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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.

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 β-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 β-cell function (HOMA-β) 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-β ≤ 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.

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.

Aims/Introduction Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the beneficial metabolic effects of equol. However, its effects on type 2 diabetes remain unclear. We investigated the association between the equol producers/non‐producers and type 2 diabetes. Materials and Methods The participants included 147 patients with type diabetes mellitus aged 70–89 years, and 147 age‐ and sex‐matched controls. To ascertain the equol producers or non‐producers, we used the comparative logarithm between the urinary equol and daidzein concentrations (cut‐off value −1.75). Results The urinary equol concentration was significantly lower in the diabetes group compared with the non‐diabetes group (P = 0.01). A significant difference in the proportion of equol producers was observed among all participants (38.8% in the diabetes group and 53.1% in the non‐diabetes group; P = 0.01). The proportion of equol producers among women was significantly lower in the diabetes group (31.4%) than in the non‐diabetes group (52.8%; P < 0.01). Additionally, the frequency of dyslipidemia in female equol producers was significantly lower than that in female non‐equol producers (P < 0.01). Among men, no such differences were observed. We found a significant positive correlation between the urinary equol and daidzein concentrations among equol producers (r = 0.55, P < 0.01). Conclusions Our study findings showed that postmenopausal women had a low proportion of equol producers with diabetes and dyslipidemia. The proportion of equol producers among women was significantly lower in the diabetes group compared with the non‐diabetes group.

Introduction: After total pancreatectomy, patients inevitably develop pancreatogenic diabetes with marked glycemic variability and high risk of malnutrition due to both endocrine and exocrine insufficiency. Weight loss and malnutrition can occur even in those with adequate dietary intake and plausible pancreatic enzyme replacement. We hypothesized that glycemic variability is associated with nutritional decline. Methods: We retrospectively analyzed 14 patients who underwent continuous glucose monitoring (CGM) after total pancreatectomy. Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI), and patients were classified into malnutrition-risk progression or nutrition-maintaining groups. Then, we evaluated glycemic indices, dietary intake, anthropometry, and pancreatic enzyme replacement therapy (PERT). Results: Insulin use, PERT dose, and dietary intake were approximately comparable between groups. In contrast, the malnutrition-risk progression group showed significantly higher mean glucose and time above range, and lower time in range (TIR). Importantly, TIR consistently showed an inverse association with malnutrition-risk progression across models adjusted for clinical covariates, including time since pancreatectomy, primary diagnosis, insulin regimen, and pancrelipase dose. These findings indicate that the observed relationship between lower TIR and worsening GNRI was independent of dietary intake and adequacy of enzyme replacement therapy, underscoring TIR as a clinically meaningful indicator of nutritional decline in this population. Conclusions: Hyperglycemia and reduced TIR were significantly associated with worsening GNRI after total pancreatectomy, independent of dietary intake or PERT. CGM-based glycemic metrics may help identify patients at risk of malnutrition and guide postoperative management.

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-β and HOMA-R, respectively). Univariate linear regression analyses revealed significant correlations between both U-NM and U-M, and HOMA-β, but adjustment for multiple factors correlated with HOMA indices abolished these (β = -0.031, p = 0.499, and β = -0.055, p = 0.135, respectively). However, the correlation between U-NM and HOMA-R observed using univariate linear regression analysis (β = 0.132, p<0.001) remained significant even after these adjustments (β = 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.

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. This study investigated coping styles associated with glucose control in people with type 2 diabetes. An adaptive emotion‐focused coping dimension supports glycemic control in people with type 2 diabetes who do not use insulin.

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-β: β =  − 0.254, p < 0.001; HOMA-R: β =  − 0.247, p < 0.001). The longitudinal study showed a significant association between FIB-4 index and the change in HOMA-β (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-β < 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.

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. Among the 504 subjects with type 2 DM, 154 (30.6%) exhibited probable insomnia. After adjustment for confounders, being female, living alone, high BMI and “high neuroticism” were found to be significantly correlated with current insomnia.The prevalence of insomnia in individuals with type 2 DM was high, and the risk factors included some personality factors.

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.