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

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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)  

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：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 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<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 <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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DOI： 10.1177/10815589221149188

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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)日本内分泌学会  

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/hjh.0000000000003362

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

AIMS: To determine the associations between combined urinary protein (UP) and a reduced estimated glomerular filtration rate (eGFR) and the risk of starting dialysis with or without diabetes mellitus (DM). METHODS: A nationwide database with claims data on 335,778 people with and without DM aged 19-72 years in Japan was used to elucidate the impact of the severities of UP and eGFR on starting dialysis. Initiation of dialysis was determined from claims using ICD-10 codes and medical procedures. Using multivariate Cox modeling, we investigated the severities of UP and eGFR to predict the initiation of dialysis with and without DM. RESULTS: Both eGFR < 60 and UP(+) were independent predictors for starting dialysis with and without DM, and their values exhibited a synergistic risk of dialysis. eGFR < 60 presented a nearly twofold risk for starting dialysis compared to UP(+) regardless of DM. Risk of starting dialysis was increased with UP(+) and eGFR ≥ 60 accompanied by DM although this association was not observed without DM. Those who had UP(-) and eGFR < 60 had a high risk of starting dialysis regardless of DM. Compared with DM(-)UP(-)eGFR ≥ 60, HRs for starting dialysis for DM(+)UP(+)eGFR ≥ 60, DM(+)UP(-)eGFR < 60 and DM(+)UP(+)eGFR < 60 significantly increased 17.7 (10.6-29.7), 25.5 (13.8-47.1) and 358.1 (239.1-536.5) times, respectively. CONCLUSIONS: eGFR < 60 and UP(+) together presented an extremely high risk of dialysis especially with DM. UP( +) increased the risk of starting dialysis regardless of the eGFR with DM. Both patient education and a treatment strategy by physicians might be helpful to avoid the progression of renal failure.

DOI： 10.1007/s13340-022-00603-z

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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：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：新潟医学会  

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Language：Japanese   Publisher：新潟医学会  

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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：新潟医学会  

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Language：Japanese   Publisher：新潟医学会  

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

DOI： 10.1111/dom.14836

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

BACKGROUND AND OBJECTIVES: To clarify whether the presence or absence of fast walking and habitual physical activity are independently associated with the incidence of functional disability. METHODS: This historical cohort study was comprised of 9,652 (4,412 men, mean age 65 years) individuals aged 39-98 years without functional disability at baseline. Functional disability was determined based on the Japanese long-term care insurance system, which specified requirements for assistance in the activities of daily living. The impact of fast walking and habitual physical activity on the incidence of functional disability was analysed by Cox proportional hazards models. RESULTS: The follow-up period was a median of 3.7 years during which 165 patients were newly certified as having functional disability. In the multivariate analysis, baseline age in 5-year increments (hazard ratio 2.42 [95% confidence interval 2.18-2.69]), no habitual physical activity (1.56 [1.07-2.27]), and not fast walking (1.89 [1.32-2.69]) significantly increased the risk of functional disability after adjustment for covariates. The stratified analysis showed that compared with physical activity (+), the impact of physical activity (-) on the incidence of functional disability was observed in those aged ≥75 years regardless of fast walking (+). Fast walking (-) significantly increased the risk of disability compared with fast walking (+) in those aged <75 years regardless of a physical activity habit. CONCLUSION: In Japanese, slow walking speed and lack of a physical activity habit were shown to be independent risk factors for incident functional disability, with their impact differing according to age.

