Frontiers in Endocrinology最新文献

[This corrects the article DOI: 10.3389/fendo.2025.1558692.].

Introduction: In patients with type 2 diabetes, factors beyond hyperglycemia may contribute to the development of sensory neuropathy. This study aimed to determine whether diabetes duration was the strongest predictor of prevalent sensory neuropathy and to compare the diagnostic performance of commonly used clinical screening methods.

Materials and methods: A total of 711 patients with type 2 diabetes from the Budapest metropolitan area were assessed between 2016 and 2022 using routine sensory neuropathy screening tests (128-Hz tuning fork and 10-g monofilament). A brief standardized questionnaire was also administered to support neuropathy detection. Independent predictors of sensory neuropathy were identified using binary logistic regression models and interrater agreement between diagnostic methods was assessed with Cohen's kappa.

Results: Agreement between diagnostic methods was only moderate (Cohen's kappa: 0.3-0.4). In the final adjusted models, age emerged as the only independent predictor of neuropathy detected by tuning fork testing (OR 1.04; 95% CI 1.02-1.06), whereas for the monofilament test, self-reported neuropathic symptoms remained independently associated. Consistent with this, positive responses to standardized symptom questions correlated with both diagnostic tests, supporting their clinical validity.

Conclusion: The overlap between routinely applied clinical methods for detecting sensory neuropathy is limited. Our findings suggest that, in an aging population with type 2 diabetes, peripheral nerve damage identified by standard screening tools is more strongly associated with age than with diabetes duration when assessed by commonly used bedside screening tools. Prospective studies are warranted to better differentiate diabetic neuropathy from age-related nerve dysfunction.

Background: While levothyroxine (L-T4) therapy is standard for hypothyroidism, its direct effects on specific echocardiographic parameters of cardiac function remain underexplored in comprehensive meta-analyses.

Methods: We systematically searched multiple databases up to June 2025 for randomized controlled trials and prospective cohort studies assessing L-T4 therapy on echocardiographic parameters in hypothyroid adults. Data on cardiac indices, intervention details, follow-up, and disease types were extracted. Risk of bias was assessed using standard tools. A random-effects model calculated mean differences (MDs) and assessed heterogeneity. Subgroup analyses evaluated treatment type, follow-up duration, and underlying disease.

Results: Six studies (2 RCTs and 4 cohort studies) were included. Overall, L-T4 intervention did not significantly alter the LV Tei Index (MD = 0.0214, 95% CI: -0.0294 to 0.0722, p=0.4083) or LVEF (MD = -0.2258, 95% CI: -0.8990 to 0.4475, p=0.5110). However, a statistically significant increase in Mitral E velocity (MD = -0.0646, 95% CI: -0.1138 to -0.0154, p=0.0100) and Mitral A velocity (MD = -0.0646, 95% CI: -0.1138 to -0.0154, p=0.0100) was observed. Subgroup analyses for LV Tei Index showed a statistically significant improvement in the 12-month follow-up subgroup (MD = 0.0672, 95% CI: 0.0161 to 0.1183) and in congenital hypothyroidism (MD = 0.0300, 95% CI: 0.0044 to 0.0556). For LVEF, a statistically significant increase was found in the 12-week follow-up subgroup (MD = -7.9300, 95% CI: -14.4844 to -1.3756) and the overt hypothyroidism subgroup (MD = -7.9300, 95% CI: -14.4844 to -1.3756). The effect of L-T4 on Mitral E and Mitral A velocities varied significantly across disease types (p=0.0304 for both), with a significant increase noted in the congenital hypothyroidism subgroup for both. No significant change was observed in the E/A ratio (MD = -0.0058, 95% CI: -0.0360 to 0.0244, p=0.7058), with no significant subgroup differences.

Conclusion: L-T4 exerts differential effects on echocardiographic measures of cardiac function, with specific improvements influenced by follow-up duration and underlying etiology.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/, CRD420251274519.

