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Urban agriculture (UA), for recreational (gardening) and or commercial (farming) purposes, is commonly practised around the world, and uptake is increasing globally. There are many claims regarding UA’s social, economic and environmental benefits with scant exploratory research. The overarching objective of this paper is to access the potential economic, social and environmental contribution of UA based on five major features that have previously been shown to be critical to optimising the benefits of UA: area, purpose (gardening or commercial), crop value (mixed, mid to high), mechanisation level (none to partial mechanisation) and market mechanism (retail versus wholesale) based on past studies focusing on Adelaide, Australia and the Kathmandu Valley, Nepal. Including the reviewed 15 past studies that closely reflect the above five features of UA, most UA research has focused on the social benefits and potential cost savings of growing food in cities, with few studies interrogating its economic viability, employment potential or opportunity to reduce greenhouse gas emissions. There is a clear need to study UA using a systems approach to ensure viability, replicability and sustainability. Real-world case studies focusing on diverse settings will help to characterise key features and corrective actions for improving overall sustainability.

This paper examines the social, economic and environmental potential of Urban Agriculture (UA) based on information from forty distinct locations in each of the two regions: Adelaide, South Australia and Kathmandu Valley, Nepal, representing the diverse developmental background. Modelling is used to estimate equivalent employment, scale appropriateness, and earnings in comparison to labour use from commercial urban farming and gardening style UA, together with carbon dioxide emissions for two vegetable types. The study investigates the influence of distance and production scale under manual to modest mechanisation for urban vegetable production, finding that the interplay between labour use and mechanisation can favour scale-appropriate UA practices with better labour productivity and economic and social advantage. The distribution (assumed to be by car for UA) contributes the largest proportion of emissions, and the production component (even with mechanisation) contributes a relatively small portion per unit of production. We recommend that governments and planners should facilitate scale-appropriate mechanisation through better planning and policy instruments for UA’s sustainability.

Urban Agriculture (UA) is the widespread practice of food production within available city space using non-commercial, commercial and hybrid production technologies. The economic viability of UA remains a concern among UA practitioners. To investigate UA’s viability; land, labour and distribution cost are analyzed, and margin and benefit–cost ratio (BCR) under vacant lot, rooftop/backyard and discretionary labour UA are calculated. We present a straightforward approach to gauge the economic viability of UA taking examples from 40 distinct locations of two divergent development contexts of Adelaide, South Australia and Kathmandu Valley, Nepal. UA seems potentially viable by selecting high-value crops in Adelaide but showed little chance of viability under low-value crop scenarios in both contexts. The high cost of land is shown to be the primary driver of cost for UA. Labour cost appears to be a critical difference between the two cities, being an important constraint for the economic viability in Adelaide, where the wage rate is high. To improve economic viability, the respective governments and planners should consider better ways to avail subsidised land through policy intervention and volunteer or subsidised labour arrangement mechanisms. Home food gardens accessing available land and labour as a discretionary/spare time activity with zero distribution cost may represent the best way to produce food without exceeding market costs in cities.

This study deals with the evaluation of the effects of deficit irrigation (DI) and water quality (WQ) on the vegetative and productive response of greenhouse-grown tomatoes (Lycopersicon esculentum Mill. cv. Izmir). A pot-based experiment was carried out over two growing seasons. Three WQ: (groundwater, recycled wastewater and a mix of both) were applied in four irrigation scenarios which targeted soil moisture content (SMC) maintaining at 60%, 70%, 80% and 100% of field capacity (FC). Results showed that both DI and WQ had significant effects on crop development, yield and water productivity. The highest values of plant height (186.0 ± 0.58 cm) and stem diameter (23.40 ± 0.02 mm) were found at 100% FC (control). Total yield ranged from 2.33 ± 0.03 kg/plant (60% FC) to 4.05 ± 0.06 kg/plant (control). However, mild water stress (SMC maintaining at 80% FC) showed a positive effect on irrigation water use efficiency (IWUE) without significant yield reduction compared to control. IWUE was at its maximum (31.77 ± 0.47 kg/m3) at 80% FC. A DI regime based on 80% FC could be an efficient irrigation strategy particularly in water-limiting condition. Recycled wastewater was superior among the three WQ for achieving a better crop growth, yield and water productivity at same DI level.

Islet amyloid polypeptide (IAPP) is a factor that regulates food intake and is secreted from both pancreatic islets and insulinoma cells. Here, we aimed to evaluate IAPP immunohistochemically in islets or insulinoma cells in association with clinical characteristics. We recruited six insulinoma patients and six body mass index-matched control patients with pancreatic diseases other than insulinoma whose glucose tolerance was confirmed to be normal preoperatively. IAPP and IAPP-insulin double staining were performed on pancreatic surgical specimens. We observed that the IAPP staining level and percentage of IAPP-positive beta cells tended to be lower ( p  = 0.1699) in the islets of insulinoma patients than in those of control patients, which might represent a novel IAPP expression pattern under persistent hyperinsulinemia and hypoglycemia.

Background/objectives: Understanding food preferences is important for weight management. However, methods for assessing food preferences are not well established, especially in Japan. This study aimed to examine detailed food preferences and their associations with actual food intake in non-obese and abdominal-obese subjects using a newly developed questionnaire tailored for the Japanese population., Methods: We developed the Japan Food Preference Questionnaire (JFPQ) to evaluate food preferences across four nutrient groups based on nutritional evidence: carbohydrate, fat, protein, and dietary fiber. A total of 38 non-obese and 30 abdominal-obese participants completed both the JFPQ and the Food Frequency Questionnaire (FFQ). Food preferences for each nutrient were compared between the two groups, and correlations between food preferences (assessed by the JFPQ) and food intake (assessed by the FFQ) were analyzed., Results: Compared with the non-obese group, the abdominal-obese group showed significantly greater preferences for carbohydrates, fat, and protein, with no significant difference in dietary fiber after adjusting for age and sex. Furthermore, in the abdominal-obese group, positive correlations were found between actual intake and preference for high-fat and high-carbohydrate foods., Conclusions: Our findings from this pilot study demonstrated that abdominal-obese individuals had greater preferences for fat and carbohydrates, which were linked to actual fat and carbohydrate intake and possibly contributed to the development of obesity.

We previously reported that a high HbA1c level 3 months before vitrectomy for vitreous hemorrhage or a large preoperative decrease in the HbA1c level over 3 months tended to increase the risk of rebleeding in diabetic retinopathy patients evaluated between 2010 and 2014. Here, we aimed to confirm these results with an extended study period and an increased number of operated eyes. This study included 121 diabetic patients who were admitted to Osaka University Hospital between 2010 and 2019 and who underwent vitrectomy for vitreous hemorrhage. Binomial logistic regression analysis was performed with the presence of postoperative bleeding as the outcome. The present study showed that the duration of the operation was associated with rebleeding (odds ratio = 1.02, p = 0.0016). A high HbA1c level just before vitrectomy tended to be associated with the bleeding (odds ratio = 1.27, p = 0.05), while preoperative HbA1c changes were not associated with rebleeding. The results of this study suggest that a high preoperative HbA1c level just before vitrectomy, not a decrease in HbA1c levels, in addition to the duration of the operation may increase the risk of postoperative bleeding after vitrectomy in diabetic retinopathy patients.

