Yuki Matsuhashi

Association between Higher Serum Cortisol Levels and Decreased Insulin Secretion in a General Population

Glucocorticoids (GCs) are well known to induce insulin resistance. However, the effect of GCs on insulin secretion has not been well characterized under physiological conditions in human. We here evaluated the effect of GCs on insulin secretion/ß-cell function precisely in a physiological condition. A population-based study of 1,071 Japanese individuals enrolled in the 2014 Iwaki study (390 men, 681 women; aged 54.1 ± 15.1 years), those excluded individuals taking medication for diabetes or steroid treatment, were enrolled in the present study. Association between serum cortisol levels and insulin resistance/secretion assessed by homeostasis model assessment using fasting blood glucose and insulin levels (HOMA-R and HOMA-ß, respectively) were examined. Univariate linear regression analyses showed correlation of serum cortisol levels with HOMA-ß (ß = -0.134, p <0.001) but not with HOMA-R (ß = 0.042, p = 0.172). Adjustments for age, gender, and the multiple clinical characteristics correlated with HOMA indices showed similar results (HOMA-ß: ß = -0.062, p = 0.025; HOMA-R: ß = -0.023, p = 0.394). The correlation between serum cortisol levels and HOMA-ß remained significant after adjustment for HOMA- R (ß = -0.057, p = 0.034). When subjects were tertiled based on serum cortisol levels, the highest tertile was at greater risk of decreased insulin secretion (defined as lower one third of HOMA-ß (≤70)) than the lowest tertile, after adjustment for multiple factors including HOMA- R (odds ratio 1.26, 95% confidence interval 1.03–1.54). In conclusion, higher serum cortisol levels are significantly associated with decreased insulin secretion in the physiological cortisol range in a Japanese population.

A Case of Adrenocortical Oncocytoma Occurring with Aldosteronoma

A 48-yr-old woman was referred to our hospital for evaluation of a left adrenal mass. An abdominal computed tomography scan demonstrated a 5.4 3.7-cm tumor in the left adrenal gland (Fig. 1, A and B). She had untreated hypertension on admission and no Cushingoid features. When in a seated position, the patient’s urinary aldosterone excretion rate was 19.4 g/d, plasma aldosterone concentration (PAC) was 20.8 ng/dl, and plasma renin activity (PRA) was 0.8 ng/ml h mid morning. Her plasma aldosterone to renin ratio was 26.0. She was diagnosed with normokalemic (serum potassium, 3.8 mmol/ liter) primary aldosteronism after captopril challenge (PAC, 15.2 ng/dl; PRA, 0.4 ng/ml h at 2 h) and furosemide-plus-upright tests (PAC, 65.4 ng/dl; PRA, 0.3 ng/ ml h at 2 h) (1). 18F-Fluorodeoxyglucose (FDG) positron emission tomography demonstrated a marked uptake of FDG in the left adrenal mass (Fig. 1, C and D). The mass was therefore clinically diagnosed as an aldosterone-producing adrenocortical carcinoma (2). After left adrenalectomy, the patient’s hypertension improved with normalizationofaldosterone to renin ratio.Lightmicroscopic examination revealed the cells within the main tumor body to have abundant eosinophilic cytoplasm and three positive scores in Weiss criteria, namely, nuclear atypia, architecture, and an eosinophilic cytoplasm (Fig. 2A). The eosinophilic tumor cells were positive for steroidogenic factor-1, but negative for steroidogenic enzymes [3 -hydroxysteroid dehydrogenase (3BHSD), P450c21, P450c17, and dehydroepiandrosterone sulfotransferase]. This main tumor body was therefore diagnosed as a true nonfunctioning adrenocortical tumor, an “oncocytoma” (3). A wellcircumscribed localized mass of clear cortical cells demonstrating marked P450 side-chain cleavage enzyme, 3BHSD and P450c21, and weak P450c17 immunoreactivity was detected around one margin of the oncocytoma (Fig. 2, B–E).Theattachedzonaglomerulosawashyperplasticbut negative for 3BHSD, evidence pointing toward a nonfunctioning albeit hyperplastic response in the neighboring normal glomerulosa. This part was therefore histopathologically diagnosed as an aldosteronoma. Although it could be one tumor with heterogeneity, this is the first

