Journal of the Endocrine Society最新文献

Objectives: To investigate longitudinal changes in SHBG and free testosterone (free T) levels among Black middle-aged African men, with and without coexistent HIV, and explore associations with incident dysglycaemia and measures of glucose metabolism.

Design: This longitudinal study enrolled 407 Black South African middle-aged men, comprising primarily 322 men living without HIV (MLWOH) and 85 men living with HIV (MLWH), with normal fasting glucose at enrollment. Follow-up assessments were conducted after 3.1 ± 1.5 years.

Methods: At baseline and follow-up, SHBG, albumin, and total testosterone were measured and free T was calculated. An oral glucose tolerance test at follow-up determined dysglycaemia (impaired fasting glucose, impaired glucose tolerance, type 2 diabetes) and glucose metabolism parameters including insulin sensitivity (Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and beta(β)-cell function (disposition index). The primary analysis focussed on MLWOH, with a subanalysis on MLWH to explore whether associations in MLWOH differed from MLWH.

Results: The prevalence of dysglycaemia at follow-up was 17% (n = 55) in MLWOH. Higher baseline SHBG was associated with a lower risk of incident dysglycaemia (odds ratio 0.966; 95% confidence interval 0.945-0.987) and positively associated with insulin sensitivity (β = 0.124, P < .001) and β-cell function (β = 0.194, P = .001) at follow-up. Free T did not predict dysglycaemia. In MLWH, dysglycaemia prevalence at follow-up was 12% (n = 10). Neither baseline SHBG nor free T were associated with incident dysglycaemia and glucose metabolism parameters in MLWH.

Conclusion: SHBG levels predict the development of dysglycaemia in middle-aged African men but do not exhibit the same predictive value in MLWH.

[This corrects the article DOI: 10.1210/jendso/bvae098.].

Context: Multiple common genetic variants have been associated with type 2 diabetes, but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in MTNR1B, which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes.

Objective: To characterize the effect of diabetes-associated genetic variation at rs10830963 in the MTNR1B locus on islet function in people without type 2 diabetes.

Design: The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon, and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose, and Disposition Indices were measured using the oral minimal model.

Setting: The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN.

Participants: Two cohorts were utilized for this analysis: 1 cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of TCF7L2 genotype at rs7903146 from the Mayo Biobank.

Intervention: Two-hour, 7-sample OGTT.

Main outcome measures: Fasting, nadir, and integrated glucagon concentrations.

Results: One or 2 copies of the G-allele at rs10830963 were associated with increased postchallenge glucose and glucagon concentrations compared to subjects with the CC genotype.

Conclusion: The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.

Context: The cardiovascular benefits of semaglutide are established; however, its effects on surrogate vascular markers and liver function are not known.

Objective: To investigate the effects of semaglutide on vascular, endothelial, and liver function in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD).

Methods: Overall, 75 consecutive subjects with T2DM and NAFLD were enrolled: 50 patients received semaglutide 1 mg (treatment group) and 25 patients received dipeptidyl peptidase 4 inhibitors (control group). All patients underwent a clinical, vascular, and hepatic examination with Fibroscan elastography at 4 and 12 months after inclusion in the study.

Results: Treatment with semaglutide resulted in a reduction of Controlled Attenuation Parameter (CAP) score, E fibrosis score, NAFLD fibrosis score, Fibrosis-4 (FIB-4) score and perfused boundary region (PBR) at 4 and at 12 months (P < .05), contrary to controls. Patients treated with semaglutide showed a greater decrease of central systolic blood pressure (SBP) (-6% vs -4%, P = .048 and -11% vs -9%, P = .039), augmentation index (AIx) (-59% vs -52%, P = .041 and -70% vs -57%, P = .022), and pulse wave velocity (PWV) (-6% vs -3.5%, P = .019 and -12% vs -10%, P = .036) at 4 and at 12 months, respectively. In all patients, ΔPWV and ΔPBR were correlated with a corresponding reduction of CAP, E fibrosis, NAFLD fibrosis, and FIB-4 scores.

Conclusion: Twelve-month treatment with semaglutide simultaneously improves arterial stiffness, endothelial function, and liver steatosis and fibrosis in patients with T2DM and NAFLD.