Purpose: Hypothyroidism, the most prevalent endocrine disorder globally, is associated with increased cardiovascular risk. This study aims to evaluate cardiovascular risk factors-including serum oxidized low-density lipoprotein (ox-LDL), serum homocysteine (Hcy), and lipid profiles-and their correlations with thyroid-stimulating hormone (TSH) levels. Early identification of these risk predictors may reduce the incidence and mortality of cardiovascular disease in hypothyroid patients.

Patients and methods: This cross-sectional study included 676 participants. Subjects were stratified into four groups: three corresponding to TSH quartiles within the reference range and a fourth comprising subclinical hypothyroidism (SCH) patients with TSH levels above this range. All participants underwent physical examinations and provided fasting blood samples for measurement of TSH, free thyroxine (FT4), free triiodothyronine (FT3), blood glucose, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein(a) [Lp(a)], ox-LDL, and Hcy.

Results: Across the four subgroups, LDL-C, ApoB, ox-LDL, and Hcy levels exhibited significant increasing trends (all p < 0.05; specific p = 0.01, p = 0.01, p < 0.01, p < 0.01, respectively), whereas HDL-C decreased significantly (p < 0.01). Specifically, compared to the T1 subgroup (TSH: 0.27-1.58 mIU/L), the SCH subgroup (TSH ≥ 4.20 mIU/L) had significantly higher levels of ox-LDL (1.78 ± 0.49 ng/mL vs. 1.05 ± 0.68 ng/mL, p < 0.01) and Hcy (9.87 (interquartile range (IQR): 8.45-11.42) μmol/L vs. 9.22 (IQR: 8.11-10.11) μmol/L, p < 0.01), and lower levels of HDL-C (1.29 ± 0.36 mmol/L vs. 1.43 ± 0.39 mmol/L, p < 0.01). After adjusting for age and sex, TSH levels demonstrated positive correlations with body mass index (BMI), triglycerides, total cholesterol, LDL-C, ApoB, ox-LDL, and Hcy (all p < 0.05), and a negative correlation with HDL-C (p = 0.01). Multiple linear regression analysis revealed that TSH levels were independently associated with elevated ox-LDL (β = 0.18, p < 0.01) and Hcy (β = 0.11, p < 0.01), and reduced HDL-C (β = -0.16, p = 0.01).

Conclusion: The observed correlations between ox-LDL, Hcy, and dyslipidemia in subclinical hypothyroidism may indicate a proatherogenic state. Elevated ox-LDL and Hcy emerge as independent factors associated with accelerated atherosclerosis in this condition.

Background: Type 5 Diabetes Mellitus (T5DM), denoting pancreatogenic diabetes from fibro-inflammatory pancreatic injury, is a distinct yet under-recognised entity. Current WHO and ADA classifications overlook its complex, concurrent endocrine-exocrine failures, contributing to misdiagnosis, treatment gaps, and suboptimal outcomes.

Objectives: This review aims to critically analyze current scientific understanding of the pathogenesis, diagnostic criteria, metabolic consequences, and therapeutic needs of T5DM and suggest a precise framework of medicine that justifies the need for T5DM to be formally recognized as a sub-type of diabetes.

Methods: An integrative review was conducted using recent literature on pancreatic pathophysiology, molecular biomarkers, radiomics, diagnostic imaging, glycemic control technologies, and machine learning. The focus was on the recent literature to elucidate the biological, diagnostic, and treatment aspects of the clinical studies, guidelines, and mechanistic research available from the publications.

Key findings: T5DM involves loss of insulin and glucagon alongside exocrine pancreatic insufficiency, malnutrition, and significant glycaemic variability. A tiered diagnostic framework-integrating pancreatic imaging, endocrine-exocrine testing, autoimmune exclusion, and emerging biomarkers-enhances accuracy. Management requires coordinated hormonal and enzyme replacement, structured nutritional support, and targeted surveillance for malignancy and micronutrient deficits. Radiomics, quantitative imaging, and AI-driven analytics offer valuable tools for earlier detection, improved risk stratification, and personalised therapy.

