Synthesis, Structural Characterization, and Optical Properties of Benzene-Fused Tetracyclic and Pentacyclic Stiboles.

The expectation that antimony (Sb) compounds should display phosphorescence emissions based on the "heavy element effect" prompted our interest in the introduction of antimony to a biaryl as the bridging atom in a fused heterole system. Herein, the synthesis, molecular structures, and optical properties of novel benzene-fused heteroacenes containing antimony or arsenic atoms are described. The stiboles and arsole were prepared by the condensation of dibromo(phenyl)stibane or dichloro(phenyl)arsine with dilithium intermediates derived from the corresponding dibromo compounds. Nuclear magnetic resonance (NMR) spectroscopy and X-ray crystal analysis revealed that the linear pentacyclic stibole was highly symmetric in both the solution and crystal states. In contrast, the curved pentacyclic stibole adopted a helical structure in solution, and surprisingly, only M helical molecules were crystallized from the racemate. All synthesized compounds produced very weak or no emissions at room temperature or in the solid state. In contrast, the linear penta- and tetracyclic stiboles exhibited clear phosphorescence emissions in the CHCl3 frozen matrix at 77 K under aerobic conditions.

Nutrient consumption-dependent association of a glucagon-like peptide-1 receptor gene polymorphism with insulin secretion.

Since type 2 diabetes (DM) is a life-style related disease, life-style should be considered when association between genetic factors and DM are examined. However, most studies did not examine genetic associations in consideration with lifestyle. Glucagon-like peptide-1 (GLP-1) receptor (GLP1R) mediates the insulinotropic action of GLP-1 in ß-cells. We here examined the association while taking into consideration of interactions between the gene polymorphism and various nutrient factors. Participants from the population-based Iwaki study of Japanese subjects held in 2014-2017 with information on nutritional intake evaluated by self-administered dietary history questionnaire, and GLP1R genotype (rs3765467: A/G), were included (n = 1,560). Although not significant, insulin secretion indices assessed by homeostasis model assessment of ß-cell function (HOMA-ß) in subjects with the GG genotype tended to be lower than in those with the AA+AG genotypes in most groups stratified into tertiles based on daily nutrient consumptions (high, middle, and low). Stratification also showed that the GG genotype was a significant risk for decreased insulin secretion (HOMA-ß ≤ 30) even after adjustment for multiple factors (age, body mass index, alcohol consumption), but only in the highest tertiles of energy, protein and carbohydrate consumption in men [odds ratios (95% confidence interval) 3.95 (1.03-15.1), 15.83 (1.58-158.9), and 4.23 (1.10-11.2), respectively]. A polymorphism of the GLP1R gene was associated with decreased insulin secretion in a nutrient consumption-dependent manner in Japanese men, indicating an interaction between GLP1R and nutritional factors in the pathophysiology of DM.

FIB-4 index is a marker for a subsequent decrease in insulin secretion in a non-diabetic Japanese population.

Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of type 2 diabetes (DM), therefore, early diagnosis of NAFLD is important to prevent incident DM. FIB-4 index, a biomarker, often used to evaluate severity of NAFLD, may be useful to evaluate risk for incident DM in ordinary clinical setting. Here, we determined the association of FIB-4 index with changes in indices representing glucose metabolism with aging in a non-diabetic population. From among the participants of the population-based Iwaki study of Japanese people conducted during 2014-2017, 1,268 non-diabetic individuals with complete data sets (age: 51.4 ± 15.9 years; men/women: 485/773) were enrolled in a cross-sectional study. In addition, of the participants, 439 who attended consecutive appointments between 2014 and 2017 were enrolled in a longitudinal study that aimed to evaluate the changes in insulin secretion and resistance with aging (age: 53.1 ± 13.7 years; men/women: 178/261). The cross-sectional study showed significant correlations of FIB-4 index with homeostasis model of assessment (HOMA) indices, even after adjustment for multiple factors (HOMA-ß: ß = - 0.254, p < 0.001; HOMA-R: ß = - 0.247, p < 0.001). The longitudinal study showed a significant association between FIB-4 index and the change in HOMA-ß (p < 0.001) but not HOMA-R (p = 0.639) during the 3-year study period. Use of the optimal cut-off value of the FIB-4 index for the prediction of decreased insulin secretion (HOMA-ß < 30), determined using receiver operating characteristic analysis (1.592), showed that individuals at risk had a hazard ratio of 2.22 (confidence interval 1.17-4.06) for decreased insulin secretion, after adjustment for confounders. FIB-4 index may represent a useful predictor of a subsequent decrease in insulin secretion, at least in a non-diabetic Japanese population.

