Journal of the Endocrine Society最新文献

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.

Introduction: Congenital and acquired damage to hypothalamic nuclei or neuronal circuits controlling satiety and energy expenditure results in hypothalamic obesity (HO). To date, successful weight loss and satiety has only been achieved in a limited number of affected patients across multiple drug trials. Glucagon-like peptide-1 (GLP-1) acts via central pathways that are independent from the hypothalamus to induce satiety. GLP-1 receptor agonists (GLP-1RAs) may provide an alternative approach to treating HO.

Methods: We performed a comprehensive search in Medline, Google Scholar, and clinical trials registries (ClinicalTrials.gov; clinicaltrialsregister.eur). This nonsystematic literature review was conducted to identify scientific papers published from January 2005 to February 2024 using the Pubmed and Embase databases. Key words used were GLP-1, GLP-1RA, hypothalamic obesity, suprasellar tumor, and craniopharyngioma.

Results: Our search identified 7 case studies, 5 case series, and 2 published clinical trials relating to the use of GLP-1RAs in HO. All case studies demonstrated weight loss and improved metabolic function. In contrast, results from case series were variable, with some showing no weight loss and others demonstrating moderate to significant weight loss and improved metabolic parameters. In the ECHO clinical trial, nearly half the subjects randomized to weekly exenatide showed reduced body mass index (BMI). Paradoxically, BMI reduction was greater in patients with more extensive hypothalamic injuries.

Conclusion: GLP-1RAs potentially offer a new approach to treating HO. There is a need to stratify patients who are more likely to respond. Further randomized controlled trials are required to determine their efficacy either in isolation or combined with other therapies.

Objective: To assess ethnic disparities in the association between indirect and direct measures of adiposity in African American (AA) and European American (EA) adults.

Methods: We analyzed the indirect [weight, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR)] and direct [total fat, trunk fat, fat-free mass (FFM)] adiposity measures in healthy AA and EA adults. Assessments included anthropometry, oral glucose tolerance test, body composition by dual-energy X-ray absorptiometry (DXA), and calculation of direct-to-indirect adiposity ratios (total fat/BMI, trunk fat/WC, trunk fat/WHtR, and FFM/weight).

Results: A total of 314 subjects (167 AA, 147 EA) underwent DXA. All participants (mean age 44.2 ± 10.6 years) had normal fasting and 2-hour glucose values. The BMI (AA vs EA) was 31.2 ± 7.42 kg/m² vs28.8 ± 6.78 kg/m² (P = .0014); WC 95.3 ± 16.0 cm vs 92.9 ± 15.0 cm (P = .15). Significant correlations (P < .0001) were observed between BMI and total fat (r = 0.68), WC, and trunk fat (r = 0.61) and WHtR vs trunk fat (r = 0.77) for the combined cohort, with heterogeneity in the strength of association by sex and ethnicity. Fat-free mass was higher in AA vs EA participants (P = .03). Total fat/BMI was lower in AA vs EA participants (P = .0047); trunk fat/WC (P = .004) and trunk fat/WHtR (P = .0026) were lower in AA men vs EA men.

Conclusion: The BMI overestimated body fat in AA participants vs EA participants, and WC overestimated trunk fat in AA men vs EA men. These data indicate ethnic disparities in the fidelity of indirect measures of adiposity and argue for ethnic-specific BMI thresholds for determination of overweight/obesity.

Context: Evidence for a beneficial role of vitamin D on blood pressure (BP) outcomes is inconclusive.

Objective: This work aimed to investigate the effect of 2 doses of cholecalciferol (vitamin D₃) supplementation coadministered with calcium on systolic blood pressure (SBP) and diastolic blood pressure (DBP).

Methods: Exploratory analyses were conducted from a 1-year, multicenter, double-blind, randomized controlled trial (RCT). Total of 221 ambulatory older overweight individuals received calcium dose and oral vitamin D₃, at the equivalent of 600 IU/day or 3750 IU/day.

Results: SBP and DBP decreased significantly in the overall group, and in the high-dose group at 6 and 12 months. Similar trends were observed in the low-dose group, but did not achieve statistical significance. In participants with a body mass index (BMI) greater than 30, SBP decreased significantly in both treatment groups whereas DBP significantly decreased in the high-dose group only. In the subgroups of hypertensive participants (N = 143), there was a decrease in SBP and DBP at 6 and 12 months, with both vitamin D doses and independently of BMI levels. Using multivariate linear mixed models with random effects in the overall group of participants, SBP at 6 and 12 months was significantly predicted by BMI (β = .29; P = .05) and by baseline SBP (β = .16; P < .001), but not by vitamin D treatment dose.

Conclusion: Vitamin D and calcium decrease SBP and DBP in overweight older individuals, but more is not necessarily better. This effect is seen in individuals with BMI greater than 30, in hypertensive patients, and seems to be largely independent of dose.

Purpose: To assess whether simultaneous normalization of late-night salivary cortisol (LNSC) and mean urinary free cortisol (mUFC) in patients with Cushing disease treated with osilodrostat is associated with better clinical outcomes than control of mUFC or LNSC alone.

Methods: Pooled data from two phase III osilodrostat studies (LINC 3 and LINC 4) were analyzed. Both comprised a 48-week core phase and an optional open-label extension. Changes in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life (QoL) were evaluated across the following patient subgroups: both LNSC and mUFC controlled, only mUFC controlled, only LNSC controlled, and neither controlled.

Results: Of 160 patients included in the analysis, 85.0% had both LNSC and mUFC uncontrolled at baseline. At week 72, 48.6% of patients had both LNSC and mUFC controlled; these patients generally exhibited greater improvements in cardiovascular/metabolic-related parameters than those with only mUFC controlled or both LNSC and mUFC uncontrolled: systolic/diastolic blood pressure, -7.4%/-4.9%, -6.0%/-5.5%, and 2.3%/0.8%, respectively; fasting plasma glucose, -5.0%, -4.8%, and 1.9%; glycated hemoglobin, -5.1%, -4.8%, and -1.3%. Weight, waist circumference, and body mass index improved with control of LNSC and/or mUFC; physical manifestations of hypercortisolism generally improved regardless of LNSC/mUFC control. Patients with both LNSC and mUFC controlled or only mUFC controlled had the greatest improvement from baseline to week 72 in QoL.

Conclusion: In osilodrostat-treated patients with Cushing disease, normalization of LNSC and mUFC led to improvements in long-term outcomes, indicating that treatment should aim for normalization of both parameters for optimal patient outcomes.

Clinical trial identifiers: NCT02180217 (LINC 3); NCT02697734 (LINC 4).