Journal of the Endocrine Society最新文献

Globally, nearly 9 million people are living with type 1 diabetes (T1D). Although the incidence of T1D is not affected by socioeconomic status, the development of complications and limited access to modern therapy is overrepresented in vulnerable populations. Diabetes technology, specifically continuous glucose monitoring and automated insulin delivery systems, are considered the gold standard for management of T1D, yet access to these technologies varies widely across countries and regions, and varies widely even within high-income countries. This review focuses on disparities in diabetes technology use among adolescents and young adults with T1D, barriers to access and use, and summarizes common themes emerging across countries and regions. We conducted a survey among medical technology manufacturers and physicians in various countries across diverse geographical regions and performed extensive literature searches. Across all countries and regions, economic barriers stand out as the largest and most common barriers, either preventing market penetrance of technology into a country or limiting its access to the individual with diabetes due to high out of pocket costs. Other common barriers include structural or accessibility barriers, such as stringent eligibility requirements by insurance providers, regardless of whether the insurance was private or government-based, and provider/individual level barriers. Based on the evidence presented, we suggest the need for a joint effort involving governments, private health insurers, technology manufacturers, and healthcare providers to address the global disparities of diabetic technology utilization and ensure equitable access for all individuals living with T1D worldwide.

Context: Oxytocin supplementation improves obstructive sleep apnea (OSA), and animal studies suggest involvement of oxytocin in respiratory control. However, the relationship between endogenous oxytocin signaling and human sleep status remains undetermined.

Objective: In this study, we approached the contribution of the intrinsic oxytocin-oxytocin receptor (OXTR) system to OSA by genetic association analysis.

Methods: We analyzed the relationship between OXTR gene polymorphisms and sleep parameters using questionnaire data and sleep measurements in 305 Japanese participants. OSA symptoms were assessed in 225 of these individuals.

Results: The OXTR rs2254298 A allele was more frequent in those with OSA symptoms than in those without (P = .0087). Although total scores on the Pittsburgh Sleep Quality Index questionnaire did not differ between the genotypes, breathlessness and snoring symptoms associated with OSA were significantly more frequent in individuals with rs2254298 A genotype (P = .00045 and P = .0089 for recessive models, respectively) than the G genotype. A multivariable analysis confirmed these genotype-phenotype associations even after adjusting for age, sex, and body mass index in a sensitivity analysis. Furthermore, objective sleep efficiency measured by actigraph was not significantly different between genotypes; however, subjective sleep efficiency was significantly lower in the rs2254298 A genotype (P = .013) compared with the G genotype. The frequency of the A allele is higher in East Asians, which may contribute to their lean OSA phenotype.

Conclusion: The OXTR gene may contribute to OSA symptoms via the respiratory control system, although it could be in linkage disequilibrium with a true causal gene.

Background: Cardiovascular disease (CVD) is the leading cause of noncancer-related mortality among differentiated thyroid cancer (DTC) survivors, which accounts for a large portion of subsequent primary malignancies in childhood cancer survivors. This study aims to assess the risk of cardiovascular mortality among DTC as a second primary malignancy (DTC-2) patients compared with DTC as a first primary malignancy (DTC-1) and the general population.

Methods: Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 159 395 DTC-1 and 20 010 DTC-2 patients diagnosed older than 30 between 1975 and 2020 and the corresponding US population (71 214 642 person-years; 41 420 893 cardiovascular deaths). Compared with general-population and DTC-1 patients, we calculated incidence rate ratios (IRRs) of cardiovascular deaths among DTC-2 patients using Poisson regression. To adjust for unmeasured confounders, we performed a nested, case-crossover analysis among DTC-2 patients who died from CVD.

Results: Although DTC-2 patients had a comparable risk compared with the population (IRR 1.01) and a mildly increased risk of cardiovascular mortality compared with DTC-1 patients (IRR 1.26), the association was pronounced among individuals aged 30 to 74 years, especially 30 to 44 years (DTC-2 vs population: IRR 8.89; DTC-2 vs DTC-1: IRR 3.00). The risk elevation was greatest within the first month after diagnosis, compared with the population. The case-crossover analysis confirmed these results.

Conclusion: DTC-2 patients are at increased risk of cardiovascular mortality. Clinicians should carefully monitor CVD and manage other CVD-related factors, such as exogenous thyroxine and emotional distress, for DTC-2 patients, especially for those under 75 years.

Novelty and impact statements: This study is the first comprehensive investigation into the cardiovascular mortality of DTC-2, revealing a higher risk compared to DTC-1 and the general population, especially for cases between 30 and 74 years old. The risk elevation was greatest within the first month after diagnosis. These findings emphasize the restriction of thyroid hormone suppression therapy and reinforce stress management to prevent premature DTC-2 patients from cardiovascular death.

Context: Primary aldosteronism (PA), a frequent but underdiagnosed cause of hypertension, is associated with a significant burden of cardiovascular and renal complications. Studies have reported divergent results regarding the diagnostic performance of seated saline infusion test (SSIT) and oral sodium loading test (OSLT), 2 confirmatory tests recommended by the Endocrine Society Clinical Practice Guidelines. To our knowledge, no study directly compared the results of SSIT and OSLT to diagnose overt PA.