DOI： 10.1093/fampra/cmac087

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BACKGROUND: To determine the impact of metabolic syndrome (MetS) and/or metabolic dysfunction-associated fatty liver disease (MAFLD), which are pathophysiologically similar and include insulin resistance, on the development of new-onset cardiovascular disease with and without type 2 diabetes and according to sex. METHODS: This study included 570,426 individuals without a history of cardiovascular disease who were enrolled in a nationwide claims database from 2008 to 2016 and were classified by the presence or absence of MetS and/or MAFLD stratified by the presence or absence of type 2 diabetes and sex. The fatty liver index was used to determine the presence or absence of fatty liver that required a diagnosis of MAFLD. Risks of developing coronary artery disease (CAD) and cerebrovascular disease (CVD) in each category were analyzed using a multivariate Cox proportional hazard model. RESULTS: During a median follow-up of 5.2 years, 2252 CAD and 3128 CVD events occurred. Without type 2 diabetes the hazard ratio (HR) (95% CI) for CAD/CVD compared with neither MAFLD nor MetS was 1.32 (1.17-1.50)/1.41(1.28-1.57) for MAFLD only (without MetS), 1.78 (1.22-2.58)/1.66 (1.34-2.06) for MetS only (without MAFLD), and 2.10 (1.84-2.39)/1.73 (1.54-1.95) for MAFLD + MetS. For those with type 2 diabetes, the HR for CAD for MAFLD only (compared with neither MAFLD nor MetS) was 1.29 (1.06-1.58), for MetS only 1.34 (0.84-2.13), and for MAFLD + MetS 1.22 (1.02-1.47). For CVD, there was a significant increase in HR only in MAFLD + MetS [1.44 (1.18-1.76)]. The results of the analysis stratified by sex showed that MAFLD had a greater impact in men, and MetS had a greater impact in women regarding the development of CAD. CONCLUSIONS: Distinguishing between MetS and/or MAFLD in the presence or absence of type 2 diabetes and according to sex may aid in accurately identifying patients at high risk of cardiovascular disease.

DOI： 10.1186/s12933-022-01518-4

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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：English   Publishing type：Research paper (scientific journal)  

Previous cohort study reported that high physical activity was associated with a low risk of self-reported hearing loss in women. However, no studies have examined the association between physical activity and the development of hearing loss as measured using an objective assessment of hearing loss in men and women. Here, we used cohort data to examine the association between leisure-time physical activity and incidence of objectively assessed hearing loss in men and women. Participants included 27 537 Japanese adults aged 20-80 years without hearing loss, who completed a self-administered physical activity questionnaire between April 2001 and March 2002. The participants were followed up for the development of hearing loss as measured by audiometry between April 2002 and March 2008. During follow-up, 3691 participants developed hearing loss. Compared with the none physical activity group, multivariable adjusted hazard ratios (HRs) for developing hearing loss were 0.93 (95% confidence interval (CI), 0.86-1.01) and 0.87 (0.81-0.95) for the medium (<525 MET-min/week) and high (≥525 MET-min/week) physical activity groups, respectively (p for trend = 0.001). The magnitude of risk reduction was slightly greater in vigorous-intensity activity than in moderate-intensity activity (p for interaction = 0.01). Analysis by sound frequency showed that the amount of physical activity was inversely associated with high frequency hearing loss development (p for trend <0.001), but not with low frequency hearing loss development (p for trend = 0.19). Higher level of leisure-time physical activity was associated with lower incidence of hearing loss, particularly for vigorous-intensity activities and high sound frequencies.

DOI： 10.1111/sms.14089

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

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title><sec>
<title>Background</title>
Although both a history of cerebrovascular disease (CVD) and glucose abnormality are risk factors for CVD, few large studies have examined their association with subsequent CVD in the same cohort. Thus, we compared the impact of prior CVD, glucose status, and their combinations on subsequent CVD using real-world data.


</sec><sec>
<title>Methods</title>
This is a retrospective cohort study including 363,627 men aged 18–72 years followed for ≥ 3 years between 2008 and 2016. Participants were classified as normoglycemia, borderline glycemia, or diabetes defined by fasting plasma glucose, HbA1c, and antidiabetic drug prescription. Prior and subsequent CVD (i.e. ischemic stroke, transient ischemic attack, and non-traumatic intracerebral hemorrhage) were identified according to claims using ICD-10 codes, medical procedures, and questionnaires.