We aimed to clarify the relationship between intra- and periorgan fats, visceral fat, and subcutaneous fat. We used abdominal computed tomography to evaluate intra- and periorgan fat accumulations in the pancreas, liver, spleen, renal parenchyma, renal sinus, and skeletal muscle. The relationships between these fats, visceral fat, and subcutaneous fat were examined by using partial correlation and covariance analysis, adjusting for BMI. We found that visceral fat and all intra- and periorgan fat accumulations were positively correlated, whereas subcutaneous fat and accumulations of all intra- and periorgan fats and visceral fat were negatively correlated. Individuals with excessive visceral fat accumulation had significantly greater accumulations of fat in the pancreas, liver, renal sinus, and skeletal muscle than those without excessive visceral fat accumulation (P = 0.01, 0.006, 0.008, and 0.02, respectively). In conclusion, all intra- and periorgan fat accumulations show a positive correlation with visceral fat and a negative correlation with subcutaneous fat, independent of BMI., (© 2024 by the American Diabetes Association.)

Background & Aims: Ectopic fat deposition is associated with worsening of glycemic control. This study was conducted to determine whether liraglutide reduces ectopic fat deposition, especially in pancreas, in patients with type 2 diabetes (T2D)., Methods: We retrospectively recruited T2D patients who underwent abdominal unenhanced CT scans both before and after administration of liraglutide (N = 13) or glimepiride (N = 29). Using CT values of pancreas (P), liver (L) and spleen (S), we defined the indices of intrapancreatic and liver fat as P-S value and L-S value, respectively. Increase of each value suggests the reduction of each fat deposition., Results: The values of HbA1c (p = 0.0017) and body weight (p = 0.0081) decreased, and L-S (p = 0.0024) increased significantly after administration of liraglutide compared with those at baseline. Similarly, P-S tended to increase in the liraglutide group (p = 0.0547) and increased significantly in the liraglutide subgroup with fatty pancreas (p = 0.0303), defined as having baseline P-S less than -5. In the glimepiride group, P-S did not increase regardless of baseline P-S. Among patients with fatty pancreas, administration of liraglutide tended to be a significant factor for the change in P-S after adjustment for the change in HbA1c (p = 0.1090) and the change in visceral fat area (p = 0.1030)., Conclusions: Intrapancreatic fat deposition was decreased after treatment with liraglutide, but not glimepiride, in T2D patients with fatty pancreas. Liraglutide might reduce intrapancreatic fat deposition independently of decreases in HbA1c and visceral fat volume., Competing Interests: Declaration of competing interest JK and IS have received lecture fees from Novo Nordisk Pharma Ltd. IS has received research funds from Novo Nordisk Pharma Ltd. Other authors have no conflict of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This pilot study examined the feasibility of a new lifestyle modification program involving a "Teaching Kitchen" in Japan. Our goal was to explore (1) feasibility of the program; (2) acceptability for class frequency (weekly vs. bi-weekly); and (3) changes in biometrics, dietary intakes, and lifestyle factors., Methods: A total of 24 employees with obesity in a Japanese company were recruited. Participants were randomly divided into two groups (weekly or bi-weekly group), each attending the program consisting of four two-hour classes (lectures on nutrition, exercise, mindfulness, and culinary instructions). Participants were observed for changes in dietary intakes, biometrics, and health related quality of life over the subsequent 3 months. We tested the between-group differences in changes using linear mixed-effect models., Results: The program completion rates were 83.3% in total (91.7% for weekly group and 75.0% for bi-weekly group). From baseline to post-intervention, significant decreases were observed in weight ( p < 0.001), body mass index ( p < 0.001), diastolic blood pressure ( p = 0.03), body fat mass ( p < 0.001), and dietary intakes in total fat ( p = 0.03) and sodium ( p = 0.008) among 17 participants who were available for measurements. Improvements in biometrics remained significant 1 month after the intervention (all p ≤ 0.03 in 14 participants). Participants' health related quality of life was significantly improved in bodily pain, general health, vitality, and mental component score (all p ≤ 0.047)., Conclusions: The new Japanese Teaching Kitchen program is feasible with high program completion rates in Japanese office workers with obesity. While this was a small feasibility study, significant multiple improvements in dietary intakes, biometrics, and health related quality of life suggest that this line of inquiry warrants further exploration to address obesity and obesity-related diseases in Japan., Competing Interests: MB and HO are members of the Department of Lifestyle Medicine, a sponsored course endowed by Kubara Honke Group Co., Ltd. YusF and AY were employed by the Cancerscan, Inc, Tokyo, Japan. TS and TK were employed by Kubara Honke Group Co., Ltd, Fukuoka, Japan. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Baden, Kato, Niki, Hara, Ozawa, Ishibashi, Hosokawa, Fujita, Fujishima, Nishizawa, Kozawa, Muraki, Furuya, Yonekura, Shigyo, Kawabe, Shimomura and Eisenberg.)

Aims: The excess deposition of intra-pancreatic fat deposition (IPFD) has been reported to be associated with type 2 diabetes, chronic pancreatitis, and pancreatic ductal adenocarcinoma. In the current study, we aimed to identify a relationship between lifestyle factors and IPFD., Materials and Methods: 99 patients admitted to the Osaka University Hospital who had undergone abdominal computed tomography were selected. We evaluated the mean computed tomography values of the pancreas and spleen and then calculated IPFD score. Multiple regression analyses were used to assess the associations between IPFD score and lifestyle factors., Results: Fast eating speed, late-night eating, and early morning awakening were significantly associated with a high IPFD score after adjusting for age, sex, diabetes status and Body Mass Index (p=0.04, 0.01, 0.01, respectively)., Conclusion: The current study has elucidated the significant associations of fast eating speed, late-night eating, and early morning awakening with IPFD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mitsushio, Baden, Kato, Niki, Ozawa, Motoda, Ishibashi, Hosokawa, Fujita, Tokunaga, Nammo, Kozawa and Shimomura.)

