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

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...

Background Plasma aldosterone-to-renin ratio (ARR) is popularly used for screening primary aldosteronism (PA). Some medications, including diuretics, are known to have an effect on ARR and cause false-negative and false-positive results in PA screening. Currently, there are no studies on the effects of sodium–glucose cotransporter-2 (SGLT2) inhibitors, which are known to have diuretic effects, on ARR. We aimed to investigate the effects of SGLT2 inhibitors on ARR. Methods We employed a retrospective design; the study was conducted from April 2016 to December 2018 and carried out in three hospitals. Forty patients with diabetes and hypertension were administered SGLT2 inhibitors. ARR was evaluated before 2 to 6 months after the administration of SGLT2 inhibitors to determine their effects on ARR. Results No significant changes in the levels of ARR (90.9 ± 51.6 vs. 81.4 ± 62.9) were found. Body mass index, diastolic blood pressure, heart rate, fasting plasma glucose, and hemoglobin A1c were significantly decreased by SGLT2 inhibitors. Serum creatinine was significantly increased. Conclusion SGLT2 inhibitor administration yielded minimal effects on ARR and did not increase false-negative results in PA screening in patients with diabetes and hypertension more than 2 months after administration.

These results demonstrate that PA including normotensive subjects exists more commonly than that expected in the general population. We suggest further investigation about the cause and progression of PA associated with sex and aging.

Experimental models recently suggested an interaction between aldosterone and adipose tissue, but clinical investigation has been limited. We studied the effects of eplerenone compared to hydrochlorothiazide (HCTZ) on blood pressure (BP), glucose, and lipid levels in 50 patients with essential hypertension (EHT) and type 2 diabetes mellitus whose BP failed to reach target levels with 8 mg of candesartan alone. BP improved similarly in both groups over the 12-month study period, but BMI, waist circumference, and LDL-cholesterol were decreased in the eplerenone group, while glycohemoglobin was elevated in the HCTZ group.

Word count (including references , but not tables and legends): 3979 words Number of tables: 1 Number of figures: 6Number of supplementary digital content files: NONE Key terms: noncoding exons; nuclear receptor; CYP11B2; artery; adrenal cortex, aldosteroneproducing adenoma; cardiac muscle. 3Abstract Objective: Nuclear receptors are involved in a wide variety of functions, including aldosteronogenesis. Nuclear receptor families NR4A (NGFIB,NURR1,NOR1) and NR2F (COUP-TFI,COUP-TFII,NR2F6) activate, whereas NR5A1 (SF1) represses CYP11B2 (aldosterone synthase) gene transcription. The present study was undertaken to elucidate the mechanism of differential regulation of nuclear receptors between cardiovascular and adrenal tissues. Methods:We collected tissues of artery (n=9), cardiomyopathy (CM) muscle (n=9), heart muscle (non-CM) (n=6),adrenal gland (n=9) and aldosterone-producing adenoma (APA) (n=9). 5'-rapid amplification of cDNA ends (5'-RACE) identified transcription start sites. Multiplex RT-PCR determined use of alternative noncoding exons 1 (ANEs). Results: In adrenocortical H295R cells, angiotensin II, KCl or cAMP all stimulated CYP11B2transcription and NR4A was up-regulated, whereas NR2F and NR5A1 were down-regulated. The NR4A mRNA levels in artery were high compared to cardiac and adrenal tissues, whereas the NR5A1 mRNA level in adrenal tissues was extremely high compared to cardiovascular tissues.Conclusions: NR4A and NR5A1 genes are complex in terms of alternative promoter use. The use of ANEs may be associated with the pathophysiology of the heart and adrenal gland.4

Summary Fulminant type 1 diabetes (FT1D) is a subtype of diabetes characterized by rapid progression of β-cell destruction, hyperglycemia, and diabetic ketoacidosis (DKA). The pathogenesis of this disease remains unclear. However, viral infections, HLA genes, and immune checkpoint inhibitor use were reportedly involved in this disease. A 51-year-old Japanese man with no chronic medical condition was admitted to our hospital with complaints of nausea and vomiting. Cough, sore throat, nasal discharge, and diarrhea were not noted. He had a medical history of at least two influenza infections. His vaccination history was notable for receiving an inactive split influenza vaccine 12 days prior to developing these symptoms. He was diagnosed with DKA associated with FT1D. His HLA class II genotypes were nonsusceptible to FT1D, and he had a negative history of immune checkpoint inhibitor use. The destruction of the pancreas by cytotoxic T cells is reported to be involved in FT1D. Inactive split influenza vaccines do not directly activate cytotoxic T cells. However, these could activate the redifferentiation of memory CD8-positive T cells into cytotoxic T cells and induce FT1D, as this patient had a history of influenza infections. Learning points Influenza split vaccination could cause fulminant type 1 diabetes (FT1D). The mechanism of influenza split vaccine-induced FT1D might be through the redifferentiation of CD8-positive memory T cells into cytotoxic T cells.