Publishing type：Research paper (scientific journal)  

DOI： 10.1111/jdi.14394

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OBJECTIVE: To evaluate the association between dietary fiber intake and obesity in Japanese outpatients with type 2 diabetes, as well as the demographic and dietary factors influencing this association. DESIGN: Cross-sectional study with nationwide registry data on Japanese type 2 diabetes outpatients (2014-2019). Diet was self-reported via a Food Frequency Questionnaire. Obesity was defined as BMI ≥25 kg/m2. SETTING: Clinics throughout Japan. PARTICIPANTS: 1,565 Japanese outpatients with type 2 diabetes (63.1% men; age range 30-89 years). RESULTS: Multivariate analysis revealed that a higher dietary fiber intake was associated with a lower risk of obesity in all participants (95% CI = 0.439-0.795, p < 0.001). Stratified analysis showed a significant inverse association between fiber intake and obesity in men and the older age groups (59-89 years), but not in women or the younger age group (30-58 years). In men, higher fiber intake was associated with healthier lifestyle behaviors, including increased physical activity (p < 0.001) and non-smoking (p < 0.001), with stronger associations compared to women. Vegetables, fruits, and soybeans/soy products were strongly correlated with fiber, while grains had a weak correlation. Folate was the micronutrient most strongly correlated with fiber. CONCLUSION: Higher fiber intake was associated with lower obesity risk, particularly in men and older age groups. These findings emphasize the need for targeted public health initiatives promoting the intake of diverse fiber-rich foods to effectively manage obesity. Further research is needed to understand sex- and age-specific factors in the fiber-obesity relationship in diverse populations.

DOI： 10.1017/S136898002500014X

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OBJECTIVE: Differing from the overall consumption of alcohol, whether consuming large quantities of alcohol per drinking occasion is associated with higher risk of developing severe diabetic retinopathy remains unknown. METHODS: We examined whether the quantity per drinking occasion (QPO), including a large QPO, and the combinations of the frequency of alcohol consumption (FAC) and QPO were associated with higher risk of developing severe diabetic retinopathy or diabetic macular edema (DME) using adjusted Cox models. Severe diabetic retinopathy or DME was designated as a vision-threatening treatment-required diabetic eye disease (TRDED). For each man with type 2 diabetes who participated in this longitudinal retrospective cohort study, the date of the earliest health check-up during the inclusion period (April 2008 to August 2016) was set as the start date of follow-up. RESULTS: A TRDED was observed in 425 of 21,392 Japanese men aged 22-74 years with type 2 diabetes during a mean follow-up of 4.3 years (4.6/1000 person-years). Multivariable Cox analysis showed that a large QPO, defined as drinking three drinks or more per occasion, in low- (hazard ratio [HR], 4.76; 95 % CI, 2.06-10.97), intermediate- (HR, 1.58; 95 %CI, 1.001-2.50), and high-frequency categories (HR, 2.01; 95 % CI, 1.20-3.36) was significantly associated with elevated risks of TRDED. CONCLUSIONS: In addition to the total amount of ethanol, these findings imply the necessity of avoiding the consumption of large amounts of alcohol on a single occasion to prevent severe diabetic retinopathy or DME.

DOI： 10.1016/j.ypmed.2025.108220

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OBJECTIVE: To examine the association between a positive family history (parents, siblings, and grandparents) of type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia and their prevalence and incidence in the same population. PATIENTS AND METHODS: Data on 41,361 participants who underwent health examinations between January 1, 1997, and December 31, 2007, were analyzed, and the results of logistic and Cox regression analyses in the same cohort were examined. RESULTS: Cross-sectional analyses showed that the prevalence of all three diseases increased with a positive family history, especially T2DM, with an odds ratio (OR) of 12.00 (95% CI, 7.82 to 18.41) when the number of affected relatives was greater than or equal to 3 with an OR of 20.43 (95% CI, 11.0 to 37.8) for a positive family history across three generations compared with no family history. However, redefining family history from "parents, siblings, and grandparents" to "parents and siblings" or "parents only" did not significantly change ORs for each disease. Among those with a positive family history and body mass index greater than or equal to 30.0 kg/m2 hypertension was 19 times more prevalent compared with no family history and body mass index of 18.5 to 24.9 kg/m2. In the longitudinal study, family history strongly influenced incident T2DM (hazard ratio[HR], 2.40; 95% CI, 1.93 to 2.98), hypertension (HR, 1.43; 95% CI, 1.26 to 1.62), and dyslipidemia (HR, 1.41; 95% CI, 1.08 to 1.83), respectively. CONCLUSION: Obtaining a family history of these diseases was useful in identifying high-risk groups. Also, for T2DM, the influence of a positive family history was strongest with a marked increase in risk with overlap of affected family members, suggesting that a family history is useful for early detection and prevention.

DOI： 10.1016/j.mayocp.2024.10.020

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BACKGROUND: Previous studies demonstrated that diabetes remission can occur during intensive intervention and in real-world settings. However, the impact of diabetes remission in real-world settings on the incidence of cardiovascular disease (CVD) remains unclear. METHODS: This retrospective cohort study included 299,967 individuals aged 20-72 years who underwent multiple checkups between 2008 and 2020 and completed ≥ 3 years of follow-up. Patients were divided into four groups according to changes in glycated hemoglobin levels and the use of diabetes medications during the 1-year baseline period: diabetes mellitus (DM)+/no remission, DM+/remission, DM-/no progression, and DM-/progression. The risk of CVD was evaluated using multivariable Cox regression analysis. RESULTS: The median follow-up period was 5.0 years. The rates of CVD in the DM+/no remission, DM+/remission, DM-/no progression, and DM-/progression groups were 7.96, 4.76, 1.99, and 5.47 per 1000 person-years, respectively. Compared with DM+/no remission, DM+/remission reduced the risk of CVD [hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.57-0.89]. Meanwhile, the HR for CVD in the DM+/remission group was 0.75 (95% CI = 0.56-0.99) for change in BMI ≤ 0%, versus 0.66 (95% CI = 0.45-0.96) for change in BMI > 0%. CONCLUSIONS: In a real-world setting without intensive intervention, diabetes remission decreased the risk of CVD by approximately 30% regardless of changes in BMI, suggesting that diabetes remission can prevent CVD without weight loss in routine care and emphasizing the importance of achieving remission.

DOI： 10.1186/s12933-025-02578-y

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BACKGROUND & AIMS: This study assessed the association of remission of type 2 diabetes mellitus (DM) or metabolic dysfunction-associated steatotic liver disease (MASLD)/related SLD (r-SLD; MASLD with excessive alcohol intake) as defined by the fatty liver index with the risk of cardiovascular disease (CVD). METHODS: Health examination data at baseline and after 2 years (2-Years) were extracted from a nationwide claims database in Japan. Among participants aged 18-72 years with at least 3 years of follow-up, 9345 participants with DM-associated MASLD/r-SLD and 71 932 participants with non-DM MASLD/r-SLD at baseline were included in the study. The participants were stratified by the achievement of remission of MASLD/r-SLD or DM at 2-Years. In each group after stratification, the risk of new-onset CVD during the observation period was analysed using multivariate Cox proportional hazards models. RESULTS: During a median follow-up of 4.9 years (starting from 2-Years), 1368 cases of CVD were observed. The hazard ratio (95% confidence interval) for CVD was 0.50 (0.31-0.80) for participants with remission of DM, 0.65 (0.47-0.91) for participants with remission of MASLD/r-SLD, and 0.34 (0.15-0.77) for participants with remission of both DM and MASLD/r-SLD. Conversely, remission of MASLD/r-SLD was not linked to a reduced risk of CVD in participants with non-DM MASLD/r-SLD. CONCLUSION: The association of MASLD/r-SLD remission with CVD risk differs greatly in the presence and absence of DM. In patients with DM-MASLD/r-SLD, MASLD/r-SLD remission can significantly reduce CVD risk similarly as remission of DM.