Exacerbation of Hyperparathyroidism, Secondary to a Reduction in Kidney Function, in Individuals With Vitamin D Deficiency.

Aims/Introduction: Chronic kidney disease (CKD)-mineral and bone disorders (CKD-MBD) are an adverse outcome derived from decreases in kidney function, where abnormality of serum concentrations of calcium (Ca), phosphorus, parathyroid hormone (PTH), and vitamin D can be seen simultaneously. To identify individuals at risk for CKD-MBD or secondary hyperparathyroidism, the relationships between estimated glomerular filtration rate (eGFR) and serum PTH concentration were evaluated, allowing for confounding factors, in particular vitamin D status, in a general Japanese population. Materials and Methods: Nine-hundred-and-thirty participants in the population-based Iwaki study conducted in 2016 who were not on drugs affecting mineral metabolism nor hemodialysis, were included in the study (326 men and 604 women; age: 55.4 ± 15.9 years). Results: Regression analysis showed a significant correlation between eGFR and serum intact PTH concentration, after adjustment for possible confounding factors (ß = -0.122, p < 0.001). The smoothed spline curve applied for the correlation analysis revealed a biphasic correlation, with a division at an eGFR of ~60 mL/min/1.73 m2, below which the correlation coefficient was higher (ß = -0.405, p < 0.001). Stratification on the basis of vitamin D status showed that the correlation was present only in participants with vitamin D deficiency (25-dihydroxyvitamin D3: <15 pg/mL) (ß = -0.154, p < 0.001). Conclusions: These results indicate that a reduction in eGFR is a significant risk factor for an increase in serum PTH concentration when it is <60 mL/min/1.73 m2 and vitamin D is deficient, in the general Japanese population.

Association between higher urinary normetanephrine and insulin resistance in a Japanese population.

Since activation of the sympathetic nervous system is associated with both impaired insulin secretion and insulin resistance, or namely with diabetes, evaluation of such activation in ordinary clinical settings may be important. Therefore, we evaluated the relationships between urinary concentrations of the catecholamine metabolites, urinary normetanephrine (U-NM) and urinary metanephrine (U-M), and glucose metabolism in a general population. From 1,148 participants in the 2016 population-based Iwaki study of Japanese, enrolled were 733 individuals (gender (M/F): 320/413; age: 52.1±15.1), who were not on medication affecting serum catecholamines, not diabetic, and had complete data-set and blood glucose levels appropriate for the evaluation of insulin secretion and resistance, using homeostasis model assessment (HOMA-ß and HOMA-R, respectively). Univariate linear regression analyses revealed significant correlations between both U-NM and U-M, and HOMA-ß, but adjustment for multiple factors correlated with HOMA indices abolished these (ß = -0.031, p = 0.499, and ß = -0.055, p = 0.135, respectively). However, the correlation between U-NM and HOMA-R observed using univariate linear regression analysis (ß = 0.132, p<0.001) remained significant even after these adjustments (ß = 0.107, p = 0.007), whereas U-M did not correlate with HOMA-R. Furthermore, use of the optimal cut-off value of U-NM for the prediction of insulin resistance (HOMA-R >1.6) determined by ROC analysis (0.2577 mg/gCr) showed that individuals at risk had an odds ratio of 2.65 (confidence interval: 1.42-4.97) after adjustment for the same factors used above. Higher U-NM concentrations within the physiologic range are a significant risk factor for increased insulin resistance in a general Japanese population.

Coping styles associated with glucose control in individuals with type 2 diabetes mellitus.

AIMS/OBJECTIVES: Glycemic control varies according to stress level and the efficacy of control measures, affecting the outcomes of diabetes. Although detailed coping styles have not been well studied in patients with type 2 diabetes mellitus, problem-focused coping strategies are believed to be related to better control of blood glucose. Associations between coping profiles/dimensions and blood glucose control were examined in individuals with type 2 diabetes. MATERIALS AND METHODS: The participants included 503 Japanese patients (mean age 63.9 ± 12.6 years) with type 2 diabetes. The average glycated hemoglobin A1c (HbA1c) levels were calculated from HbA1c levels measured more than four times within the 12 months before the assessment. Coping profiles were assessed using the Brief Scale for Coping Profile. Lifestyle factors were also included in the analyses. RESULTS: Factors other than age were not associated with HbA1c levels in patients who used insulin. Conversely, habitual alcohol consumption, single status, the adaptive emotion-focused coping dimension, and changing mood and changing one's point of view profiles were associated with HbA1c levels. CONCLUSIONS: These findings suggest that adaptive emotion-focused coping supports glycemic control in type 2 diabetes patients who do not use insulin. Additional studies using a longitudinal design are required to further examine the relationships between psychological factors and glycemic control.

