Journal of Clinical Endocrinology & Metabolism最新文献

Context: Growth hormone (GH) enhances muscle strength and aerobic capacity in adults with GH deficiency, but GH effects in skeletal muscle are less well characterized in youth.

Objective: To investigate the impact of GH on skeletal muscle in boys with significant short stature (SS) compared with age-matched, normally growing controls.

Methods: This was an open-label comparator at an outpatient endocrine clinic. Participants were 45 prepubertal boys, SS, n = 30 (isolated GH deficiency or idiopathic SS) (mean [SE] age: 8.9 ± 0.3 years; height SDS: -2.3 ± 0.1); controls, n = 15 (8.8 ± 0.4 years; HT SDS: -0.3 ± 0.2). Anthropometry, fat-free mass, resting energy expenditure (REE) and muscle testing was performed at baseline, and 6 and 12 months after daily GH (SS group) or observation (controls). The main outcome measures were skeletal muscle strength (isometric dynamometry (flexion/extension) upper and lower extremities) (principal), power (vertical jump), endurance (modified pushups), and agility (timed shuttle-runs); fat-free mass accrual and REE (secondary).

Results: At baseline, the SS group had lower muscle strength in upper body (P ≤ .027) and lower body (P ≤ .007) vs controls, similar lower body muscle power and agility, but lower endurance (P = .048). Baseline differences were significantly less after GH treatment, with values in children approaching those of controls by 12 months. Adjusting for height SDS and fat-free mass between groups decreases detected differences in upper extremity muscle strength and endurance, but lower extremity muscle strength differences persist. No differences in REE were detected.

Conclusion: Boys with significant SS have quantifiable deficits in upper and lower body skeletal muscle strength, and lower physical endurance than normally statured controls. GH treatment for 12 months can improve these metrics in prepubertal boys with SS.

Context: Type 2 diabetes mellitus (T2DM) is a major driver of coronary atherosclerosis progression, yet its impact is highly heterogeneous. Insulin resistance contributes to a complex interplay of metabolic disturbances that accelerate atherogenesis to varying degrees. Identifying biomarkers that refine cardiovascular risk prediction in this population remains a clinical priority.

Objective: To evaluate the association between small high-density lipoprotein (HDL) particle concentration and the incidence/progression of coronary artery calcium (CAC) in individuals with T2DM.

Methods: We analyzed 4331 participants from the ELSA-Brasil cohort. CAC incidence/progression was compared between individuals with and without T2DM. A subgroup of 461 non-statin users with T2DM and no baseline atherosclerotic cardiovascular disease (ASCVD) was further assessed for associations between small HDL particles (<8 nm, HDLp1) and CAC outcomes.

Results: Individuals with T2DM showed increased CAC incidence/progression rates compared to nondiabetic participants. Among 461 non-statin users with T2DM, 143 (31.0%) experienced CAC incidence/progression. Higher plasma concentrations of HDLp1 (third tertile) were associated with a 140% (95% CI, 32%-341%; P < .001) greater likelihood of CAC incidence/progression compared to the first tertile. The inclusion of HDLp1 significantly improved CAC risk classification, with a net reclassification improvement (NRI) of 13.6% (95% CI, 2.8%-18.8%; P = .004).

Conclusion: HDLp1 concentration is significantly associated with CAC incidence/progression in individuals with T2DM and may improve risk discrimination for coronary atherosclerosis progression in this population.

Context: Thyroid cancer (TC) is a prevalent endocrine malignancy with rising incidence attributed to advancements in diagnostic technology. Despite its generally favorable prognosis, postsurgical complications, including hypoparathyroidism, can cause long-term health challenges.

Objective: This study evaluated the risk of nonskeletal complications in patients with TC with hypoparathyroidism (TC with hypoP).

Methods: A retrospective cohort study was conducted using the National Health Insurance Service-National Sample Cohort (2002-2019), including patients with TC diagnosed between 2006 and 2019. Participants were categorized into TC with hypoP, TC without hypoparathyroidism (TC without hypoP), and matched controls. Propensity score matching and Cox proportional hazards models evaluated the incidence and risk of nonskeletal complications, including diabetes mellitus, dyslipidemia, cardiovascular and renal outcomes, and cataracts.