DOI： 10.1111/dom.16196

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AIMS: Many guidelines recommend increases in potassium intake. However, the relationship of dietary potassium intake with incident cardiovascular disease (CVD) has not been examined in those with type 2 diabetes (T2DM), including sodium acting antagonistically with potassium. We investigated these relationships in Japanese patients with T2DM. MATERIALS AND METHODS: The investigation was part of the JDCP study, a nationwide prospective study begun in 2007. Analysed were 1477 persons with T2DM, 40-75 years of age, who completed a brief-type, self-administered Diet History Questionnaire at baseline. Primary outcome was a CVD event during the follow-up median 7 years (3.9-8.1 years). Hazard ratios (HRs) for CVD were estimated by Cox regression adjusted for confounders of daily potassium intake categorized by tertiles. Tertiles of sodium intake were also analysed. RESULTS: Mean daily potassium intake in tertiles was 1877, 2627 and 3532 mg, respectively, and significant associations were not shown between potassium intake and incidence of CVD. When HRs for CVD were stratified for potassium intake in tertiles (reference group, bottom tertile) and sodium intake (reference group, bottom tertile), potassium intake in the bottom tertile and sodium intake in the second and top tertiles were associated with significantly elevated HR for CVD (2.79 [1.02-7.63] and 3.92 [1.30-11.79], respectively). CONCLUSIONS: Low potassium intake in conjunction with high sodium intake was significantly associated with increased incident CVD in persons with T2DM. However, CVD incidence was not related to high potassium intake, regardless of sodium intake.

DOI： 10.1111/dom.16035

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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AIM: To investigate the association between low-density lipoprotein-cholesterol (LDL-C) levels and coronary artery disease (CAD) incidence based on combining high-density lipoprotein-cholesterol (HDL-C) levels and glucose status. MATERIALS AND METHODS: In this retrospective cohort study, we used data from a nationwide claims database (1,524,289 individuals without a history of CAD or familial hypercholesterolaemia; 2008-2019). Cox proportional hazards modelling identified the risk of incident CAD by a novel combination of four HDL-C levels, seven LDL-C levels and glucose status. RESULTS: During the follow-up period (mean: 5.5 years), 8301 (0.99/1000 person-years) events occurred. The risk of CAD increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of the glucose status. Using the most favourable levels of HDL-C and LDL-C (i.e. 60-99 mg/dL and <80 mg/dL, respectively) as references, the hazard ratios (95% confidence interval) for the group with HDL-C levels <40 mg/dL and LDL-C levels <80 mg/dL were 2.74 (1.47-5.11), 2.52 (1.30-4.91) and 2.85 (1.68-4.84) for normoglycaemia, borderline glycaemia and diabetes, respectively. Comparison of the most favourable levels of HDL-C and LDL-C with their least favourable levels (i.e. <40 mg/dL and 180-199 mg/dL, respectively) revealed that the risk of new-onset CAD exhibited a 19-, nine- and seven-fold increase in individuals with normoglycaemia, borderline glycaemia and diabetes, respectively. CONCLUSIONS: To prevent CAD, LDL-C levels should be strictly controlled in patients with low HDL-C levels regardless of glucose tolerance. Individualized treatment, which involves setting target LDL-C levels based on glucose tolerance and HDL-C values, is required.

DOI： 10.1111/dom.15956

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Publishing type：Research paper (scientific journal)  

DOI： 10.1111/dom.15887

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DOI： 10.1016/j.dsx.2024.103168

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：English   Publishing type：Research paper (scientific journal)  

AIMS/INTRODUCTION: History of coronary artery disease (CAD), cerebrovascular disease (CeVD), type 2 diabetes and their combined effect on cardiovascular disease are essential for cardiovascular risk management. We investigated the association of prior CAD, prior CeVD, type 2 diabetes and their combination with the risk of cardiovascular disease. MATERIALS AND METHODS: This is a historical cohort study including 342,033 participants (aged 18-72 years) followed up for ≥5 years between 2008 and 2016. Participants were classified into eight groups (with or without prior CAD, prior CeVD and type 2 diabetes). Type 2 Diabetes was defined by fasting plasma glucose and glycated hemoglobin levels, and antidiabetic drug prescription. Prior and subsequent CAD and CeVD were identified according to claims using International Classification of Diseases 10th Revision codes, medical procedures and questionnaires. Cox regression models were used to evaluate the risk of cardiovascular events. RESULTS: The median follow-up period was 6.4 years. The incidence of composite cardiovascular events of CAD and CeVD in the CAD-/CeVD-, CAD+/CeVD-, CAD-/CeVD+ and CAD+/CeVD+ groups were 1.92 and 6.94, 25.14 and 31.98 per 1,000 person-years in non-diabetes participants, and 8.66, 18.04, 39.98 and 60.72 in type 2 diabetes patients, respectively. Hazard ratios of cardiovascular events compared with CAD-/CeVD-/non-diabetes were 1.66 (95% confidence interval 1.55-1.78) in CAD-/CeVD-/type 2 diabetes and 1.84 (1.56-2.18) in CAD+/CeVD-/non-diabetes. CeVD+ was linked to a 4-7-fold increase in the risk of cardiovascular events regardless of CAD+ or type 2 diabetes. CONCLUSIONS: Type 2 diabetes increased the risk of cardiovascular disease as high as a history of CAD, whereas prior CeVD alone increased the risk of future CeVD without additional effects by type 2 diabetes.

DOI： 10.1111/jdi.14277

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AIMS: To clarify the impact of Breslow's scores consisting of only lifestyle habits or American Heart Association's (AHA) Life's Simple 7 scores consisting of lifestyle habits and control targets on starting dialysis in people with or without diabetes mellitus (DM). METHODS: To pursue the study aims, we examined a nationwide database on 294,647 individuals with and without DM aged 19-72 y in Japan to pursue the study aims. Using multivariate Cox modeling, we evaluated and compared 5 risk factors based on the unfavorable lifestyle factors in Breslow's scores and the unfavorable lifestyle factors and clinical values in AHA Life's Simple 7 scores. RESULTS: DM increased the risk of the initiation of dialysis 5- to sixfold but that risk did not increase with worsening of Breslow risk factors. Compared with no risk factor, 5 risk factors derived from AHA's Life's Simple 7 presented 9.8-fold and 4.2-fold risks for the initiation of dialysis in non-DM and DM, respectively. In comparison with non-DM and no risk factor, risk of the initiation of dialysis dramatically increased up to 32.3 times according to the number of AHA risk factors in those with DM. CONCLUSIONS: DM and risk factors derived from AHA's Life's Simple 7 synergistically increased the risk of the initiation of dialysis. Factors similar to those used to predict cardiovascular disease would also be useful to predict the initiation of dialysis. These approaches might be helpful in clinical practice and patient education. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-024-00739-0.

DOI： 10.1007/s13340-024-00739-0

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：Japanese   Publisher：(一社)日本臨床栄養協会  

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: GH-releasing peptide-2 (GHRP2) can be used for provocative growth hormone testing (GHT). Since it acts as a powerful stimulus for GH secretion, cut-off peak GH level in GHRP2 loading test (GHRP2T) is higher than in other GHT. Nevertheless, data on response at adolescents are limited. This report aimed to investigate peak GH levels in GHRP2T in adolescents. METHODS: Clinical data of adolescents after onset of puberty who underwent GHRP2T at our institution from May 2010 to March 2023 were collected retrospectively. Subjects were classified into three groups according to underlying diseases. RESULTS: A total of 23 patients were included: 12 in organic or genetic GHD (o/gGHD) group, three in idiopathic GHD (iGHD) group, and eight in short stature (SS) group. The median GH peak levels were 3.4 ng/mL in o/gGHD group, 88.9 ng/mL in iGHD group, and 90.1 ng/mL in SS group, indicating a robust response of GH peak levels in iGHD and SS groups. Two patients exceeded the cut-off for GHRP2T but below for other GHT, indicating the current cut-off for GHRP2T may miss some GHD patients. CONCLUSIONS: The GH response to GHRP2T in adolescents except the o/gGHD group may be robustly responsive. For the correct diagnosis of GHD, the cut-off peak GH levels in GHRP2T in adolescents may require revisiting.