Immune checkpoint inhibitors (ICIs) could cause type 1 diabetes (T1D). However, the underlying mechanism remains unclear. We immunohistochemically analyzed pancreatic specimens from three individuals with ICI-related T1D, and their histopathological data were compared those from three patients who had received ICI therapy but did not develop T1D (non-T1D) and seven normal glucose-tolerant subjects as control subjects. All ICI-related T1D patients had susceptible HLA haplotypes. In ICI-related T1D, the β-cell area decreased and the α-cell area increased compared with non-T1D and control subjects. The number of CD3-positive cells around islets increased in ICI-related T1D and non-T1D compared with control subjects, while the number of CD68-positive cells around islets increased in ICI-related T1D compared with non-T1D and control subjects. The expression ratios of programmed death-ligand 1 (PD-L1) on islets decreased in non-T1D and almost completely disappeared in ICI-related T1D, while PD-L1 expression was observed in most cells of pancreatic islets in control subjects. This study, therefore, indicates that ICI therapy itself could reduce PD-L1 expression on islets in all subjects, which may be related to β-cell vulnerability. In addition, we showed that absence of PD-L1 expression on β-cells, genetic susceptibility, and infiltration of macrophages as well as T lymphocytes around islets might be responsible for T1D onset., (© 2023 by the American Diabetes Association.)

Background: Ectopic fat is fat that accumulates in or around specific organs or compartments of the body including myocardium. The clinical features of type 2 diabetes patients with high fat accumulation in the myocardium remain unknown. Moreover, little is known about the influence of myocardial fat accumulation in type 2 diabetes on coronary artery disease and cardiac dysfunction. We aimed to clarify the clinical features, including cardiac functions, of type 2 diabetes patients with myocardial fat accumulation., Methods: We retrospectively enrolled type 2 diabetes patients who underwent ECG-gated coronary computed tomography angiography (CCTA) and abdominal computed tomography (CT) scan examinations within 1 year of CCTA from January 2000 to March 2021. High fat accumulation in the myocardium was defined as the low mean myocardial CT value of three regions of interest, and the associations between CT values and clinical characteristics or cardiac functions were assessed., Results: In total, 124 patients were enrolled (72 males and 52 females). The mean age was 66.6 years, the mean BMI was 26.2 kg/m 2 , the mean ejection fraction (EF) was 67.6%, and the mean myocardial CT value was 47.7 Hounsfield unit. A significant positive correlation was found between myocardial CT value and EF (r = 0.3644, p = 0.0004). The multiple regression analyses also showed that myocardial CT value was independently associated with EF (estimate, 0.304; 95% confidence interval (CI) 0.092 to 0.517; p = 0.0056). Myocardial CT value showed significant negative correlations with BMI, visceral fat area and subcutaneous fat area (r = - 0.1923, - 0.2654, and -0.3569, respectively, p < 0.05). In patients who were ≥ 65 years or female, myocardial CT value showed significant positive correlations with not only EF (r = 0.3542 and 0.4085, respectively, p < 0.01) but also early lateral annular tissue Doppler velocity (Lat e') (r = 0.5148 and 0.5361, respectively, p < 0.05). The multiple regression analyses showed that myocardial CT value was independently associated with EF and Lat e' in these subgroups (p < 0.05)., Conclusions: Patients with type 2 diabetes, especially in elderly or female patients, who had more myocardial fat had more severe left ventricular systolic and diastolic dysfunctions. Reducing myocardial fat accumulation may be a therapeutic target for type 2 diabetes patients., (© 2023. The Author(s).)

Importance: The current Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of total and cause-specific mortality., Objective: To examine the associations of dietary scores for 4 healthy eating patterns with risk of total and cause-specific mortality., Design, Setting, and Participants: This prospective cohort study included initially healthy women from the Nurses' Health Study (NHS; 1984-2020) and men from the Health Professionals Follow-up Study (HPFS; 1986-2020)., Exposures: Healthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED) score, Healthful Plant-based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI)., Main Outcomes and Measures: The main outcomes were total and cause-specific mortality overall and stratified by race and ethnicity and other potential risk factors., Results: The final study sample included 75 230 women from the NHS (mean [SD] baseline age, 50.2 [7.2] years) and 44 085 men from the HPFS (mean [SD] baseline age, 53.3 [9.6] years). During a total of 3 559 056 person-years of follow-up, 31 263 women and 22 900 men died. When comparing the highest with the lowest quintiles, the pooled multivariable-adjusted HRs of total mortality were 0.81 (95% CI, 0.79-0.84) for HEI-2015, 0.82 (95% CI, 0.79-0.84) for AMED score, 0.86 (95% CI, 0.83-0.89) for HPDI, and 0.80 (95% CI, 0.77-0.82) for AHEI (P < .001 for trend for all). All dietary scores were significantly inversely associated with death from cardiovascular disease, cancer, and respiratory disease. The AMED score and AHEI were inversely associated with mortality from neurodegenerative disease. The inverse associations between these scores and risk of mortality were consistent in different racial and ethnic groups, including Hispanic, non-Hispanic Black, and non-Hispanic White individuals., Conclusions and Relevance: In this cohort study of 2 large prospective cohorts with up to 36 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of total and cause-specific mortality. These findings support the recommendations of Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.