Conclusion: T5DM warrants recognition as a distinct diabetes entity owing to its unique pathophysiology, clinical behaviour, and therapeutic needs. Harmonised diagnostic criteria, validated biomarker and imaging pathways, and multicentre registries are essential to integrate T5DM into global classification systems and advance mechanism-based, personalised care.

Aim: Dorzagliatin is a glucokinase (GK) activator, restoring glucose homeostasis in type 2 diabetes. We investigated the effects of dorzagliatin on cognitive traits using Mendelian randomization (MR), with validation in a spontaneous diabetic rat model.

Methods: A two-sample MR study was conducted to investigate the causal effects of GK activation on neurodegenerative traits. Utilizing genome-wide association study summary statistics, we selected independent genetic variants of GCK (encodes GK) associated with lower HbA1c as instrumental variables to mimic GK activation. An animal validation study was further performed. Goto Kakizaki rats and Wistar rats were treated with vehicle or low-dose dorzagliatin (8mg/kg, i.g, bid, below the therapeutic level) for 36 weeks. Morris water maze (MWM) test, western blot analyses were carried out to investigate the neuroprotective effects of dorzagliatin and explore the potential mechanisms.

Results: Genetically mimicked GK activation causally decreased risk of memory loss (OR 0.21 per 1% lower HbA1c, 95% CI 0.05-0.91) and was associated with higher scores of prospective memory task, symbol digit substitution task and intelligence. MR results also implied that GK activation had cognitive protective effects not solely attributed to glucose-lowering. Low-dose dorzagliatin treatment in young Goto Kakizaki rats prevented spatial memory impairment occurred in adulthood in the MWM test. It also significantly prevented the reduced expression of insulin receptors, glucose transporters, and synaptic proteins in the brains of Goto Kakizaki rats.

Conclusions: Dorzagliatin protects against cognitive impairment under diabetes conditions. Maintaining glucose homeostasis directly regulates insulin pathway and glucose uptake, as well as enhances neurotransmission processes in the hippocampus. These findings not only highlight dorzagliatin as a promising therapeutic option for preventing diabetes-associated cognitive decline but also provide critical mechanistic insights into the role of GK modulated glucose homeostasis in preserving brain function, offering a potential translational strategy for clinical intervention.

Multiple Endocrine Neoplasia Type 1 (MEN1) is an autosomal dominant inherited disease characterized by the combined occurrence of tumors in multiple endocrine organs. As a rare disease, the clinical manifestations of MEN1 are currently considered to be associated with the development of combinations of more than 20 different tumors, such as parathyroid adenomas, neuroendocrine tumors, pituitary tumors, as well as lipomas, thymic carcinoids, pheochromocytomas, adrenal adenomas, and ovarian tumors. However, the concurrent occurrence of MEN1 and teratoma is extremely rare in reported cases to date. Herein, we report a case of a female patient with MEN1 who was diagnosed with teratoma. Genetic testing identified the NM_130799.2: c.512G>A (p.Arg171Gln) variant, which was classified as a variant of uncertain significance (VUS). After extracting whole blood DNA from the patient and her relatives (7 individuals in total) for genetic testing, this mutation was found to be present in multiple members of the family, including some who were affected by MEN1. This finding suggests the potential pathogenicity of the mutation, although further research and longer-term follow-up are required to confirm this observation.

Objective: CEL-related Maturity-Onset Diabetes of the Young (CEL-MODY) is a rare form caused by carboxyl ester lipase (CEL) gene mutations. It is characterized by dysglycemia and pancreatic exocrine dysfunction. We described a case to highlights the heterogeneity of clinical manifestations of the CEL gene mutations in pediatric patients.

Case presentation: We report a 12-year-old boy presenting with impaired fasting glucose. The patient reported no abdominal pain. Magnetic resonance imaging (MRI) of the pancreas revealed no evidence of pancreatic atrophy, fatty infiltration, or other abnormalities. Additionally, the fecal elastase level was within the normal range. Genetic analysis identified a novel heterozygous mutation in the CEL gene (c.1809dupC). The child exhibited only early-stage diabetes without concomitant pancreatic exocrine insufficiency, indicating a phenotypically mild form.

