Endocrine Connections最新文献

Objective: This study aimed to assess the latent threat of depression and suicide/self-injury associated with the combination of glucagon-like peptide-1 agonists (GLP-1RAs) and metformin versus GLP-1RAs monotherapy, through analyzing the data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Methods: We systematically searched the FAERS database for reports on the concomitant use of GLP-1RAs and metformin compared with GLP-1RAs monotherapy in diabetic or obese patients. Reports were categorized on the basis of the medical dictionary for regulatory activities (MedDRA) terminology. Reporting odds ratio (ROR) of ≥1, ≥3 cases, and information component (IC)025 > 0 were considered to be significant.

Results: The addition of metformin increased the risk of death (38.5% vs 12.4%, P<0.001) and hospitalization-initial or prolonged (13.5% vs 7.2%, P=0.035) attributed to suicide/self-injury received GLP-1RAs. Furthermore, GLP-1RAs combined with metformin was disproportionately linked to a higher incidence of suicide/self-injury (ROR=50.89, 95%CI 40.79-63.48, IC025=5) and depression (except suicide and self-injury) (ROR=17.28, 95%CI 13.65-21.87, IC025=3.64) when compared with GLP-1RAs monotherapy. The addition of metformin was confirmed to have shorter intervals to time-to-onset (TTO) than GLP-1RAs monotherapy.

Conclusions: The combination of GLP-1RAs and metformin is linked to higher risk of depression and suicide/self-injury compared with GLP-1RAs monotherapy.

Background: Type 2 diabetes increases the risk of cognitive decline and dementia. Data on ethnic differences in dementia prevalence among patients with diabetes remain limited.

Methods: We conducted a retrospective matched case-control study of Clalit Health Services members aged 60 or older. Matching (1:3) was based on age, sex, language, and socioeconomic status. Ethnicity was determined by spoken language or place of birth. Prescriptions and refills for antidiabetic medications were recorded for the two years preceding the index date. Clinical, anthropometric, and comorbidity data were analysed.

Results: During follow-up, 39% of participants were diagnosed with dementia over a maximum observation period of 20 years (crude proportion). However, given a median follow-up of 9.6 years, dementia incidence was primarily evaluated using time-specific competing-risk analyses. When accounting for death as a competing event, the 10-year cumulative incidence of dementia was approximately 9-10%, varying across ethnic groups. However, in multivariable competing-risk models adjusting for age, sex, socioeconomic status, and comorbidities, ethnicity was no longer independently associated with dementia incidence. In matched analyses, the use of SGLT-2 inhibitors and DPP-4 inhibitors was associated with a lower probability of dementia. In time-to-event analyses of dementia-related mortality, treatment with SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors was associated with significantly reduced mortality risk.

Conclusion: Ethnic differences in dementia incidence were attenuated after adjustment for demographic and clinical factors. SGLT-2 and DPP-4 inhibitors were associated with a lower risk of dementia, whereas GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors were associated with reduced dementia-related mortality.

Objective: To determine the prevalence and clinical impact of rhabdomyolysis (RML) among adults hospitalized with diabetic ketosis.

Design: Ten-year retrospective single-centre cohort study.

Methods: We reviewed adults admitted with diabetic ketosis, including isolated ketosis and diabetic ketoacidosis (2015-2024). RML was defined as peak creatine kinase >1,000 U/L; patients with confirmed acute myocardial infarction were excluded. The primary endpoint was a composite poor outcome, defined as in-hospital death or discharge against medical advice (DAMA) due to critical illness with a grave prognosis. Predictors of poor outcome were assessed using Firth-corrected multivariable logistic regression.

Results: Of 920 eligible patients, 18 (1.96%) developed RML. Compared with controls, patients with RML were older and more likely to have neurological comorbidities, recent falls, impaired consciousness, infection, effective serum osmolality > 320 mOsm/kg, leukocytosis, higher C-reactive protein, elevated creatinine, acute kidney injury, markedly raised myoglobin and elevated troponin I. RML was associated with longer hospital stay, higher costs, higher in-hospital mortality (11.1% vs 0.67%) and a higher rate of the composite poor outcome (16.7% vs 1.11%). Leukocytosis (>9.5×10^9/L; adjusted OR 4.29, 95% CI 1.35-14.37, P=0.014) and troponin I >0.03 ng/mL (adjusted OR 5.79, 95% CI 1.56-21.86, P=0.009) independently predicted poor outcome.

Conclusions: RML is an uncommon but important complication of diabetic ketosis, conferring higher short-term mortality, healthcare use and composite poor outcome. Routine screening for RML and concurrent inflammatory or cardiac injury provides a crucial window for early risk stratification, enabling clinicians to optimize therapeutic strategies and resource use for high-risk individuals.