Introduction: This study aimed to identify the associations between lifestyle factors and intrapancreatic fat deposition in patients with type 2 diabetes., Research Design and Methods: The participants were 185 patients with type 2 diabetes who were hospitalized at Osaka University Hospital between 2008 and 2020 and underwent abdominal CT during hospitalization. Information regarding lifestyle factors, including the number of meals consumed per day, snacking habits, exercise habits, exercise at work, smoking habits, alcohol intake, insomnia, sleep apnea syndrome, and night-shift working, was acquired from self-administered questionnaires or medical records. We measured the mean CT values for the pancreas (P), liver (L), and spleen (S), and the visceral fat area (VFA), and quantified intrapancreatic and liver ectopic fat accumulation as P-S and L-S, respectively., Results: After adjustment for age, sex, hemoglobin A1c, and body mass index (BMI), participants who consumed two meals per day had significantly lower P-S (higher intrapancreatic fat deposition, p=0.02) than those who consumed three meals per day. There were no significant associations between the number of meals consumed and liver ectopic fat accumulation and VFA (p=0.73 and p=0.67, respectively)., Conclusions: Patients with diabetes who consumed two meals per day showed greater intrapancreatic fat deposition than those who consumed three meals per day, even after adjustment for BMI. These findings support the current guideline for diabetes treatment that skipping meals should be avoided., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims/hypothesis: Plant-based diets, especially when rich in healthy plant foods, have been associated with a lower risk of type 2 diabetes. However, whether plasma metabolite profiles related to plant-based diets reflect this association was unknown. The aim of this study was to identify the plasma metabolite profiles related to plant-based diets, and to evaluate the associations between the identified metabolite profiles and the risk of type 2 diabetes., Methods: Within three prospective cohorts (Nurses' Health Study, Nurses' Health Study II and Health Professionals Follow-up Study), we measured plasma metabolites from 10,684 participants using high-throughput LC MS. Adherence to plant-based diets was assessed by three indices derived from the food frequency questionnaire: an overall Plant-based Diet Index (PDI), a Healthy Plant-based Diet Index (hPDI), and an Unhealthy Plant-based Diet Index (uPDI). Multi-metabolite profiles related to plant-based diet were identified using elastic net regression with a training/testing approach. The prospective associations between metabolite profiles and incident type 2 diabetes were evaluated using multivariable Cox proportional hazards regression. Metabolites potentially mediating the association between plant-based diets and type 2 diabetes risk were further identified., Results: We identified multi-metabolite profiles comprising 55 metabolites for PDI, 93 metabolites for hPDI and 75 metabolites for uPDI. Metabolite profile scores based on the identified metabolite profiles were correlated with the corresponding diet index (Pearson r = 0.33-0.35 for PDI, 0.41-0.45 for hPDI, and 0.37-0.38 for uPDI, all p<0.001). Metabolite profile scores of PDI (HR per 1 SD higher = 0.81 [95% CI 0.75, 0.88]) and hPDI (HR per 1 SD higher = 0.77 [95% CI 0.71, 0.84]) showed an inverse association with incident type 2 diabetes, whereas the metabolite profile score for uPDI was not associated with the risk. Mutual adjustment for metabolites selected in the metabolite profiles, including trigonelline, hippurate, isoleucine and a subset of triacylglycerols, attenuated the associations of diet indices PDI and hPDI with lower type 2 diabetes risk. The explainable proportion of PDI/hPDI-related diabetes risk by these metabolites ranged between 8.5% and 37.2% (all p<0.05)., Conclusions/interpretation: Plasma metabolite profiles related to plant-based diets, especially a healthy plant-based diet, were associated with a lower risk of type 2 diabetes among a generally healthy population. Our findings support the beneficial role of healthy plant-based diets in diabetes prevention and provide new insights for future investigation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the association of plant-based diet index (PDI) with early onset of natural menopause in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII)., Methods: We conducted a prospective study with a mean follow-up time of 20 years among premenopausal women living across the US. Participants of the NHS (n = 121,701) and NHSII (n = 116,429) were included from 1984 (age mean [standard deviation]; 44.9 [4.3]) and 1991 (age mean [standard deviation]; 36.4 [4.6]), respectively. Early menopause was self-reported and defined as natural menopause before age 45 years. PDI was derived from semiquantitative food frequency questionnaires administered every 4 years. Cox proportional hazards models were used to assess the association between PDI in quintiles and early menopause in NHS and NHSII separately, and fixed-effect models to pool the results from both cohorts., Results: During follow-up, 715 and 2,185 women experienced early natural menopause in NHS and NHSII, respectively. After adjustment for potential confounders, no association was observed between PDI and incidence of early natural menopause in either cohort, or when pooling the results from both cohorts, with an exception for unhealthy plant-based diet index which was associated with higher risk of early menopause with increasing levels of consumption (P trend = 0.04)., Conclusion: Adherence to PDI was not associated with timing of menopause while unhealthy plant-based diet might be associated with higher risk of experiencing early menopause., Competing Interests: Financial disclosures/conflicts of interest: M.Y.B. received a fellowship from the Manpei Suzuki Diabetes Foundation. E.R.B.-J., F.B.H., and A.H.E. received funding from the National Institute of Health. The other authors have nothing to declare., (Copyright © 2022 by The North American Menopause Society.)

Introduction: We previously reported several factors that cross-sectionally correlate with treatment satisfaction in Japanese patients with type 2 diabetes visiting diabetes clinics. The aim of this study is to identify factors associated with longitudinal changes in treatment satisfaction in patients with type 2 diabetes., Methods: The study included 649 patients with type 2 diabetes treated with oral glucose-lowering agents who completed the first questionnaire in 2016. The collected data included scores from the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and other parameters regarding diabetes treatment. We analyzed 1-year longitudinal changes in DTSQ scores and investigated factors associated with these changes., Results: Univariate linear regression analyses showed that changes in body weight, adherence to diet therapy, adherence to exercise therapy, cost burden, motivation for treatment, regularity of mealtimes, and perceived hypoglycemia correlated with changes in DTSQ scores. On the basis of multiple linear regression analyses, a decrease in hypoglycemia (β ± SE = - 0.394 ± 0.134, p = 0.0034), cost burden (β ± SE = - 0.934 ± 0.389, p = 0.017), and an increase in treatment motivation (β ± SE = 1.621 ± 0.606, p = 0.0077) correlated with DTSQ score increases, suggesting that motivation for treatment had the strongest impact on score increases. Subgroup analyses revealed that an increase in motivation for treatment most significantly correlated with a DTSQ score increase in obese and poor glycemic control groups, regardless of age., Conclusion: This is the first longitudinal study clarifying that an increase in motivation for treatment most strongly correlates with an increase in DTSQ score in patients with type 2 diabetes., (© 2022. The Author(s).)

Objective: To determine whether a healthful plant-based diet is related to lower stroke risk, we examined the associations of plant-based diet quality with risk of total, ischemic, and hemorrhagic stroke., Methods: The participants were 73,890 women in Nurses' Health Study (NHS; 1984-2016), 92,352 women in NHSII (1991-2017), and 43,266 men in Health Professionals Follow-Up Study (1986-2012) without cardiovascular disease and cancer at baseline. Plant-based diet quality was evaluated by the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). Participants who reported that their meat and/or fish intakes were 0 or <1 serving per month were categorized as vegetarians, and others were classified as nonvegetarians. Strokes with available medical records were subtyped as ischemic or hemorrhagic., Results: During the follow-up, 6,241 total stroke cases (including 3,015 ischemic and 853 hemorrhagic strokes) were documented. Compared to participants with the lowest PDIs, among participants with the highest PDIs, the hazard ratios (HRs) for total stroke were 0.94 (95% confidence interval 0.86-1.03) for PDI, 0.90 (0.83-0.98) for hPDI, and 1.05 (0.96-1.15) for uPDI. Participants in the highest hPDI showed marginally lower HR for ischemic stroke (0.92 [0.82-1.04]) and no consistent associations for hemorrhagic stroke. We observed no association between a vegetarian diet and total stroke (1.00 [0.76-1.32]), although the number of cases was small., Conclusion: Lower risk of total stroke was observed by those who adhered to a healthful plant-based diet., (© 2021 American Academy of Neurology.)

