Journal of Clinical and Translational Endocrinology最新文献

Background and aim

Gut microbiota influences energy homeostasis in part through circulating hormones. Insulin-like growth factor-binding protein (IGFBP)-2 is a biomarker whose increase in systemic circulation is associated with positive effects on body weight and metabolism. In a recent clinical trial, probiotic Lacticaseibacillus rhamnosus HA-114 supplementation showed positive effects on eating behaviors and insulin resistance in overweight participants undergoing a weight-loss intervention. In this context, this ancillary study aimed at assessing the impact of L. rhamnosus HA-114 supplementation on plasma IGFBP-2 levels in these individuals, and whether this modulation correlated with changes in fat mass, energy metabolism, and eating behaviors.

Methods

Fasting plasma IGFBP-2 concentrations were quantified in 100 overweight or obese men and women enrolled in a 12-week diet-based weight reduction program (−500 kcal/day), in combination with probiotic L. rhamnosus HA-114 or placebo supplementation. Baseline and changes in circulating IGFBP-2 concentrations were correlated with anthropometric parameter, glucose and lipid metabolism, cardiorespiratory function and eating behaviors.

Results

On average, the intervention reduced BMI by 4.6 % and increased IGFBP-2 by 13 %, regardless of supplementation group. Individuals who presented an increase in IGFBP-2 levels had significantly greater reductions in BMI. Changes in IGFBP-2 levels were correlated with loss in fat mass (r = 0.2, p < 0.001) in the probiotic-supplemented group, but not with other metabolic parameters or eating behaviors. Baseline IGFBP-2 levels were not associated with weight loss or improvements in cardiometabolic parameters.

Conclusion

Probiotic supplementation with L. rhamnosus HA-114 did not modulate plasma IGFBP-2 levels. Changes in IGFBP-2 levels were correlated with greater reductions in BMI, but not with other metabolic parameters or eating behaviors, indicating that the benefits of HA-114 on eating behaviors are likely independent of IGFBP-2. Additional changes in microbiota might be required to modulate IGFBP-2 and observe its associations with eating behaviors and cardiometabolic improvements.

Background

1.8% of youth identify as transgender; a growing proportion are transgender male (female sex, male gender identity). Many receive gonadotropin releasing hormone agonist (GnRHa) therapy to suppress endogenous puberty and/or will start testosterone to induce secondary sex characteristics that align with gender identity.

Objective(s)

To determine the effects of 12 months of testosterone on cardiometabolic health among transgender youth, including insulin sensitivity, body composition, and bone mineral density and whether changes in outcomes differ based on prior GnRHa treatment.

Methods

Participants (n = 19, baseline age 15.0 ± 1.0 years) were examined prior to and 12 months after testosterone therapy in a longitudinal observational study. Fasted morning blood draw, a 2-hour 75-gram oral glucose tolerance test, body composition and bone mineral density (dual-energy X-ray absorptiometry) were assessed at baseline and 12 months. Insulin sensitivity was estimated by HOMA-IR and Matsuda index. Changes were compared with mixed linear regression models evaluating time (baseline, 12 months), group (GnRHa treatment yes/no), and their interaction.

Results

In the entire cohort, fasted insulin decreased (median [25,75 %ile]: −3 [-5, 0] mIU/L, p = 0.044) and 2-hour glucose increased (mean ± standard deviation): +18.5 ± 28.9 mg/dL, p = 0.013 from baseline after 12 months of testosterone therapy. There were no significant changes in HOMA-IR (p = 0.062) or Matsuda index (p = 0.096), nor by GnRHa status. Absolute (+6.2 [4.7, 7.5] kg, p = 0.016) and percent fat-free mass increased (+7.3 [5.4, 9.1] %, p = 0.003) and percent fat mass declined (−7.4 [-9.3, 5.3]%, p = 0.005) for the entire cohort. There were time*group interactions for absolute (p = 0.0007) and percent fat-free mass (p = 0.033). There were time*group interactions for bone mineral content (p = 0.006).

Conclusions

Twelve months of testosterone in transgender adolescents resulted in changes in body composition and bone mineral density, with baseline differences between the +/-GnRHa group and convergence after 12 months. There were no changes in insulin sensitivity over time or between groups.

Gender Affirmation Surgery (GAS) is a super specialized subset within the field of plastic and reconstructive surgery (PRS) that is ever evolving and of increasing interest to the PRS community. It is a multifaceted process which, in addition to surgical therapy, involves mental health therapy and hormonal therapy. One rapidly emerging interest within GAS is the role that gender affirming hormone therapy (GAHT) plays in enhancing surgical outcomes. GAHT has been used adjunctively with GAS as a comprehensive therapy to ameliorate gender dysphoria. This literature review will examine the positive effects of GAHT on the surgical outcomes on GAS, as well as other important considerations prior to surgery. As such, the primary objective of this literature review is to evaluate and assess the current evidence concerning the efficacy and safety of GAHT, as it relates to Gender Affirmation Surgery procedures.