DOI： 10.1515/jpem-2024-0115

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：English   Publishing type：Research paper (scientific journal)  

AIMS: To evaluate and compare the association of incident cardiovascular disease (CVD) with the Health Practice Index (HPI) reflecting only lifestyle habits and Ideal Cardiovascular Health Metrics (ICVHMs) consisting of lifestyle habits and factors targeted for control in the same population according to glucose status. METHODS: This retrospective cohort study included 1,28,162 participants aged 18-72 years with no history of CVD followed for ≥ 3 years between 2008 and 2016. Participants were classified according to normal glucose tolerance (86,174), prediabetes (36,096), or diabetes (5892). HPI and ICVHMs scores were classified into three groups (high/medium/low). Multivariate Cox regression hazard analysis examined CVD risk. RESULTS: During a mean follow-up of 5.2 years, 1057 CVD events occurred. In prediabetes, CVD risk was significantly higher in groups with both medium and low HPI scores and ICVHMs scores compared to high scores for normal glucose tolerance (hazard ratios [HRs] for high/medium/low HPI scores were 0.95 [0.78-1.17], 1.56 [1.29-1.89], and 2.41 [1.74-3.34] and for ICVHMs scores were 0.74 [0.50-1.11], 1.58 [1.26-1.98], and 2.63 [2.10-3.31], respectively). Regarding diabetes, compared with high HPI/ICVHMs scores in the normal glucose tolerance group, a significantly increased CVD risk was observed in the high-score HPI group, but not in the high-score ICVHMs group (HPI high/medium/low HR, 1.63 [1.22-2.18], 2.19 [1.69-2.83], and 2.26 [1.34 -3.83]; ICVHMs high/medium/low HR, 1.14 [0.47-2.81], 2.38 [1.75-3.23], and 3.31 [2.50-4.38], respectively). CONCLUSIONS: In diabetes, ideal lifestyle practices alone were insufficient for primary prevention of CVD but had a greater impact on primary prevention of CVD in prediabetes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-024-00708-7.

DOI： 10.1007/s13340-024-00708-7

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

A FH of T2DM, HT, and DL are known risk factors; however, few studies have compared the impact of a FH of the 3 diseases in the same population. We examined the impact of a detailed FH of these conditions (i.e., in fathers, mothers, siblings and grandparents) on their prevalence and incidence in the study population. Data on 41,931 participants who underwent health checkups were examined and the results of a logistic regression and (Cox regression model in the same cohort were examined. Results of the cross-sectional study showed that odds ratios increased with the degree of a positive FH for all three diseases. Furthermore, in T2DM, the group with a three-generation positive FH was approximately 20 times larger than the control group which had no FH (Figure). In the longitudinal study, FH had a strong influence on the incidence of T2DM, HT, and DL, in that order, with a hazard ratio of 2.40 (1.93-2.98) for T2DM. A detailed FH was extremely useful for both quantitative screening for each disease and predicting the incidence of the three diseases, especially T2DM, for which a high risk was indicated in multiple generations with overlapping of positivity for a particular disease.

<p></p> Disclosure

I. Ikeda: None. K. Fujihara: None. Y. Takeda: None. M. Hatta: None. S. Wu: None. S. Kodama: None. Y. Mori: None. T. Kadowaki: None. R. Yamamoto-Honda: None. Y. Arase: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

DOI： 10.2337/db24-1474-p

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

Although control of multiple risk factors is essential to prevent FD with and without DM, longitudinal studies are scarce that directly and quantitatively compare effects of such control. Thus, we assessed whether reaching multifactorial targets for HbA1c, blood pressure, non-HDLC, and lifestyle risks such as smoking and no physical activity are associated with FD in those with and without DM.

Enrolled were 9652 Japanese aged 39-98 y. FD was defined based on the Japanese long-term care insurance system, and targets were based on ADA and Japanese guidelines.

Of 8,861 non-DM persons, 6.3, 25.2 and 49.1% were on target for 0-2, 3 and 4 factors, respectively. Of 791 persons with DM, 12.4, 68.0 and 19.3% were on target for 0-2, 3-4 and 5 factors, respectively.

Multivariate Cox analysis showed increased FD with decreased targets reached regardless of DM (Table, upper). Compared with people with non-DM who achieved 4 targets, non-DM persons who achieved 0 to 2 targets and DM persons who achieved 3 to 4 targets had nearly twice the incidence of FD (Table, lower). Moreover, people with DM who achieved only 0 to 2 targets had an approximately 4 times higher incidence of FD (Table, lower). Control of modifiable risk factors was effective regardless of DM. Achievement of all 5 targets among people with DM may reduce FD to the same level as in non-DM persons who achieved all 4 targets.

<p></p> Disclosure

H. Shiozaki: None. K. Fujihara: None. K. Tsuruoka: None. I. Ikeda: None. M. Kitazawa: None. Y. Matsubayashi: None. M. Yamamoto: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

Funding

the Japan Society for the Promotion of Science (21K11569); Daiwa Securities Health Foundation

DOI： 10.2337/db24-1259-p

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

Previous systematic reviews showed benefits of low-carbohydrate eating plans compared with low-fat eating plans in the treatment of diabetes (T2D) on parameters of cardiovascular disease (CVD) risk. However, studies on the relationship between fat intake as the % of total energy (F%E) and incidence of CVD in persons with T2D are insufficient. Therefore, we investigated this relationship as part of the JDCP study, a nationwide study launched in 2007. A total of 1477 persons with T2D aged 40-75 years completed a brief self-administered Diet History Questionnaire at baseline, and we analyzed the resultant data. Primary outcome was the 7-year risk of a CVD event. Hazard ratios for CVD according to quartiles of F%E (Q1-4) were estimated by Cox regression adjusted for confounders including sex, age, various laboratory tests, medication use, smoking history, drinking habits, physical activity, energy intake, protein intake, dietary fiber intake, and sodium intake. Mean F%E in Q1 to Q4 were 16.6%E, 21.8%E, 25.4%E, and 30.9%E, respectively. HbA1c, body mass index, triglycerides, and blood pressure were well controlled. No significant associations between F%E and incidence of CVD were shown for Q2, Q3, and Q4 relative to Q1 (Q2: 1.03 [95% CI, 0.47-2.28], Q3: 1.27 [0.58-2.76], and Q4: 1.10 [0.44-2.73]). Stratified analysis by sex and age also showed no significant difference between F%E and incidence of CVD. When %E from saturated fatty acids (SFA%E) was analyzed according to quartiles 1 and 4 SFA%E values were 4.9%E and 7.1%E, respectively. There were no significant differences in incidence of CVD among quartiles (Q1: Reference, Q2: 1.31 [0.66-2.61], Q3: 0.47 [0.18-1.25], and Q4: 1.02 [0.44-2.39]). Findings suggested that most Japanese with T2D during the study period consumed &amp;lt; 30% of F%E and &amp;lt;10% of SFA%E. No significant differences in incident CVD were observed within these ranges.

