Therapeutic Advances in Endocrinology and Metabolism最新文献

A 34-year-old male developed bilateral recurrent pheochromocytomas 10 years after laparoscopic adrenal-sparing surgery for pheochromocytomas. Based on his clinical manifestations and germline REarranged during Transfection (RET) variant, the patient was ultimately diagnosed with multiple endocrine neoplasia type 2B. Based on drug susceptibility testing results from organoid-guided precision therapy, the patient underwent secondary adrenalectomy for the right lesion and received oral pralsetinib to control the left ones. Over 16 months of pralsetinib therapy, we found that the patient achieved sustained therapeutic benefits, specifically characterized by symptomatic relief, significant reduction in hormone levels, and shrinkage of the left adrenal masses. These findings indicate that pralsetinib is effective and safe for treating pheochromocytomas associated with RET missense mutation, but further clinical practices are warranted to confirm its efficacy and safety profile.

Aims: To assess the real-world impact of transitioning from the Dexcom G6^® to G7^® system in individuals with type 1 diabetes (T1D) using the Tandem t:slim X2™ with Control-IQ™. Primary outcomes included glycemic control changes, while secondary outcomes evaluated patient-reported outcomes (PROMs) and experiences (PREMs).

Methods: A 3-month prospective, multicenter, observational study was conducted in individuals previously using Dexcom G6 and Control-IQ. Glycemic control was assessed via TIR_70-180 and HbA_1c. PREMs and PROMs were measured using validated questionnaires (Diabetes Quality of Life (DQoL), Type 1 Diabetes Life (ViDa1), Diabetes Distress Scale (DDS), and Diabetes Treatment Satisfaction Questionnaire). Statistical analyses were stratified by baseline TIR_70-180 (>70% vs <70%) and sex.

Results: The study included 92 participants (mean age 38 ± 13 years), with a baseline TIR_70-180 of 76% ± 10%. The overall TIR_70-180 remained stable throughout the study. However, among participants with baseline TIR_70-180 <70%, a significant increase in TIR_70-180 was observed, rising from 61% ± 9% to 65% ± 7% (p = 0.007). In consonance, HbA_1c levels showed a significant decline, from 7.3% ± 0.9% to 7.0% ± 0.6% (p = 0.001). In addition, both glucose management indicator (GMI) and mean glucose levels significantly decreased over time, reflecting an overall improvement in glycemic control. These changes (GMI and glucose levels) were consistent across groups, with no significant differences based on baseline TIR_70-180 stratification. Quality of life and diabetes distress improved (DQoL, ViDa1, and DDS), especially in participants with lower baseline TIR_70-180 and in women. Some reported increased connectivity issues, but none led to treatment discontinuation.

Conclusion: In Control-IQ users, the transition to G7^® did not significantly impact glycemic control overall. However, a subgroup of patients with suboptimal baseline control (TIR_70-180 <70%) may benefit from this change, and enhanced quality of life and diabetes distress, especially in women.

Background: Adequate glucose control is an important, yet a challenging task, in the early postoperative care after liver transplantation (LTx). Potential of continuous glucose monitoring (CGM) in this context had not been fully explored because of concerns about sensors' precision in critical care.

Objectives: We initiated a trial to assess feasibility, accuracy, and benefit of CGM used in addition to standard blood glucose (BG) management.

Design: Prospective randomized trial.

Methods: Patients undergoing LTx were included and randomized to wearing (1) unblinded ("active") CGM which could help guiding insulin therapy, (2) blinded CGM serving as controls. Dexcom G6 was applied immediately after surgery, arterial BG values measured with blood gas analyzer served as reference and for calibration. We evaluated mean absolute relative difference (MARD), Diabetes Technology Society (DTS) Error Grid zones, bias, 15/15 agreement rate, evolvement of accuracy over time, and possible interfering factors. Fisher test, Mann-Whitney test, DTS software, and linear mixed model were used for statistical analysis.

Results: We included 155 LTx recipients, 13 were excluded (1 died during surgery, 12 experienced sensor failure-6 from each group), data from 142 patients (80 in active and 62 in blinded CGM group) were analyzed. Overall, MARD was 9.1% in active and 10.7% in the blinded group (p < 0.0001). DTS error grid in active group had shown 90% in zone A versus 85.3% in the blinded group. These results were consistent for reference glucose ranges 3.9-10 mmol/L and above 10 mmol/L, with less precision in the low ranges (these values were however rare). Sensor accuracy peaked on days 2-3 and deteriorated over time with significant worsening from day 7 on in both groups.