Chronic kidney disease (CKD) is a progressive and incurable condition that imposes a significant burden on an aging society. Although the exact prevalence of this disease is unknown, it is estimated to affect at least 800 million people worldwide. Patients with diabetes or hypertension are at a higher risk of developing chronic kidney damage. As the kidneys play a crucial role in vital physiological processes, damage to these organs can disrupt the balance of water and electrolytes, regulation of blood pressure, elimination of toxins, and metabolism of vitamin D. Early diagnosis is paramount to prevent potential complications. Treatment options such as dietary modifications and medications can help slow disease progression. In our narrative review, we have summarized the available therapeutic options to slow the progression of chronic kidney disease. Many new drug treatments have recently become available, offering a beacon of hope and optimism in CKD management. Nonetheless, disease prevention remains the most critical step in disease management. Given the significant impact of CKD on public health, there is a pressing need for further research. With the development of new technologies and advancements in medical knowledge, we hope to find more effective diagnostic tools and treatments for CKD patients.

Objectives

To report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D.

Research Design and Methods

Eighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team.

Results

Overall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event.

Conclusions

The use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.

ClinicalTrials.gov number: NCT04233034.

Background

Known barriers to family planning in the transgender population include low utilization of cryopreservation and decisional regret. There is growing data on the risk of infertility with GAHT, and on to what degree transgender adolescents feel informed about fertility and family planning options.

Objective

Assess preferences regarding options for family planning and fertility preservation in transgender adolescents treated with GAHT in a pediatric endocrinology gender clinic. The goal is to enhance patient education about potential effects of GAHT on fertility and options for family planning.

Methods

Forty one adolescents aged 10 years and older treated with GAHT in an urban outpatient pediatric endocrinology clinic were surveyed over a 6-month period from January to June 2022. Survey questions were multiple choice, Likert scale, and open-ended. Participants were at least 10 years of age, actively followed in the clinic, and receiving GAHT at time of enrollment.

Results

Forty one participants completed the survey. Four (10 %) expressed interest in discussing family planning with their provider. Eighteen (45 %) were open to discussion in the future; 16 (39 %) were not interested at all. 12 (30 %) participants were planning for future parenthood, and 16 (40 %) participants were undecided. Of those interested in parenthood 7 (53.8 %) planned to adopt or foster. Barriers to family planning expressed included financial concerns, potential need to pause GAHT, and social stigma of transgender parenthood. Twenty (50 %) participants recalled prior family planning discussion with their endocrinologist.

Conclusion

Family planning discussions may not be optimally impactful given that 50 % of participants did not recall the conversations. Family planning is a lower priority in this population as most desired to postpone discussion with their provider despite choosing treatment that could influence fertility. It is essential to identify methods to engage transgender youth in discussions related to family planning during GAHT.

Background

ω-N^G,N^G-asymmetric dimethylarginine (ADMA) regulates vascular tone and may participate in the pathogenesis of diabetic nephropathy (DN).

Objective

To investigate whether single-nucleotide polymorphisms (SNPs) around the protein arginine N-methyltransferase 1 gene (PRMT1) influence ADMA dynamics and DN incidence and severity.

Methods

This study utilized a hospital-based database containing 310 Japanese patients with type 2 diabetes mellitus (T2DM). The association of PRMT1-related tagged SNPs with DN stage distribution was examined using a dominant model of minor alleles. PRMT1 mRNA, serum ADMA, reactive hyperemia-peripheral arterial tonometry index (RHI), and brachial-ankle pulse wave velocity (baPWV) were compared between the genotype-based subgroups of causal SNP, and correlations between these variables were evaluated.

Results

The composition of DN stages significantly differed between the GG and GA + AA subgroups of rs892151 (p = 0.026). In a propensity-matching cohort of rs892151, the GA + AA subgroup had an increased incidence of overt DN (odds ratio 2.92, 95 % confidence interval 1.12–7.62, p = 0.028), along with higher PRMT1 mRNA, serum ADMA levels, and baPWV than the GG subgroup (p < 0.001, p = 0.023 and 0.047, respectively). There were correlations between PRMT1 mRNA and serum ADMA levels, between serum ADMA levels and RHI, and between baPWV and urinary albumin excretion (r = 0.335, p < 0.001, r = -0.221, p = 0.029, and r = 0.254, p = 0.004, respectively).

Conclusions

T2DM patients carrying the PRMT1-related variant rs892151 were susceptible to overt DN. ADMA-mediated endothelial dysfunction and arterial stiffness may be involved in the variant-related pathogenesis of overt DN.

Background

Gender-affirming hormone therapy with either estradiol or testosterone for transgender persons can significantly impact chemistry and hematology laboratory tests. The sex used for assignment of reference intervals (RIs) in the electronic health record (EHR) will influence normal/abnormal flagging of test results.

