Effects of azilsartan compared with telmisartan on insulin resistance in patients with essential hypertension and type 2 diabetes mellitus: An open-label, randomized clinical trial.

BACKGROUND: Based on non-clinical data, it is expected that azilsartan, an angiotensin II receptor blocker, will help improve insulin resistance in addition to its hypotensive action. The present study is aimed to explore the effect of azilsartan compared to telmisartan on insulin sensitivity in hypertensive patients in the clinical setting. METHODS: This multicenter, randomized, open-label, parallel-group exploratory study was conducted in Japan. We randomized adult patients (≥20 years old) with grade I or II essential hypertension and coexisting type 2 diabetes (1:1) to receive either oral azilsartan (20 mg/day;17 patients) or telmisartan (40 mg/day;16 patients) for 12 weeks. The primary endpoint was the change in the homeostasis model assessment ratio of insulin resistance (HOMA-R) from the baseline at the end of the treatment period. We also evaluated its safety and efficacy on other diabetes-related variables and blood pressure. FINDINGS: The mean changes in HOMA-R at the end of treatment were 0.22 (95% CI, -1.09-1.52) in the azilsartan group and -0.23 (95% CI, -0.72-0.27) in the telmisartan group. We found no clinically remarkable changes between the groups in diabetes-related variables such as fasting blood glucose, fasting insulin, HbA1c (NGSP), HOMA-ß, or 1,5-anhydroglucitol. Reductions in clinic systolic and diastolic blood pressure were observed at week 4 and the reduced levels were maintained throughout the treatment period in both groups. No serious treatment-emergent adverse events (TEAEs) were observed. Only one drug-related TEAE (mild decrease in blood pressure) was reported in one patient in the azilsartan group. CONCLUSION: Neither azilsartan nor telmisartan had any clinically remarkable effects on insulin resistance parameters when administered for 12 weeks to patients with grade I or II essential hypertension and coexisting type 2 diabetes mellitus. Azilsartan (20 mg/day) and telmisartan (40 mg/day) exerted comparable antihypertensive effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT02079805.

Conservative Treatment for Idiopathic Adrenal Hemorrhage Tracked by a Long-term Series of CT Images.

A 55-year-old man was transported to our hospital after a sudden onset of left lower abdominal pain while driving. Computed tomography (CT) of the abdominal region revealed an extensive iso-intense signal region that had a maximum area of 14×15 cm, which we treated conservatively. A series of follow-up CT images showed the gradual decrease of the left peritoneal mass, while continuity with the left adrenal gland became apparent. He was diagnosed with idiopathic adrenal hemorrhage. Adrenal hemorrhage presenting with huge retroperitoneal tumors is rare, and most cases are treated surgically. Therefore, CT images with conservative treatment are rare, holding both clinical interest and significance.

Osmotic demyelination syndrome complicating diabetes with anti-glutamic acid decarboxylase antibodies and Graves' disease: A case report.

ODS associated with hyperglycemia is rare, with few reports.Immune responses have been recently reported as a mechanism of ODS onset. In the present case, an autoimmune predisposition may have contributed to ODS pathogenesis.

Adipsia increases risk of death in patients with central diabetes insipidus.

Central diabetes insipidus (CDI) is caused by deficiency of arginine vasopressin, an antidiuretic hormone. Patients with CDI manifest polyuria which is usually compensated for by increases in water intake. However, some patients are not able to sense thirst due to the destruction of osmoreceptors in the hypothalamus. These adipsic CDI patients are easily dehydrated and the consequent dehydration could be life-threatening. The objective of this study was to investigate the prognosis of adipsic CDI patients. We have reviewed 149 patients with CDI in three hospitals using databases of the electronic medical recording systems, and examined whether adipsia could affect the morbidity and mortality in CDI patients with multivariable analyses. Twenty-three patients with CDI were adipsic while the remaining 126 patients were non-adipsic. The multivariate analyses showed that the incidence of serious infections which required hospitalization was significantly higher in the adipsic CDI patients compared to that in non-adipsic CDI patients (p <0.001). A total of 6 patients with CDI died during the follow-up (median duration; 60 months, range 1 to 132 months). Four of them were adipsic, three of whom died of infection. The statistical analyses revealed that the risk of death in adipsic CDI patients was significantly higher than in non-adipsic patients (p =0.007). It is thus suggested that adipsic CDI patients were susceptible to serious infections which could be the causes of death.

[Analysis of thyroid lesions in childhood recipients after hematopoietic stem cell transplantation].

We performed a physical examination and ultrasonography of the thyroid gland in 24 patients who had received hematopoietic stem cell transplantation with a total-body irradiation (TBI)-containing regimen during childhood. When ultrasonography revealed thyroid nodules larger than 1 cm in diameter, fine-needle aspiration biopsies were performed. Of 5 patients with palpable masses and thyroid nodules larger than 1 cm, adenomatous goiter was diagnosed in 4 cases and thyroid cancer in 1. Of the remaining 19 patients in whom no palpable mass was detected in the physical examination, 5 had thyroid nodules (including 1 adenomatous goiter), 6 had cystic lesions, and 8 exhibited no abnormalities on ultrasonography. No significant differences in sex, age at transplantation, interval between transplantation and evaluation, primary disease, preconditioning regimen, status at transplantation, stem cell source, chronic graft-versus-host disease, hypogonadism, or hypothyroidism were observed between patients with and without nodules. Individuals who received hematopoietic stem cell transplantation with a TBI-containing regimen are at risk of secondary thyroid cancer due to radiotherapy and require regular clinical evaluations of the thyroid gland by palpation, and ultrasonography should be incorporated into these checkups.