</sec><sec>
<title>Results</title>
Participants’ mean age was 46.1 ± 9.3, and median follow up was 5.2 (4.2, 6.7) years. Cox regression analysis showed that prior CVD + conferred excess risk for CVD regardless of glucose status (normoglycemia: hazard ratio (HR), 8.77; 95% CI 6.96–11.05; borderline glycemia: HR, 7.40, 95% CI 5.97–9.17; diabetes: HR, 5.73, 95% CI 4.52–7.25). Compared with normoglycemia, borderline glycemia did not influence risk of CVD, whereas diabetes affected subsequent CVD in those with CVD- (HR, 1.50, 95% CI 1.34–1.68). In CVD-/diabetes, age, current smoking, systolic blood pressure, high-density lipoprotein cholesterol, and HbA1c were associated with risk of CVD, but only systolic blood pressure was related to CVD risk in CVD + /diabetes.


</sec><sec>
<title>Conclusions</title>
Prior CVD had a greater impact on the risk of CVD than glucose tolerance and glycemic control. In participants with diabetes and prior CVD, systolic blood pressure was a stronger risk factor than HbA1c. Individualized treatment strategies should consider glucose tolerance status and prior CVD.


</sec>

DOI： 10.1186/s12933-021-01367-7

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Other Link： https://link.springer.com/article/10.1186/s12933-021-01367-7/fulltext.html

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PURPOSE: Our purpose in the research was to clarify the impact of medication adherence to oral hypoglycemic agents during a 1-year period and subsequent glycemic control on the risk of micro- and macrovascular diseases. METHODS: Examined was a nationwide claims database on 13,256 individuals with diabetic eye disease without requiring prior treatment, 7,862 without prior initiation of dialysis, 15,556 without prior coronary artery disease, 16,243 without prior cerebrovascular disease, and 19,386 without prior heart failure from 2008 to 2016 in Japan. Medication adherence was evaluated by the proportion of days covered. Patients were considered to have poor adherence if the proportion of days covered was <80%. Multivariate Cox regression model identified risks of micro- and macrovascular diseases. RESULTS: In each group, mean age was 53 to 54 years, HbA1c was 7.1% to 7.2%, and median follow-up period was 4.6 to 5.1 years, and the percentage of poor adherence was approximately 30%. During the study period, 532 treatment-requiring diabetic eye disease, 75 dialysis, 389 coronary artery disease, 316 cerebrovascular disease, and 144 heart failure events occurred. Multivariate Cox regression model revealed that the hazard ratio (95% confidence interval) of dialysis in the poor adherence group was 2.04 (1.27-3.30) compared with the good adherence group. The hazard ratios in the poor adherence/poor glycemic control group were 3.34 (2.63-4.24) for treatment-requiring diabetic eye disease, 4.23 (2.17-8.26) for dialysis, 1.69 (1.23-2.31) for coronary artery disease, and 2.08 (1.25-3.48) for heart failure compared with the good adherence/good glycemic control group. CONCLUSIONS: Poor medication adherence was an independent risk factor for the initiation of dialysis, suggesting that clinicians must pay close attention to these patients.

DOI： 10.1016/j.amjmed.2021.10.018

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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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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/dom.14387

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/dom.14387

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  

DOI： 10.2337/dc20-2252

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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：(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)  

BACKGROUND: The prevalence of diabetes is rising, and diabetes develops at a younger age in East Asia. Although lower limb amputation negatively affects quality of life and increases the risk of cardiovascular events, little is known about the rates and predictors of amputation among persons with diabetes from young adults to those in the "young-old" category (50-72 y). METHODS: We analyzed data from a nationwide claims database in Japan accumulated from 2008 to 2016 involving 17,288 people with diabetes aged 18-72 y (mean age 50.2 y, HbA1c 7.2%). Amputation occurrence was determined according to information from the claims database. Cox regression model identified variables related to lower limb amputation. RESULTS: The mean follow-up time was 5.3 years, during which time 16 amputations occurred (0.17/1000 person-years). Multivariate Cox regression analysis showed that age (hazard ratio [HR] 1.09 [95% confidence intervals] 1.02-1.16, p = 0.01) and HbA1c (HR 1.46 [1.17-1.81], p < 0.01) were independently associated with amputations. Compared with those aged < 60 years with HbA1c < 8.0%, the HR for amputation was 27.81 (6.54-118.23) in those aged ≥60 years and HbA1c ≥8.0%. CONCLUSIONS: Age and HbA1c were associated with amputations among diabetic individuals, and the rates of amputation were significantly greater in those ≥60 years old and with HbA1c ≥8.0%.