Objective

To analyze common non-hormonal laboratory tests with sex-specific RIs ordered in patients with sexual orientation/gender identify (SOGI) field differences (one or more differences between legal sex, sex assigned at birth, and gender identity) in the EHR at an academic medical center in midwestern United States.

Methods

We utilized a previously characterized data set of patients at our institution that included chart review information on gender identity and gender-affirming therapy. We focused on the subset of these patients that had orders for 18 common laboratory tests in calendar year 2021.

Results

A total of 1336 patients with SOGI field differences (1218 or 91.2% identifying as gender-expansive; 892 or 66.8% receiving estradiol or testosterone as gender-affirming therapy) had a total of 9374 orders for 18 laboratory tests with sex-specific RIs. Hemoglobin, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and high-density lipoprotein were the most frequently ordered tests. For patients taking estradiol, 128 of 970 (13.2%) creatinine and 39 of 193 (20.2%) hemoglobin measurements were within the RI for one sex but not the other. For those taking testosterone, 119 of 531 (22.4%) creatinine and 49 of 120 (40.8%) hemoglobin measurements were within the RI for one sex but not the other. Values above the cisgender female RI but within the cisgender male RI were common for hemoglobin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in patients taking testosterone.

Conclusions

Clinicians should be aware of the potential impact of gender-affirming therapy on laboratory tests and what sex/gender is being used in the EHR to assign RIs.

Introduction

Feminizing and masculinizing gender-affirming hormone therapy (fGAHT, mGAHT) results in bone mineral density (BMD) maintenance or improvement over time in transgender and gender diverse (TGD) adults. Mostly European TGD studies have explored GAHT’s impact on BMD, but the association of BMI and BMD in TGD adults deserves further study.

Objective

To determine whether GAHT duration or BMI are associated with BMD and Z-scores among TGD young adults.

Methods

Cross-sectional study of nonsmoking TGD adults aged 18–40 years without prior gonadectomy or gonadotropin-releasing hormone agonist (GnRHa) therapy taking GAHT for > 1 year. BMD and Z-scores were collected from dual-energy x-ray absorptiometry. Associations between femoral neck, total hip, and lumbar spine BMDs and Z-scores and the predictors, GAHT duration and BMI, were estimated using linear regression.

Results

Among 15 fGAHT and 15 mGAHT, mean BMIs were 27.6 +/- standard deviation (SD) 6.4 kg/m² and 25.3 +/- 5.9 kg/m², respectively. Both groups had mean BMDs and Z-scores within expected male and female reference ranges at all three sites. Higher BMI among mGAHT was associated with higher femoral neck and total hip BMDs (femoral neck: β = 0.019 +/- standard error [SE] 0.007 g/cm², total hip: β = 0.017 +/- 0.006 g/cm²; both p < 0.05) and Z-scores using male and female references. GAHT duration was not associated with BMDs or Z-scores for either group.

Conclusions

Z-scores in young, nonsmoking TGD adults taking GAHT for > 1 year, without prior gonadectomy or GnRHa, and with mean BMIs in the overweight range, were reassuringly within the expected ranges for age based on male and female references. Higher BMI, but not longer GAHT duration, was associated with higher femoral neck and total hip BMDs and Z-scores among mGAHT. Larger, prospective studies are needed to understand how body composition changes, normal or low BMIs, and gonadectomy affect bone density in TGD adults.

Aim

The aim of this study was to conduct a systematic review and meta-analysis of changes in low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides following initiation of feminizing or masculinizing gender affirming hormone therapy (GAHT).

Methods

A search of Ovid MEDLINE, Embase, Web of Science, SCOPUS, and CINAHL databases identified potentially relevant articles published from 1990 through 2024. Both observational and randomized trials of adults receiving feminizing or masculinizing GAHT with baseline and follow-up measures were included. Articles were reviewed for eligibility using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. The risk of bias in each study was quantified using the NHLBI Study Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group. Random effects models were used to compute the before-and-after meta-differences in mean values for each parameter along with the I² statistic to assess heterogeneity of results.

Results

Thirty-five studies met the criteria for inclusion in the meta-analysis. Masculinizing GAHT was associated with significant changes in serum lipids from baseline up through the 60-month timepoint with meta-difference of means (95% CI) estimates of 26.2mg/dL (23.3,29.0) for LDL-C, 26.1mg/dL (22.8,29.4) for total cholesterol, 30.7mg/dL (6.9,54.6) for triglycerides and –9.4mg/dL (–12.1, –6.7) for HDL-C. Studies evaluating the effects of feminizing GAHT on balance demonstrated no notable changes in HDL-C or triglycerides while the results for LDL-C and total cholesterol were inconsistent. Heterogeneity of results ranged from minimal (I² = 0%) to substantial (I² = 90%).

Conclusions

While the results for transfeminine individuals on GAHT appear somewhat reassuring, transmasculine patients receiving testosterone may benefit from closer monitoring of lipid profiles.