Experimental and Clinical Endocrinology & Diabetes最新文献

Introduction Endogenous hypercortisolism presents with variable phenotypes. Etiological factors accounting for the level of hypercortisolism or varying severity of associated comorbidities are lacking. Recently, the adrenal ATP-binding cassette B1 (ABCB1) gene was identified as a modulator of glucocorticoid secretion.

Objective To evaluate the effect of ABCB1 polymorphism rs2032582 on steroid metabolome and clinical phenotypes in patients with endogenous hypercortisolism.

Methods In this cross-sectional cohort study, 137 patients prospectively enrolled in the German Cushing’s registry were included (41 with ACTH-producing pituitary adenoma, 21 with cortisol-producing adrenal adenoma, and 75 with excluded hypercortisolism). In all patients, ABCB1 polymorphism was analyzed using a TaqMan genotyping assay, glucocorticoid metabolite excretion in 24-hour urine samples was analyzed by gas chromatography-mass spectrometry, and the clinical phenotype was assessed systematically.

Results In patients with cortisol-producing adrenal adenomas, but not in patients with ACTH-producing pituitary adenomas, homozygous major allele GG of ABCB1 polymorphism rs2032582 was associated with higher overall cortisol metabolite secretion (median 13515 [IQR 10347; 25669] µg/24h vs. 9645 [6146; 10732] µg/24h in minor homo- and heterozygotes, p=0.036) and elevated major cortisol metabolites αTHF, THF and THE (9339 [6929; 17789] µg/24h vs. 6288 [4184; 7455] µg/24h, p=0.045). Moreover, these patients showed higher mean arterial pressure (116 [111; 131] mmHg in major homozygotes vs. 105 [96; 112] mmHg in minor homo- and heterozygotes, p=0.036).

Conclusion The genotype of drug transporter gene ABCB1 rs2032582 polymorphism is associated with the degree of cortisol metabolite secretion in cortisol-producing adrenal adenomas and could, therefore, represent a modifier of disease severity in this context.

Objective Changes in postmenopausal hormone levels are associated with a variety of disorders. This study elucidated the mechanism by which follicle-stimulating hormone (FSH) increases cortisol production involved in development of menopause-related diseases.

Methods The expression of FSH receptors (FSHRs) in murine adrenal zona fasciculata (AZF) cells and ATC7 cells was verified by immunofluorescence, western blotting and RT–PCR. The function of FSHR in promoting cortisol production was analyzed by cell culture and molecular biological methods. FSHR signaling pathways in ATC7 cells were analyzed by ELISA, qRT–PCR, and western blotting. Further, a mouse model was established by ovariectomy. Ovariectomized mice were treated with GnRHa. Ovariectomized mice initially received physiological doses of estrogen and were then injected with recombinant FSH. Then serum FSH, luteinizing hormone (LH), estradiol, and cortisol, and bone mineral density (BMD), blood pressure (BP) and heart rate (HR) were determined.

Results FSHRs were expressed in murine AZF cells and ATC7 cells. FSH accelerated cortisol production through activated protein kinase A (PKA), cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), protein kinase B (PKB/AKT) and 5ʼ AMP-activated protein kinase (MAPK) signaling pathways by Gsα-coupled FSHRs in ATC7 cells. Serum FSH levels (P<0.001) were elevated in ovariectomized mice with concurrent increases in cortisol (P<0.01), areal BMD (aBMD) (P<0.05), volumetric BMD (vBMD) (P<0.05), systolic BP (SBP) (P<0.05), diastolic BP (DBP) (P<0.05), and HR (P<0.05). However, the administration of GnRHa suppressed the increase in FSH levels and the elevation of cortisol, aBMD, vBMD, SBP, DBP, and HR induced by ovariectomy, even in the presence of normal serum estradiol levels.

Conclusion The study findings indicate that elevated FSH levels stimulate cortisol secretion, through a mechanism related to FSHRs expression in AZF cells.

Objectives To investigate the association between liver fibrosis score and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM).

Methods A total of 897 hospitalized patients with T2DM were included in this study. Each patient completed DKD screening. Logistic regression analysis was used to assess the predictive value of non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) for the occurrence of DKD and risk for DKD progression, respectively.

Results The prevalence of DKD and risk for its progression significantly increased with increasing NAFLD-FS risk category. DKD prevalence also increased with increasing FIB-4 risk category. Multivariate logistic regression analysis showed that the “high-risk” NAFLD-FS had a significantly higher risk of DKD (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.16–3.08) and risk for DKD progression (OR: 2.88, 95% CI: 1.23–6.78), and the “intermediate-risk” FIB-4 had a significantly higher risk of DKD (OR: 1.41, 95% CI: 1.00–1.98). Subgroup analysis showed that the association between NAFLD-FS and FIB-4 and DKD was significant in the female subgroup, whereas the association between the “high-risk” NAFLD-FS and risk for DKD progression was significant in the male subgroup.