Results: This study included 430 and 850 patients in the TC with hypoP and TC without hypoP groups, respectively, and their matched controls. The TC with hypoP group showed significantly higher risks of diabetes mellitus (HR 1.31, 95% CI 1.01-1.68), dyslipidemia (HR 1.29, 95% CI 1.06-1.57), urinary stones (HR 1.61, 95% CI 1.00-2.57), and cataracts (HR 1.50, 95% CI 1.15-1.95) than controls (all P < .05). Hypertension risk was higher in the TC with hypoP group vs the TC without hypoP group (HR 1.39, 95% CI 1.00-1.93, P = .048). Women had higher urinary stone risk, while cataract risk increased in patients aged over 50.

Conclusion: Patients with TC with hypoP are at an increased risk for specific nonskeletal complications, particularly older adults and women. These findings underscore the need for targeted monitoring and management strategies in this population. Further prospective studies are warranted to validate these associations and elucidate the underlying mechanisms.

Context: Endocrinology telemedicine visits increased during the COVID-19 pandemic with unclear impacts on patient outcomes.

Objective: To determine the relationship between different rates and types of telemedicine use and glycemic control in patients with diabetes.

Methods: This was a retrospective cohort study conducted in endocrinology clinics at an integrated health system. Patients were adults with a baseline glycated hemoglobin (HbA1c) measurement in 2020, at least 2 diabetes visits in 2021, and an outcome HbA1c assessment in 2022. The proportion of total visits in 2021 conducted by video or phone was analyzed and the primary outcome was the change in HbA1c between baseline and the 2022 assessment.

Results: The study population (n = 8867) was 51.39% female, with a mean age of 63.90 years and baseline HbA1c of 7.72%. Patients had a mean of 35.09% telemedicine visits in 2021 (25.18% video, 9.91% phone). Between 2020 and 2022, HbA1c decreased by a mean of 0.17%. Multivariable regression analysis adjusted for demographic and clinical covariates demonstrated that higher rates of phone (P = .009) but not video visits were associated with a smaller decrease in HbA1c. When stratified by baseline HbA1c, higher rates of phone visits were associated with a smaller decrease in HbA1c in patients with a baseline HbA1c ≥ 8.0% (P = .001) but not in those with a baseline HbA1c < 8.0%.

Conclusion: Higher rates of phone but not video visits were associated with worse glycemic control in patients with higher baseline HbA1c. Additional research is needed to determine possible causes and strategies for bridging the digital divide.

Context: Medical therapy for Cushing syndrome (CS) typically aims to reduce daily cortisol output without addressing circadian rhythm restoration. No licensed drugs target this goal.

Objective: We investigated the efficacy and safety of timed, once-daily osilodrostat administration in improving circadian cortisol profiles in CS.

Methods: A prospective, multicenter study evaluated patients with well-controlled CS on a stable twice-daily osilodrostat therapy before and 60 to 90 days after transitioning to a single equivalent daily dose at 19:00 ± 1 hour. Circadian steroid analysis was performed on saliva, serum, and urine using ultra-high performance liquid chromatography-tandem mass spectrometry. Additional assessments included cardio-metabolic markers, quality of life, sleep function, and safety outcomes.

Results: Sixteen patients (4 males; 7 pituitary, mean age 53.3 ± 11.8 years) were enrolled. At baseline, CS was well-controlled with a mean osilodrostat dose of 4.2 ± 1.3 mg. After transitioning, salivary cortisol exposure decreased significantly during the afternoon to early morning period (AUC16:00-08:00: -6.1 [-0.15 to -12.1] ng/mL/h, P = .029). Quality of life and sleep improved (CushingQoL: +4.2, P = .029; Pittsburgh Sleep Quality Index: -1.7, P = .049). Serum steroid precursors, including 11-deoxycorticosterone (-3.1 ng/mL/h, P = .008) and 11-deoxycortisol (-17.8 ng/mL/h, P = .005), decreased. Eight patients advancing dosing to 16:00 ± 1 hour showed comparable reductions, with phase shifts in acrophase and nadir. No patients developed adrenal insufficiency, liver toxicity, electrocardiogram abnormalities, or loss of disease control.

Conclusion: Once-daily osilodrostat effectively and safely treats patients with biochemically controlled CS, improving circadian cortisol profiles, quality of life, and sleep. Findings support further exploration of chronotherapy-based approaches in CS management.

