Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association最新文献

This brief narrative review discusses the clinical manifestations, diagnosis, and management of trigeminal nerve-related conditions, such as neuropathy and neuralgia, in patients with diabetes mellitus. Although these conditions are not very common, there is a solid connection between them in diabetes patients. Symptoms typically include facial pain, sensory disturbances, and muscle weakness for neuropathy and severe, stabbing pain for neuralgia. Diagnosis is based on characteristic clinical manifestations, along with laboratory investigation and magnetic resonance imaging to exclude other potential causes, such as tumours, multiple sclerosis, or vascular compression. Treatment focuses on strict glycaemic control, modification of vascular risk factors, pharmacological agents (carbamazepine and oxcarbazepine), and neurostimulation to improve symptoms and quality of life.

Type 2 diabetes mellitus (T2DM) is often recognised as a major comorbidity of chronic obstructive pulmonary disease (COPD) and is being increasingly linked with elevated risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Accordingly, the potential utility of antidiabetic medication, mostly in subjects suffering from both AECOPD and T2DM, has been investigated. The most widely studied medication is metformin. Although some studies showed no particular benefit, others assessed a diminished risk of AECOPD by up to 37% and reductions in hospitalisations, re-admissions, or the use of antibiotics and/or corticosteroids. The same holds true for sulfonylureas and thiazolidinediones. Conversely, dipeptidyl-peptidase 4 inhibitors (DPP-4is) were not associated with any benefit. Data on insulin use are scarce, but insulin in AECOPD management has been linked with adverse outcomes. The strongest effect has been shown with glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2is): the former limited severe exacerbations by 30% and the latter by 32-36%. With SGLT-2is, the incidence diminished by 46% compared with DPP-4is, while approximately three out of four emergency visits or hospitalisations were prevented. In conclusion, existing evidence suggests a benefit of antidiabetic medication in AECOPD-related outcomes, suggesting that this effect merits further investigation.

Limited research has explored the efficacy of β-blockers in combination with unilateral total, subtotal, or partial adrenalectomy in ARMC5-mutated patients with primary bilateral macronodular adrenocortical hyperplasia (PBMAH). Additionally, there is no consensus on determining the optimal side for adrenal gland resection. To assess the clinical utility of three unilateral adrenalectomy (ULA) modalities-total, subtotal, and partial-combined with β-blocker treatment in patients with PBMAH and Cushing's syndrome (CS). This study was conducted at a single tertiary referral center involving a series of four patients with suspected CS. Diagnosis of PBMAH was confirmed through dexamethasone suppression testing, evaluation of ectopic receptor expression, and whole-exome sequencing. Three patients underwent unilateral total, subtotal, or partial adrenalectomy, respectively, while one patient declined surgery. All patients received β-blocker treatment. The median treatment duration among the four ARMC5-mutuated PBMAH patients was 30.5 months (range: 6-45 months). Two patients who underwent total or subtotal adrenalectomy on the side with more pronounced nodularity showed postoperative improvement in clinical CS signs, glycemic control, and hypertension. These two patients, along with another patient with bilateral diffuse (non-nodular) adrenal hyperplasia who declined surgery, showed further improvement in hypercortisolism and cortisol/adrenocorticotropic hormone (ACTH) ratio (CAR: plasma cortisol (nmol/L)/plasma ACTH (pg/ml), newly reported as a reliable parameter of cortisol secretory capacity in patients with adrenal CS) after propranolol treatment. The patient who underwent partial adrenalectomy on the side with less pronounced nodularity showed no significant improvement in hypercortisolism or CAR, and the response to propranolol was also unsatisfactory. All four cases harbored pathogenic variants in the ARMC gene, including two novel germline mutations.In ARMC5-mutuated patients with PBMAH, unilateral total adrenalectomy on the side with more pronounced nodularity appears to be an effective treatment option. Propranolol may be considered as an alternative or adjunctive therapy to ULA for managing hypercortisolism in those with ARMC5 mutations.

