Search

Recent attempts to classify adult-onset diabetes using only six diabetes-related variables (GAD antibody, age at diagnosis, BMI, HbA1c, and homeostatic model assessment 2 estimates of b-cell function and insulin resistance (HOMA2-B and HOMA2-IR)) showed that diabetes can be classified into five clusters, of which four correspond to type 2 diabetes (T2DM). Here, we classified nondiabetic individuals to identify risk clusters for incident T2DM to facilitate the refinement of prevention strategies. Of the 1167 participants in the population-based Iwaki Health Promotion Project in 2014 (baseline), 868 nondiabetic individuals who attended at least once during 2015–2019 were included in a prospective study. A hierarchical cluster analysis was performed using four variables (BMI, HbA1c, and HOMA2 indices). Of the four clusters identified, cluster 1 (n = 103), labeled as "obese insulin resistant with sufficient compensatory insulin secretion", and cluster 2 (n = 136), labeled as "low insulin secretion", were found to be at risk of diabetes during the 5-year follow-up period: the multiple factor-adjusted HRs for clusters 1 and 2 were 14.7 and 53.1, respectively. Further, individuals in clusters 1and 2 could be accurately identified: the area under the ROC curves for clusters 1and 2 were 0.997 and 0.983, respectively. The risk of diabetes could be better assessed on the basis of the cluster that an individual belongs to. [ABSTRACT FROM AUTHOR]

The relationship between serum adiponectin concentration (S-Adipo) and various diseases, such as type 2 diabetes (T2D) is conflicting. We hypothesized that the extent of kidney damage in patients with T2D may be responsible for this inconsistency and, thus, examined association between S-Adipo and T2D after consideration for the extent of kidney damage present. Of the 1816 participants in the population-based Iwaki study of Japanese people, 1751 participants with a complete dataset were included. Multivariate logistic regression analyses revealed that low S-Adipo was independently associated with T2D (<0.001), as was high urinary albumin to creatinine ratio (uACR) (<0.001). Principal components analysis showed that the relative value of S-Adipo to uACR (adiponectin relative excess) was significantly associated with T2D (odds ratio: 0.49, p < 0.001). Receiver operating curve analyses revealed that an index of adiponectin relative excess the ratio of S-Adipo to uACR was superior to S-Adipo per se as a marker of T2D (area under the curve: 0.746 vs. 0.579, p < 0.001). This finding indicates that the relationship between S-Adipo and T2D should be evaluated according to the extent of kidney damage present and may warrant similar analyses of the relationships between S-Adipo and other medicalconditions, such as cardiovascular disease. [ABSTRACT FROM AUTHOR]