Context: Real-world data add value to outcomes from randomized controlled trials on the use of hybrid closed-loop systems in the management of children and adolescents with type 1 diabetes.

Objective: This multicenter prospective observational cohort study assessed real-world changes in glycemic and person-reported outcomes 1 year after Control-IQ initiation in children and adolescents with type 1 diabetes.

Methods: Between December 2021 and December 2022, all children aged 6-18 years who started Control-IQ at 13 Belgian centers were consecutively recruited. Data were collected at start of Control-IQ and after 4, 8, and 12 months. Person-reported outcomes were evaluated through questionnaires (Diabetes Quality of Life for Youth [DQOLY], Hypoglycemia Fear Survey [HFS], HAPPI-D). Data are reported as mean ± SD or least-squares mean (95% CI).

Results: A total of 114 children were included, with a mean age of 12.0 ± 3.2 years and of whom 61.4% were girls. Time in range (3.9-10.0 mmol/L) increased from start (51.6% [47.6-55.5]) to 12 months (64.4% [61.2-67.5]) (P < 0.001). After 12 months, HbA1c decreased from 62 mmol/mol (60-65) (7.8% [7.6-8.1]) to 54 mmol/mol (52-57) (7.1% [6.9-7.3]) and time <3.9 mmol/L from 3.9% (3.1-4.8) to 2.7% (1.9-3.5) (all P < 0.001). Children scored better on DQOLY satisfaction (70.4 [67.8-73.0] vs 74.0 points [71.3-76.6]) and DQOLY impact (54.6 [50.9-58.3] vs 51.3 points [47.4-55.1]), and parents on HAPPI-D (22.5 [21.1-23.9] vs 19.6 points [18.2-21.0]) and HFS worry (25.0 [21.6-28.4] vs 20.3 points [17.0-23.5]) (all P < 0.001). Children missed fewer days of school (287 vs 30 days/100 person-years, P < 0.001) and parents missed fewer days of work (247 vs 47 days/100 person-years, P < 0.001).

Conclusion: One-year use of Control-IQ was associated with improved glycemic management, more diabetes-related quality of life and fewer school/work absences.

Context: The beneficial effects of a ketogenic diet (KD) on neurodegenerative conditions such as mild cognitive impairment (MCI) and Alzheimer disease (AD) are increasingly acknowledged, with potential implications for the general population as well.

Objective: Thus, our study aimed to explore the effect of a KD on cerebral blood flow (CBF) and brain-derived neurotrophic factor (BDNF) in healthy individuals. We hypothesized that a KD would increase CBF and BDNF, thereby presenting itself as an approach to prevent cognitive decline.

Methods: In total, 11 cognitively healthy individuals with overweight participated in a randomized, crossover trial consisting of 2 different 3-week interventions: (i) a KD; and (ii) a standard diet (SDD). Each diet period concluded with a positron emission tomography (PET) study day, accompanied by a separate magnetic resonance imaging (MRI) scan. Blood samples were collected prior to the PET scan to measure β-hydroxybutyrate (β-OHB) and BDNF levels. CBF was assessed using a [15O]H2O PET scan co-registered with an MRI scan.

Results: A KD led to increased basal plasma β-OHB levels compared to the SDD (647 [418-724] vs 50 [50-60] μmol/L, P < .05), increased CBF by 22% (P = .02), and elevated BDNF levels by 47% (P = .04). Moreover, a correlation was observed between β-OHB levels and CBF measurements across the 2 diets (R2 = 0.54, P < .001).

Conclusion: Implementing a KD improved CBF and raised BDNF levels in cognitively healthy individuals, indicating that a KD should be assessed for as a potential treatment for conditions associated with reduced CBF.

Context: Despite the efficacy of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), many patients with type 2 diabetes (T2D) require additional therapy to achieve glycated hemoglobin (HbA1c) targets. Few studies have explored real-world outcomes following GLP-1 RA failure.

Objective: This analysis evaluates different intensification approaches, timing, and outcomes in patients with T2D on GLP-1 RAs.