Disclosure

C. Horikawa: None. M. Takahara: None. N. Katakami: Speaker's Bureau; Abbott Japan Co., Ltd., Kowa Company, Ltd., MSD, Mitsubishi Tanabe Pharma Corporation, Lilly Diabetes, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Kyowa Kirin Co., Ltd., Daiichi Sankyo, Boehringer-Ingelheim, Sanofi. Y. Takeda: None. M. Takeuchi: None. K. Fujihara: None. H. Suzuki: Speaker's Bureau; Abbott Japan Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Boehringer-Ingelheim, Terumo Corporation, AstraZeneca, Bayer Inc., Kyowa Kirin Co., Ltd. N. Yoshioka: None. H. Shimano: None. J. Satoh: Speaker's Bureau; Lilly Diabetes, Merck &amp; Co., Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Boehringer-Ingelheim. Y. Hayashino: Speaker's Bureau; Eli Lilly and Company, Merck &amp; Co., Inc., Boehringer-Ingelheim, Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk A/S. N. Tajima: None. R. Nishimura: Speaker's Bureau; Abbott. Advisory Panel; Abbott Japan Co., Ltd. Speaker's Bureau; Boehringer-Ingelheim, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Medtronic, Sanofi, Taiho Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Eli Lilly and Company, Novo Nordisk A/S. Consultant; Terumo Corporation. Y. Yamasaki: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

Funding

The Japan Diabetes Society, the Japan Society for the Promotion of Science(23K10873).

DOI： 10.2337/db24-1372-p

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

Heritability and obesity are strongly associated with the prevalence of T2DM, HT, and DL. We compared the effects of an FH of T2DM, HT, and DL combined with obesity on the prevalence of each in the same population. Of 41931 participants who underwent health checkups, the effects of an FH and BMI on the prevalence of those conditions were analyzed cross-sectionally. Prevalences of T2DM, HT, and DL were 5%, 20%, and 48%, respectively. Logistic regression analysis showed that ORs increased for all three as the number of FH positive cases increased and was most pronounced for T2DM. An FH of obesity and increased BMI were additively associated with the prevalence of the three diseases compared to BMI 20.0-21.9 and no positive FH (Fig. A). In addition, the combination of the number of family members with FH positivity (0,1, 2, ≥3) and obesity was additively associated with an increased FH of the three diseases compared to non-obesity and no FH of any of these diseases (Fig. B). For T2DM, the OR increased sharply in non-obese participants when the number of those with an FH of T2DM was ≥3 (14.4 [8.88-23.5]), but in obese participants the OR increased sharply when the number of those with an FH of T2DM was 2 (12.2 [8.85-16.9]) (Fig. B). Results suggest that, especially for T2DM, avoidance of obesity may be effective in reducing the prevalence of these disorders in those with many FH-positive family members.

<p></p> Disclosure

I. Ikeda: None. K. Fujihara: None. Y. Takeda: None. C. Horikawa: None. S. Kodama: None. E.D. Ferreira: None. Y. Mori: None. T. Kadowaki: None. R. Yamamoto-Honda: None. Y. Arase: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

DOI： 10.2337/db24-1666-p

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

Childhood obesity mostly transitions into adulthood and leads to non-communicable diseases such as type 2 diabetes and metabolic syndrome. We aimed to examine individual-level transitions in metabolic parameters during adolescence and young adulthood. We analyzed metabolic parameters in 523 participants (311 males) who underwent health examinations at the ages of 14 y (8th grade) and 20 y. Weight status was assessed by the International Obesity Task Force at 14 y and by BMI (thinness: &amp;lt;18.5; normal: 18.5-24.9; obesity: ≥25.0) at 20 y. HbA1c ≥5.7% was defined as high. Clustered metabolic risk score (CMR) was calculated by summing the sex-age specific Z-scores of each metabolic factor (mean arterial pressure, non-HDLC, and HbA1c) with ≥1 SD defined as high. Among participants who were obese at 14 y, 56% of males and 29% of females remained obese at 20 y. In both sexes, 30-50% had high HbA1c and 30-50% had high CMR as tracked from adolescence to adulthood (table). Furthermore, the high CMR of obese females increased markedly from about 20% at 14 y to 50% at 20 y. In addition, 60% of females who were obese at both 14 y and 20 y had high HbA1c at 20 y. Results suggested the importance of lifestyle interventions from childhood, as about half of the high metabolic parameters observed in adolescents were tracked into adulthood, and obesity complications, which were rarely shown at 14 y, appeared in many at age 20 y.

<p></p> Disclosure

I. Ikeda: None. K. Fujihara: None. H. Shiozaki: None. S.Y. Morikawa: None. C. Horikawa: None. Y. Takeda: None. H. Ishiguro: None. T. Yamada: None. S. Kodama: None. Y. Ogawa: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

DOI： 10.2337/db24-1148-p

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

Avoidance of FD and the deterioration of care level needs leading to a decline in ADL and increased medical costs is urgent. We aimed to clarify the association between lifestyle habits, non-communicable diseases (i.e., DM, HT, and dyslipidemia) and their combinations and the incidence of severe FD and deterioration of the care-level. Followed for a median of 3.7 years were 9673 people who underwent health checkups. Care-level ≥2 (total assistance needed) indicates severe FD and worsening from the initial examination indicates deterioration. During the study period, 111 cases of severe FD occurred. Multivariate analysis showed that aging (per 5y) (OR 2.24 [1.95-2.56]), male (1.76 [1.16-2.66]), BMI&amp;lt;18.5 (2.46 [1.40-4.35]), DM (1.81 [1.06-3.08]), HT (1.58 [1.05-2.38]), and lack of physical activity (PA) (2.17 [1.37-3.45]) were associated with severe FD. Prevalence of DM additively associated with severe FD. DM and ≥2 risk factors had a 10 times greater association than non-DM and no risk factor. Of 85 cases with worsening care needs, only DM was significantly associated with deterioration (2.88 [1.08-7.65]). DM is a significant risk factor for with double the increased risk of severe FD and triple care-need deterioration compared with those without DM. Also, in DM patients, low BMI, HT, and lack of PA greatly increased the risk of severe FD, suggesting the need for comprehensive treatment strategies.

<p></p> Disclosure

I. Ikeda: None. K. Fujihara: None. H. Shiozaki: None. S.Y. Morikawa: None. K. Tsuruoka: None. Y. Yuko: None. L. Khin: None. S. Wu: None. N. Yagyuda: None. C. Horikawa: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.

DOI： 10.2337/db24-1264-p

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Language：English   Publishing type：Research paper (scientific journal)  

Diabetic neuropathy (DN) is a major complication of diabetes mellitus. Chondroitin sulfate (CS) is one of the most important extracellular matrix components and is known to interact with various diffusible factors; however, its role in DN pathology has not been examined. Therefore, we generated CSGalNAc-T1 knockout (T1KO) mice, in which CS levels were reduced. We demonstrated that diabetic T1KO mice were much more resistant to DN than diabetic wild-type (WT) mice. We also found that interactions between pericytes and vascular endothelial cells were more stable in T1KO mice. Among the RNA-seq results, we focused on the transforming growth factor β signaling pathway and found that the phosphorylation of Smad2/3 was less upregulated in T1KO mice than in WT mice under hyperglycemic conditions. Taken together, a reduction in CS level attenuates DN progression, indicating that CS is an important factor in DN pathogenesis.

DOI： 10.1016/j.isci.2024.109528

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Language：English   Publishing type：Research paper (scientific journal)  

AIMS: We attempted to clarify whether the multiple criteria for metabolic syndrome (MetS) can sufficiently predict cardiovascular disease, whether waist circumference (WC) should be required, and whether sex-specific thresholds for each component are necessary. Only a few large-scale studies among East Asians have addressed the ability of MetS to predict cardiovascular disease. METHODS: We analyzed the data of 330,051 men and 235,028 women aged 18-74 years with no history of coronary artery disease (CAD) or cerebrovascular disease (CVD) from a nationwide Japanese claims database accumulated during 2008-2016. The association of each MetS component with CAD or CVD (CAD/CVD), MetS associated with CAD/CVD according to various criteria, and utility of modified criteria with more specific optimal values for each component were examined using multivariate Cox regression and receiver operating characteristic (ROC) analysis. RESULTS: During the study, 3,934 men (1.19%) and 893 women (0.38%) developed CAD/CVD. For each current MetS criteria, there was a 1.3- to 2.9-fold increased risk of CAD/CVD. Optimal thresholds for predicting CAD/CVD were WCs of 83 and 77 cm, triglycerides levels of 130 and 90 mg/dl, high-density lipoprotein cholesterol levels of 50 and 65 mg/dl, blood pressures of 130/80 and 120/80 mmHg, and fasting plasma glucose levels of 100 and 90 mg/dl for men and women, respectively. The existing MetS criteria and modified criteria were not significantly different in predicting CAD/CVD, but using the modified criteria markedly increased the prevalence of MetS and percentage of people with MetS developing CAD/CVD. CONCLUSIONS: Although various criteria for MetS similarly predicted CAD/CVD, the new criteria greatly reduced the number of high-risk individuals, especially women, overlooked by the current criteria.