Studies have covered a possible relevance between fibroblast growth factor 21 (FGF21) and obesity-related metabolic complications and cardiovascular disease (CVD). Nevertheless, whether FGF21 is a causative factor in these diseases is not known. Using a bidirectional, two-sample Mendelian randomization (MR) approach, this study sought to establish a causal relationship between FGF21 and seven metabolic diseases and six CVDs. A large-scale meta-analysis dataset of genome-wide association studies (GWAS) was analyzed to generate summary-level statistics for FGF21. The diseases we studied included non-alcoholic fatty liver disease (NAFLD), obesity, type 2 diabetes (T2DM), hypertension, gestational diabetes (GDM), gestational hypertension (GHTN), pre-eclampsia or eclampsia (PE), atherosclerosis, cardiomyopathy (CMP), coronary heart disease (CHD), coronary atherosclerosis, heart failure (HF), myocardial infarction (MI) and the corresponding summary GAWS data were retrieved from the FinnGen Biobank and IEU Open GWAS Project database. The inverse variance-weighted (IVW) algorithm was the primary approach utilized for the MR analysis. The MR-Egger regression and MR-PRESSO tests were implemented to evaluate horizontal pleiotropy. The heterogeneity of instrumental variables was subsequently assessed utilizing Cochran's Q statistics.When diseases are used as exposures, MR analysis results of the IVW method indicated that NAFLD (Beta=- 0.047, 95% CI=- 0.08 to - 0.014; p=0.006), obesity (Beta=0.087, 95% CI=0.021-0.153; p=0.009), T2DM (Beta=0.071, 95% CI=0.037-0.106; p<0.001) correlated causally with FGF21. Nevertheless, FGF21 was not causally related to the remaining metabolic diseases and CVDs, according to the results of the MR analysis (p>0.05). It was demonstrated that the aforementioned results were robust and devoid of pleiotropy.Our study supports a causal association between NAFLD, obesity, and T2DM with FGF21. No substantial evidence exists to establish a causal relationship between FGF21 and other diseases. This study provides opportunities for the early prevention and innovative therapy of NAFLD, obesity, and T2DM.

Gout and type 2 diabetes mellitus (T2DM) often coexist and are associated with chronic kidney disease (CKD) and increased mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors, commonly used in T2DM, may offer additional benefits, such as reducing inflammation and uric acid levels. This study aimed to assess the impact of DPP-4 inhibitors on gout flare frequency, serum uric acid (sUA) levels, and survival in patients with gout, T2DM, and CKD.A cross-sectional, retrospective, longitudinal study was conducted over 6 years between 2016 - 2022, including patients with gout and T2DM from the largest healthcare provider in Israel. Patients were divided into treatment and control groups based on DPP4-inhibitor status treatment. The primary outcome was the number of gout arthritis attacks over 1 year, reflected by the number of emergency room visits. Secondary outcomes included mean serum high-sensitive C-reactive protein (hs-CRP) levels and survival rates over the study period.DPP-4 inhibitor treatment significantly reduced sUA levels (5.2±1.3 mg/dL vs. 5.9±2.2 mg/dL, p=0.05) and hs-CRP levels (0.50±0.19 mg/dL, p<0.001). Kaplan-Meier survival analysis suggested a trend towards improved survival in the DPP-4 inhibitor group (HR=0.834, 95% CI: 0.6-1.04, p=0.05), particularly among patients with chronic kidney disease (CKD), although without statistical significance. The emergency room visits due to gout attacks were fewer in the DPP-4 inhibitor group, although this difference did not achieve statistical significance.DPP-4 inhibitors may offer benefits beyond glycemic control in T2DM and gout, including reduced sUA and hs-CRP levels and improved survival in CKD patients. Larger, randomized trials are warranted to explore these potential benefits.

Transforming growth factor-β (TGF-β), a local growth factor, is essential for bone remodeling; when administered in bone tissues, it stimulates bone formation. On the other hand, transmembrane protein 119 (Tmem119) is a crucial factor for osteoblastic bone formation related to the TGF-β signaling molecule, Smad3. However, the role of Tmem119 in TGF-β-mediated effects on osteoblasts and osteoclasts remains unclear.The function of Tmem119 in TGF-β-mediated effects was examined for osteoblastic differentiation, bone matrix protein expression, and osteoclast formation in mouse osteoblasts, adipose tissue-derived stromal cells, and bone marrow cells from wild-type and Tmem119-deficient mice. Tmem119 deficiency significantly reversed the TGF-β-induced expressions of type I collagen and matrix-Gla protein (MGP) in mouse osteoblasts but did not affect TGF-β-suppressed alkaline phosphatase activity in mouse adipose tissue-derived stromal cells, even when TGF-β could suppress alkaline phosphatase (ALP) activity in mouse osteoblasts regardless of Tmem119 deficiency. Tmem119 deficiency significantly reduced osteoclast formation and Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) mRNA levels in mouse bone marrow cells.Tmem119 is involved in regulating type I collagen and MGP expressions and TGF-β-induced osteoclast formation, but does not affect TGF-β-suppressed osteoblastic differentiation in mouse cells.