Personality Traits Do Not Have Influence on Glycemic Control in Outpatients with Type 2 Diabetes Mellitus.

OBJECTIVE: Glycemic control varies based on lifestyle factors and stress coping mechanisms, which are influenced by personality. The psychological factors associated with glycemic control have not yet been established in patients with type 2 diabetes mellitus (T2DM). The relationship between a 5-factor model of personality and glycemic control was evaluated in individuals with T2DM. METHODS: The subjects were 503 Japanese outpatients with T2DM. Glycated hemoglobin A1c (HbA1c) levels, depressive status, insomnia and personality traits were assessed. Lifestyle factors of the patients, such as habitual alcohol consumption and smoking, were also included in the analyses. RESULTS: Because the influence of insulin therapy on HbA1c is so strong, we stratified the patients according to insulin use. Simple regression analysis showed a significant correlation between HbA1c and neuroticism in patients who did not use insulin. After adjustment for confounders, multiple regression analyses revealed that none of the personality factors, including neuroticism, were found to be associated with HbA1c. CONCLUSION: These findings suggest that personality traits do not have a large impact on glycemic control. Further studies are required to confirm the relationships between psychological factors and glycemic control using a longitudinal study design.

Coping behaviors and depressive status in individuals with type 2 diabetes mellitus.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with a high prevalence of depression, which is influenced by personality traits and coping style. However, these psychological factors have not been well studied in individuals with T2DM. The association between coping behaviors and the reported levels of depressive symptoms was examined in individuals with T2DM. METHODS: The subjects were 435 T2DM patients (mean age 63.1 ± 12.6 years). Depressive status, personality traits and coping behaviors were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Brief Scale for Coping Profile (BSCP). Lifestyle factors and glycated hemoglobin A1c (HbA1c) levels in the patients were also included in the analyses. RESULTS: Among the 435 subjects with T2DM, 130 (29.9%) exhibited possible depression, and 68 (15.6%) displayed probable depression. After adjustment for confounders, logistic and multiple regression analyses revealed that certain coping profile scores, such as Changing one's point of view, Emotional expression involving others and Avoidance and suppression, were consistently and significantly associated with the presence and severity of depression. No relationship was found between depression and HbA1c. CONCLUSION: These findings indicate that Maladaptive emotion-focused coping strategies, such as Emotional expression involving others and Avoidance and suppression, are protective factors and that Adaptive emotion-focused coping, such as Changing one's point of view, is a risk factor for depression in T2DM patients. Psychological intervention focusing on the coping profile may reduce depressive symptoms. Additional studies are needed to examine the relationships between psychological factors and depressive symptoms using a longitudinal study design.

Personality associated with depressive status in individuals with type 2 diabetes mellitus.

Objective: Type 2 diabetes mellitus (T2DM) is associated with a high prevalence of depression, and depression is influenced by personality traits; however, these psychological factors have not been well studied in individuals with T2DM. The association between the use of a 5-factor model of personality and depressive symptoms was examined in individuals with T2DM. Methods: The subjects were 435 T2DM patients (mean age 63.1±12.6 years). Depressive status and personality traits were assessed using the Center for Epidemiologic Studies Depression Scale and the Ten-Item Personality Inventory, Japanese version, respectively. Lifestyle factors and glycated hemoglobin A1c levels in the patients were also included in the analyses. Results: Among the 435 subjects with T2DM, 130 (29.9%) exhibited possible depression, and 68 (15.6%) exhibited probable depression. After adjustment for confounders, Extraversion, Agreeableness and Neuroticism were found to be significantly associated with the presence of depression. No relationships were found between depression and HbA1c. Conclusion: These findings indicate that Extraversion and Agreeableness are protective factors, and Neuroticism is a risk factor for depression in T2DM patients. Psychological therapy focusing on personality may reduce depressive symptoms. Additional studies are needed to examine the relationships between psychological factors and depressive symptoms using a longitudinal study design.

Adequate taylor couette flow-mediated shear stress is useful for dissociating human iPS cell-derived cell aggregates.

Pluripotent stem cell including induced pluripotent stem cells (iPSC) are promising cell sources for regenerative medicine and for three-dimensional suspension culture technologies which may enable the generation of robust numbers of desired cells through cell aggregation. Although manual procedure is widely used for dissociating cell aggregates, the development of non-manual procedures using devices will contribute to efficient cell manufacturing. In the present study, we developed novel cell aggregate dissociation devices with a rotating cylinder inside based on taylor couette flow-mediated shear stress. The shear stress can be increased according to an increase in the size of the rotating cylinder inside the devices and the rotation rate. Adequate device size and suitable rotation rate efficiently dissociated cell aggregates after the undifferentiated expansion and the cardiac differentiation of human iPSC. These finding suggest that non-manual device procedure might be useful for harvesting single cells from human iPSC-derived cell aggregates.