Conclusions NAFLD-FS and FIB-4 are strongly associated with DKD and risk for DKD progression in patients with T2DM. Additionally, sexual dimorphism exists in this association.

Aim: To evaluate the effects of aerobic training on hippocampal volume and cognitive function in patients with type 2 diabetes mellitus (T2DM) with normal cognition.

Materials and methods: One hundred patients with T2DM aged 60-75 years who met inclusion criteria were randomized into the aerobic training group (n=50) and control group (n=50). The aerobic training group received 1 year of aerobic training, while the control group maintained their lifestyle without additional exercise intervention. The primary outcomes were hippocampal volume measured by MRI and Mini-mental State Examination (MMSE) score or Montreal Cognitive Assessment scale (MoCA) scores.

Results: Eighty-two participants completed the study (aerobic training group, n=40; control group, n=42). There was no significant difference between the two groups at baseline (P>0.05). After one year of moderate aerobic training, increase in total and right hippocampal volume in the aerobic training group were significantly higher than in the control group (P=0.027, P=0.043, respectively). In the aerobic group, total hippocampal volume significantly increased after the intervention compared with baseline (P=0.034). The between-group difference in the change of MMSE and MoCA scores was statistically significant (P=0.015, P=0.027, respectively). Logistic regression showed strong correlations between aerobic training and increase in total hippocampal volume (OR:1.091, [95%CI 0.969, 1.228], P=0.002), improvement of MMSE scores (OR:1.127, [95%CI 1.005, 1.263], P=0.041) or MoCA scores (OR:2.564, [95%CI 2.098.2.973], P=0.045).

Conclusions: One-year moderate aerobic training increased total and right hippocampal volume and protected cognitive function for T2DM patients with normal cognition. Early intervention focusing on cognition protection should be considered for T2DM patients in clinical settings.

Aim: This study investigated the effects of insulin glargine and exenatide on the muscle mass of patients with newly diagnosed type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD).

Methods: We performed a post-hoc analysis of our previously study, a 24-week randomized controlled multicenter clinical trial (ClinicalTrials.gov, NCT02303730). Seventy-six patients were randomly assigned 1:1 to receive insulin glargine or exenatide treatment. The changes in psoas muscle area (PMA) (mm²) were obtained with the cross-sectional Dixonfat magnetic resonance images at the fourth lumber vertebra.

Results: There were no significant differences in age, BMI, gender, and PMA in insulin glargine and exenatide groups at baseline. After treatment, PMA tended to increase by 13.13 (-215.52, 280.80) mm² in the insulin glargine group and decrease by 149.09 (322.90-56.39) mm² in the exenatide group (both p>0.05). Subgroup analysis showed a 560.64 (77.88, 1043.40) (mm²) increase of PMA in the insulin group relative to the Exenatide group in patients with BMI<28 kg/m² (p0.031) after adjusting for gender, age, and research center. Interaction analysis showed an interaction between BMI and treatment (p0.009). However, no interaction was observed among subgroups with a BMI≥28 kg/m² or with different genders and ages.

Conclusion: Compared to exenatide, insulin glargine can relativity increase PMA in patients with T2DM having BMI<28 kg/m² and NAFLD.

Idiopathic isolated adrenocorticotrophic hormone deficiency (IIAD) is rare, with high clinical omission and misdiagnosis rates. This study retrospectively collected information on clinical presentation, laboratory findings, and treatment response of 17 patients with IIAD at Jining No. 1 People's Hospital from January 2014 to December 2022. The clinical characteristics were summarized, and the pertinent data were analyzed. As a result, most of the patients with IIAD were male (94.12%), with age at onset ranging from 13 to 80 years. The primary manifestations were anorexia (88.24%), nausea (70.59%), vomiting (47.06%), fatigue (64.71%), and neurological or psychiatric symptoms (88.24%). The median time to diagnosis was 2 months and the longest was 10 years. Laboratory tests mostly showed hyponatremia (88.24%) and hypoglycemia (70.59%). The symptoms and laboratory indicators returned to normal after supplementing patients with glucocorticoids. IIAD has an insidious onset and atypical symptoms; it was often misdiagnosed as gastrointestinal, neurological, or psychiatric disease. The aim of this study was to improve clinicians' understanding of IIAD, patients with unexplained gastrointestinal symptoms, neurological and psychiatric symptoms, hyponatremia, or hypoglycemia should be evaluated for IIAD and ensure early diagnosis and treatment.