Background: Age at puberty determines timing of pubertal growth spurt. Whether the intensity of the peri-pubertal growth velocity is also affected by pubertal timing in boys remains to be elucidated.

Objective: To study changes in growth velocity in relation to pubertal timing, Insulin-like Growth Factor-I (IGF-I) and fasting insulin in healthy boys.

Design, setting and participant: Longitudinal study with biannual assessment of testicular volume (TV), growth velocity, IGF-I and fasting insulin levels. Peak height velocity (PHV) was calculated. 105 boys (947 examinations) were included. Pubertal onset was available in 62 boys - the rest remained prepubertal throughout the study period or were in puberty at baseline.

Results: Age at pubertal onset (TV > 3 ml) was negatively correlated with PHV (ρ = -0.48; p < 0.001). The early (age of onset < 33,3 percentile) tertile of maturing boys had significantly higher growth velocity (mean Δ 0.48 (0.14 - 0.82) cm/year; p < 0.006) than late maturing boys (> 66,7 percentile) over the 6 years peri-pubertal period. However, the late maturing boys remained significantly taller throughout the study (p < 0.05). IGF-I levels were similar between the 3 groups of boys. In all boys, the increase in growth velocity was associated with a larger increase in IGF-I (p < 0.001) during the first 2 years of puberty.

Conclusion: Early maturation was associated with increased growth velocity and PHV in healthy boys. However, it was not sufficient to compensate for the shorter total growth period. IGF-I was positively associated with growth velocity.

Background and aims: This study aimed to explore whether a younger age of diabetes onset is associated with an increased risk of CVD events.

Methods: This study included 621 patients with younger-onset T2DM (age, ≤50 years) and 573 with older-onset T2DM (age, >50 years) from the original Da Qing Diabetes Prevention Study. For comparison, 310 younger individuals without diabetes (age, ≤50 years) were included in the control group. We followed-up participants for 34 years to assess the incidence of CVD events. The association between the age of diabetes onset and the risk of CVD events was analysed.

Results: The younger-onset T2DM patients had higher incidence of components of CVD events per 1000 person-years than those of the older-onset T2DM and younger non-diabetes controls ( 19.20, 15.14, and 9.22 for stroke, 7.78, 4.67 and 2.15 for myocardial infarction, and 5.38, 2.76 and 1.11 for heart failure, respectively).The more than double high risk of composite CVD events was found in the younger onset T2DM compared with the older onset T2DM (HR=2.05, 95%CI 1.64-2.55) and non-diabetic controls (HR=3.45, 95%CI 2.39-4.98) even after adjusting for the strongest confounder diabetes duration.

Conclusions: Chinese adults with younger-onset T2DM have a higher risk of developing CVD events than those with older-onset T2DM over a 34-year follow-up period.

Objective: CT attenuation value is useful in the differential diagnosis of adrenal masses, and values < 10 Hounsfield units (HU) can exclude malignancy and pheochromocytoma. However, few reports have examined the reliability of CT attenuation measurements. We examined the reliability of CT attenuation measurements made by surgeons not specialized in image reading.

Design: A retrospective analysis of 313 patients (325 lesions) who underwent surgery at a single institution was performed.

Methods: One general surgeon and one endocrine surgeon independently measured CT attenuation values. The intraclass correlation coefficient and Cohen's kappa coefficient were used to analyze interobserver reliability. All cases were subjected for endocrine function tests, and histopathologically diagnosed. Additional analyses included segmented regression for size-related measurement variability and multivariable analyses comparing aldosterone-producing adenomas (APAs) and cortisol-producing adenomas (CPAs).

Results: The intraclass correlation coefficient between observers was 0.938 (95%CI, 0.923-0.949) and Cohen's kappa coefficient was 0.851 (95%CI, 0.781-0.922). Both observers measured all malignant adrenal tumors (such as adrenocortical carcinoma, metastatic adrenal carcinoma, and malignant lymphoma) and pheochromocytomas as ≥ 10 HU. CT attenuation values were significantly higher in CPAs than in APAs, independent of mass size (p < 0.001 for both observers).

Conclusions: CT attenuation value was shown to be reliable enough for simple measurements that could be performed by non-radiologists and was useful for excluding malignancy and pheochromocytoma.

Significance statement: This study reinforced evidence for the reliability of CT attenuation value. Even with a simple method that can be performed by non-radiologists, CT attenuation values were highly reliable and useful for excluding malignancy and pheochromocytoma. In addition, all lesions in this study were evaluated both endocrinologically and pathologically, giving high validity to the reference standard. These findings complement and further substantiate the latest clinical practice guidelines of the European Society of Endocrinology.