Upon food digestion, the gut microbiota plays a pivotal role in energy metabolism, thus affecting the development of type 2 diabetes (DM). We aimed to examine the influence of the composition of selected nutrients consumed on the association between the gut microbiota and DM. This cross-sectional study of a general population was conducted on 1019 Japanese volunteers. Compared with non-diabetic subjects, diabetic subjects had larger proportions of the genera Bifidobacterium and Streptococcus but smaller proportions of the genera Roseburia and Blautia in their gut microbiotas. The genera Streptococcus and Roseburia were positively correlated with the amounts of energy (p = 0.027) and carbohydrate and fiber (p = 0.007 and p = 0.010, respectively) consumed, respectively. In contrast, the genera Bifidobacterium and Blautia were not correlated with any of the selected nutrients consumed. Cluster analyses of these four genera revealed that the Blautia-dominant cluster was most negatively associated with DM, whereas the Bifidobacterium-dominant cluster was positively associated with DM (vs. the Blautia-dominant cluster; odds ratio 3.97, 95% confidence interval 1.68–9.35). These results indicate the possible involvement of nutrient factors in the association between the gut microbiota and DM. Furthermore, independent of nutrient factors, having a Bifidobacterium-dominant gut microbiota may be a risk factor for DM compared to having a Blautia-dominant gut microbiota in a general Japanese population. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) treatment can result in endocrine immune-related adverse events (irAEs), including pituitary dysfunction. Quick diagnosis of secondary adrenal insufficiency (AI) is challenging because no universal definition of ICI-induced secondary AI has been agreed. The aim of this study was to clarify the clinical features of ICI-induced secondary AI that can be used for screening in standard clinical practice. This retrospective study was performed using the medical records of patients who received ICIs at Hirosaki University Hospital between 1 September 2014 and 31 January 2021. Longitudinal clinical data of patients who developed AI were analyzed and compared with the data of thyroid irAEs. Regression analysis showed a significant correlation between ICI-induced secondary AI and absolute or relative eosinophil counts at pre-onset of AI, as well as differences or rate of increase in eosinophil counts at baseline and at pre-onset. Absolute eosinophil counts > 198.36/µL or relative eosinophil counts > 5.6% at pre-onset, and a difference of 65.25/µL or a rate of eosinophil count increase of 1.97 between the baseline and at pre-onset showed the best sensitivity and specificity. This is the first report to demonstrate that eosinophil counts can be a predictor of ICI-induced secondary AI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Xylitol is an approved food additive that is widely used as a sweetener in many manufactured products. It is also used in pharmaceuticals. Secondary oxalosis resulting from high dietary oxalate has been reported. However, reported cases of oxalosis following xylitol infusion are rare.Case Presentation: A 39-year-old man with a 16-year history of organic psychiatric disorder was hospitalized for a laparoscopic cholecystectomy because of cholecystolithiasis. He had been treated with several antipsychotics and mood stabilizers, including lithium. The patient had polyuria (> 4000 mL/day) and his serum sodium levels ranged from 150 to 160 mmol/L. Urine osmolality was 141 mOsm/L, while serum arginine vasopressin level was 6.4 pg/mL. The patient was diagnosed with nephrogenic diabetes insipidus (NDI), and lithium was gradually discontinued. Postoperative urine volumes increased further to a maximum of 10,000 mL/day, and up to 10,000 mL/day of 5% xylitol was administered. The patient's consciousness level declined and serum creatinine increased to 4.74 mg/dL. This was followed by coma and metabolic acidosis. After continuous venous hemodiafiltration, serum sodium improved to the upper 140 mmol/L range and serum creatinine decreased to 1.25 mg/dL at discharge. However, polyuria and polydipsia of approximately 4000 mL/day persisted. Renal biopsy showed oxalate crystals and decreased expression of aquaporin-2 (AQP2) in the renal tubules. Urinary AQP2 was undetected. The patient was discharged on day 82 after admission.Conclusions: Our patient was diagnosed with lithium-induced NDI and secondary oxalosis induced by excess xylitol infusion. NDI became apparent perioperatively because of fasting, and an overdose of xylitol infusion led to cerebrorenal oxalosis. Our patient received a maximum xylitol dose of 500 g/day and a total dose of 2925 g. Patients receiving lithium therapy must be closely monitored during the perioperative period, and rehydration therapy using xylitol infusion should be avoided in such cases. [ABSTRACT FROM AUTHOR]

aimon,3 Norio Sugawara1,41Department of Psychiatry, Dokkyo Medical University School of Medicine, Tochigi, Japan; 2Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; 3Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; 4Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the article, the authors present a case of 47-year-old woman with diabetes who was rushed to a hospital to improve her glycemic control to discuss how neprilysin inhibitor could increase urinary C-peptide excretion in diabetic patients. Also cited are the use of sacubitril valsartan sodium hydrate or dual angiotensin receptor-neprilysin inhibitor (ARNi) to treat her uncontrolled hypertension, and the use of electrochemiluminescence immunoassay to measure C-peptide concentration.

