Our novel QCA was rapidly and easily performed at the point of care and improved the rate of successful AVS.
Background: The mineralocorticoid receptor (MR) is expressed in the kidneys and in adipose tissue, and
Background DNA methylation is believed to be maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not stable. We demonstrate that stimulatory signals can change the DNA methylation status around transcription factor binding sites and a transcription start site and activate expression of the aldosterone synthase gene (CYP11B2).Methods and Results DNA methylation of CYP11B2 was analyzed in aldosterone‐producing adenomas, nonfunctioning adrenal adenomas, and adrenal glands and compared with the gene expression levels. CpG dinucleotides in the CYP11B2 promoter were found to be hypormethylated in tissues with high expression, but not in those with low expression, of CYP11B2. Methylation of the CYP11B2 promoter fused to a reporter gene decreased transcriptional activity. Methylation of recognition sequences of transcription factors, including CREB1, NGFIB (NR4A1), and NURR1 (NR4A2) diminished their DNA‐binding activity. A methylated‐CpG‐binding protein MECP2 interacted directly with the methylated CYP11B2 promoter. In rats, low salt intake led to upregulation of CYP11B2 expression and DNA hypomethylation in the adrenal gland. Treatment with angiotensin II type 1 receptor antagonist decreased CYP11B2 expression and led to DNA hypermethylation.Conclusions DNA demethylation may switch the phenotype of CYP11B2 expression from an inactive to an active state and regulate aldosterone biosynthesis.
Purpose of Review Artificial intelligence (AI) can make advanced inferences based on a large amount of data. The mainstream technologies of the AI boom in 2021 are machine learning (ML) and deep learning, which have made significant progress due to the increase in computational resources accompanied by the dramatic improvement in computer performance. In this review, we introduce AI/ML-based medical devices and prediction models regarding diabetes. Recent Findings In the field of diabetes, several AI-/ML-based medical devices and regarding automatic retinal screening, clinical diagnosis support, and patient self-management tool have already been approved by the US Food and Drug Administration. As for new-onset diabetes prediction using ML methods, its performance is not superior to conventional risk stratification models that use statistical approaches so far. Summary Despite the current situation, it is expected that the predictive performance of AI will soon be maximized by a large amount of organized data and abundant computational resources, which will contribute to a dramatic improvement in the accuracy of disease prediction models for diabetes.
Adrenocortical hormone excess, due to primary aldosteronism (PA) or hypercortisolemia, causes hypertension and cardiovascular complications. In PA, hypomethylation of aldosterone synthase (CYP11B2) is associated with aldosterone overproduction. However, in hypercortisolemia, the role of DNA methylation of 11β-hydroxylase (CYP11B1), which catalyzes cortisol biosynthesis and is highly homologous to CYP11B2, is unclear. The aims of our study were to determine whether the CYP11B1 expression was regulated through DNA methylation in hypercortisolemia with cortisol-producing adenoma (CPA), and to investigate a possible relationship between DNA methylation and somatic mutations identified in CPA. Methylation analysis showed that the CYP11B1 promoter was significantly less methylated in CPA than in adjacent unaffected adrenal tissue and white blood cells. Furthermore, in CPA with somatic mutations in either the catalytic subunit of protein kinase A (PRKACA) or the guanine nucleotide-binding protein subunit alpha (GNAS) gene, the CYP11B1 promoter was significantly hypomethylated. In addition, DNA methylation reduced CYP11B1 promoter activity using a reporter assay. Our study results suggest that DNA methylation at the CYP11B1 promoter plays a role in the regulation of CYP11B1 expression and cortisol production in CPA, and that somatic mutations associated with CPA reduce DNA methylation at the CYP11B1 promoter.