The incidence of lymph node metastasis in papillary thyroid carcinoma (PTC) is common and a significant risk factor for local recurrence; however, its impact on recurrence patterns among low-risk patients remains uncertain. We aimed to elucidate the effect of metastatic lymph node on recurrence type. The medical records of 1209 patients with stage T1 PTC who underwent unilateral thyroidectomy with ipsilateral central lymph node dissection were retrospectively analyzed. The study first identified risk factors for different types of recurrence and then categorized patients as high or low risk based on their lymph node positive ratio (LNPR). The diagnostic accuracy of LNPR in predicting recurrence was compared using receiver operating characteristic (ROC) curve analysis, while differences in recurrence-free survival were assessed using the Kaplan-Meier method. During follow-up, a total of 502 (41.5%) patients had central lymph node metastasis and 52 (4.3%) patients experienced recurrence. Notably, LNPR was significantly higher in relapsed patients compared to nonrelapsed patients, with mean values of 0.45 and 0.23, respectively (P < .001). The recurrence rate of residual thyroid did not differ significantly across different T stages (P = .679), N stages (P = .415), or LNPR risk groups (P = .175). However, the recurrence rate of lymph nodes showed a significant correlation with LNPR (P < .001). The area under the ROC curves for LNPR risk stratification at 5 and 10 years were approximately 0.691 and 0.634, respectively, both of which outperformed N stage. The findings underscore the significance of LNPR's reliability as a prognostic indicator for local lymph node recurrence in patients diagnosed with T1 stage PTC.

Objective: To estimate decadal trends in the prevalence of metabolic syndrome (MetS) in economically developed regions in China and its association with city economic levels.

Methods: Using a comprehensive Chinese healthcare database, repeated cross-sectional studies were conducted on adults who had annual health check-ups from 2012 to 2021 in 4 economically developed cities. MetS was defined by the criteria of the Chinese Diabetes Society in 2013. The crude prevalence of MetS adjusted for sex and age was reported. The association between prevalence, calendar year, and city gross domestic product (GDP) per capita was analyzed by regression model.

Results: 158 274 participants aged 18 years and older were included. The unadjusted prevalence of MetS increased from 15.5% (95% CI: 14.2%-16.8%) to 20.0% (95% CI: 19.5%-20.5%) from 2012 to 2021. The adjusted overall prevalence has increased steadily from 12.8% to 20.8% after controlling age and sex (P < .001). Male and older age groups had a higher MetS prevalence. In the regression model of the association between the MetS prevalence, calendar year, and city GDP per capita, calendar year had a positive association with the prevalence (P < .001, 95% CI: 0.648-1.954) and city GDP per capita had a negative association (P = .030, 95% CI: -0.136 to -0.007).

Conclusion: The MetS prevalence increased steadily in the economically developed regions in China among the health check-up population during 2012-2021. The MetS prevalence is shown to be negatively associated with GDP per capita in the study population.

Context: The rise in continuous glucose monitor (CGM) use has been characterized by widening disparities between the least and most socially marginalized. Given access barriers, there is limited CGM patient experience information that is inclusive of those with type 2 diabetes mellitus from socially marginalized backgrounds.

Objective: To understand the CGM usage experience in the primary care setting across a US Medicaid population with type 2 diabetes at federally qualified health centers.

Methods: This qualitative study used semi-structured phone interviews with 28 English- or Spanish-speaking participants prescribed the CGM who were enrolled in a US Medicaid program that subsidized CGMs. Audio recordings of interviews were transcribed and analyzed by reflective thematic analysis.

Results: Twenty-eight participants (75% female, median age 56 years with interquartile-range 48-60 years) were interviewed. Participants were from different racial/ethnic backgrounds: 21% non-Hispanic White, 57% Hispanic, and 18% non-Hispanic Black. Participants primarily spoke English (68%) or Spanish (32%), and 53% reported 9 or fewer years of formal education. We identified 6 major themes: initial expectations and overcoming initiation barriers, convenience and ease promote daily use, increased knowledge leads to improved self-management, collaboration with provider and clinical team, improved self-reported outcomes, and barriers and burdens are generally tolerated.

Conclusion: CGM use was experienced as easy to understand and viewed as a tool for diabetes self-efficacy. Expanded CGM access for socially marginalized patients with type 2 diabetes can enhance diabetes self-management to help mitigate diabetes outcome disparities.

