Endocrine最新文献

Aims: This study investigated the protective role of Perilipin 5 (PLIN5) in pancreatic β-cell dysfunction under diabetic conditions, focusing on its regulatory effects on lipid metabolism and mitochondrial dynamics.

Materials and methods: Diabetic db/db mice and pancreatic beta cell line INS-1 were employed to investigate the role of PLIN5 in insulin secretion and lipid metabolism under high glucose (HG) conditions. The phenotypic changes were evaluated by staining and measurement of biochemical indexes. The molecular mechanism was explored by biological techniques such as Western blotting, qPCR, immunofluorescence and lentivirus infection.

Results: PLIN5 was decreased under diabetic conditions which was related to lipid accumulation in the pancreas. The in vitro knockdown of PLIN5 promoted apoptosis in INS-1 cells, leading to a reduction in insulin secretion mediated by lipid accumulation. PLIN5 knockdown also promoted mitochondrial dysfunction in normal-glucose-cultured INS-1 cells mainly through decreasing PGC-1α and increasing Drp1 levels. In contrast, PLIN5 overexpression reversed the damage caused by HG in INS-1 cells, such as increased apoptosis and lipid accumulation, mitochondrial dysfunction and weakened capacity of insulin secretion. PLIN5 overexpression also blunted the inhibitory effects of HG on PGC-1α and Drp1 expressions. The reduced expression of PLIN5 also led to decreased binding of PGC-1α to the promoter region of Drp1.

Conclusions: Our data indicate that PLIN5 acts as a potent regulator of lipid accumulation in pancreatic β cells treated with HG through the modulation of PGC-1α and Drp1.

Purpose: Sarcopenia can develop at a younger age as a complication in patients with type 1 diabetes (T1D). This study aimed to evaluate the association of sarcopenia with diabetic kidney disease (DKD) in non-elderly patients with T1D.

Methods: This cross-sectional study enrolled 100 patients with T1D, including 50 individuals with DKD and 50 without. Median age of patients was 31 years (25-75th percentile: 24.2-44) and a median duration of T1D was 10.1 years (25-75th percentile: 9-13). Hand grip strength (HGS), skeletal muscle mass index (SMMI) were utilized to assess the presence of sarcopenia. The Sarcopenia Quality of Life (SarQoL) and Pittsburgh Sleep Quality questionnaires were used to evaluate the quality of life.

Results: Sarcopenia was diagnosed in 19 out of 100 patients (19%). The prevalence of sarcopenia was 36% (18 out of 50) in the DKD group and 2% (1 out of 50) in the non-DKD group. Sarcopenia was more prevalent in the DKD group (p < 0.001). Urinary albumin-to-creatinine ratio (UACR) levels were a significant predictor of sarcopenia (odds ratio 1.031, 95% CI 1.009-1.058; p = 0.005). The median HGS and SMMI values were lower in the sarcopenia group than in the non-DKD group (p = 0.006 and p = 0.001 respectively). Furthermore, the SarQol scores and sleep quality were lower in the sarcopenia group compered to the non-DKD group (p = 0.018 and p < 0.05, respectively).

Conclusions: Sarcopenia may occur earlier in non-elderly patients with T1D and DKD, adversely affecting the quality of life. Early screening for sarcopenia should be considered in individuals with DKD.

Purpose: Non-aldosterone producing-adrenal-adenomas (NAPACAs) and polycystic ovary syndrome (PCOS) are associated with insulin-resistance (IR). Whether the co-existence of the two diseases leads to accentuated adverse metabolic profile remains unknown. Aim of this study is the assessment of cardiometabolic risk factors in women with NAPACAs with and without PCOS.

Methods: We conducted a retrospective multicenter study including adult premenopausal women categorized as NAPACA (n = 45), PCOS (=20) or NAPACA+PCOS (n = 24), excluding women with hormonally active adenomas, congenital-adrenal-hyperplasia, diabetes, systemic steroid medication or active malignancy.

Results: NAPACA patients were significantly older than the other two groups (P < 0.001). All groups did not differ in blood pressure, HbA1c, fasting plasma glucose (P > 0.05) or in body-mass-index (P = 0.06). NAPACA+PCOS patients displayed significantly increased insulin resistance (IR) (GIR:P < 0.05, HOMA: P < 0.05, QUICKI:P < 0.05, MATSUDA-index: P < 0.05). Cortisol levels upon 1-mg-dexamethasone-suppression-test (DST) did not differ among the groups; DHEA-S (P < 0.05) and testosterone (P < 0.01) were significantly higher in the two groups with PCOS patients. Free-androgen-index positively correlated with IR in NAPACA (GIR P < 0.01, HOMA P < 0.05, QUICKI P < 0.05) and PCOS (GIR P < 0.01, HOMA P < 0.01, QUICKI P < 0.01, MATSUDA P < 0.01), while 1mg-DST positively correlated with IR in NAPACA+PCOS (GIR P = 0.05, HOMA P < 0.05, QUICKI P < 0.05, MATSUDA P < 0.05). Younger age, higher IR and lower HDL levels predicted the PCOS presence in NAPACA patients whereas the multivariate analysis revealed age and HDL levels as the most important predictors of this association.

Conclusion: These findings provide evidence for a distinct metabolic pattern in NAPACA+PCOS patients compared to NAPACA patients. Further prospective studies with larger patient cohorts will be necessary to elucidate this observation.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) manage type 2 diabetes mellitus (T2DM) via increased urinary glucose excretion; however, their use is associated with an elevated risk of genitourinary infections. This study aims to evaluate this risk by synthesizing evidence from randomized controlled trials (RCTs) and characterizing clinical features using data from the FDA Adverse Event Reporting System (FAERS).