Conclusion: Children with CEL gene mutations appear to exhibit significant phenotypic heterogeneity. It may be correlated with both the specific mutation type and age at disease onset. Thus, lifelong, systematic monitoring of pancreatic endocrine and exocrine function is clinically necessary.

Background: Hyperuricemia has been identified as a significant independent risk factor for kidney stones. However, a paucity of research has been conducted on the correlation between hyperuricemia in the general population and the prevalence of kidney stones. Southern China has a high incidence of kidney stones, and analysis of data from health check-ups can help to identify those at risk of developing kidney stones. This is of positive clinical significance for the prevention of kidney stones in hyperuricemia populations.

Methods: A multicentre cross-sectional study was conducted using data from medical examination centres in four hospitals located in three southern Chinese provinces from 2022 to 2024. The analysis employed a combination of statistical methods, including logistic regression to identify independent risk factors for kidney stones in individuals with hyperuricemia. Additionally, a restricted cubic spline (RCS) method was utilised to examine the dose-response relationship between age, BMI, and serum uric acid levels and the risk of kidney stones. The study also employed a threshold effect analysis to identify the threshold inflection point between age and the risk of kidney stones.

Results: The total health data of 2739 medical examiners were included in this study. The prevalence of kidney stones was found to be 25.48% (1.28% in females and 24.21% in males) in the hyperuricemia population. The application of logistic regression revealed that age, BMI, serum uric acid, sex, urine leukocyte abnormality, and urine erythrocyte abnormality functioned as independent risk factors, while water intake was identified as a protective factor. Furthermore, the results of the RCS indicated a nonlinear relationship between age and the prevalence of renal stones (P nonlinear < 0.001). Threshold effect results showed that for individuals under the age of 44, the risk of developing kidney stones increased by 6.3% with each additional year of age (P < 0.05).

Conclusion: In the hyperuricemic population, age, BMI, serum annual acid, sex, abnormal leukocytes in urine and abnormal red blood cells in urine were identified as independent risk factors for developing kidney stones, while water intake was found to be a protective factor. The relationship between age and the development of kidney stones in hyperuricemia is non-linear.

Objectives: To explore the association between type 2 diabetes mellitus (T2D) and pulmonary cavitation in male with HIV-tuberculosis (TB) coinfection, as well as to quantify the relationships between glycemic indicators [HbA1c and fasting plasma glucose (FPG)] and cavity size. The robustness of these correlations was further validated in a non-HIV TB sample.

Methods: This comparative cross-sectional study based on exposure status included 132 men with HIV-TB and T2D (exposed group) and 131 age-matched men with HIV-TB without T2D (non-exposed group). Multivariable regression models, subgroup analyses, and interaction tests were used to evaluaterelationships and effect modification. A validation cohort of 100 non-HIV TB patients was analyzed using the same analytical framework.

Results: In men coinfected with HIV and TB, T2D was linked to a higher incidence of pulmonary cavitation (adjusted OR = 3.892, 95% CI = 1.895-7.992, P<0.001). HbA1c (B = 1.039, P = 0.049) and FPG (B = 0.869, P<0.001) are positively correlated with cavity size. A notable interaction was detected between T2D and sputum positivity (P<0.001), indicating the greatest incidence of cavitation in sputum-positive T2D patients (OR = 10.492, 95% CI = 3.266-33.711). Consistent results were found in the non-HIV TB group (T2D-related cavitation OR = 4.110, P = 0.014), demonstrating that the effect of T2D is not modified by HIV status.

Conclusion: T2D is a significant risk factor for pulmonary cavitation in males with HIV-TB coinfection, and poor glycemic management is linked with increased cavity size. Sputum-positive patients with T2D represent an exceptionally high-risk subgroup. Incorporating glycemic evaluation and optimal metabolic management into TB care may assist to lower cavitation risk in this population.