DOI： 10.5551/jat.64380

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(公社)日本栄養・食糧学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: The peptide-based cancer vaccine targeting Wilms' tumor 1 (WT1) is a promising immunotherapeutic strategy for hematological malignancies. It remains unclear how long and to what extent the WT1-specific CD8 + cytotoxic T cell (CTL) persist after WT1 peptide vaccination. METHODS: The WT1 peptide vaccine was administered with written consent to a patient with CML in the chronic phase who did not respond well to imatinib, and the patient was followed for 12 years after vaccination. Immune monitoring was performed by specific amplification of WT1-specific CTLs using a mixed lymphocyte peptide culture. T-cell receptors (TCRs) of amplified WT1-specific CTLs were analyzed using next-generation sequencing. This study was approved by the Institutional Review Board of our institution. RESULT: WT1-specific CTLs, which were initially detected during WT1 peptide vaccination, persisted at a frequency of less than 5 cells per 1,000,000 CD8 + T cells for more than 10 years. TCR repertoire analysis confirmed the diversity of WT1-specific CTLs 11 years after vaccination. CTLs exhibited WT1 peptide-specific cytotoxicity in vitro. CONCLUSION: The WT1 peptide vaccine induced an immune response that persists for more than 10 years, even after cessation of vaccination in the CML patient.

DOI： 10.1007/s12185-024-03723-1

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.hnm.2024.200257

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DOI： 10.11005/jbm.2024.31.1.21

Scopus

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本疫学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Publishing type：Research paper (scientific journal)   Publisher：Japan Endocrine Society  

DOI： 10.1507/endocrj.ej23-0343

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Language：Japanese   Publisher：日本先進糖尿病治療研究会  

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Language：Japanese   Publisher：(株)インフォノーツパブリッシング  

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Language：English   Publishing type：Research paper (scientific journal)  

AIMS: Although conventional interventions for people at high risk of developing type 2 diabetes are usually conducted face-to-face, such interventions are burdensome for healthcare providers. We developed a lifestyle intervention program combining lifestyle coaching via a smartphone application augmented by intermittently scanned continuous glucose monitoring (isCGM) without burdening healthcare providers. Its effectiveness for glycemic control and body weight reduction in people at risk of type 2 diabetes was investigated. MATERIALS AND METHODS: For this 12-week randomized unblinded trial with offline recruitment, participants with HbA1c 5.6-6.4% or fasting blood glucose 110-125 mg/dl and body mass index (BMI) > 23 kg/m2 but <40 kg/m2 were randomly assigned to the Intervention group (App) and Control group (C). Primary endpoint was the difference in time in range (TIR) of blood glucose 70-140 mg/dL (3.9-7.8 mmol/L) before and after the study period between the two groups. RESULTS: Among 168 patients (mean age 48.1 y, mean BMI 26.6 kg/m2, and male 80.4%), 82 and 86 were assigned to the App group and C group, respectively. After 12 weeks, TIR of blood glucose 70-140 mg/dL significantly improved in the App group compared to the C group (-2.6 min/day vs. + 31.5 min/day, p = 0.03). Changes in time above range did not differ, whereas time below range (blood glucose <70 mg/dL;  + 23.5 min/day vs. -8.9 min/day, p = 0.02) improved in the App group. BMI (-0.26 vs. -0.59, p = 0.017) was reduced in the App group compared to the C group. CONCLUSION: Intervention with a smartphone app and isCGM increased glycemic control accompanied by decreased carbohydrate intake and weight loss. Further trials are needed to confirm whether these interventions can reduce incident type 2 diabetes.

DOI： 10.1210/clinem/dgad639

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Language：English   Publishing type：Research paper (scientific journal)  

The endoplasmic reticulum (ER)-embedded transcription factors, sterol regulatory element-binding proteins (SREBPs), master regulators of lipid biosynthesis, are transported to the Golgi for proteolytic activation to tune cellular cholesterol levels and regulate lipogenesis. However, mechanisms by which the cell responds to the levels of saturated or unsaturated fatty acids remain underexplored. Here, we show that RHBDL4/RHBDD1, a rhomboid family protease, directly cleaves SREBP-1c at the ER. The p97/VCP, AAA-ATPase complex then acts as an auxiliary segregase to extract the remaining ER-embedded fragment of SREBP-1c. Importantly, the enzymatic activity of RHBDL4 is enhanced by saturated fatty acids (SFAs) but inhibited by polyunsaturated fatty acids (PUFAs). Genetic deletion of RHBDL4 in mice fed on a Western diet enriched in SFAs and cholesterol prevented SREBP-1c from inducing genes for lipogenesis, particularly for synthesis and incorporation of PUFAs, and secretion of lipoproteins. The RHBDL4-SREBP-1c pathway reveals a regulatory system for monitoring fatty acid composition and maintaining cellular lipid homeostasis.

DOI： 10.1093/pnasnexus/pgad351

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Language：English   Publishing type：Research paper (scientific journal)  

Type 2 diabetes (T2D) is a progressive disorder denoted by hyperglycemia and impaired insulin secretion. Although a decrease in β-cell function and mass is a well-known trigger for diabetes, the comprehensive mechanism is still unidentified. Here we carried out single-cell RNA sequencing (scRNA-seq) of pancreatic islets from prediabetic and diabetic db/db mice, an animal model of T2D. We discovered a diabetes-specific transcriptome landscape of endocrine and nonendocrine cell types with subpopulations of β and α cells. We recognized a new prediabetic gene, Anxa10, that was induced by, and regulated Ca2+ influx from metabolic stresses. Anxa10-overexpressed β cells displayed suppression of glucose-stimulated intracellular Ca2+ elevation and potassiuminduced insulin secretion. Pseudotime analysis of β cells predicted this Ca2+-surge responder-cluster proceeded to mitochondria dysfunction and also endoplasmic reticulum stress. Other trajectories comprised dedifferentiation and transdifferentiation, emphasizing acinar-like cells in diabetic islets. Altogether, our data provides a new insight into Ca2+ allostasis and β cell failure processes.

DOI： 10.2337/db23-0212

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：Japanese   Publisher：(NPO)日本臨床運動療法学会  

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：English   Publisher：(一社)日本血液学会  

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：English   Publisher：(一社)日本血液学会  

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Language：English   Publisher：(一社)日本血液学会  

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Language：English   Publisher：(一社)日本血液学会  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Aim was to examine associations among metabolic health, weight status, and various physical fitness (PF) components in 1744 Japanese adolescents aged 13-14. Anthropometric measurements and PF tests (20 m shuttle run test [20mSRT], handgrip strength/body mass [HG], standing long jump [SLJ], and sit ups [SU]) were administered. The bottom sex-specific quintile of PF indicated "low fit". Participants were classified as non-overweight (non-OW) or overweight/obese (OW) according to the International Obesity Task Force. Clustered metabolic risk was defined as the sum of Z scores for mean arterial pressure, non-high-density lipoprotein cholesterol, and HbA1c, divided by three, and ≥ 1 SD. Combination of weight status and scores for HG or SU were additively associated with clustered metabolic risk. Compared with the non-OW-moderate-high fit group, the OW-low HG group was 3.05 (95%CI: 1.88-4.97) times more likely to have clustered metabolic risk although risk was not significantly elevated in the OW-moderate-high HG group (1.52 [95%CI: 0.88-2.62]). A similar association was observed between OW and low SU scores but not between OW and low 20mSRT or SLJ scores. Adolescents with OW and moderate-high HG or SU scores had a lower prevalence of an unfavourable metabolic state than those with OW and low HG or SU results.