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. [ABSTRACT FROM AUTHOR]

The gut microbiota composition was investigated by applying the quantitative real-time polymerase chain reaction (q-PCR) method targeting the V3-V4 region of the prokaryotic 16S rRNA genes, as previously described [23]." The gut microbiota composition was investigated by conducting a next-generation sequencing analysis targeting the V3-V4 region of the prokaryotic 16S rRNA genes, as previously described [23]. Interrelations between Gut Microbiota Composition, Nutrient Intake and Diabetes Status in an Adult Japanese Population. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: 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 with such consideration, as the case of glucagon-like peptide-1 receptor (GLP-1R) gene. We examined the association in consideration with the interaction between the gene polymorphism and various nutrient factors. Research Design and Methods: Among participants of the population-based Iwaki study of Japanese held in 2014-2017, those with information of the genotype of GLP-1R polymorphism (db SNP ID: rs3765467: A/G)(p.Alg131Gln) as well as nutrients consumed (n=1817) were included. The following individuals were also excluded: 64 on medication for DM, and 52 with FBG levels below 63 mg/dl or over 140 mg/dl (to evaluate HOMA indices precisely). After these exclusions, 1,560 individuals (587 men, 973 women) aged 53.3± 16.1 years were included in the study. Results: Though not significant, insulin secretion indices assed by homeostasis model assessment (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 their daily nutrients consumptions (high, middle, and low groups). The stratification also showed that the genotype GG was a significant risk for a decreased insulin secretion (HOMA-ß ≤ 30) even after adjustment for multiple factors (age, BMI, drinking alcohol) only in the highest tertiles of energy, protein and carbohydrate consumption in men (odds ratios (95% CI) in high energy, protein and carbohydrate consumption groups: 3.95 (1.03-15.1), 15.83 (1.58-158.9), and 4.23 (1.10-11.2), respectively). Conclusions: The GLP-1R gene was associated with a decreased insulin secretion dependently of nutrients consumption, which indicates interaction between GLP-1R and nutrient factors on pathophysiology leading to DM. Disclosure: Y. Nishiya: None. M. Daimon: None. H. Murakami: None. M. Murabayashi: None. S. Mizushiri: None. T. Fujita: None. Y. Matsuhashi: None. [ABSTRACT FROM AUTHOR]