Objective: We evaluated the associations between changes in plant-based diets and subsequent risk of type 2 diabetes., Research Design and Methods: We prospectively followed 76,530 women in the Nurses' Health Study (NHS) (1986-2012), 81,569 women in NHS II (1991-2017), and 34,468 men in the Health Professionals Follow-up Study (1986-2016). Adherence to plant-based diets was assessed every 4 years with the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs). We pooled results of the three cohorts using meta-analysis., Results: We documented 12,627 cases of type 2 diabetes during 2,955,350 person-years of follow-up. After adjustment for initial BMI and initial and 4-year changes in alcohol intake, smoking, physical activity, and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest decrease (>10%) in PDI and hPDI over 4 years had a 12-23% higher diabetes risk in the subsequent 4 years (pooled HR, PDI 1.12 [95% CI 1.05, 1.20], hPDI 1.23 [1.16, 1.31]). Each 10% increment in PDI and hPDI over 4 years was associated with a 7-9% lower risk (PDI 0.93 [0.91, 0.95], hPDI 0.91 [0.87, 0.95]). Changes in uPDI were not associated with diabetes risk. Weight changes accounted for 6.0-35.6% of the associations between changes in PDI and hPDI and diabetes risk., Conclusions: Improving adherence to overall and healthful plant-based diets was associated with a lower risk of type 2 diabetes, whereas decreased adherence to such diets was associated with a higher risk., (© 2020 by the American Diabetes Association.)

Few studies have evaluated the association between a healthful plant-based diet and health-related quality of life (HRQoL). We followed 50 290 women in the Nurses' Health Study (NHS; 1992-2000) and 51 784 women in NHSII (1993-2001) for 8 years to investigate changes in plant-based diet quality in relation to changes in physical and mental HRQoL. Plant-based diet quality was assessed by three plant-based diet indices: overall plant-based diet index (PDI), healthful PDI (hPDI) and unhealthful PDI (uPDI). Physical and mental HRQoL were measured by physical component score (PCS) and mental component score (MCS) of the 36-Item Short Form Health Survey. Diet was assessed 2 years before the HRQoL measurements and both were updated every 4 years. The associations between 4-year changes in PDIs and HRQoL were evaluated. Each 10-point increase in PDI was associated with an improvement of 0·07 (95 % CI 0·01, 0·13) in PCS and 0·11 (95 % CI 0·05, 0·16) in MCS. A 10-point increase in hPDI was associated with an increment of 0·13 (95 % CI 0·08, 0·19) in PCS and 0·09 (95 % CI 0·03, 0·15) in MCS. Conversely, a 10-point increase in uPDI was associated with decreases in PCS and MCS (-0·07 (95 % CI -0·12, -0·02) and -0·10 (95 % CI -0·16, -0·05), respectively). Compared with a stable diet, an increase in hPDI was significantly associated with improvements in physical HRQoL in older women and with mental HRQoL in younger women. In conclusion, adherence to a healthful plant-based diet was modestly associated with improvements in both physical and mental dimensions of HRQoL.

Importance: The 2015-2020 Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of cardiovascular disease (CVD)., Objective: To examine the associations of dietary scores for 4 healthy eating patterns with risk of incident CVD., Design, Setting, and Participants: Prospective cohort study of initially healthy women from the Nurses' Health Study (NHS) (1984-2016) and the NHS II (1991-2017) and men from the Health Professionals Follow-up Study (HPFS) (1986-2012). The dates of analysis were July 25 to December 4, 2019., Exposures: Healthy Eating Index-2015 (HEI-2015), Alternate Mediterranean Diet Score (AMED), Healthful Plant-Based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI)., Main Outcomes and Measures: Cardiovascular disease events, including fatal and nonfatal coronary heart disease (CHD) and stroke., Results: The final study sample included 74 930 women in the NHS (mean [SD] baseline age, 50.2 [7.2] years), 90 864 women in the NHS II (mean [SD] baseline age, 36.1 [4.7] years), and 43 339 men in the HPFS (mean [SD] baseline age, 53.2 [9.6] years). During a total of 5 257 190 person-years of follow-up, 23 366 incident CVD cases were documented (18 092 CHD and 5687 stroke) (some individuals were diagnosed as having both CHD and stroke). Comparing the highest with the lowest quintiles, the pooled multivariable-adjusted hazard ratios (HRs) of CVD were 0.83 (95% CI, 0.79-0.86) for the HEI-2015, 0.83 (95% CI, 0.79-0.86) for the AMED, 0.86 (95% CI, 0.82-0.89) for the HPDI, and 0.79 (95% CI, 0.75-0.82) for the AHEI (P for trend <.001 for all). In addition, a 25-percentile higher dietary score was associated with 10% to 20% lower risk of CVD (pooled HR, 0.80 [95% CI, 0.77-0.83] for the HEI-2015; 0.90 [95% CI, 0.87-0.92] for the AMED; 0.86 [95% CI, 0.82-0.89] for the HPDI; and 0.81 [95% CI, 0.78-0.84] for the AHEI). These dietary scores were statistically significantly associated with lower risk of both CHD and stroke. In analyses stratified by race/ethnicity and other potential risk factors for CVD, the inverse associations between these scores and risk of CVD were consistent in most subgroups., Conclusions and Relevance: In 3 large prospective cohorts with up to 32 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of CVD. These findings support the recommendations of the 2015-2020 Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.

Objective: To identify sleep duration trajectories from early to middle adulthood and their associations with incident type 2 diabetes., Research Design and Methods: Using a group-based modeling approach, we identified sleep duration trajectories based on sleep duration in ages 20-25, 26-35, 36-45, and 46+ years, which were retrospectively assessed in 2009 among 60,068 women from the Nurses' Health Study II (median age 54.9 years) who were free of diabetes, cardiovascular disease, and cancer. We investigated the prospective associations between sleep duration trajectories and diabetes risk (2009-2017) using multivariable Cox proportional hazards models., Results: We documented 1,797 incident diabetes cases over a median follow-up of 7.8 years (442,437 person-years). Six sleep duration trajectories were identified: persistent 5-, 6-, 7-, or 8-h sleep duration and increased or decreased sleep duration. After multivariable adjustment for diabetes risk factors, compared with the persistent 7-h sleep duration group, the hazard ratio was 1.43 (95% CI 1.10, 1.84) for the 5-h group, 1.17 (1.04, 1.33) for the 6-h group, 0.96 (0.84, 1.10) for the 8-h group, 1.33 (1.09, 1.61) for the increased sleep duration group, and 1.32 (1.10, 1.59) for the decreased sleep duration group. Additional adjustment for time-updated comorbidities and BMI attenuated these associations, although a significantly higher risk remained in the decreased sleep duration group (1.24 [1.03, 1.50])., Conclusions: Persistent short sleep duration or changes in sleep duration from early to middle adulthood were associated with higher risk of type 2 diabetes in later life. These associations were weaker after obesity and metabolic comorbidities were accounted for., (© 2020 by the American Diabetes Association.)