DOI： 10.1080/02640414.2023.2268358

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Language：English   Publishing type：Research paper (scientific journal)  

Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune modulation by interacting with cell growth factors and inducing cell adhesion. However, its precise effects on immune function are unclear than those of other proteoglycan families. Thus, we investigated the significance of CS within donor cells in acute GVHD development utilizing CSGalNAc T1-knockout (T1KO) mice. To determine the effects of T1KO, the mice underwent allogenic bone marrow transplantation from major histocompatibility complex-mismatched donors. While transplantation resulted in hepatic GVHD with inflammatory cell infiltration of both CD4+ and CD8+ effector memory T cells, transplantation in T1KO-donors showed milder cell infiltration and improved survival with fewer splenic effector T cells. In vitro T-cell analyses showed that the ratio of effector memory T cells was significantly lower via phorbol myristate acetate/ionomycin stimulation. Moreover, quantitative PCR analyses showed significantly less production of inflammatory cytokines, such as IFN-γ and CCL-2, in splenocytes of T1KO mice. These results suggest that reduction of CS in donor blood cells may suppress the severity of acute GVHD after hematopoietic stem cell transplantation.

DOI： 10.1038/s41598-023-40367-3

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/DOM.15206

Web of Science

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Low serum amylase values are cross-sectionally associated with the prevalence of type 2 diabetes mellitus (T2DM) but have not been shown to be longitudinally associated with its incidence. This retrospective cohort (ie, historical cohort) study aimed to examine the association of previously lowered levels of serum amylase with incident T2DM. RESEARCH DESIGN AND METHODS: Examined were 8316 individuals who had annual health examinations for 6 years (ie, 7 times) at the Toranomon Hospital Health Management Center. The trajectory of serum amylase as the study exposure was classified into two elements: (1) serum amylase level at entry and (2) change in serum amylase, which was expressed as the annual change rate. The annual change rate was calculated by dividing the change in the amylase values according to follow-up periods. Regression analyses were performed to examine the association between low and decreased levels of serum amylase and the incidence of T2DM. RESULTS: Analyzed were 6917 individuals who had not developed T2DM within 1 year after cohort entry. T2DM thereafter occurred in 1021 patients. Cox regression indicated that the adjusted HR (95% CI) for incident T2DM for amylase ≤57 IU/L (quintile (Q) 1) was 0.97 (0.84 to 1.13) compared with amylase ≥58 IU/L (Q2-Q5). Logistic regression indicated that the adjusted OR (95% CI) for an annual change rate of amylase ≤-2.0% (Q1) vs ≥-1.9% (Q2-Q5) was 3.53 (3.00 to 4.16). The adjusted ORs were consistently significant throughout sensitivity analyses according to baseline amylase and the combination of age, body mass index, and hemoglobin A1c. CONCLUSIONS: Results showed that not low but previously decreased serum amylase was a risk factor for T2DM, suggesting the significance of periodic examinations of serum amylase values to detect individuals at high risk of T2DM.

DOI： 10.1136/bmjdrc-2023-003482

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Language：English  

We report a 76-year-old man who was treated for hyperglycemia and metabolic acidosis after chemotherapy with enfortumab vedotin and pembrolizumab administered after his surgery for bladder cancer. He had an approximately 20-year history of diabetes. His body mass index was 18.6, and he received metformin 1000 mg/day, sitagliptin 50 mg/day, mitiglinide 30 mg/day, and voglibose 0.6 mg/day with hemoglobin A1c was approximately 7%. He underwent total cystectomy and ileal conduit reconstruction. After relapse, he received chemotherapy but later developed hyperglycemia and metabolic acidosis. His hyperglycemia was caused by enfortumab vedotin, and metabolic acidosis was attributable to the ileocecal canal. These symptoms should be remembered as important complications of this standard treatment, which prompted this case report.

DOI： 10.1210/jcemcr/luad092

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

Although DR are important in managing diabetes, the traditional method, such as weighing foods and calculating nutrients, is burdensome to both patients and medical care providers. Although photo DR with smartphones using AI to identify the dish and calculate nutrients can be expected to reduce this burden, accuracy not been clarified. Furthermore, it is not clear to what extent accuracy improves when users and dietitians adjust the name of the dish and the portion consumed compared with AI only. In this study, photo DR taken with the smartphone app were analyzed by AI only, then adjusted by the users followed by further adjustments by a dietitian. We compared the nutrients calculated by AI, users, and dietitians to those by the traditional weighing method. Analyzed were 180 participants (mean age 58.7 y, BMI 26.7 kg/m2, 94/86 women/men, 22 with diabetes, energy intake [EI] 1640 kcal/day) The EIs (kcal/day) were calculated as 1502, 1619, and 1674 for AI, users, and dietitians, respectively, those were lower than that with the weighing method Spearman's rank correlation coefficients compared to the weighing method were 0.48, 0.88, and 0.88 for AI, users and dietitians, respectively, showing a weak correlation for AI and a strong correlation for users and dietitians. The user's adjustments greatly improved accuracy without increasing the burden on the dietitians.

<p></p> Disclosure

M.Kitazawa: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. C.Horikawa: None. I.Ikeda: None. Y.Takeda: None. E.D.Ferreira: None. M.Takeuchi: None. S.Y.Morikawa: None. K.Fujihara: None. S.Kodama: None.

Funding

Grants-in-Aid for Scientific Research (21K17637)

DOI： 10.2337/db23-329-or

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

Although weight management plays a central role in diabetes treatment, the association between body weight and diabetic complications is not fully elucidated. Therefore, we investigated the relationship between BMI and risk of diabetic complications in patients with diabetes mellius (DM) using nationwide claims data. Analyzed were 91097 patients with DM without prior treatment-requiring diabetic eye disease (TRDED), initiation of dialysis (dialysis), coronary artery disease (CAD), cerebrovascular disease (CVD), heart failure (HF) or amputation (mean age 52 y, HbA1c 7.2%, median follow-up 4.5 y). Participants were divided into 6 groups according to BMI (BMI&amp;lt;20.0, 20.0-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.0, ≥30.0). Risk of diabetic complications was examined by Cox regression analysis. There was an inverse correlation between the risk of dialysis and BMI; hazard ratio (HR) for dialysis in patients with BMI ≥30.0 was 0.46 (0.29-0.74). There was a U-shaped relationship between the risk of HF and BMI; HRs for HF in patients with BMI &amp;lt;20.0 and ≥30.0 were 1.97 (1.15-3.37) and 1.76 (1.27-2.45), respectively (Figure). High BMI was significantly associated with a higher risk of HF, but lower risks of TRDED and dialysis. The relationship between BMI and diabetic complications was inconsistent among complications, suggesting that the target weight should be individualized according to diabetic complications.

<p></p> Disclosure

Y.Yaguchi: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. K.Fujihara: None. L.Khin: None. S.Wu: None. E.D.Ferreira: None. T.Sato: None. C.Horikawa: None. Y.Matsubayashi: None. K.Kato: None.