Objective: Since gut microbiota activity results in the production of specific microbial-derived metabolites (short-chain fatty acids) and structural components (LPS and peptidoglycans), changes in such microbiota composition appears to be involved in pathophysiology of common chronic disorders such as diabetes. Indeed, differences in gut microbiota between diabetic and nondiabetic subjects have been reported frequently in many ethnic groups, but not frequently in Japanese populations. Research Design and Methods: Among participants of the population-based Iwaki study of Japanese held in 2016, those with information of gut microbiota evaluated using 16S rRNA sequencing were included in the study (gender (M/F): 446/672; age: 54.8±15.6). Diabetic (n=122): either on treatment for diabetes or HbA1c levels ≥6.5% or FBG ≥126 mg/dl; Nondiabetic (n=996): others. Results: When examined the differences in gut microbiota in taxonomy category genus, proportions of several genuses were different between diabetic and nondiabetic subjects. Especially, proportions of the genus Streptococcus (4.79±9.53% vs. 2.12±3.74%, p=0.011) and Lactobacillus (3.11±8.10% vs. 0.344±1.95%, p <0.01), which are known to produce lactic acid, were higher, and genus Blautia (5.52±4.26% vs. 7.31±4.37%, p <0.01) and Bacteroides (8.14±9.38% vs. 10.8±7.84%, p <0.01), which are known to produce short chain fatty acids, were lower in diabetics subjects than those in nondiabetic subjects. Conclusions: Differences in gut microbiota proportion were also found between diabetic and nondiabetic subjects in a Japanese population. Since lactic acid is known to have an effect of suppressing pathogenic bacteria, the increase in lactic acid producing bacteria may have effects against infection. Further, since short chain fatty acids act as signal transduction molecules that affect energy metabolism, the decrease in short-chain fatty acid producing bacteria may be involved in the development of diabetes. Disclosure: M. Murabayashi: None. M. Daimon: None. H. Murakami: None. Y. Matsuhashi: None. A. Kamba: None. S. Mizushiri: None. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HR-QOL) assessment is considered an important aspect of outcome in diabetes treatment. Objective: We investigated the association between QOL and clinical characteristics of patients with diabetes. Methods: Among 571 patients with type 2 diabetes and 958 healthy control subjects, the target subjects who were matched by age and sex were divided into two groups (504 in the diabetic group and 504 in the nondiabetic group). The 36-Item Short Form Health Survey questionnaire (SF-36) was used to evaluate HR-QOL. Unpaired Student's tests and Pearson's chi-square test were used for statistical analyses. Results: (1) Scores of physical functioning, role physical (physical and mental), general health, and social functioning were significantly lower in the diabetic group than in the nondiabetic group (P<0.01). (2) The physical component summary score (PCS) was significantly lower in the diabetic group (P<0.01). There was no significant difference in the mental component summary score (MCS) between the two groups. (3) The PCS score was significantly decreased (P<0.01) with age in both groups. Reduction in the PCS score was faster in the diabetic group than the nondiabetic group, with an approximate difference of 11 years. (4) In the diabetic group, patients with retinopathy, nephropathy, or neuropathy demonstrated a significant reduction in the PCS score (P<0.01); however, no difference was observed in the MCS score. (5) Regarding the association of complications, such as retinopathy, nephropathy, or neuropathy, more were the complications, significantly lower was the PCS score (P<0.01). Conclusions: QOL was significantly decreased in patients with type 2 diabetes compared with that in healthy subjects. QOL of patients with diabetic complications was significantly decreased; thus, such conditions should be taken into account when providing treatment to patients with diabetes. Disclosure: H. Murakami: None. T. Fujita: None. M. Murabayashi: None. S. Mizushiri: None. S. Osonoi: None. Y. Matsuhashi: None. M. Daimon: None. [ABSTRACT FROM AUTHOR]

Objective: Although increase in type 2 diabetes (DM) along with aging is well documented, change in insulin secretion along with aging and factors related to its change in general, nondiabetic, population has not been well examined so far. Therefore, we evaluated the relationships between insulin secretion and age, or aging, in a general population. Methods: 1. cross sectional study: Among participants of the population-based Iwaki study of Japanese people held in 2014-2017, those without diabetes were enrolled (gender (M/F): 536/882; age: 53.0±16.0) 2. longitudinal study: Among participants described above, those attended the study consecutively in 2014 and 2017 were enrolled (gender (M/F): 257/401; age: 53.7±14.1). Insulin secretion was evaluated using homeostasis model assessment (HOMA-β). Results: 1: Univariate regression analyses revealed that the relationship between HOMA-β and age appeared to be non-linear but L-shaped, with an inflection point at about 55 and 50 years for men and women, respectively. Under the ages, HOMA-β are correlated with age (β= -0.32, p<0.01, and β=-0.16, p<0.01, for men and women, respectively), while above the age, such correlation was not observed (p=0.06 and 0.42, respectively).2: Analyses to evaluate factors associated with such decreases in HOMA-β in the 3-year duration showed no significant factor for men but HDL-c (β= -0.30, p<0.01), FIB-4 index representing degree of fibrotic change of liver (β=0.25, p=0.01) and for women after adjustment for multiple factors such as BMI, serum lipid parameters, and, so on. Conclusions: Insulin secretion seems to decrease along with aging till middle age, but after the age, it dose not decrease or stays similar throughout in a general Japanese population, indicating that aging per se may not be a major determinant for impaired insulin secretion in a general, or physiological condition. Further, factors related to abnormal liver function can be markers to predict decrease in insulin secretion, at least, in women. Disclosure: T. Fujita: None. M. Daimon: None. H. Murakami: None. Y. Nishiya: None. M. Murabayashi: None. S. Mizushiri: None. Y. Matsuhashi: None. [ABSTRACT FROM AUTHOR]