Context: Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls.

Objective: We compared CVD burden and biomarker profiles between TW and matched cisgender men (CM).

Methods: Adult TW on GAHT (n = 29) were recruited for a cross-sectional study (2018-2020). CM (n = 48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary CT angiography; sex hormone and biomarker concentrations were measured centrally from stored samples.

Results: Overall, median age was 53 years and BMI 29 kg/m²; 69% were non-white. All participants with HIV (71%) had viral suppression on ART. Only 31% of TW had testosterone suppression (<50 ng/dL, TW-S). Traditional CVD risk factors were similar between groups, except that TW-S had higher BMI than TW with non-suppressed testosterone (TW-T). TW-S had no evidence of non-calcified coronary plaque or advanced coronary stenosis, whereas TW-T and CM had similar burden. TW had lower prevalence of any coronary plaque, calcified plaque and mixed plaque than CM, regardless of testosterone concentrations and HIV serostatus. Estradiol but not testosterone concentrations moderately and negatively correlated with the presence of coronary plaque and stenosis. Small sample size limited statistical power.

Conclusion: Older TW with suppressed total testosterone on GAHT had no CT evidence of non-calcified coronary plaque or advanced coronary stenosis. Longitudinal studies to understand relationships between GAHT and CVD risk in TW are needed.

Objects: This study aimed to explore the association between the Systemic Immune-Inflammation Index (SII) and diabetes mellitus (DM) and to assess its influence on the prognosis of the DM and no-DM groups.

Methods: The study used data from the National Health and Nutrition Examination Survey; 9643 participants were included. Logistic regression analysis was employed to evaluate connections between SII and DM. We used the Cox proportional hazards model, restricted cubic spline, and Kaplan-Meier curve to analyze the relationship between SII and mortality.

Results: The logistic regression analysis indicated that a significant increase in the likelihood of developing DM with higher SII levels (odds ratio, 1.31; 95% CI, 1.09-1.57, P = .003). The Cox model showed that there is a positive association between increased SII and higher all-cause mortality. The hazard ratios for SII were 1.53 (1.31, 1.78), 1.61 (1.31, 1.98), and 1.41 (1.12, 1.78) in the total, DM and non-DM groups, respectively. We observed a linear correlation between SII and all-cause mortality in DM participants, whereas non-DM participants and the total population showed a nonlinear correlation.

Conclusion: Elevated SII levels are linked to an augmented risk of DM. Those with DM and higher SII levels demonstrated an elevated risk of mortality.

Context: The association of obesity with bone fragility fractures is complex and non-linear. Despite good efficacy on weight loss, bariatric surgery (BS) is also associated with bone loss. However, we lack information on risk factors of the long-term deleterious effects of BS on the skeleton.

Objective: We aimed to assess the factors associated with low bone mineral density (BMD) performed a long time after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG).

Methods: This cross-sectional study involved patients at a long distance from their BS that underwent dual-energy x-ray absorptiometry (DXA) with biological factors (vitamins, micronutrients, bone and inflammation biomarkers). Simple and multiple linear models (stepwise and parsimony approach) were developed.

Results: A total of 131 patients (91 RYGB, 40 SG) underwent DXA (51.8 ± 11.08 years, 87.8% women). At a mean of 6.8 ± 3.7 years after surgery, the mean weight loss was -28.6 ± 9.6%, and only 6 patients (5.7%) had a T-score less than or equal to -2.5. On univariate analysis, BMD was lower in the RYGB than in the SG group (P < .001) at all sites, despite similar fat and fat-free mass and weight loss. Serum parathyroid hormone and phosphate levels were higher in RYGB than SG patients. A total of 10.1% of patients showed vascular calcifications. On multivariable analysis, BMD remained different between surgery groups after adjustment for age, body mass index, ethnicity, and sex. The model-adjusted R ² values were 0.451 for the total hip; 0.462 the femoral neck, and 0.191 the lumbar spine for the inflammation model; 0.458, 0.462, and 0.254, respectively, for the bone marker model; and 0.372, 0.396, and 0.142 for the vitamin model. Serum zinc, ferritin, and uric acid levels were the markers associated with BMD to a low extent.

Conclusion: BMD differed depending on the BS procedure. A few biological markers may be associated weakly with BMD well after the surgery.