the menopause, as per their questionnaire response, were categorised as ‘peri-menopausal’. Logistic regression modelling, which included adjustment for potential confounders, was performed using r(version 4.3.1). Results Our study included 23388 patients, including 3785 peri-menopausal patients and 20774 post-menopausal patients, with a mean age of 47.5 (SD:3.0) and 66.1 (SD:10.4) respectively. The prevalence of fragility fractures was greater in the post-menopausal than peri-menopausal cohort (42.8% vs 25.5% respectively; p &amp;lt; 0.001). Across post-menopausal patients, following adjustment for the other FRAX risk factors, significant predictors of increased fracture risk were age (odds ratio (OR): 1.04 (95% CI:1.03-1.04, p &amp;lt; 0.001), smoking (OR:1.16 (CI:1.09-1.23, p &amp;lt; 0.001), alcohol (OR:1.54, CI:1.36-1.74, p &amp;lt; 0.001), and a family history of fracture(s) (OR:1.21 (CI:1.13-1.29, p &amp;lt; 0.001). Comparatively, across peri-menopausal patients, only alcohol (OR:1.57, CI:1.08-2.26, p = 0.016) and smoking (OR:1.22 (CI:1.00-1.48, p = 0.045) positively predicted fracture risk. Corticosteroid use was associated with a reduced fracture risk across both post-menopausal (OR:0.84, CI:0.79-0.90, p &amp;lt; 0.001) and peri-menopausal (OR:0.79, CI: 0.64-0.97, p = 0.024) cohorts. Conclusion Different FRAX risk factors predict fracture occurrence across post-menopausal and peri-menopausal patients; notably, only smoking and alcohol consumption predict an increased fracture risk in the latter group. Interestingly, corticosteroids were associated with a reduced risk of fractures across both groups. This finding may be elucidated by the fact that low-dose corticosteroids can exert an anti-inflammatory effect, and may protect bone cells. However, our finding is limited by the fact that the indication, dose and duration of corticosteroids were unknown. More generally, our study is limited by the fact that patients’ peri-menopausal status was not clinically confirmed, but inferred based on patients’ age and self-reported menopause status. Our results suggest that the FRAX risk factors, which were derived from analysis of predominantly 50-80 year old patients, may require adjustment for peri-menopausal patients (many of whom are aged &amp;lt;50). Future studies should assess whether our conclusions apply to specific fracture sites, and are replicated across more demographically diverse patient populations. Disclosure K. Song: None. M. Bukhari: None.

Muscle loss phenotype in COPD is associated with adverse outcomes in the UK Biobank

BackgroundChronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder with systemic consequences that can cause a muscle loss phenotype (MLP), which is characterized by the loss of muscle mass, muscle strength, or loss of both muscle and fat mass. There are limited data comparing the individual traits of MLP with clinical outcomes in a large unbiased cohort of COPD patients. Our aim was to determine the proportion of patients who met criteria for MLP in an unbiased sample of COPD patients at the population-level. We also determined if specific MLP features were associated with all-cause and COPD-related mortality.MethodsA retrospective population-based cohort analysis of the UK Biobank was performed. COPD was defined by a FEV1/FVC ratio < 0.7, physician established diagnosis of COPD, or those with a COPD-related hospitalization before baseline assessment. MLP included one or more of the following: 1) Low fat-free mass index (FFMI) on bioelectric impedance analysis (BIA) or 2) Appendicular skeletal muscle index (ASMI) on BIA, 3) Low muscle strength defined by handgrip strength (HGS), or 4) Low muscle and fat mass based on body mass index (BMI). Cox regression was used to determine the association between MLP and all-cause or COPD-related mortality. All models were adjusted for sex, age at assessment, ethnicity, BMI, alcohol use, smoking status, prior cancer diagnosis and FEV1/FVC ratio.ResultsThere were 55,782 subjects (56% male) with COPD followed for a median of 70.1 months with a mean(± SD) age at assessment of 59 ± 7.5 years, and FEV1% of 79.2 ± 18.5. Most subjects had mild (50.4%) or moderate (42.8%) COPD. Many patients had evidence of a MLP, which was present in 53.4% of COPD patients (34% by ASMI, 26% by HGS). Of the 5,608 deaths in patients diagnosed with COPD, 907 were COPD-related. After multivariate adjustment, COPD subjects with MLP had a 30% higher hazard-ratio for all-cause death and 70% higher hazard-ratio for COPD-related death.ConclusionsEvidence of MLP is common in a large population-based cohort of COPD and is associated with higher risk for all-cause and COPD-related mortality.