Objective: Chronic hyperglycemia increases glycation as well as oxidization, and, thus, facilitates production of advanced glycation end products (AGEs), whose accumulation is involved in the pathophysiology of diabetic complications. Although association between AGE and insulin resistance has been reported thoroughly, association between AGE and insulin secretion has not been well examined, especially in relation with age. Research Design: Among participants of the population-based Iwaki study of Japanese held in 2014, those who attended the Iwaki study consecutively in 2014 and 2015 were enrolled in this study (n=518; model A), and we excluded fasting blood glucose levels <63 and >140 to calculate HOMA-β and IR (n=489; model B). We used skin autofluorescence as AGE, and also measured blood levels of Pentosidine and urine albumin-to-creatinine ratio. Results: 1. AGE levels significantly increased from 1.93±0.52 to 1.97±0.44 (p=0.014) in the 1 year period. 2. Regression analysis showed correlations between ∆AGE (change in AGE in the 1 year period) and age, BUN, FPG and log10uACR in model A, and, age, log10uACR, and log10HOMA-ß in model B. However, these correlations became none-significant after adjustment for multiple factors mentioned above as well as factors representing glucose control levels such as HbA1c, except for age in models A and B, respectively. 3. Subjects were stratified into tertiles (mildly, moderately, rapidly progress) based on their ∆AGE, Logistic analysis revealed the aging is a significant risk for the accumulation of AGE (rapidly progress) (OR: 1.02. 95%CI: 1.01-1.03). ROC analysis showed the age of 60 as an optimal cut-off value for determining the risk subjects for the increase in AGE (OR: 1.74, 95%CI: 1.20-2.51). Conclusions: The accumulation of AGEs may increase with increasing speed, which becomes rapid over the age of 60 independent of glycemic levels, uACR and HOMA-ß, indicating that not glycemic control levels but aging per se is a major contributor for AGE accumulation. Disclosure: S. Mizushiri: None. M. Daimon: None. H. Murakami: None. A. Kamba: None. M. Murabayashi: None. Y. Nishiya: None. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Periodontal disease, caused by infection with gram-negative anaerobic bacteria, is the biggest risk factor for losing teeth in most westernized countries. Recently, periodontal disease has been regarded as complication of diabetes, since it develops frequently and progress rapidly in diabetic subject. However, although association between diabetes and minimal chronic inflammation induced by periodontal disease has been reported, association between differences in microbiota and periodontal diseases in diabetic subject have not been well examined. Research Design and Methods: Among participants of the population-based Iwaki study of Japanese held in 2016, those with information of oral cavity environment evaluated by the salivary multi-test, and microbiota of saliva samples evaluated using 16S rRNA sequencing were included in the study (n=1078). Diabetes: HbA1c levels ≧6.5% or FBG ≧126 mg/dl; normal glucose tolerance (NGT): HbA1c levels <6.0% or FBG <100 mg/dl. Results: The number of dental caries-causing bacterium was significantly higher (3.15±1.61 vs. 2.61±1.61, p <0.01), and the saliva buffer capacity was significantly lower (71.9±10.8 vs. 77.8±10.4, p <0.01) in diabetic subjects compared to those with NGT. Further, proportion of the phylum Firmicutes was higher (41.3±12.4% vs. 37.2±11.6%, p <0.01), and the phylum Bacteroidetes was significantly lower (18.9±8.5% vs. 20.9±8.3%, p=0.01) in diabetic subjects compared to those with NGT. Conclusions: Abnormal glucose tolerance may change oral microbiota, induce dental caries, and be a risk factor for periodontal disease. We will further examine association between microbiota and diabetes in taxonomic category below phylum, and, also, in consideration with nutrients consumed. Disclosure: S. Mizushiri: None. M. Daimon: None. H. Murakami: None. M. Murabayashi: None. Y. Matsuhashi: None. A. Kamba: None. [ABSTRACT FROM AUTHOR]