Methods: This retrospective cohort study was based on the AMD Annals database. From 191 041 patients on GLP-1 RAs between 2010 and 2022, individuals receiving a first therapeutic intensification were selected. Patients were stratified by intensification strategy; baseline characteristics were compared alongside HbA1c and weight changes at 6 and 12 months.

Results: Among the 37 198 intensified patients, the majority received oral antihyperglycemic drugs (OADs), particularly those with higher body mass index, lower HbA1c, and shorter disease duration. Basal insulin (BI) was mainly added in those with higher HbA1c (8.9%) and longer diabetes. Intensification with BI or switch to fixed ratio combinations (FRCs) yielded the greatest HbA1c reduction (-0.92 and -0.85%; P < .001) and weight neutrality, whereas OADs led to a higher target achievement rate (36% with HbA1c < 7%) and persistent weight loss. Switching to BB was reserved for more complicated patients and it was associated with weight gain (+2.9 kg; P < .001) and lower target achievement rate (16.8% HbA1c < 7%). Suboptimal insulin titration was observed across all strategies.

Conclusion: Adding OADs or BI/FRCs to GLP-1 RAs are optimal intensification strategies to provide glycemic control while avoiding weight gain. Target achievement rates are poor in individuals switched to insulin therapy. Therapeutic inertia remains a critical issue in clinical practice.

Objective: Muscle mass and function are impaired in type 1 diabetes (T1D); however, the relevance to bone health is unknown. This study aimed to examine the relationship between muscle mass, muscle strength, and bone in adults with childhood onset of T1D.

Methods: This cross-sectional study population includes 111 Danish men and women with T1D onset before age 18 years and 37 sex- and age-matched controls. Lean mass was assessed through dual-energy x-ray absorptiometry, and hand grip strength was measured using a dynamometer. Bone mineral density (BMD), bone size, and bone material strength index were assessed by dual-energy x-ray absorptiometry, high-resolution peripheral quantitative computed tomography, and microindentation.

Results: Participants had a median age of 43.2 years and body mass index of 26.9 kg/m2, with no differences between groups. Total and appendicular lean mass were comparable in persons with and without T1D (P = .41 and P = .75), as was grip strength (P = .52). BMD, bone size (cortical area and perimeter), and bone material strength index did not differ between groups (P > .05). Within the T1D group, appendicular lean mass/height2 was positively associated with femoral neck BMD (R2 = 0.12) and total hip BMD (R2 = 0.337). Similarly, grip strength was associated with femoral neck-BMD (R2 = 0.104), and total hip-BMD (R2 = 0.137). The associations between muscle indices and BMD measures did not differ significantly between groups.

Conclusion: We observed a strong association between muscle and bone regardless of T1D status. Overall, the associations did not differ between the T1D and control groups, suggesting that the muscle-bone crosstalk is not affected by T1D.

Context: Sex hormone-binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk.

Objective: This work aimed to investigate whether the associations between SHBG, testosterone, and T2D risk differ by HIV and menopausal status in Black African women living with HIV (WH) and without HIV (WOH).

Methods: This cross-sectional observational study took place at the Health Research Unit in Soweto, Johannesburg, South Africa. A total of 81 premenopausal (57 WOH, 24 WH) and 280 postmenopausal (236 WOH, 44 WH) women from the Middle-Aged Soweto Cohort (MASC) participated. Main outcome measures included circulating SHBG and sex hormones, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (Matsuda index), secretion (insulinogenic index) and clearance, and β-cell function (disposition index, DI). Dysglycemia was defined as either impaired fasting or postprandial glucose or T2D.

Results: SHBG was higher and total and free testosterone were lower in postmenopausal WH than WOH (all P ≤ .023). Irrespective of HIV serostatus, SHBG was positively associated with Matsuda index, insulin clearance, and DI and inversely with HOMA-IR (all P < .011). The association between SHBG and Matsuda index was stronger in premenopausal than postmenopausal women (P = .043 for interaction). Free testosterone (and not total testosterone) was only negatively associated with basal insulin clearance (P = .021) and positively associated with HOMA-IR (homeostatic model assessment of insulin resistance) in premenopausal and not postmenopausal women (P = .015 for interaction).

Conclusion: We show for the first time that midlife African WH have higher SHBG and lower total and free testosterone than WOH, which corresponded to their higher β-cell function, suggesting a putative protective effect of SHBG on T2D risk in WH.