Objective: We assessed the diagnostic performance of SSIT and OSLT in a group of patients with hypertension and elevated screening aldosterone-renin ratio (ARR). The diagnostic standard was defined as hypertension with or without hypokalemia with an elevated screening ARR and at least 1 abnormal confirmation test including OSLT and SSIT.

Methods: A monocentric retrospective study was conducted, including 87 patients with hypertension with a positive screening who underwent both SSIT and OSLT. A diagnostic performance analysis was conducted using urinary aldosterone at a threshold of 27 nmol/day as the criterion for OSLT, in comparison to a plasma aldosterone concentration (PAC) exceeding 140 pmol/L following the saline infusion.

Results: A statistically significant difference in sensitivity was observed between OSLT and SSIT, with OSLT demonstrating superior performance (P = .025). The aforementioned test exhibited concordance in 59 cases (65.5%), indicating that these methods are not equivalent (McNemar test P = .036).

Conclusion: OSLT demonstrated a significantly higher sensitivity for diagnosing overt PA in comparison with the SSIT in our cohort of patients with hypertension with an abnormal screening ARR.

Objective: To examine the effect of underweight maternal body mass index (BMI) on pregnancy complications and neonatal outcomes.

Design: Cohort study.

Setting: Tertiary academic center.

Patients: A total of 16 361 mothers who delivered a singleton between 2015-2021 with either a BMI <18.5 kg/m² (n = 732) or normal BMI (18.5 ≥ BMI <23 or 25 kg/m², n = 15 629) at the initial prenatal visit or within 6 months of the initial visit.

Main outcome measures: Birthweight, gestational age, neonatal intensive care unit admission, preterm birth, and fetal death; obstetrical complications including preeclampsia/eclampsia, premature rupture of membranes, preterm premature rupture of membranes, and postpartum hemorrhage.

Results: Underweight women were younger and less likely to have private insurance (P < .01 for both) than normal-weight women. Approximately 23% of infants born to underweight mothers were small for gestational age and 15% were low birth weight vs 13.5% and 9% of infants of normal-weight mothers, respectively (P < .01 for both). These differences remained significant after adjusting for potential confounders. In adjusted logistic regression models, underweight women had a decreased risk of premature rupture of membranes and postpartum hemorrhage compared to normal-weight women.

Conclusion: Underweight BMI during pregnancy is associated with an increased risk of small for gestational age and low birth weight infants and a decreased risk of premature rupture of membranes and postpartum hemorrhage. These findings suggest underweight BMI during pregnancy increases the risk of adverse neonatal outcomes, while maternal-related pregnancy outcomes are less affected.

Context: Cardiovascular-kidney-metabolic (CKM) syndrome is a recently introduced term that is a complex disease consisting of cardiovascular disease, renal disease, obesity, and diabetes. The association of social determinants of health (SDOH) with CKM syndrome is not fully known.

Objective: We aimed to assess SDOH affecting CKM syndrome among adult patients with diabetes at follow-up at a tertiary hospital in Ethiopia.

Methods: A cross-sectional hospital-based study was used. Data were collected using a Kobo toolbox and entered into SPSS version 29 for further analysis.

Results: A total of 422 adult patients with diabetes were included in this study. The mean ± SD age of the patients was 54.14 ± 13.74 years. Fifty-two percent of the patients were male. In this study, 52.4% had cardiovascular kidney metabolic syndrome. Male patients (AOR: 1.73; 95% CI, 1.01-2.94), lost to follow-up for more than a year due to lack of money (AOR: 2.69; 95% CI, 1.01-7.22), missed an appointment due to lack of transportation in the past 1 year (AOR: 2.98; 95% CI, 1.21-7.33), were patients with disability (AOR: 1.97; 95% CI, 1.12-3.48), had hypertension (AOR: 3.12; 95% CI, 1.85-5.28), had obesity (AOR: 2.27, 95% CI, 1.17, 4.40), and were in retirement (AOR: 2.12; 95% CI, 1.04-4.30) these being more significantly associated with CKM syndrome.

Conclusion: More than half of patients had CKM syndrome. More attention should be given to SDOH, including male sex, financial constraints, transportation issues, disability, and retirement.

Background: Assessments for hyperglycemia are vital to pregnancy and postpartum (PP) care, but gold-standard oral glucose tolerance tests (OGTTs) are burdensome. We examined changes in 1,5 anhydroglucitol (1,5AG) levels during gestation and PP and assessed for associations with other measures of glycemia.

Study design: Pregnant participants (n = 50) in the Study of Pregnancy Regulation of Insulin and Glucose cohort underwent OGTTs at a mean of 13 weeks ([visit 1 (V1)] and 26 weeks [visit 2 (V2)] of gestation and PP. Nonpregnant controls had a single OGTT. 1,5AG was measured using frozen plasma samples. Changes in 1,5AG across pregnancy were assessed with longitudinal mixed effects linear models. We assessed relationships between 1,5AG and glycemia at each timepoint using Spearman correlations and linear regression models. To determine the relationship of 1,5AG with breastfeeding (BF) status, stratified analyses were performed.