Prevalence of Dysbetalipoproteinemia in the UK Biobank According to Different Diagnostic Criteria

Abstract Context Dysbetalipoproteinemia (DBL) is a multifactorial disorder that disrupts the normal metabolism of remnant lipoproteins, causing increased risk of cardiovascular disease. However, establishing a proper diagnosis is difficult, and the true prevalence of the disease in the general population remains unknown. Objective The objectives were to study the prevalence of the disease and to validate the performance of different clinical diagnostic criteria in a large population-based cohort. Methods This study included 453 437 participants from the UK Biobank. DBL was established in participants having an ε2ε2 genotype with mixed dyslipidemia or lipid-lowering therapy use (n = 964). The different diagnostic criteria for DBL were applied in individuals without lipid-lowering medication (n = 370 039, n = 534 DBL), to compare their performance. Results Overall, 0.6% of participants had an ε2ε2 genotype, of which 36% were classified as DBL, for a disease prevalence of 0.2% (1:469). The prevalence of DBL was similar between the different genetic ancestries (≤0.2%). Several diagnostic criteria showed good sensitivity for the diagnosis of DBL (&amp;gt;90%), but they suffered from a very low positive predictive value (0.6-15.4%). Conclusion This study reported for the first time the prevalence of DBL in the UK Biobank according to genetic ancestry. Furthermore, we provided the first external validation of different diagnostic criteria for DBL in a large population-based cohort and highlighted the fact that these criteria should not be used to diagnose DBL alone but should rather be used as a first screening step to determine which individuals may benefit from genetic testing to confirm the diagnosis.

Adverse Pregnancy Outcomes and Long-Term Mortality in Women

Women with adverse pregnancy outcomes, such as preterm delivery or preeclampsia, have higher future risks of cardiometabolic disorders; however, little is known about their long-term mortality risks. A better understanding of such risks is needed to facilitate early identification of high-risk women and preventive actions. To determine long-term mortality risks associated with 5 major adverse pregnancy outcomes in a large population-based cohort of women. This national cohort study in Sweden used the Swedish Medical Birth Register, containing prenatal and birth information for nearly all deliveries in Sweden since 1973, to identify women who had a singleton delivery during 1973 to 2015. All 2 195 667 such women with information for pregnancy duration and infant birth weight were included in the study. Data were analyzed from March to September 2023. Adverse pregnancy outcomes (preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes), identified from nationwide birth records. All-cause and cause-specific mortality through December 31, 2018. Cox regression was used to compute hazard ratios (HRs) for mortality associated with specific adverse pregnancy outcomes, adjusted for other maternal factors. Cosibling analyses assessed for confounding by shared familial (genetic or environmental) factors. In 56 million person-years of follow-up to a median (IQR) age of 52 (42-61) years, 88 055 women (4%) died (median [IQR] age at death, 59 [50-67] years). All 5 adverse pregnancy outcomes were independently associated with increased mortality. Across the entire follow-up (≤46 years after delivery), adjusted HRs for all-cause mortality associated with specific adverse pregnancy outcomes were as follows: gestational diabetes, 1.52 (95% CI, 1.46-1.58); preterm delivery, 1.41 (95% CI, 1.37-1.44); small for gestational age, 1.30 (95% CI, 1.28-1.32); other hypertensive disorders, 1.27 (95% CI, 1.19-1.37); and preeclampsia, 1.13 (95% CI, 1.10-1.16). All HRs remained significantly elevated even 30 to 46 years after delivery. These effect sizes were only partially (0%-45%) reduced after controlling for shared familial factors in cosibling analyses. Women who experienced multiple adverse pregnancy outcomes had further increases in risk. Several major causes of death were identified, including cardiovascular and respiratory disorders and diabetes. In this large national cohort study, women who experienced any of 5 major adverse pregnancy outcomes had increased mortality risks that remained elevated more than 40 years later. Women with adverse pregnancy outcomes need early preventive evaluation and long-term follow-up for detection and treatment of chronic disorders associated with premature mortality.

Gender associations between phthalate exposure and biomarkers of oxidative stress: A prospective cohort study.

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.