Primary hyperparathyroidism (PHPT), increasingly diagnosed in its asymptomatic form, is associated with clinically significant neuromuscular dysfunction. Growing evidence indicates that skeletal muscle is a direct target of parathyroid hormone (PTH), with chronic PTH excess impairing mitochondrial bioenergetics, promoting proteolysis, and altering muscle-bone-adipose endocrine crosstalk. Experimental studies confirm PTH receptor type 1 (PTHR1) expression in muscle fibers and satellite cells, while transcriptomic analyses of PHPT muscle reveal dysregulation of calcium signaling and oxidative metabolic pathways. Clinically, patients with PHPT, irrespective of hypercalcemia, demonstrate reduced grip strength, slower gait speed, impaired chair-stand performance, and diminished postural stability. Parathyroidectomy improves several of these deficits, with studies reporting increases in grip strength, knee extension force, ambulatory capacity, and, in some cohorts, improved muscle composition and metabolic gene expression. However, available data are heterogeneous and derived primarily from small cohorts with variable functional measures. Current evidence implicates PTH-mediated skeletal muscle dysfunction as a reversible component of PHPT, yet key mechanistic and clinical gaps remain. Standardized functional assessments and larger prospective studies are needed to clarify biological pathways, identify predictors of postoperative recovery, and inform the integration of muscle health into PHPT management. The focus of this review was to explore evidence linking PTH excess and skeletal muscle pathophysiology and review the relationship between PHPT and parathyroidectomy on physical function.

Background: Epidermal growth factor (EGF) plays a crucial role in cellular growth, differentiation, and pancreatic β-cell maintenance. Despite reports on EGF deficiency in diabetic animal models, its relevance in type 2 diabetes (T2D), particularly in relation to obesity, remains underexplored. The present study aimed to evaluate plasma EGF levels in individuals with and without T2D, assess its associations with glycaemic status and clinical parameters, and evaluate the influence of obesity on these relationships.

Methods: A total of 838 eligible participants were selected from the Kuwait Diabetes Epidemiology Program. Of those, 428 were included in a 1:1 case-control analysis (214 T2D and 214 non-diabetics). EGF was measured in plasma using ELISA. Associations between EGF with glycaemic and clinical variables were evaluated using Pearson's correlation, multiple linear regression, and logistic regression analyses.

Results: Plasma EGF levels were significantly lower in individuals with T2D compared to non-diabetics (P < 0.001). Among non-diabetics, obese participants had a significantly lower EGF level than their non-obese counterparts (P = 0.03), while no such difference was observed in T2D. EGF negatively correlated with fasting blood glucose in both non-diabetics (P = 0.004) and T2D individuals (P < 0.001). In T2D, EGF negatively correlated with haemoglobin A1C (HbA1C) (P = 0.001), triglyceride (TG) (P = 0.021), and waist-to-hip ratio (WHR) (P = 0.014). Logistic regression confirmed that lower EGF levels were independently associated with T2D but not with general obesity (OR = 0.996, P = 0.001).

Conclusion: Reduced EGF levels are associated with poor glycaemic control in T2D. These findings highlight EGF's potential as a biomarker for glycaemic dysregulation and support further investigation into its role in diabetes pathophysiology and complications.

Purpose: Ketosis-prone diabetes (KPD) is a new subtype of diabetes distinct from traditional type 2 diabetes, and the role of muscle mass in KPD remains unclear. Serum creatinine-to-cystatin C ratio (CCR) has been identified as a marker of muscle mass. The present study aims to investigate the value of CCR in newly diagnosed KPD.

Methods: Two hundred and ninety patients with newly diagnosed T2D were included in the study and were divided into T2D (n = 195) and KPD (n = 95) groups according to the occurrence of ketosis. The cutoff value of CCR in identifying KPD was analyzed by receiver operating characteristic (ROC) curves. Logistic regression was used to assess the relationship between CCR and KPD and the independent influences on KPD.

Results: The serum CCR level of the KPD group was significantly higher than that of the T2D group. After adjustment for all confounders, the risk of KPD was significantly increased with elevated CCR levels. The optimal cutoff value for CCR was 69.775 for male and 63.365 for female, with areas under the ROC curve of 0.639 for male and 0.648 for female. Postprandial blood glucose and CCR were independent risk factors, whereas age and postprandial C-peptide were independent protective factors for the KPD.

Conclusion: High levels of CCR are significantly associated with the odds of KPD, suggesting that higher muscle mass (estimated by CCR) may be linked to higher KPD incidence. Our study suggests that CCR may be a useful marker for the incidence of KPD, providing new insights into the mechanisms of KPD.