Conclusion: Our study demonstrates feasibility and acceptable accuracy of CGM comparable to reports from the outpatient care. We believe this could be attributed to sensor calibration, reflected by more favorable outcomes in the active CGM group. In addition, we demonstrate decline in accuracy over time, suggesting their use in critical care could be limited to less days to secure sufficient reliability.

Trial registration: This study is part of an ongoing prospective trial registered on ClinicalTrials.gov (NCT05585801) and was registered on October 12, 2022.

Familial dysalbuminemic hyperthyroxinemia (FDH) is a form of euthyroid hyperthyroxinemia caused by ALB gene variants that is commonly misdiagnosed in clinical practice. When coexisting with papillary thyroid carcinoma (PTC), this condition may complicate postoperative management strategies. This study aims to enhance clinical recognition of the coexistence of FDH and PTC and explore evidence-based management approaches. We retrospectively analyzed the diagnostic and therapeutic course of a patient with concurrent FDH and PTC in our clinic and reviewed the current literature. The proband exhibited unsuppressed thyrotropin (TSH) by levothyroxine (L-T4) monotherapy after PTC surgery, with abnormal, persistently elevated total thyroxine (T4) and free T4 levels. Further review of the medical records revealed a similar pattern of thyroid function abnormalities preoperatively. Genetic testing confirmed FDH caused by an ALB gene c.725G>A mutation. Sanger verification confirmed that both the proband's mother and daughter carried the same variant. The proband ultimately achieved adequate TSH suppression with the combination therapy of L-T4 and desiccated thyroid extract (DTE). This case highlights the importance of considering FDH when postoperative T4 and TSH levels show discordance in PTC patients. Increased albumin-T4 binding affinity in these patients may prevent adequate TSH suppression with L-T4 monotherapy, while DTE directly delivers triiodothyronine, without requiring peripheral conversion. Therefore, combination therapy with L-T4 and DTE may achieve effective TSH suppression in these patients.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that was previously considered a lifelong disease and requires long-term reliance on hypoglycemic medications. However, recent studies have shown that certain patients may achieve remission through various intervention strategies, which may alter the ultimate therapeutic targets for clinicians. This review aims to summarize and update the latest clinical evidence and research advancements regarding remission strategies for T2DM, primarily including intensive lifestyle interventions, metabolic surgery, short-term intensive insulin therapy, and non-insulin hypoglycemic drugs (e.g., glucagon-like peptide-1 receptor agonists and dorzagliatin) treatments, to guide the selection of appropriate treatment modalities for diverse patient populations. Additionally, the durability of sustained diabetes remission is briefly discussed.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become essential medications in the management of type 2 diabetes mellitus and obesity due to their ability to improve glucose control and facilitate weight loss by enhancing insulin secretion, reducing glucagon release, and slowing gastric emptying. These mechanisms make GLP-1RAs highly effective for metabolic disorders, benefiting patients who require both glycemic control and weight reduction. However, despite their clinical efficacy, GLP-1RAs have been associated with an increased risk of gallbladder disease, including gallstone formation known as cholelithiasis and inflammation of the gallbladder called cholecystitis, especially with prolonged use and higher doses. This review explores the potential mechanisms by which GLP-1RAs may contribute to biliary disease, focusing on the roles of cholecystokinin suppression, bile acid receptor signaling, and alterations in gut-brain pathways. In addition, we present a novel algorithm designed to outline strategies to address the risks of biliary disease in patients treated with GLP-1RAs.

SHORT syndrome is a rare genetic multisystemic disorder caused by a loss-of-function mutation in the phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) gene. The disease's acronym represents its key features: short stature, hyperextensibility, ocular depression, Rieger anomaly, and teeth delay. Insulin resistance, hyperglycemia, and diabetes mellitus are common endocrinological manifestations of this condition. Currently, there are no established guidelines for the treatment of diabetes in SHORT syndrome patients. In this report, we describe a young adult male patient of Chinese descent with atypical diabetes mellitus associated with SHORT syndrome. This case was challenging due to the patient's young-onset diabetes and poor diabetes control, complicated by insulin resistance from lipodystrophy, and a strong aversion to insulin injections. By utilizing a combination of oral anti-glycemic agents with complementary mechanisms of action (metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, sulfonylureas, thiazolidinediones, and GLP-1 agonists), insulin therapy was delayed. The patient's blood glucose levels improved significantly, with HbA1c decreased from 14% to 8.8% within 6 months of starting the multi-agent regimen, and further improved to 7.4% with a fasting plasma glucose of 4.8 mmol/L. With an oral medication regimen that the patient found acceptable, both his quality of life and adherence to treatment improved. These findings provide useful insights into tailoring an individualized diabetes treatment plan.