DOI： 10.1186/s13047-021-00474-8

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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)日本内分泌学会  

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

AIMS/INTRODUCTION: This study investigated the impact of the dipeptidyl peptidase-4 inhibitor, anagliptin, on hepatic insulin clearance (HIC) in Japanese type 2 diabetes patients and explored its relationship to glycemic status. MATERIALS AND METHODS: Data on 765 participants in anagliptin phase 2 and 3 studies were analyzed. Adjusted changes in variables during 12 weeks of anagliptin therapy were compared with a placebo. HIC was calculated as the ratio, C-peptide area under the curve 0-120 min to insulin area under the curve 0-120 min, after a meal tolerance test. To explore the effects of baseline HIC levels on variables, participants receiving anagliptin were divided according to quartiles of baseline HIC. Furthermore, multivariate analysis investigated the association between baseline HIC levels and glycemic status. RESULTS: Anagliptin significantly reduced glycosylated hemoglobin levels (P < 0.001 vs placebo) and HIC levels (P < 0.01). Longer duration of diabetes, lower body mass index, higher glycosylated hemoglobin and lower insulin secretion capacity were observed with increases in baseline HIC levels. Improvements in glycosylated hemoglobin, glycoalbumin and 1,5-anhydroglucitol levels were greater in the relatively higher HIC group (baseline HIC levels ≥median) than in the lower HIC group (<median). CONCLUSIONS: Anagliptin affected HIC levels according to HIC baseline levels. Higher baseline HIC values might result in improved hyperglycemia through reduced HIC.

DOI： 10.1111/jdi.13543

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/pds.5213

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To determine associations between severity of hypertension and risk of starting dialysis in the presence or absence of diabetes mellitus (DM). A nationwide database with claims data on 258 874 people with and without DM aged 19-72 years in Japan was used to elucidate the impact of severity of hypertension on starting dialysis. Initiation of dialysis was determined from claims using International Classification of Diseases-10 codes and medical procedures. Using multivariate Cox modeling, we investigated the severity of hypertension to predict the initiation of dialysis with and without DM. Hypertension was significantly associated with the initiation of dialysis regardless of DM. The incidence of starting dialysis in those with systolic blood pressure (SBP) ≤119 mm Hg and DM (DM+) was almost the same as in those with SBP ≥150 mm Hg and absence of DM (DM-). In comparison with SBP ≤119 mm Hg, SBP ≥150 mm Hg significantly increased the risk of the initiation of dialysis about 2.5 times regardless of DM+ or DM-. Compared with DM- and SBP ≤119 mm Hg, the HR for DM+ and SBP ≥150 mm Hg was 6.88 (95% CI 3.66 to 12.9). Although the risks of hypertension differed only slightly regardless of the presence or absence of DM, risks for starting dialysis with DM+ and SBP ≤119 mm Hg were equivalent to DM- and SBP ≥150 mm Hg, indicating more strict blood pressure interventions in DM+ are needed to avoid dialysis. Future studies are required to clarify the cut-off SBP level to avoid initiation of dialysis considering the risks of strict control of blood pressure.