Objective: This study aimed to investigate the prospective interrelationships among biomarkers that may provide mechanistic insights into obesity-related diseases., Methods: A total of 850 women in the Nurses' Health Study II with two fasting blood measurements (1996-1999 and 2010-2011) of adiponectin, leptin, soluble leptin receptor, insulin, retinol-binding protein 4, high-sensitivity C-reactive protein (hsCRP), and interleukin-6 were included. Biomarker interrelationships were examined in the following three ways: (1) cross-sectional associations at baseline and follow-up, (2) longitudinal associations of concurrent biomarker changes, and (3) prospective associations of each baseline biomarker with other biomarker changes., Results: In cross-sectional analyses, most biomarkers were correlated after multivariable adjustment including BMI, with the strongest correlations observed between leptin and insulin and between hsCRP and interleukin-6. In longitudinal analyses, similar results were observed after multivariable adjustment including weight change. However, in prospective analyses, only three associations observed in cross-sectional and longitudinal analyses were consistently significant (P < 0.05). Every doubling in baseline adiponectin was associated with -9.0% insulin change. The corresponding estimate was 9.3% for baseline leptin and hsCRP change and 3.1% for baseline hsCRP and leptin change., Conclusions: Baseline adiponectin concentrations were inversely associated with subsequent insulin change, whereas baseline leptin concentrations were positively associated with hsCRP change and vice versa., (© 2019 The Obesity Society.)

Objectives: Work engagement is defined as a positive, fulfilling feeling about one's job and is associated with higher productivity and morale. We performed a cross-sectional study to investigate whether work engagement is related to healthier dietary behaviors among Japanese workers., Methods: The present study was part of the Japanese Study of Health, Occupation, and Psychosocial Factors Related to Equity. A validated food frequency questionnaire was used to evaluate daily nutritional intake. The following seven nutrients were considered: salt intake, dietary fat (saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids), dietary fiber, folate, and isoflavone. Multivariable linear regression analysis was performed, adjusting for job stress, psychological distress, and other confounders. The baseline survey inquired about work engagement among 2,233 employees of 12 workplaces in Japan, representing a range of industries., Results: The mean age of the sample was 43.4 ± 9.7 years and 89.7% of the participants were male. The mean score of work engagement was 2.9 ± 1.0. Higher work engagement was significantly positively associated with higher salt intake (β = 0.17, SE = 0.06, P = .006), monounsaturated fatty acids (β = 0.29, SE = 0.13, P = .03), polyunsaturated fatty acids (β = 0.28, SE = 0.09, P = .001), dietary fiber (β = 0.23, SE = 0.09, P = .012), and folate (β = 10.2, SE = 2.9, P = .005) consumption, but not saturated fatty acid (β = 0.16, SE = 0.11, P = .13) or isoflavone (β = 0.64, SE = 0.36, P = .072)., Conclusion: The present study suggested that higher work engagement is associated with a healthier pattern of dietary behaviors among workers. Improving work engagement may be a novel target for workplace health promotion., (© 2020 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Background: Plant-based diets have been associated with lower risk of type 2 diabetes mellitus and cardiovascular disease (CVD) and are recommended for both health and environmental benefits. However, the association between changes in plant-based diet quality and mortality remains unclear., Methods: We investigated the associations between 12-year changes (from 1986 to 1998) in plant-based diet quality assessed by 3 plant-based diet indices (score range, 18-90)-an overall plant-based diet index (PDI), a healthful PDI, and an unhealthful PDI-and subsequent total and cause-specific mortality (1998-2014). Participants were 49 407 women in the Nurses' Health Study (NHS) and 25 907 men in the Health Professionals Follow-Up Study (HPFS) who were free from CVD and cancer in 1998. Multivariable-adjusted Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% CIs., Results: We documented 10 686 deaths including 2046 CVD deaths and 3091 cancer deaths in the NHS over 725 316 person-years of follow-up and 6490 deaths including 1872 CVD deaths and 1772 cancer deaths in the HPFS over 371 322 person-years of follow-up. Compared with participants whose indices remained stable, among those with the greatest increases in diet scores (highest quintile), the pooled multivariable-adjusted HRs for total mortality were 0.95 (95% CI, 0.90-1.00) for PDI, 0.90 (95% CI, 0.85-0.95) for healthful PDI, and 1.12 (95% CI, 1.07-1.18) for unhealthful PDI. Among participants with the greatest decrease (lowest quintile), the multivariable-adjusted HRs were 1.09 (95% CI, 1.04-1.15) for PDI, 1.10 (95% CI, 1.05-1.15) for healthful PDI, and 0.93 (95% CI, 0.88-0.98) for unhealthful PDI. For CVD mortality, the risk associated with a 10-point increase in each PDI was 7% lower (95% CI, 1-12%) for PDI, 9% lower (95% CI, 4-14%) for healthful PDI, and 8% higher (95% CI, 2-14%) for unhealthful PDI. There were no consistent associations between changes in plant-based diet indices and cancer mortality., Conclusions: Improving plant-based diet quality over a 12-year period was associated with a lower risk of total and CVD mortality, whereas increased consumption of an unhealthful plant-based diet was associated with a higher risk of total and CVD mortality.

Background: A healthful plant-based diet is associated with lower risk of cardiometabolic diseases. However, it is still unclear whether such benefits are due to its favorable effects on adiposity-associated biomarkers., Objective: We investigated the associations between biomarkers and 3 plant-based diet indices: an overall plant-based diet index (PDI); a healthful plant-based diet index (hPDI); and an unhealthful plant-based diet index (uPDI)., Methods: In the Nurses' Health Study II, 831 women [baseline mean age: 45 y; body mass index (BMI, kg/m2): 24.6] were randomly selected from those who provided 2 blood samples in 1996-1999 and 2010-2011 to measure plasma concentrations of adiponectin, leptin, soluble leptin receptor (sOB-R), insulin, retinol-binding protein-4, high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6). Plant-based diet indices were derived from semiquantitative food frequency questionnaires assessed at each blood collection. Linear mixed models were used to evaluate cross-sectional associations, and general linear models were used to evaluate longitudinal associations., Results: In cross-sectional analyses with multivariable adjustment including BMI, higher hPDI was associated with lower concentrations of leptin, insulin, and hsCRP, and higher adiponectin and sOB-R concentrations (biomarker differences per 10-point higher hPDI: -7.2%, -10.0%, -13.6%, 3.0%, and 1.9%, respectively; P ≤ 0.025). A higher uPDI was associated with higher concentrations of leptin and insulin (4.4% and 4.8%, respectively; P ≤ 0.048). In longitudinal analyses with multivariable adjustment including weight change, an increase in hPDI (improved plant-based diet quality) was inversely associated with changes in leptin and hsCRP (biomarker changes per 10-point hPDI increase: -7.7% and -17.8%, respectively; P ≤ 0.005), whereas an increase in uPDI (worsened plant-based diet quality) was positively associated with changes in leptin, hsCRP, and IL-6 (10.1%, 13.5%, and 12.4%, respectively; P ≤ 0.021)., Conclusions: Adherence to a healthful plant-based diet is associated with favorable long-term changes in adiposity-associated biomarker concentrations in women., (Copyright © American Society for Nutrition 2019.)