The use of potentially interacting supplement–drug pairs in adults with type 2 diabetes: A large population-based cohort study in the UK Biobank

AimsTo examine the patterns of use of potentially interacting supplement–drug pairs in adults with type 2 diabetes (T2D) in real-world settings, and to explore the impact of potentially interacting supplement–drug pairs on downstream outcomes. MethodsPotentially interacting supplement–drug pairs were identified from four tertiary databases. We categorized the potential pharmacodynamic interactions into different clinical types according to their related outcomes and explored their associations with incident outcomes using Cox models. Results26,394 participants with T2D in the UK Biobank were included. Half (48.5 %) were supplement users, of whom 85.0 % were taking potentially interacting supplement–drug pairs. The potential pharmacodynamic interactions were related to various clinical outcomes, including reducing the effects of glucose-lowering drugs (50.7 %), hypotension (49.8 %), bleeding (50.4 %) and hepatotoxicity (34.8 %). Exploratory analyses found that the use of potentially interacting supplement–drug pairs was associated with incident hepatic diseases (hazard ratio = 1.26, 95 % confidence interval 1.10–1.44, P < 0.001). ConclusionsReal-world data suggests that most adults with T2D who concurrently used supplements and drugs were on potentially interacting supplement-drug combinations, with the potential of causing adverse outcomes such as incident hepatic diseases. Clinicians should communicate with patients and assess the potential risk of supplement–drug interactions in clinical settings.

Large-scale assessment of physical activity in a population using high-resolution hip-worn accelerometry: the German National Cohort (NAKO)

Large population-based cohort studies utilizing device-based measures of physical activity are crucial to close important research gaps regarding the potential protective effects of physical activity on chronic diseases. The present study details the quality control processes and the derivation of physical activity metrics from 100 Hz accelerometer data collected in the German National Cohort (NAKO). During the 2014 to 2019 baseline assessment, a subsample of NAKO participants wore a triaxial ActiGraph accelerometer on their right hip for seven consecutive days. Auto-calibration, signal feature calculations including Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation (MAD), identification of non-wear time, and imputation, were conducted using the R package GGIR version 2.10-3. A total of 73,334 participants contributed data for accelerometry analysis, of whom 63,236 provided valid data. The average ENMO was 11.7 ± 3.7 mg (milli gravitational acceleration) and the average MAD was 19.9 ± 6.1 mg. Notably, acceleration summary metrics were higher in men than women and diminished with increasing age. Work generated in the present study will facilitate harmonized analysis, reproducibility, and utilization of NAKO accelerometry data. The NAKO accelerometry dataset represents a valuable asset for physical activity research and will be accessible through a specified application process.

Genomics in Diabetic Kidney Disease: A 2024 Update

Abstract: Diabetic Kidney Disease (DKD) remains the leading cause of Chronic and End Stage Kidney Disease (ESKD) worldwide, with an increasing epidemiological burden. However, still, the disease awareness remains low, early diagnosis is difficult, and therapeutic management is ineffective. These might be attributed to the fact that DKD is a highly heterogeneous disease, with disparities and variability in clinical presentation and progression patterns. Besides environmental risk factors, genetic studies have emerged as a novel and promising tool in the field of DKD. Three decades ago, family studies first reported that inherited genetic factors might confer significant risk to DKD development and progression. During the past decade, genome-wide association studies (GWASs) screening the whole genome in large and multi-ethnic population-based cohorts identified genetic risk variants associated with traits defining DKD in both type 1 and 2 diabetes. Herein, we aim to summarize the existing data regarding the progress in the field of genomics in DKD, present how the revolution of GWAS expanded our understanding of pathophysiologic disease mechanisms and finally, suggest potential future directions.

Overfeeding polyunsaturated fat compared with saturated fat does not differentially influence lean tissue accumulation in individuals with overweight: a randomized controlled trial

BackgroundFatty acids may influence lean tissue volume and skeletal muscle function. We previously reported in young lean participants that overfeeding PUFA compared with SFA induced greater lean tissue accumulation despite similar weight gain. ObjectivesIn a double-blind randomized controlled trial, we aimed to investigate if the differential effects of overfeeding SFA and PUFA on lean tissue accumulation could be replicated in individuals with overweight and identify potential determinants. Further, using substitution models, we investigated associations between SFA and PUFA concentrations with lean tissue volume in a large population-based sample (UK Biobank). MethodsSixty-one males and females with overweight [BMI (kg/m2): 27.3 (interquartile range (IQR), 25.4–29.3); age: 43 (IQR, 36–48)] were overfed SFA (palm oil) or n–6 (ω-3) PUFA (sunflower oil) for 8 wk. Lean tissue was assessed by MRI. We had access to n = 13,849 participants with data on diet, covariates, and MRI measurements of lean tissue, as well as 9119 participants with data on circulating fatty acids in the UK Biobank. ResultsBody weight gain mean (SD) was similar in PUFA (2.01 ± 1.90 kg) and SFA (2.31 ± 1.38 kg) groups. Lean tissue increased to a similar extent [0.54 ± 0.93 L and 0.67 ± 1.21 L for PUFA and SFA groups, respectively, with a difference between groups of 0.07 (−0.21, 0.35)]. We observed no differential effects on circulating amino acids, myostatin, or IL-15 and no clear determinants of lean tissue accumulation. Similar nonsignificant results for SFA and PUFA were observed in UK Biobank, but circulating fatty acids demonstrated ambiguous and sex-dependent associations. ConclusionsOverfeeding SFA or PUFA does not differentially affect lean tissue accumulation during 8 wk in individuals with overweight. A lack of dietary fat type-specific effects on lean tissue is supported by specified substitution models in a large population-based cohort consuming their habitual diet.This trial was registered at clinicaltrials.gov identifier as NCT02211612.