Objective: Aging is one of the risks for abnormal glucose tolerance or diabetes. Although association between age and, insulin secretion and resistance has been reported in various cross sectional studies, few studies evaluated changes of insulin resistance and secretion along with aging. Research Design and Methods: Among participants of the population-based Iwaki study of Japanese, those participated consecutively from 2014 to 2017 and were nondiabetic were included in this study (Men/Women: 200/294; Age: 21-90 (54.2 ± 13.5)). The effects of aging on homeostasis model assessment indices for insulin resistance (HOMA-R) and β-cell function (HOMA-β) were examined. Results: During the 3-year periods, HOMA-R significantly increased (p<0.0001), while HOMA-β significantly decreased (p<0.0001). Repeatedly measures ANOVA with adjustments for possible confounding and/or intermediating factors showed that the increase in HOMA-R became insignificant after adjustment with factors related to adiposity such as BMI and leptin (p=0.564), while the decrease in HOMA-β stayed significant even after such adjustments (p=0.046). Despite the facts, stepwise multiple regression analysis showed significant association of leptin not only with increases in HOMA-R (p=0.022) but also with decreases in HOMA-β (p =0.003). Conclusion: Insulin resistance increases along with aging probably due to a simultaneous adiposity, while insulin secretion decreases along with aging at least in part independently of such adiposity. However, the association between leptin and decreases in HOMA-β may suggest that adiposity of β-cells may be in part blamed for the decreases. Further, leptin may be a marker to predict those at risk of decreasing insulin secretion. We are now examining such association in details in consideration with blood metabolites and amino acids levels. Disclosure: T. Fujita: None. M. Daimon: None. H. Murakami: None. S. Mizushiri: None. Y. Matsuhashi: None. S. Osonoi: None. M. Murabayashi: None. K. Takahashi: None. Y. Nishiya: None. [ABSTRACT FROM AUTHOR]

Background: Sleep disorders are associated with type 2 diabetes, and result in a low quality of life. However, there are few reports on the prevalence and correlates of sleep disorders in diabetics. This study investigated the prevalence and factors, including personality traits, associated with sleep disorders in type 2 diabetics. Research Design and Methods: A case-control study was performed in patients with type 2 diabetes mellitus (223 males, 208 females; age 60.8 ± 12.8-years-old; HbA1c, 7.2 ± 0.9%) compared with age-/sex-matched healthy controls (219 males, 217 females; age 60.8 ± 13.0-years-old; HbA1c, 5.6 ± 0.3%). Participants used self-administered questionnaires on sleep attitude (Pittsburgh Sleep Quality Index; PSQI), quality of life (SF-36), depression (CES-D), and personality (Ten Item Personality Inventory). Results: The number of subjects with sleep disorders (PSQI > 5) was higher in diabetic patients (26.9%) than control subjects (17.4%) (p < 0.01). Sleep latency was longer in diabetic patients (20.2 ± 0.8 minutes) than control subjects (13.7 ± 0.5 minutes) (p < 0.01). Among diabetic patients, patients with sleep disorders were significantly younger (p = 0.04) and showed higher body mass index (p=0.04), higher percentages of females (p = 0.03), depression (p < 0.01), overactive bladder (p = 0.01), and benign prostatic hyperplasia (p < 0.01). Diabetic patients with sleep disorders scored higher neuroticism (p < 0.01), lower agreeableness (p = 0.01) and lower conscientiousness (p < 0.01) scale than patients without sleep disorders. All SF-36 scores were lower in patients with sleep disorders. No differences were found in HbA1c, stage of diabetic retinopathy and nephropathy between patients with the presence or absence of sleep disorders. Conclusions: The prevalence of sleep disorders was high in patients with type 2 diabetes, and their quality of life was impaired. Therefore, clinicians should monitor sleep disorders among these patients. Disclosure: H. Murakami: None. M. Daimon: None. S. Mizushiri: None. Funding: Japan Society for the Promotion of Research [ABSTRACT FROM AUTHOR]