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

AIMS/INTRODUCTION: 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. MATERIALS AND METHODS: The participants were 504 type 2 diabetes mellitus patients (mean age 63.9 ± 12.5 years). Sleep disturbance and personality traits were evaluated using the Pittsburgh Sleep Quality Index-Japanese version and the Ten-Item Personality Inventory Japanese version, respectively. Lifestyle factors, glycated hemoglobin levels and depressive status of the patients were also included in the analyses. RESULTS: Among the 504 participants with type 2 diabetes mellitus, 154 (30.6%) showed probable insomnia. After adjustment for confounders, being female, living alone, high body mass index and "high neuroticism" were found to be significantly correlated with current insomnia. No other relationships between insomnia and glycated hemoglobin or lifestyle factors, such as smoking, drinking alcohol or exercise frequency, were found. CONCLUSIONS: The prevalence of insomnia in individuals with type 2 diabetes mellitus was high, and the risk factors included some personality factors. Future prospective studies are required to confirm the therapeutic effects of behavioral interventions for insomnia in patients with type 2 diabetes mellitus.

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 (ß = 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.

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.

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-ß). Univariate linear regression analyses showed a correlation between PC2 and HOMA-ß (ß = -0.248, p < 0.0001), but not between PC1 and HOMA-ß (ß = -0.004, p = 0.9048). The correration between PC2 and HOMA-ß persisted after adjustment for multiple factors (ß = -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-ß (≤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.

Investigation of the influence of fluid dynamics on thrombus growth at the interface between a connector and tube.

Thrombus formation at the interface between connectors and tubes is a potential risk factor for complications. We investigated time-dependent relationships between formation of thrombus and hemodynamic factors at the interface between connectors and tubes using optical coherence tomography (OCT) under pulsatile flow. A swept-source OCT with the center wavelength of 1330 nm was employed. The sequential process of thrombus formation at the interface of connectors and tubes in the inlet and outlet was investigated. Connectors with and without tapers were tested using identical 50-ml air-contactless circuits. Fresh human blood from healthy volunteers was circulated under pulsatile flow. Thrombus initially formed at the interface between the connector tip and the tube. Geometries of thrombus growth were different between the 2 connectors, and between the inlet and the outlet. Growth of thrombus was observed at the interface between the connectors and tubes over time in 60 min circulation, except at the outlet part of connector without tapers. At the connector without tapers outlet, thrombus propagation length from the connector edge toward the flow downstream was comparable at 10 and 60 min (0.55 ± 0.35 vs. 0.51 ± 0.32 mm, p = 0.83). Analysis using particle image velocimetry showed the presence of a flow reattachment point 1.5 mm downstream from the connector edge. These results suggest that the flow reattachment point inhibits downstream thrombus growth. We quantitatively demonstrated sequential thrombus process at the interface between the connectors and tubes under pulsatile flow of human blood using OCT.

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.

Premedication with fast-acting oxycodone hydrochloride hydrate effectively reduced oxaliplatin-induced severe vascular pain.

Oxaliplatin is a platinum-based chemotherapeutic agent that holds a prominent position in the treatment of colorectal and gastric cancers. However, severe oxaliplatin-related vascular pain can be problematic for patients. Here we describe seven patients who experienced severe vascular pain caused by oxaliplatin administration. All seven patients were treated with capecitabine and oxaliplatin or capecitabine plus oxaliplatin with bevacizumab as an adjuvant or a treatment for recurrent colorectal cancer, respectively. Patients experienced intolerable vascular pain during oxaliplatin administration, which continued for several days. Moreover, vascular pain also induced insomnia and appetite loss in all patients. We recommended implantation of a central venous (CV) port to the patients; however, all patients declined this treatment. In addition, various known countermeasures were taken, but were ineffective. Therefore, patients were orally administered oxycodone hydrochloride hydrate (Oxinorm®) 45 min prior to oxaliplatin administration. This pretreatment successfully reduced vascular pain and improved subsequent chemotherapy. Oxinorm® is a fast-acting opioid that can be an effective and practical option for severe vascular pain induced by oxaliplatin. The present report is the first description that emphasizes the usefulness of Oxinorm® to overcome the vascular pain induced by administration of oxaliplatin via a peripheral vein.

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.