Background: Metabolic disorders significantly contribute to global morbidity and mortality. However, data on these trends in the Arab region remain limited despite rising obesity rates and declining metabolic health.

Objectives: This study aims to investigate the trends and burdens of metabolic diseases, including diabetes mellitus, cardiovascular disease (CVD), chronic kidney disease (CKD), metabolic dysfunction-associated fatty liver disease (MAFLD), and ischemic stroke and related risk factors in the Arab region.

Design: A retrospective analysis of metabolic diseases based on the Global Burden of Disease 2021 database.

Methods: We analyzed age-standardized rates of disease prevalence, incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021, using data from the Global Burden of Disease Study 2021.

Results: In 2021, the Arab region faced a substantial burden: 34.6 million with diabetes, 30.8 million with CVD, 32 million with CKD, 109.4 million with MAFLD, and 3 million with stroke. Mortality and DALYs for these diseases often exceeded global averages.

Conclusion: The Arab region faces a significant public health challenge due to increasing metabolic disease burdens and inconsistent mortality reduction. A comprehensive approach addressing lifestyle factors and improving healthcare access is crucial to improving health outcomes and managing this growing burden.

Background: Studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may modulate asthma-related immune pathways, but evidence directly linking the use of GLP-1 RAs to asthma onset remains limited.

Objectives: We aimed to evaluate whether the use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) is associated with a reduced risk and severity of asthma development.

Design: This retrospective cohort study was designed to evaluate asthma onset and severity in patients with T2DM treated with GLP-1 RAs, using data from the National Health Insurance Database (2011-2015).

Methods: Asthma onset and severity were evaluated in 1345 patients with T2DM treated with GLP-1 RAs from a cohort of 1,936,512 individuals, excluding those with pre-existing asthma. Asthma risk was assessed across four severity levels.

Results: The study demonstrated a mean follow-up duration of 2.92 ± 1.82 years. Notably, treatment with GLP-1 RAs significantly reduced asthma risk compared with the non-GLP-1 RA group, as indicated by an adjusted hazard ratio (HR) of 0.67 (95% confidence interval (CI), 0.45-0.76), suggesting a consistent class effect. A protective trend was observed across various severity levels of asthma. The HRs for the GLP-1 RA group compared with the non-GLP-1 RA group for cases with no acute exacerbations (No-AE), acute exacerbations (AE), and status asthmaticus (Status) were 0.55 (95% CI, 0.37-0.62), 0.59 (95% CI, 0.39-0.66), and 0.83 (95% CI, 0.56-0.93), respectively. However, in cases requiring endotracheal intubation, the HR was 0.96 (95% CI, 0.65-1.09).

Conclusion: Our study highlights a consistent effect of GLP-1 RAs in reducing asthma risk and severity, except in cases requiring endotracheal intubation, suggesting that GLP-1 RAs may contribute to reducing asthma incidence and severity in patients with T2DM.

Metformin is the most widely used antihyperglycemic agent for the treatment of a wide range of diseases. Activation of AMP-activated protein kinase (AMPK) is the best-known mechanism by which metformin exerts most of its beneficial effects. In recent years, research and applications of metformin in bone metabolism have made significant progress. The molecular mechanisms of its action are being elucidated with an increasingly complex understanding, raising the question of whether metformin acts directly or indirectly on bone. This review examines the indirect role of metformin in improving the bone marrow microenvironment by regulating autophagy, oxidative stress, inflammation, and skeletal aging. Furthermore, we focus on the direct mechanisms of metformin on osteoblasts, osteocytes, bone marrow adipocytes, and osteoclasts. In summary, metformin has been shown to affect bone in multiple ways and to exert osteoprotective effects. In light of the positive benefits of metformin in preventing osteoporosis, future treatment plans for patients with osteoporosis, particularly those with diabetes who are at high risk for fractures, may consider prioritizing the use of metformin as antidiabetic drug for bone protection. While metformin has been shown to improve bone health, particular attention should be paid to renal function, vitamin B12 status, and individual patient factors.