DOI： 10.2337/db23-1357-p

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

Many guidelines recommend increased potassium intake. However, the relationship between dietary potassium intake and incidence of CVD in persons with T2D has not been explored, nor is it known if this relationship varies with sodium intake in such persons. Therefore, we investigated these relationships as part of the JDCP study, a nationwide study launched in 2007. A total of 1477 persons with T2D aged 40-75 years completed a brief self-administered Diet History Questionnaire at baseline, and resultant data were analyzed. Primary outcome was the 7-year risk of a CVD event. Hazard ratios (HRs) for CVD according to tertiles of dietary potassium and sodium intake were estimated by Cox regression adjusted for confounders in addition to a stratified analysis of tertiles of sodium intake. Mean daily potassium and sodium intakes in tertiles 1 to 3 were 1.9, 2.6, and 3.5 g and 3.3, 4.2, and 5.3 g, respectively. HbA1c, BMI, triglycerides, and blood pressure were well controlled. No significant associations between potassium and sodium intakes and incidence of CVD were shown for the second and third tertiles relative to the first tertile (potassium: 0.64 [95% CI, 0.34-1.23] and 0.59 [0.28-1.25]; sodium: 1.02 [0.51-2.04] and 1.15 [0.58-2.30]). In the stratified analysis of tertiles of sodium intake, in the high sodium intake groups (T2 and T3) HRs for CVD in the high potassium intake group were significantly lower compared to the low potassium intake group (T2: 0.40 [0.12-1.35] and 0.06 [0.01-0.69]; T3: 0.23 [0.07-0.82] and 0.26 [0.07-0.88]). Associations of potassium intake with CVD in those with low sodium intake (T1) were not significant. Findings suggested that high potassium intake under high sodium intake is associated with a deceased incidence of CVD in persons with T2D although potassium intake under low sodium intake was not associated with incident CVD.

Disclosure

C.Horikawa: None. H.Shimano: None. J.Satoh: None. Y.Hayashino: Advisory Panel; Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Sumitomo Dainippon Pharma Co., Ltd., Santen, Daiichi Sankyo, Kowa Company, Ltd. N.Tajima: None. R.Nishimura: Speaker's Bureau; Sanofi K.K., Medicure Inc., Boehringer Ingelheim Inc., Takeda Pharmaceutical Company Limited, Kissei Pharmaceutical Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., Novo Nordisk, Merck &amp; Co., Inc., Abbott Japan Co., Ltd., Astellas Pharma Inc., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca. Y.Yamasaki: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. Jdcp study group: n/a. M.Takahara: None. N.Katakami: Speaker's Bureau; Abbott Japan Co., Ltd., Daiichi Sankyo, MSD, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Ono Pharmaceutical Co., Ltd., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Bayer Inc., Lilly, Teijin Pharma Limited, Kyowa Kirin Co., Ltd., Boehringer Ingelheim Japan, Inc., Sanofi. Y.Takeda: None. M.Takeuchi: None. K.Fujihara: None. H.Suzuki: None. K.Tsuda: None. N.Yoshioka: None.

DOI： 10.2337/db23-1381-p

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

We analyzed the association between dietary Mn intake and obesity measured by BMI after adjustment for intake of nutrients and food groups in people with T2DM in Japan. Participants were 1567 people, 63% male, aged 30 to 89 y who were in the Japan Diabetes Clinical Data Management Study Group (JDDM), one of the largest cohorts of Japanese with diabetes. Intake of food groups was determined by a validated self-administered food frequency questionnaire based on food groups. Obesity was defined as BMI ≥25 kg/m2. Multivariate logistic regression analysis assessed the relationship between quartiles of dietary Mn intake and obesity stratified by age. Participants aged 30 to 89 y were grouped according to the following quartiles for age: 30-54 y, 55-63 y, 64-71 y, and 72-89 y. Compared to the lowest quartile (Q1) for Mn, a significant negative association between Mn and BMI was found in males for all quartiles of Mn (OR [95%CI] of Q2= 0.643 [0.424 - 0.973], Q3= 0.607 [0.374 - 0.986], Q4= 0.398 [0.218 - 0.728], p trend = 0.028) with adjustment for characteristics such as age, sex, current smoking, drinking, insulin, oral hypoglycemic agents treatment, activity, energy intake and macronutrients intake. However, statistical significance disappeared after adding total fiber as a covariate. Compared to the lowest quartile for Mn, the highest quartile of Mn was inversely associated with BMI in the younger age group (30-54 y [OR= 0.296 [0.088 - 0.996]]) even after total fiber adjustment. Multivariate analysis of food groups (rice, vegetables, soy products) that were highly correlated with Mn as covariates showed that the relationships between Mn intake and obesity were maintained (p trend for rice, vegetables, soy = &amp;lt;0.001, 0.187, 0.010) in all participants. In summary, higher dietary Mn intake was independently associated with a lower BMI, especially in the younger group and males. Future prospective or intervention studies are expected to confirm this result.

Disclosure

L.Khin: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. Jddm study group: n/a. K.Fujihara: None. M.Hatta: None. Y.Takeda: None. S.Y.Morikawa: None. C.Horikawa: None. N.Kato: None. M.Kato: None. H.Maegawa: None.

DOI： 10.2337/db23-1713-p

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Publishing type：Research paper (scientific journal)   Publisher：American Diabetes Association  

We examined the effects of a lifestyle intervention program with a smartphone app augmented by intermittently scanned continuous glucose monitoring (isCGM) of persons at high risk of developing diabetes in a 12-week randomized open-label trial (UMIN00004640). The program monitored blood glucose fluctuations and lifestyle habits and displayed them in an easy-to-understand interface as well as provided personalized lifestyle intervention messages. The primary endpoint was the change in time in range (TIR) of 70-140 mg/dL between intervention (App) and control (C) groups. Among 168 patients (mean age 48.1 y, mean BMI 26.6 kg/m2, and male 80.4%), 82 and 86 were assigned to the App group and C group, respectively. After 12 weeks, TIR of 70-140 mg/dL significantly improved in the App group compared to the C group (-2.6 min/day vs. +31.5 min/day, p=0.03). Changes in time above range (&amp;gt;140 mg/dL; -20.9 min/day vs. -22.6 min/day, p=0.86) did not differ, whereas time below range (&amp;lt;70 mg/dL; +23.5 min/day vs. -8.9 min/day, p=0.02) improved in App compared to C. BMI (-0.26 vs. -0.59, p=0.017) and carbohydrate intake (-4.4 kcal/day vs. -22.7 kcal/day, p=0.049) also improved in App compared to C. Intervention with a smartphone app and isCGM increased glycemic control with a decrease in carbohydrate intake and weight loss.

<p></p> Disclosure

M.Kitazawa: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. H.Suzuki: None. C.Horikawa: None. Y.Takeda: None. I.Ikeda: None. M.Hatta: None. M.Iwanaga: None. T.Yamada: None. K.Fujihara: None.

DOI： 10.2337/db23-738-p

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Publishing type：Research paper (scientific journal)  

DOI： 10.1111/jdi.13991

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.amjmed.2022.12.027

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Language：Japanese   Publisher：(一社)日本血栓止血学会  

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DOI： 10.1111/DOM.15100

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DOI： 10.1016/J.DIABRES.2023.110674

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DOI： 10.1177/10815589221149188

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Language：Japanese   Publisher：新潟県医師会  

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DOI： 10.52082/JSSM.2023.98

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Language：Japanese   Publisher：(公社)日本栄養・食糧学会  

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DOI： 10.1111/JDI.13977

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Publishing type：Research paper (scientific journal)  

DOI： 10.1097/HJH.0000000000003362

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DOI： 10.1007/S13340-022-00603-Z

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DOI： 10.1038/S41440-022-01049-1

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DOI： 10.31989/ffhd.v13i11.1231

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DOI： 10.1016/j.bbadva.2023.100078

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DOI： 10.3389/FPUBH.2023.1090146

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DOI： 10.3389/FNUT.2023.1193530

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DOI： 10.1152/ajpgi.00090.2022

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DOI： 10.3390/nu14193920

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DOI： 10.1016/j.bbrc.2022.06.050