DOI： 10.1136/jim-2020-001489

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Language：Japanese   Publisher：新潟県医師会  

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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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BACKGROUND: Applications of machine learning for the early detection of diseases for which a clear-cut diagnostic gold standard exists have been evaluated. However, little is known about the usefulness of machine learning approaches in the decision-making process for decisions such as insulin initiation by diabetes specialists for which no absolute standards exist in clinical settings. OBJECTIVE: The objectives of this study were to examine the ability of machine learning models to predict insulin initiation by specialists and whether the machine learning approach could support decision making by general physicians for insulin initiation in patients with type 2 diabetes. METHODS: Data from patients prescribed hypoglycemic agents from December 2009 to March 2015 were extracted from diabetes specialists' registries, resulting in a sample size of 4860 patients who had received initial monotherapy with either insulin (n=293) or noninsulin (n=4567). Neural network output was insulin initiation ranging from 0 to 1 with a cutoff of >0.5 for the dichotomous classification. Accuracy, recall, and area under the receiver operating characteristic curve (AUC) were calculated to compare the ability of machine learning models to make decisions regarding insulin initiation to the decision-making ability of logistic regression and general physicians. By comparing the decision-making ability of machine learning and logistic regression to that of general physicians, 7 cases were chosen based on patient information as the gold standard based on the agreement of 8 of the 9 specialists. RESULTS: The AUCs, accuracy, and recall of logistic regression were higher than those of machine learning (AUCs of 0.89-0.90 for logistic regression versus 0.67-0.74 for machine learning). When the examination was limited to cases receiving insulin, discrimination by machine learning was similar to that of logistic regression analysis (recall of 0.05-0.68 for logistic regression versus 0.11-0.52 for machine learning). Accuracies of logistic regression, a machine learning model (downsampling ratio of 1:8), and general physicians were 0.80, 0.70, and 0.66, respectively, for 43 randomly selected cases. For the 7 gold standard cases, the accuracies of logistic regression and the machine learning model were 1.00 and 0.86, respectively, with a downsampling ratio of 1:8, which were higher than the accuracy of general physicians (ie, 0.43). CONCLUSIONS: Although we found no superior performance of machine learning over logistic regression, machine learning had higher accuracy in prediction of insulin initiation than general physicians, defined by diabetes specialists' choice of the gold standard. Further study is needed before the use of machine learning-based decision support systems for insulin initiation can be incorporated into clinical practice.

DOI： 10.2196/22148

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Le Carbone (LC), a fiber-enriched activated charcoal dietary supplement, claimed to be effective against inflammation associated with colitis, trimethylaminuria, and sclerosis. The study aimed to investigate the underlying mechanisms of LC to protect liver damage and its progression in non-alcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mice. To induce this model, C57BL/6J male baby mice were injected with a low-dose of streptozotocin and fed with a high-fat diet (HFD) 32 during 4 weeks-16 weeks of age. The LC suspension was administered orally at a dose of 5 mg/mouse/day started at the age of 6 weeks and continued until 16 weeks of age along with HFD32 feeding. At the end of the experiment, serum and liver tissues were collected for the biochemical, histological, and molecular analysis. We found that LC suspension improved the histopathological changes, serum aminotransferases in NASH mice. The hepatic expression of metabolic proteins, p-AMPKα and sirtuin 1, and proteins responsible for β-oxidation of fatty acids, peroxisome proliferator-activated receptor (PPAR) γ coactivator-α, PPARα were significantly repressed in NASH mice. LC treatment markedly restored these expressions. LC treatment significantly reduced the hepatic proteins expressions of PPARγ, tissue inhibitor of metalloproteinases 4, p47phox, p-JNK, p-ERK1/2, glypican-3, and prothrombin in NASH mice. Our findings demonstrate that LC prevents the liver damage and progression of NASH, possibly by enhancing the AMPK-SIRT1 signaling pathway.