Methods: In this systematic review and meta-analysis, we searched PubMed and Embase up to June 2024 for RCTs reporting genital mycotic infection (GMI) and urinary tract infection (UTI) events associated with SGLT-2is. The primary outcome was the risk of GMI and UTI related to SGLT-2is, quantified using the risk ratio (RR) with a 95% confidence interval (CI). Additionally, a retrospective pharmacovigilance study of FAERS extracted the cases of genitourinary infections related to SGLT-2is up to June 2024. Disproportionality was calculated using the frequentist and bayesian based data mining algorithms.

Results: A total of 98 RCTs (91,756 participants) were included, treatment with SGLT-2is significantly increased the risk of GMI compared to placebo (RR: 3.65, 95% CI: 3.22- 4.14, p = <0.0001) and active control (RR: 4.29; 95% CI: 3.42-5.38, p = <0.0001). Subgroup analysis showed significant differences by individual drug, gender, and duration. Disproportionality analysis revealed significant signals for all SGLT-2is with genitourinary tract infections, persisting after signal refinement.

Conclusion: SGLT-2is significantly increase the risk of GMI among T2DM patients, while the association with UTI remains inconsistent. Additional research is required to elucidate the potential risk factors.

Purpose: To assess and predict the therapeutic efficacy of intravenous glucocorticoids (IVGC) in thyroid eye disease (TED) patients with clinical activity score (CAS) < 3, but presenting magnetic resonance imaging (MRI)-confirmed intraorbital inflammation.

Methods: We retrospectively analyzed the clinical data of 91 active TED patients with low CAS that received IVGC treatment (4.5 g, 12 weeks). In terms of treatment response evaluation, the EUGOGO standard (Two-Item Standard) and a One-Item Standard modified on this basis were implemented. Univariate and multivariable logistic regression analyses were used to establish prediction models. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated.

Results: Under Two-Item Standard, 31 of the 91 patients (34.1%) were determined as responsive to IVGC, and 60 (65.9%) were unresponsive. MRD-1 was significantly different between responsive and unresponsive groups (P-value < 0.05). Under One-Item Standard, 43 (47.3%) were responsive, and 48 (52.7%) were unresponsive. MRD-2 and exophthalmos were significantly different between two groups (P-value < 0.05). By implementing multivariable regression, the reliability of predicting treatment response of IVGC in active TED patients with low CAS reached AUC = 0.709 under the Two-Item Standard and AUC = 0.792 under the One-Item Standard.

Conclusion: It is suggested that MRI-based intraorbital active TED patients with low CAS and significant symptoms should be considered for anti-inflammatory therapy, particularly those with specific clinical and radiological features. Clinical assessment and radiological evaluations are valuable for predicting IVGC effectiveness and achieving precision treatment.

Background: Diabetes mellitus (DM) is a chronic metabolic disorder associated with severe complications, including cataracts, a leading cause of blindness. Diabetic patients are at a higher risk of developing cataracts earlier and experiencing poorer surgical outcomes. While cataract surgery is effective, limited research has explored its impact on diabetic patients. This study aims to analyze post-cataract surgery outcomes in diabetics using a meta-analysis approach, addressing gaps in existing research and evaluating the influence of advancements in diabetes management on surgical recovery.

Method: This systematic review and meta-analysis followed PRISMA guidelines to assess the impact of diabetes on cataract surgery outcomes. Quality assessment employed the ROBINS-I tool, ROB2, and Newcastle-Ottawa Scale. Statistical synthesis was performed via STATA 18 and Review Manager 5.4.1. The outcome measures include the incidence of cataract development, post-surgical visual acuity, proportion of good vision outcomes, central retina thickness, and post-surgical complications.

Results: Nine hundred eighty-six articles were identified, and 30 met the inclusion criteria. Key risk factors for cataract in people with diabetes were high HbA1c, longer diabetes duration, and retinopathy. Our pooled effect size indicated that non-diabetics had significantly better BCVA post-surgical outcomes than people with diabetes, logMAR 0.07 (SMD 0.07, 95% CI: 0.01, 0.12; p = 0.02). Cataract surgery among non-diabetic patients was significantly associated with good visual acuity compared to poor visual outcomes (OR 42.09, 95% CI: 13.92, 127.33; p < 0.00001). Conversely, central retinal thickness (CRT) was comparable in diabetic and non-diabetic patients (MD -0.18 µm, 95% CI: -3.44 µm, 3.07 µm; p = 0.91). The incidence of macular edema among patients after cataract surgery was 49% (0.49, 95% CI: 0.23, 74; p = 0.01). Diabetic patients were significantly associated with pigment dispersion than non-diabetics post-cataract surgery (OR 2.91, 95% CI: 1.15, 7.31; p = 0.02), striate keratopathy (OR 1.92 95% CI: 1.16, 3.17; p = 0.01), and posterior capsular opacity (OR 2.92 95% CI: 1.80, 4.72; p < 0.00001).

Conclusion: Cataract surgery among diabetic patients was associated with higher risks of complications like macular edema, striate keratopathy, and posterior capsular opacity. Additionally, non-diabetic patients were associated with better BCVA and good visual outcomes compared to diabetic patients post-cataract surgery.