Association between serum prolactin levels and insulin resistance in non-diabetic men

Prolactin (PRL) has roles in various physiological functions. Although experimental studies showed that PRL has both beneficial and adverse effects on type 2 diabetes mellitus, clinical findings in subjects with hyperprolactinemia indicate adverse effects on glucose metabolism. However, effects of PRL within the physiological range in human are controversial. A population-based study of 370 Japanese men enrolled in the 2014 Iwaki study (aged 52.0 ± 14.8 years). In this cross-sectional study, associations between serum PRL levels and homeostatic model assessment (HOMA) indices representing glucose metabolism in a physiological setting were examined using multivariable regression analysis. Although univariate linear regression analyses showed significant associations between serum PRL levels and HOMA indices, adjustment with multiple factors made the association with HOMA-ß (insulin secretion) insignificant, while those with HOMA-R (insulin resistance) remained significant (ß = 0.084, p = 0.035). Non-linear regression analyses showed a regression curve with a peak at serum PRL level, 12.4 ng/mL and a positive association of serum PRL level with HOMA-R below the peak (ß = 0.119, p = 0.004). Higher serum PRL levels within the physiological range seem to be associated with insulin resistance in men.

A Brief Outline of the History of the Pancreatic Anatomy

In the middle of the 18th century, Kouan Kuriyama, a Japanese physician of the Choshu Domain, depicted the anatomy of the human pancreas in a report to his master, Toyo Yamawaki. This report is the first anatomical description of the pancreas in Japan. In the Mediterranean area, the pancreas was apparently first described about 2,000 years before his observation. Although there are quite a few reviews on the history of this complex organ, our brief essay offers a historical outline of the pancreas.

Real-time visualization of thrombus formation at the interface between connectors and tubes in medical devices by using optical coherence tomography

Background Blood-contacting devices have contributed to improving the treatment of patients. However, thrombus formation at the interface between a connector and tube is still a potential source of thrombus-related complications that induce stroke or myocardial infarction. We aimed to develop a non-blood-contacting real-time method for visualizing thrombus formation, and to experimentally investigate the time-dependent phenomenon of thrombus formation at the interface between a connector and a tube in a medical device. Methods and findings An optical coherence tomography device with a center wavelength of 1330 nm was used to visualize thrombus formation during porcine blood circulation for 50 min in a closed 50-mL circulation system isolated from ambient air. The thrombus formation sites at the interface between a tube and connector were visualized. The area of the thrombus formation at the interface between the inlet of the connector and the tube was found to be 0.012 ± 0.011 mm2. Conversely, at the interface between the outlet of the connector and the tube, the area was found to be 0.637 ± 0.306 mm2. Thus, significantly larger amounts of thrombus were formed at the outlet interface (p < 0.01). The thrombus formation area at the outlet interface increased over time. Conversely, the area of thrombus formation showed repeated increasing and decreasing behavior at the inlet interface. Flow visualization with particle image velocimetry showed the presence of a flow separated area in the minimal flow phase at the inlet interface and a large recirculating slow flow region at the outlet interface in the minimal flow phase. These data suggested that the recirculating stagnant flow region contributed to thrombus growth. Conclusions The method presented here was effective in quantitatively assessing time-dependent phenomena of thrombus formation at the connector-tube interface. The method may contribute to the assessment of thrombogenicity of a novel design of connector.