Genetic and epigenetic states of the GNAS complex in pseudohypoparathyroidism type Ib using methylation-specific multiplex ligation-dependent probe amplification assay.

CONTEXT: Pseudohypoparathyroidism type Ib (PHP-Ib) is a rare disorder resulting from genetic and epigenetic aberrations in the GNAS complex. PHP-Ib, usually defined by renal resistance to parathyroid hormone, is due to a maternal loss of GNAS exon A/B methylation and leads to decreased expression of the stimulatory G protein α (Gsα) in specific tissues. OBJECTIVE: To clarify the usefulness of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), we evaluated genetic and epigenetic changes of the GNAS locus in Japanese PHP-Ib patients. DESIGN: Retrospective case series. PATIENTS: We studied 13 subjects with PHP-Ib (three families with eight affected members and one unaffected member and four sporadic cases). MEASUREMENTS: The methylation status of GNAS differentially methylated regions (DMRs) was evaluated using MS-MLPA. The main outcome measure was the presence of deletion mutations in the GNAS locus and STX16, which were assessed using MLPA. RESULTS: In all familial PHP-Ib cases, a ~3 kb deletion of STX16 and demethylation of the A/B domain were identified. In contrast, no deletion was detected throughout the entire GNAS locus region in the sporadic cases. Broad methylation abnormalities were observed in the GNAS DMRs. CONCLUSIONS: MS-MLPA allows for precise and rapid analysis of the methylation status in GNAS DMRs as well as the detection of microdeletion mutations in PHP-Ib. Results confirm the previous findings in this disorder and demonstrate that this method is valuable for the genetic evaluation and visualizing the methylation status. The MS-MLPA assay is a useful tool that may facilitate making the molecular diagnosis of PHP-Ib.

Short-term effects of ß-adrenergic antagonists and methimazole in new-onset thyrotoxicosis caused by Graves' disease.

OBJECTIVE: ß-adrenergic antagonists (ß-blockers) are often used to attenuate the hyperadrenergic symptoms of Graves' disease (GD), including palpitation. Although ß-blockers reduce the heart rate, cardiac output and oxygen consumption, no firm evidence exists regarding the effects of combined therapy with ß-blockers and anti-thyroid drugs. The objective is to elucidate the effects of ß-blockers on anti-thyroid drug therapy in GD. METHODS: Patients newly diagnosed with mild GD were randomly assigned to receive methimazole with or without ß-blockers in a prospective multi-center survey. The heart rate and thyroid function were measured and the quality of life was assessed using original and SF-36 questionnaires at 0 and 4 weeks. RESULTS: A total of 28 patients were enrolled in the study. Fourteen patients (one man, 13 women) were randomly assigned to the group treated with ß-blockers and 14 patients (one man, 13 women) were randomly assigned to the group not treated with ß-blockers. Although no significant differences in the improvement of thyroid function were observed between the two groups, the heart rates improved more significantly in the group treated with ß-blockers. Specific symptoms, such as easy fatigability and shortness of breath, also improved more significantly with the ß-blocker treatment. In addition, 'physical functioning' assessed with the SF-36 questionnaires significantly improved only in the group treated with ß-blockers. CONCLUSION: Although ß-blockers may not reinforce the effects of anti-thyroid drugs on thyroid function, at least during the course of one month, they are effective in reducing heart rates and ameliorating specific symptoms in patients with mild GD.

Diurnal changes in arginine vasopressin gene transcription in the rat suprachiasmatic nucleus.

The diurnal changes in arginine vasopressin (AVP) mRNA and heteronuclear (hn) RNA, an indicator for gene transcription, were examined in the hypothalamus of Sprague-Dawley rats using in situ hybridization. AVP hnRNA levels in the suprachiasmatic nucleus (SCN) varied during a 24-h cycle and showed a peak at day-time [Zeitgeber time (ZT) 5], which preceded the peak in AVP mRNA levels by 4 h. AVP hnRNA was undetectable at ZT 13 and 17, indicating that the gene transcription was almost shut down at these time points. AVP mRNA levels in the SCN continued to decrease at night (ZT 13, 17 and 21) when there were minimal changes in transcription, suggesting rapid turnover of mRNA. Similar diurnal changes in AVP hnRNA levels were observed without photic cues. On the other hand, AVP hnRNA or mRNA levels in the supraoptic nucleus, where AVP is synthesized in response to plasma osmolarity and/or volume, did not show any circadian rhythm. These data suggest that both dynamic changes in AVP gene transcription and rapid turnover of mRNA contribute to the diurnal variation in AVP mRNA levels in the SCN.