Long-term cardiovascular outcome in women with preeclampsia in Korea: a large population-based cohort study and meta-analysis

Recent studies reported the long-term cardiovascular risk of preeclampsia. However, only a few studies have investigated the association between preeclampsia and long-term cardiovascular disease in Asian populations, although there could be racial/ethnic differences in the risk of cardiovascular diseases. Therefore, we aimed to evaluate the long-term effects of preeclampsia on cardiovascular disease in an Asian population. This study included 68,658 parous women in the Health Examinees Study (HEXA) cohort of South Korea and compared the risk of long-term cardiovascular disease, including ischemic heart disease and stroke, according to the history of preeclampsia. We also performed a meta-analysis combining current study data with data from existing literature in the Asian population. Among the study population, 3413 (5.23%) women had a history of preeclampsia, and 767 (1.12%) and 404 (0.59%) women developed ischemic heart disease and stroke for 22 years. Women with a history of preeclampsia were at a higher risk for both ischemic heart disease (adjusted hazard ratio 1.66 [1.19–2.04]) and stroke (adjusted hazard ratio 1.48 [1.02–2.16]) than those without. In the meta-analysis, the pooled hazard ratio of ischemic heart disease and stroke were also increased in women with a history of preeclampsia (ischemic heart disease 1.65 [1.51–1.82]; stroke 1.78 [1.52–2.10]).

Pseudomonas stutzeri bloodstream infection is a prevailing community-onset disease with important mortality rates: results from a retrospective observational study in Australia

Background The recognition of Pseudomonas stutzeri as a cause of infections in humans has been increasing. However, only case reports and small series of P. stutzeri bloodstream infections have been published. Epidemiological data on these infections are extremely scarce. Our objective was to describe the incidence, epidemiology, antimicrobial resistance rates, and outcomes of P. stutzeri bloodstream infections in a large population-based cohort in Australia. Methods Retrospective, laboratory-based surveillance study conducted in Queensland, Australia (population ≈ 5 million) during 2000–2019. Clinical information was obtained from public hospital admissions and vital statistics databases. Results In total, 228 episodes of P. stutzeri bloodstream infections were identified. Increased incidence was observed in the later years, especially in older men, and was higher during the rainy months of the year and in the warmest and more humid regions of the state. The majority of bloodstream infections were community-onset with 120 (52.6%) community-associated and 59 (25.9%) ambulatory healthcare-associated episodes. Only 49 cases (21.5%) were nosocomial. The most common foci of infection were skin and soft tissue, lower respiratory tract, and intra-abdominal. No isolate showed antimicrobial resistance. Thirty-one patients (13.6%) died. The mortality rate in patients with a respiratory infectious source was higher (21%). Conclusions P. stutzeri bloodstream infection was predominantly a community-onset condition including ambulatory healthcare related cases, with increasing incidence, especially in older males. No antimicrobial resistance was observed. Mortality was high in patients with respiratory infectious source. This new observational data have implications when considering the epidemiology of these infections and for patient management.

Glycemic control in children with type 1 diabetes: Insulin pump therapy versus multiple daily injections

While many studies compared multiple daily injections (MDI) and insulin pump therapy on various clinical outcomes, the results remain inconclusive. This multicenter retrospective cohort study included 175 patients and aimed to evaluate the effects of different insulin therapy methods on various clinical outcomes, including hemoglobin A1c (HbA1c), total daily insulin dosage, body mass index, glomerular filtration rate, in pediatric patients with type 1 diabetes. In a linear mixed-effects regression analysis, a statistically significant interaction between time and treatment type on HbA1c was found. It suggested significantly higher reduction of HbA1c values between 12-month visit and baseline in the group receiving MDIs compared to insulin pump therapy. Patients using MDIs observed higher reduction of HbA1c levels and lower total daily insulin dose relative to insulin pump therapy group. Other changes of clinical indicators were the same for group of patients. Various studies report controversial results on long term effects of these treatments on HbA1c values necessitating large population-based cohort studies in this field.