Lower serum calcium levels are a risk factor for a decrease in eGFR in a general non-chronic kidney disease population

Association between serum calcium (Ca) levels and kidney dysfunction progression in a non-chronic kidney disease (CKD) population has not been well elucidated, especially in consideration for classical metabolic risk conditions such as hypertension, dyslipidemia, and diabetes, and those related to Ca metabolism. Among participants of the population-based Iwaki study of Japanese people, those with an estimated glomerular filtration rate (eGFR) ≧60 ml/min/1.73 m2 and age ≧40 years, and who attended the study consecutively in 2014 and 2015 were enrolled (gender (M/F): 218/380; age: 58.9 ± 10.2). Regression analysis showed a significant correlation between serum Ca levels and a change in eGFR in the 1-year period (∆eGFR) after adjustment with multiple factors including those related to Ca metabolism (β = 0.184, p < 0.001). When subjects were stratified into tertiles based on their serum Ca levels (higher >9.6 mg/dL, middle 9.4–9.6 mg/dL, lower <9.4 mg/dL), lower serum Ca levels were a significant risk for a rapid decliner of eGFR designated as the lower one third of ∆eGFR (<−4.40 ml/min/1.73 m2) (odds ratio 2.41, 95% confidence interval 1.47–3.94). Lower serum Ca levels are a significant risk for rapid decrease in eGFR, independent of previously reported metabolic risk factors in this general population with non-CKD, or eGFR ≧60 ml/min/1.73 m2.

Association between insomnia and coping style in Japanese patients with type 2 diabetes mellitus

Purpose Insomnia, which is associated with type 2 diabetes mellitus (DM), results in a low quality of life, and several relationships exist between insomnia and coping style. Thus, we clarified the association between some coping styles and insomnia among Japanese type 2 DM patients. Subjects and methods The subjects included 503 type 2 DM patients (mean age 63.9±12.5 years). Sleep disturbance and personality traits were evaluated using the Japanese version of the Pittsburgh Sleep Quality Index and the Brief Scale for Coping Profile, respectively. Lifestyle factors, glycated hemoglobin A1c (HbA1c) levels, and the depression statuses of the patients were also included in the analyses. Results Among the 503 subjects with type 2 DM, 141 (28.0%) subjects exhibited probable insomnia. After adjusting for confounders, being female, living alone, and using “avoidance and suppression” were significantly correlated with current insomnia. No other relationships were found between insomnia and HbA1c or lifestyle factors, such as smoking, drinking alcohol, and exercise frequency. Conclusion The prevalence of insomnia in individuals with type 2 DM was high, and the protective factors included some emotion-focused coping styles. Future prospective studies are required to confirm the therapeutic effects of behavioral interventions on insomnia in patients with type 2 DM.

Association between insomnia and personality traits among Japanese patients with type 2 diabetes mellitus

Insomnia is associated with type 2 diabetes mellitus, and results in a low quality of life. There are several known relationships between insomnia and personality. Thus, we clarified the association between some personality traits and insomnia among Japanese type 2 diabetes mellitus patients.

Dominance of the hypothalamus-pituitary-adrenal axis over the renin-angiotensin-aldosterone system is a risk factor for decreased insulin secretion

How the association between the hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin-aldosterone system (RAAS) affects glucose metabolism were not well examined in a general population. Participants of the population-based 2015 Iwaki study were enrolled (n: 1,016; age: 54.4 ± 15.1 years). Principal component (PC) analysis identified two PCs: PC1 represented levels of the HPA axis (serum cortisol) and the RAAS (plasma aldosterone) as a whole, and PC2 represented the HPA axis relative to the RAAS (HPA axis dominance). We examined the association between these PCs and glucose metabolism using homeostasis model assessment indices of reduced insulin sensitivity (HOMA-R) and secretion (HOMA-β). Univariate linear regression analyses showed a correlation between PC2 and HOMA-β (β = −0.248, p < 0.0001), but not between PC1 and HOMA-β (β = −0.004, p = 0.9048). The correration between PC2 and HOMA-β persisted after adjustment for multiple factors (β = −0.101, p = 0.0003). No correlations were found between the PCs and HOMA-R. When subjects were tertiled based on PC2, the highest tertile was at greater risk of decreased insulin secretion (defined as the lower one third of HOMA-β (≤68.9)) than the lowest tertile after adjustment for multiple factors (odds ratio, 2.00; 95% confidence interval, 1.35–2.97). The HPA axis dominance is associated with decreased insulin secretion in a Japanese population.

Carbon-13 and Its Clinical Application

The stable isotope carbon-13 (13C) is widely used in physiological investigation and medical research. Compared with a radioactive isotope tracing (e.g. 14C and 3H), i