Aims: We conducted a national survey to clarify the characteristics and clinical course of type 1 diabetes related to anti-programmed cell death-1 therapy., Methods: We analyzed the detailed data of 22 patients that were collected using a Japan Diabetes Society survey and a literature database search., Results: Among the 22 patients, 11 (50.0%) met the criteria for fulminant type 1 diabetes and 11 (50.0%) met the criteria for acute-onset type 1 diabetes. The average patient age was 63 years. The mean duration between the date of the first anti-PD-1 antibody injection and development of type 1 diabetes was 155 days and ranged from 13 to 504 days. Flu-like symptoms, abdominal symptoms, and drowsiness were observed in 27.8, 31.6, and 16.7% patients, respectively. Mean ± standard deviation or median (first quartile-third quartile) glucose levels, HbA1c levels, urinary C-peptide immunoreactivity levels, and fasting serum C-peptide immunoreactivity levels were 617 ± 248 mg/dl, 8.1 ± 1.3%, 4.1 (1.4-9.4) μg/day, and 0.46 (0.20-0.70) ng/ml, respectively. Seventeen of 20 patients (85.0%) developed ketosis, and 7 of 18 patients (38.9%) developed diabetic ketoacidosis. Ten of 19 patients (52.6%) showed at least one elevated pancreatic enzyme level at the onset and two of seven patients showed this elevation before diabetes onset. Only one of 21 patients was anti-glutamic acid decarboxylase antibody positive., Conclusions: Anti-programmed cell death-1 antibody-related type 1 diabetes varies from typical fulminant type 1 diabetes to acute-onset type 1 diabetes. However, diabetic ketoacidosis was frequently observed at the onset of diabetes. An appropriate diagnosis and treatment should be provided to avoid life-threatening metabolic alterations., Competing Interests: Akihisa Imagawa received scholarship donations from Ono Pharmaceutical Co., Ltd. and MSD and honoraria for lectures from Ono Pharmaceutical Co., Ltd. Norio Abiru received research grants from Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb. Hiroshi Ikegami received a scholarship grant from Ono Pharmaceutical Co., Ltd. Yumiko Kawabata received a scholarship grant from Ono Pharmaceutical Co., Ltd. Other authors declare that they have no conflicts of interest.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (The Ethics Committees of the JDS, date of approval: 26 August 2016, approval number: 28-003-(2), Osaka University Hospital, date of approval: 27 April 2016, approval number: 15589, and Osaka Medical College, date of approval: 10 January 2017, approval number: 2098) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.

Aims/introduction: The present study was carried out to generate induced pluripotent stem cells (iPSCs) from patients with fulminant type 1 diabetes, and evaluate the cytokine-induced apoptotic reactions of β-like insulin-producing cells differentiated from the iPSCs., Materials and Methods: iPSCs were generated from fibroblasts of patients with fulminant type 1 diabetes by inducing six reprogramming factors. Insulin-producing cells were differentiated from the iPSCs in vitro. The proportion of cleaved caspase-3-positive or terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling-positive cells among insulin (INS)-positive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines was evaluated under treatment with tumor necrosis factor-α, interleukin-1β and interferon-γ. Ribonucleic acid sequencing was carried out to compare gene expressions in INS-positive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines., Results: Two iPSC clones were established from each of three patients with fulminant type 1 diabetes. The differentiation of insulin-producing cells from fulminant type 1 diabetes iPSC was confirmed by immunofluorescence analysis and KCl-induced C-peptide secretion. After treatment with pro-inflammatory cytokines, these INS-positive cells showed higher expression of cleaved caspase-3 than those derived from control human iPSCs. Altered expression levels of several apoptosis-related genes were observed in INS-positive cells derived from the fulminant type 1 diabetes iPSCs by ribonucleic acid sequencing., Conclusions: We generated iPSCs from patients with fulminant type 1 diabetes and differentiated them into insulin-producing cells. This in vitro disease model can be used to elucidate the disease mechanisms of fulminant type 1 diabetes., (© 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims: The onset of fulminant type 1 diabetes mellitus is sometimes accompanied by sudden death or cardiac arrest. The aim of this study was to determine the risk factors for the development of these conditions at the onset of fulminant type 1 diabetes mellitus., Methods: We conducted a search of the literature on fulminant type 1 diabetes and sudden death or cardiac arrest published up to 2012 in PubMed and Ichushi (a Japanese article database), and a questionnaire survey was administered to the authors of the articles and to diabetes specialists affiliated to the Japan Diabetes Society. We analyzed the clinical data at disease onset of 17 patients with fulminant type 1 diabetes mellitus who experienced sudden death or cardiac arrest, and those of 257 patients who did not develop these conditions., Results: Patients with sudden death or cardiac arrest were younger, had a higher rate of impaired consciousness, more severe acidosis, hyperglycemia, hyponatremia, hyperkalemia, and hypochloremia, a higher serum blood urea nitrogen level, a higher serum creatinine level, and a higher plasma osmolality level than the other patients. In multiple logistic regression analyses, plasma glucose level was positively associated with sudden death or cardiac arrest. Receiver operating characteristic curve analyses showed that patients with a plasma glucose level over 1000 mg/dl (55.5 mmol/l) were at a high risk of cardiac arrest., Conclusions: Severe metabolic derangement, especially a high plasma glucose level, is associated with sudden death or cardiac arrest at the onset of fulminant type 1 diabetes mellitus., Competing Interests: Toshiaki Hanafusa received honoraria for lectures from Ono Pharmaceutical, Mitsubishi Tanabe Pharma, and Sumitomo Dainippon Pharma. Hiroshi Ikegami received honoraria for lectures from Novo Nordisk Pharmaceuticals Industries, Inc., Sumitomo Dainippon Pharma, and Kowa Company, and scholarship grants from Ono Pharmaceutical and Novo Nordisk Pharmaceuticals Industries, Inc. Yumiko Kawabata received scholarship grants from Ono Pharmaceutical and Novo Nordisk Pharmaceuticals Industries, Inc. Other authors declare that they have no conflict of interest.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or a substitute for it was obtained from all patients before they were included in the study.