Results: 1,5AG decreased from V1 to V2 (β = -3.6 μg/mL, P < .001) and remained low PP compared to V1 (β = -1.4 μg/mL, P = .018). Comparisons between pregnant/PP and nonpregnant participants revealed lower 1,5AG values at all timepoints (V1 β = -9.9μg/mL, P < .001; V2 β = -14.0 μg/mL, P < .001, PP β = -11.4μg/mL, P < .001). There was no association between 1,5AG and glycemia. Compared to those exclusively feeding formula, 1,5AG levels were significantly lower in exclusively BF women (β = -8.8 μg/mL, P < .001) and intermediate in women feeding both breastmilk and formula (β = -6.1μg/mL, P < .001), independent of glycemia.

Conclusion: 1,5AG decreases during gestation and remains low PP. Breastfeeding is associated with lower 1,5AG levels, indicating plausible excretion into breastmilk. 1,5AG is unlikely to be useful in assessing glycemia in pregnant or PP women.

Context: X-linked hypophosphatemia (XLH) is the most common form of inherited hypophosphatemic rickets (HR), caused by pathogenic variants in the PHEX gene. Genetic diagnosis of XLH facilitates early treatment optimization, especially for patients suitable for burosumab, a recombinant anti-fibroblast growth factor-23 monoclonal antibody.

Objective: This study aimed to use whole-exome sequencing (WES) and pedigree analysis to identify patients with XLH.

Methods: Medical records at a single center in Saudi Arabia were screened between 2014 and 2024 to identify patients with suggested HR. Of the 800 patients identified, 27 had had suspected XLH. The genetic study comprised 100 patients drawn from these 27 families.

Results: Clinical manifestations were widespread and variable within families. Severe disease was reported in 55% of children and 25% of adults. At presentation, all children were receiving either conventional therapy (60%) or burosumab (40%); however, 53% of adults were not treated. WES provided a genetic diagnosis in 23 families: alterations in the PHEX gene (20 families), with homozygous ENPP1 and DMP1 variants detected in 2 and 1 families, respectively. Pathogenic/likely pathogenic variants were detected in 23 families (diagnostic yield 85%). Ten novel likely pathogenic variants were detected. Pedigree analysis provided information to support disease-specific patient management.

Conclusion: WES detected a diagnostic molecular abnormality in 85% of families with HR phenotypes; PHEX variants were the most common. Combined use of WES and pedigree analysis highlighted the underdiagnosis of adult XLH in this population, with most family members being diagnosed after the pedigree analysis.

Context: Suboptimal treatment of hypothyroidism (HT) is associated with adverse cardiovascular disease (CVD) outcomes, for which patients with diabetes mellitus (DM) are at increased risk.

Objective: This study aimed to compare CVD-related healthcare utilization in DM patients with and without HT in the US population.

Methods: Participant data were collected from the Medical Expenditure Panel Survey (MEPS) over 10 years (2011-2020). Medical conditions were identified by ICD-9/ICD-10 codes associated with expenditures. Healthcare utilization outcomes included number of emergency, hospital, and outpatient visits associated with coronary artery disease (CAD), stroke/transient ischemic attack (TIA), or heart failure; prescriptions related to CVD; and number of visits to specialty providers. A propensity score-based fine stratification matching approach was used to balance sociodemographic covariates to determine the relative risk (RR) contributed by HT on CVD-related care utilization.

Results: A total of 15 580 adult participants with DM were identified, of whom 11.9% had treated HT. In the weighted analysis, a significantly greater proportion of participants with HT had CAD and stroke/TIA-associated visits compared to those without HT (respectively, 22.4% vs 17.8%, P = .002; and 7.3% vs 5.4%, P = .020). In the matched analysis, participants with HT were more likely to see a specialist (cardiology, endocrinology, and nephrology). Participants with HT were more likely to be treated with cholesterol-lowering medications, beta-blockers, and diuretics.

Conclusion: HT as a comorbidity with DM was associated with increased healthcare utilization related to CVD, specifically visits associated with stroke/TIA, increased use of specialty care, and greater utilization of CVD-related medications.

Nuclear receptors are important in normal physiology and disease. Physicians and scientists who study nuclear receptors organize and attend conferences and symposia devoted to foundational and translational nuclear receptor research, but the field lacks a platform for early-stage investigators and aspiring leaders. In 2019, Zeynep Madak-Erdogan, Rebecca Riggins, and Matthew Sikora founded Nuclear Receptor (NR) Interdisciplinary Meeting for Progress And Collaboration Together (IMPACT, https://nrimpact.com), a collaborative group designed for early- and mid-career faculty who study nuclear receptors in any context or organism [1]. NR IMPACT addresses challenges for early- and mid-career faculty. Here, we review the progress of NR IMPACT and discuss how our peer-mentoring cohort is removing hurdles for new faculty and advancing nuclear receptor biology.