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DOI： 10.1111/dom.14836

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DOI： 10.1016/j.heliyon.2022.e10284

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DOI： 10.3390/nu14153034

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DOI： 10.1186/s12933-022-01518-4

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DOI： 10.1136/bmjopen-2021-055577

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DOI： 10.1007/s13340-022-00575-0

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DOI： 10.1111/sms.14089

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DOI： 10.1016/j.bbadis.2022.166339

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DOI： 10.2337/DB22-539-P

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DOI： 10.1182/BLOOD-2022-168616

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DOI： 10.1615/INTJMEDMUSHROOMS.2021041928

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DOI： 10.1109/WSCE56210.2022.9916029

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DOI： 10.1111/jdi.13736

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DOI： 10.1186/s12933-021-01367-7

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DOI： 10.1016/j.amjmed.2021.10.018

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DOI： 10.3390/nu13093167

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DOI： 10.1016/j.isci.2021.103117

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DOI： 10.3390/nu13103478

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DOI： 10.3390/nu13103428

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DOI： 10.1101/2021.08.24.457590

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DOI： 10.1136/bmjdrc-2021-002177

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DOI： 10.1007/s00520-021-06447-8

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DOI： 10.2169/internalmedicine.6608-20

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DOI： 10.1038/s41440-021-00632-2

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Other Link： http://www.nature.com/articles/s41440-021-00632-2

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DOI： 10.1111/dom.14387

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DOI： 10.1038/s41440-021-00645-x

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DOI： 10.1096/fj.202002784RR

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

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DOI： 10.2337/dc20-2252

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DOI： 10.1002/pds.5213

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pds.5213

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DOI： 10.1007/s12185-021-03083-0

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

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Language：Japanese   Publisher：(一社)日本血栓止血学会  

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Language：English   Publishing type：Research paper (scientific journal)  

In 2020, the COVID-19 pandemic has had unprecedented impacts on various aspects of the world. Each academic society has published a guide and/or guidelines on how to cope with COVID-19 separately. As the one and only nationwide association of academic societies that represent medical science in Japan, JMSF has decided to publish the expert opinion to help patients and care providers find specifically what they want. This expert opinion is a summary of recommendations by many academic societies and will be updated when necessary. Patients that each academic society targets differ even though they suffer from the same COVID-19, and recommendations can be different in a context-dependent manner. Readers are supposed to be flexible and adjustable when they use this expert opinion.

DOI： 10.31662/jmaj.2021-0002

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DOI： 10.1186/s13047-021-00474-8

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DOI： 10.2188/jea.JE20200034

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DOI： 10.1016/j.exphem.2021.02.003

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DOI： 10.3960/jslrt.20043

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DOI： 10.1111/jdi.13543

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/sms.13867

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DOI： 10.1136/jim-2020-001489

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DOI： 10.1007/s00535-020-01754-z

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This study investigates the associations between sodium intake and diabetes complications in a nationwide cohort of elderly Japanese patients with type 2 diabetes aged 65-85. Data from 912 individuals regarding their dietary intake at baseline is analyzed and assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes are times to diabetic retinopathy, overt nephropathy, cardiovascular disease (CVD), and all-cause mortality during six years. We find that mean sodium intake in quartiles ranges from 2.5 g to 5.9 g/day. After adjustment for confounders, no significant associations are observed between sodium intake quartiles and incidence of diabetes complications and mortality, except for a significant trend for an increased risk of diabetic retinopathy (p = 0.039). Among patients whose vegetable intake was less than the average of 268.7 g, hazard ratios (HRs) for diabetic retinopathy in patients in the second, third, and fourth quartiles of sodium intake compared with the first quartile were 0.87 (95% CI, 0.31-2.41), 2.61 (1.00-6.83), and 3.70 (1.37-10.02), respectively. Findings indicate that high sodium intake under conditions of low vegetable intake is associated with an elevated incidence of diabetic retinopathy in elderly patients with type 2 diabetes.

DOI： 10.3390/nu13020689

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Machine learning (ML) algorithms have been widely introduced to diabetes research including those for the identification of hypoglycemia. OBJECTIVE: The objective of this meta-analysis is to assess the current ability of ML algorithms to detect hypoglycemia (ie, alert to hypoglycemia coinciding with its symptoms) or predict hypoglycemia (ie, alert to hypoglycemia before its symptoms have occurred). METHODS: Electronic literature searches (from January 1, 1950, to September 14, 2020) were conducted using the Dialog platform that covers 96 databases of peer-reviewed literature. Included studies had to train the ML algorithm in order to build a model to detect or predict hypoglycemia and test its performance. The set of 2 × 2 data (ie, number of true positives, false positives, true negatives, and false negatives) was pooled with a hierarchical summary receiver operating characteristic model. RESULTS: A total of 33 studies (14 studies for detecting hypoglycemia and 19 studies for predicting hypoglycemia) were eligible. For detection of hypoglycemia, pooled estimates (95% CI) of sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 0.79 (0.75-0.83), 0.80 (0.64-0.91), 8.05 (4.79-13.51), and 0.18 (0.12-0.27), respectively. For prediction of hypoglycemia, pooled estimates (95% CI) were 0.80 (0.72-0.86) for sensitivity, 0.92 (0.87-0.96) for specificity, 10.42 (5.82-18.65) for PLR, and 0.22 (0.15-0.31) for NLR. CONCLUSIONS: Current ML algorithms have insufficient ability to detect ongoing hypoglycemia and considerate ability to predict impeding hypoglycemia in patients with diabetes mellitus using hypoglycemic drugs with regard to diagnostic tests in accordance with the Users' Guide to Medical Literature (PLR should be ≥5 and NLR should be ≤0.2 for moderate reliability). However, it should be emphasized that the clinical applicability of these ML algorithms should be evaluated according to patients' risk profiles such as for hypoglycemia and its associated complications (eg, arrhythmia, neuroglycopenia) as well as the average ability of the ML algorithms. Continued research is required to develop more accurate ML algorithms than those that currently exist and to enhance the feasibility of applying ML in clinical settings. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020163682; http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42020163682.

DOI： 10.2196/22458

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DOI： 10.1016/j.heliyon.2020.e05888

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DOI： 10.2337/DB21-795-P

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DOI： 10.1182/BLOOD-2021-147888

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DOI： 10.1182/BLOOD-2021-148212

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DOI： 10.2337/DB21-434-P

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DOI： 10.1182/BLOOD-2021-146856

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DOI： 10.1182/BLOOD-2021-146114

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DOI： 10.2337/DB21-794-P

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DOI： 10.2337/DB21-480-P

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DOI： 10.1016/j.jcmgh.2020.11.004

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DOI： 10.1016/j.pcd.2020.05.002

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DOI： 10.1111/ejh.13495

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DOI： 10.1007/s10557-020-07097-4

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1123/jpah.2019-0660

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DOI： 10.1002/ehf2.12782

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DOI： 10.1016/J.DIABET.2018.08.009

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DOI： 10.1016/j.diabet.2018.08.009

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DOI： 10.1136/bmjdrc-2020-001562

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DOI： 10.3390/nu12092649

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DOI： 10.2169/internalmedicine.4255-19

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DOI： 10.1111/dme.14279

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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DOI： 10.1016/j.neuint.2020.104745

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DOI： 10.1002/jha2.68

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DOI： 10.1507/endocrj.EJ19-0370

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DOI： 10.3390/nu12061629

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DOI： 10.1111/dom.13980

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DOI： 10.1007/s00394-019-02014-4

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DOI： 10.2337/db20-1133-P

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DOI： 10.1002/hep.30953

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DOI： 10.1111/pin.12909

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DOI： 10.1016/j.isci.2020.100930

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DOI： 10.1111/dom.13909

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DOI： 10.1007/s00277-020-03936-4

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DOI： 10.1136/bmjdrc-2019-000901

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