Aims: Viral infection is associated with pancreatic beta cell destruction in fulminant type 1 diabetes mellitus. The aim of this study was to investigate the acceleration and protective mechanisms of beta cell destruction by establishing a model of viral infection in pancreatic beta cells., Methods: Polyinosinic:polycytidylic acid was transfected into MIN6 cells and insulin-producing cells differentiated from human induced pluripotent stem cells via small molecule applications. Gene expression was analyzed by real-time PCR, and apoptosis was evaluated by caspase-3 activity and TUNEL staining. The anti-apoptotic effect of Exendin-4 was also evaluated., Results: Polyinosinic:polycytidylic acid transfection led to elevated expression of the genes encoding IFNα, IFNβ, CXCL10, Fas, viral receptors, and IFN-inducible antiviral effectors in MIN6 cells. Exendin-4 treatment suppressed the elevated gene expression levels and reduced polyinosinic:polycytidylic acid-induced apoptosis both in MIN6 cells and in insulin-producing cells from human induced pluripotent stem cells. Glucagon-like peptide-1 receptor, protein kinase A, and phosphatidylinositol-3 kinase inhibitors counteracted the anti-apoptotic effect of Exendin-4., Conclusions: Polyinosinic:polycytidylic acid transfection can mimic viral infection, and Exendin-4 exerted an anti-apoptotic effect both in MIN6 and insulin-producing cells from human induced pluripotent stem cells.

Objective: Serum adiponectin levels are affected by gender, body fat mass, several pathological factors or therapeutic interventions and it might be also affected by age. This study aimed to investigate the relationship between serum adiponectin levels and age in several physiological states., Design, Patients and Measurements: The study was carried out in 21 100 healthy subjects (12 363 men and 8737 women) and 1833 patients with type 2 diabetes (1233 men and 600 women). Physical and demographic characteristics were recorded, and blood samples were collected to measure serum adiponectin levels. Using these data, we determined the relationships between serum adiponectin levels and various parameters, including age., Results: Serum adiponectin levels increased with increasing age of healthy subjects and in patients with diabetes, in both men and women. Serum adiponectin levels were positively correlated with age in healthy subjects and patients with diabetes, in both men and women. In stepwise multiple regression analysis with serum adiponectin levels as the dependent variable and physiological characteristics as explanatory variables, age was significantly and independently associated with serum adiponectin levels in each of these groups of subjects., Conclusions: Serum adiponectin levels are significantly and positively associated with age in healthy subjects and in patients with diabetes. This association is independent of renal function, body fat status, glucose metabolism and lipid profiles., (© 2012 John Wiley & Sons Ltd.)

Objective: With the increasing prevalence of diseases related to obesity, metabolic syndrome and its key player adiponectin are now attracting considerable attention. Hypoadiponectinaemia is reported to be a risk factor for hypertension and associated with endothelial dysfunction, which is closely related to complications of obesity such as hypertension. As there is limited information regarding serum adiponectin levels in normotensive people, we undertook the large-scale study to determine the association of adiponectin with blood pressure (BP) in mainly normotensive people., Design, Patients and Measurements: In 21 100 Japanese adults (12 363 men and 8737 women) who had no apparent diseases, we examined the relationship between the serum adiponectin concentration and BP by performing a questionnaire survey, physical measurements and measurement of laboratory parameters including the serum adiponectin level., Results: Subjects with hypoadiponectinaemia had higher systolic and diastolic BPs as already reported. And interestingly, subjects with higher adiponectin had lower systolic and diastolic BP. According to linear regression analysis, adiponectin showed a significant negative correlation with systolic and diastolic BP independently of the other variables. Analysis of covariance according to adiponectin quintiles showed that systolic and diastolic BP in highest adiponectin quintile was significantly lower than in other quintiles., Conclusions: This study revealed that there were significant trends toward lower systolic and diastolic BP with higher adiponectin not only in hypertensive people but also in normotensive people., (© 2012 Blackwell Publishing Ltd.)

Background: To investigate the relationship between serum levels of cystatin C and adiponectin in patients with type 2 diabetes., Methods: We examined serum cystatin C and adiponectin levels in 234 patients with type 2 diabetes who visited our hospital., Results: The serum level of cystatin C was positively correlated with age (P < 0.001), duration of diabetes (P = 0.013), serum creatinine (P < 0.001), uric acid (P < 0.001), and adiponectin (p = 0.001), while it was inversely correlated with estimated glomerular filtration rate (P < 0.001). Serum adiponectin was significantly higher in patients with high serum cystatin C levels than in those with normal cystatin C levels (8.3 ± 4.7 and 6.2 ± 3.2 μg/mL, respectively; P < 0.001). Adiponectin was also significantly higher in male patients with high cystatin C levels, but not in females. In multiple regression analysis, serum adiponectin was also independently and significantly correlated to age, diastolic blood pressure, high-density lipoprotein cholesterol, triglyceride and serum cystatin C., Conclusions: Serum adiponectin level was correlated with serum cystatin C level on simple and multiple regression analyses in patients with type 2 diabetes. Although circulating adiponectin is increased in advanced kidney disease, it might be biologically inactive due to binding to cystatin C and thus not display an anti-arteriosclerotic effect.

Objective: Along with the increasing prevalence of obesity and related diseases, particularly atherosclerotic diseases, metabolic syndrome (MetS) is now a common and major public health issue in many countries around the world. Adiponectin, a protein secreted by the adipose tissue, has become recognized as a key player in the development of MetS. These days, not only MetS but also borderline metabolic/physiological abnormalities, such as impaired fasting glucose, high normal blood pressure and high normal plasma cholesterol, have been reported to be risk factors for atherosclerotic disease. Therefore, we undertook this study to determine the relationship between adiponectin and borderline metabolic/physiological abnormalities, as well as MetS., Design: A cross-sectional study performed from April 2007 to November 2009., Subjects: In 16 892 Japanese adults (10 008 men and 6884 women), we examined the relationship between the serum adiponectin concentration and borderline metabolic/physiological abnormalities or MetS by a questionnaire survey about medical treatment, body size measurement and measurement of laboratory parameters including the serum adiponectin concentration., Results: Adiponectin showed a significant negative correlation with the number of MetS components. In subjects without overt diabetes mellitus, hypertension or dyslipidemia, the adiponectin concentration also showed a significant negative correlation with the number of borderline metabolic abnormalities., Conclusion: The decrease of circulating adiponectin may start before the development of diabetes mellitus, hypertension, dyslipidemia or MetS. Adiponectin is an important biomarker for reflecting the adverse influence of visceral fat in persons with MetS, and also in these subclinical states.

A 66-year-old man with Cushing's syndrome due to adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) was treated for 7 years with trilostane, a 3β-hydroxysteroid dehydrogenase inhibitor. Administration of trilostane reduced the serum cortisol level to around the upper limit of normal for 7 years, and symptoms of excessive glucocorticoid production (such as moon face and obesity) were gradually improved. On the other hand, the size of both adrenal glands gradually increased despite treatment with trilostane. Though trilostane therapy could not prevent adrenal growth, it did suppress cortisol secretion over the long term, so it might be a reasonable option for AIMAH in addition to adrenalectomy.