Abstract. Obstructive sleep apnea syndrome (OSAS) is often associated with metabolic disorders such as obesity and type 2 diabetes and may contribute to cardiovascular events. A novel class of antidiabetic drugs, the sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce body weight (BW), although there is limited data on their impact on OSAS. We therefore evaluated the effect of SGLT2i on OSAS in patients with type 2 diabetes. The presented study was a retrospective design in 18 patients with type 2 diabetes with OSAS (4 males, age range 39-81 yr) administrated a SGLT2i. HbA1c, BW, body mass index (BMI), blood pressure (BP) and apnea hypopnea index (AHI) were evaluated before and after SGLT2i administration. The relationships between the reduction in AHI and the other variables were examined using Pearson correlation analysis. We have got result that SGLT2i reduced AHI from 31.9 ± 18.0 to 18.8 ± 11.5 events per hr (p = 0.003). HbA1c, BW and BMI decreased significantly, whereas BP did not. The Pearson correlation analysis showed a significant relationship between the reduction in AHI and pre-administration of AHI. In conclusion, SGLT2i reduced not only HbA1c, BW and BMI but also AHI significantly and therefore has potential as an effective treatment of OSAS.Key words: Sodium glucose cotransporter 2 inhibitors, Obstructive sleep apnea syndrome, Type 2 diabetes THE OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS) is a common and under-diagnosed disorder, associated with multiple comorbidities including obesity, metabolic syndrome, dyslipidemia and diabetes. OSAS contributes to an increased risk of cardiovascular mortality, a reduced quality of life, and is a major factor in some motor vehicle accidents by causing sleepiness of the driver [1][2][3][4]. Excess weight is considered to be the most important risk factor for OSAS [5,6] as it has been shown that between 60-70% of people with the synSubmitted Oct. 29, 2017; Accepted Jan. 11, 2018 as EJ17-0440 Released online in J-STAGE as advance publication Feb. 20, 2018 Correspondence to: Takashi Yoneda M.D., Ph.D., Kanazawa University, Takaramachi 13-1, Kanazawa, Ishikawa 920-8641, Japan. E-mail: endocrin@med.kanazawa-u.ac.jp *Equally contributing author: Shigehiro Karashima M.D., Ph.D. drome are either overweight or obese [7,8]. Furthermore, the prevalence of OSAS in obese patients with type 2 diabetes was reported to be 86% [9]. This indicates there is a close link between OSAS and type 2 diabetes and impaired glycemic control.Sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce plasma glucose levels in patients with type 2 diabetes by decreasing renal glucose reabsorption and increasing urinary glucose excretion [10]. Diuresis and calorie loss induced by SGLT2i results in reductions in body weight (BW) and blood pressure (BP), leading to improved insulin sensitivity and reduced arterial stiffness, respectively. As a consequence, SGLT2is would be expected to have pleiotropic effects in patients with type 2 diabetes, including reduced BW and severity of hypertension...
The rapid progression of chronic kidney disease and higher incidence of cardiovascular complications are well known in patients with hyperaldosteronism. However, detailed renal histopathologic characteristics of this disease have remained unknown. Therefore, renal biopsy specimens of 19 cases with unilateral hyperaldosteronism were compared with 22 autopsy renal cases of estimated glomerular filtration rate-matched essential hypertension without nephropathy or endocrine disorders to explore the hyperaldosteronism-specific histopathologic renal changes in this study. Global and segmental glomerulosclerosis, interstitial fibrosis, infiltration of inflammatory cells, arteriosclerosis, hyalinization of arterioles and immunoreactivity of mineralocorticoid receptor, 11β-hydroxysteroid dehydrogenase type 1 and 2, and renin were all quantitatively evaluated. The ultrastructural analysis was added in 3 hyperaldosteronism cases. Both mineralocorticoid receptor ( P <0.01) and 11β-hydroxysteroid dehydrogenase type 2 ( P <0.01) were significantly higher in renal tubules of hyperaldosteronism, which could result in enhancement of in situ aldosterone effects in hyperaldosteronism kidneys. Interstitial fibrosis was significantly more marked in hyperaldosteronism ( P <0.01). The proportion of segmental glomerulosclerosis was also significantly higher in hyperaldosteronism ( P <0.01). There were no significant differences of global glomerulosclerosis between 2 groups ( P =0.08). Glomerular size was significantly larger in hyperaldosteronism ( P <0.01). In medium size artery, luminal stenosis tended to be more marked ( P =0.08), and intima-to-media ratio was significantly lower ( P =0.02) in hyperaldosteronism. Arteriolar hyalinization was significantly more pronounced ( P <0.01), especially at efferent arterioles ( P <0.01) in hyperaldosteronism. Results above demonstrated more pronounced whole renal damages in hyperaldosteronism. Results of our present study also indicated the potential clinical significance of early intervention using mineralocorticoid receptor antagonists or blockers.
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