Miyuki Yanagimachi

Association Between Pituitary-Adrenal Axis Dominance Over the Renin-Angiotensin-Aldosterone System and Hypertension

CONTEXT The hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin aldosterone system (RAAS) are well known to be associated with hypertension. However, the extent of the effects is not yet well elucidated in general conditions. OBJECTIVE To separately determine the effect of the HPA axis and the RAAS on hypertension in a general population. DESIGN, SETTING, AND PARTICIPANTS A population-based study of 859 Japanese individuals enrolled in the 2014 Iwaki study and without hypertension or steroid treatment (age, 50.2 ± 14.7 years). MAIN OUTCOME MEASURES Hypertension prevalence, plasma concentration of aldosterone, ACTH, cortisol, and plasma renin activity. RESULTS Principal component (PC) analysis using these four hormones identified two PCs (PC1 and PC2), which represent levels of these hormones as a whole, and dominance between the HPA axis (ACTH and cortisol) and the RAAS (plasma renin activity and plasma concentration of aldosterone), respectively. Association between these PCs and hypertension was significant (PC1, high vs low, odds ratio [OR], 1.48; 95% confidence interval [CI], 1.09-2.02; and PC2, HPA axis vs RAAS dominancy, OR, 2.08; and 95% CI, 1.51-2.85). However, association between the hormone levels as a whole and hypertension became insignificant after adjustment for multiple factors including these PCs together. However, association between the HPA axis dominance and hypertension remained significant even after the adjustment (the HPA axis vs the RAAS, OR, 1.73; 95% CI, 1.20-2.48). CONCLUSIONS The HPA axis dominance over the RAAS is significantly associated with hypertension in a Japanese population.

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.

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.

Energy metabolism during the perioperative period of gastric endoscopic submucosal dissection

The aim of this study was to investigate the change in the energy metabolism and invasiveness in the perioperative period of endoscopic submucosal dissection for early gastric cancer. Fifty-two consecutive patients were enrolled into the study between July 2013 and May 2014 and examined resting energy expenditure using an indirect calorimeter, body weight and basal energy expenditure using the Harris–Benedict equation before and after endoscopic submucosal dissection. Resting energy expenditure/body weight and resting energy expenditure/basal energy expenditure were 20.2 ± 3.0 kcal/kg/day and 0.96 ± 0.11 on the day of endoscopic submucosal dissection, whereas one day after the endoscopic submucosal dissection they were 21.7 ± 3.2 kcal/kg/day and 1.03 ± 0.14, showing significant increases (p<0.001, respectively). The stress factor on the postoperative day 1 was computed as 1.07. This increase was low in comparison to that experienced for surgery, suggesting that the degree of perioperative invasiveness in patients receiving endoscopic submucosal dissection is lower in comparison to that during surgery (The study of the resting energy metabolism and stress factor using an indirect calorimeter in the perioperative period of endoscopic operation: UMIN000027135).

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.

Estimation of perioperative invasiveness of colorectal endoscopic submucosal dissection evaluated by energy metabolism

The aim of this study was to assess the perioperative invasiveness of endoscopic submucosal dissection for colorectal cancer quantitatively by using energy metabolism. In fifty-three patients who underwent endoscopic submucosal dissection for colorectal cancer, resting energy expenditure using an indirect calorimeter, body weight and basal energy expenditure using the Harris–Benedict equation before and after endoscopic submucosal dissection. Resting energy expenditure/body weight and resting energy expenditure/basal energy expenditure were 19.7 ± 2.5 kcal/kg/day and 0.96 ± 0.12 on the day of endoscopic submucosal dissection, whereas one day after the endoscopic submucosal dissection they increased to 21.0 ± 2.9 kcal/kg/day and 1.00 ± 0.13 (p<0.001 and p<0.05, respectively). The stress factor on the postoperative day 1 was computed as 1.06. The increase was lower comparing with that experienced for surgery, suggesting that the perioperative invasiveness of colorectal endoscopic submucosal dissection is lower in comparison to that during surgery. Furthermore, in spite of technical difficulty, stress factor of colorectal endoscopic submucosal dissection was approximately equal to that of gastric endoscopic submucosal dissection. (The study of the resting energy metabolism and stress factor using an indirect calorimeter in the perioperative period of endoscopic operation: UMIN000027135)

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.