DOI： 10.1016/j.heliyon.2020.e05888

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

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/sms.13867

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/sms.13867

Publishing type：Research paper (scientific journal)   Publisher：Human Kinetics  

<bold>Background</bold>: To examine the association between muscular and performance fitness (MPF) and the incidence of glaucoma. <bold>Methods</bold>: A total of 27,051 glaucoma-free participants aged 20–87 years underwent physical fitness tests between April 2001 and March 2002. The MPF index was calculated using an age- and sex-specific summed <italic>z</italic>-score from grip strength, vertical jump, single-leg balance, forward bending, and whole-body reaction time. The participants were divided into quartiles according to the MPF index and each physical fitness test. Participants were followed up for the development of glaucoma, which was defined based on physician-diagnosed glaucoma at an annual health examination between April 2002 and March 2008. Hazard ratios for the incidence of glaucoma were estimated using Cox proportional hazards models. <bold>Results</bold>: During follow-up, 303 participants developed glaucoma. Compared with the lowest MPF index group, hazard ratio (95% confidence interval) of developing glaucoma was 0.64 (0.46–0.89) for the highest MPF index group (<italic>P</italic> for trend = .001). Vertical jump and whole-body reaction time were associated with incident glaucoma (<italic>P</italic> for trend = .01 and &lt;.001, respectively). There were no associations between the other physical fitness tests and the incidence of glaucoma. <bold>Conclusion</bold>: Higher MPF is associated with lower incidence of glaucoma.

DOI： 10.1123/jpah.2019-0660

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Other Link： https://journals.humankinetics.com/downloadpdf/journals/jpah/17/11/article-p1171.xml

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：English   Publishing type：Research paper (scientific journal)  

PURPOSE: This network meta-analysis aimed to assess the current efficacy of decreasing the uric acid (UA) level with drugs to reduce mortality in patients with heart failure (HF). METHODS: Electronic literature searches using EMBASE and MEDLINE of studies published from 1 Jan 1950 to 26 Dec 2019 were conducted for randomized controlled trials or non-randomized cohort studies that included at least one group of patients who took UA-lowering drugs and with a study outcome of all-cause mortality. A random-effects network meta-analysis was performed within a frequentist framework. Hierarchy of treatments was expressed as the surface under the cumulative ranking curve (SUCRA) value, which is in proportion to mean rank (best is 100%). RESULTS: Nine studies, which included seven different types of groups, were eligible for analysis. The "untreated uricemia" group in which patients had hyperuricemia but without treatment had a significantly higher risk of mortality than the "no uricemia" group in which patients had no hyperuricemia (relative risk (RR)(95% confidence interval (CI), 1.43 (1.08-1.89)). The "start-allo" group wherein patients started to take allopurinol did not have a significantly lower risk of mortality than the "untreated uricemia" group (RR (95% CI), 0.68 (0.45-1.01)). However, in the "start-allo" group the SUCRA value was comparable to that in the "no uricemia" group (SUCRA: 65.4% for "start-allo"; 64.1% for "no uricemia"). CONCLUSIONS: Results suggested that allopurinol therapy was not associated with a significantly improved prognosis in terms of mortality but could potentially counteract the adverse effects associated with longstanding hyperuricemia in HF patients.

DOI： 10.1007/s10557-020-07097-4

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

DOI： 10.1016/j.diabet.2018.08.009

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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：(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)日本内分泌学会  

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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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BACKGROUND: Several cross-sectional studies have linked higher physical fitness with better hearing sensitivity but have not established a causal relation; none have used a prospective design that is less susceptible to bias. We used a prospective cohort study to investigate the association between muscular and performance fitness and the incidence of hearing loss. METHODS: In total, 21,907 participants without hearing loss received physical fitness assessments between April 2001 and March 2002. Muscular and performance fitness index, an age- and sex-specific summed z-score based on grip strength, vertical jump height, single-leg balance, forward bending, and whole-body reaction time was calculated. Participants were classified into quartiles according to the muscular and performance fitness index as well as each physical fitness test. They were followed up for the development of hearing loss, assessed by pure-tone audiometry at annual health examinations between April 2002 and March 2008. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hearing loss incidence were estimated using Cox proportional hazards regression models. RESULTS: During follow-up, 2765 participants developed hearing loss. The HRs (95% CIs) for developing hearing loss across the muscular and performance fitness index quartiles (lowest to highest) were 1.00 (reference), 0.88 (0.79-0.97), 0.83 (0.75-0.93), and 0.79 (0.71-0.88) (Ptrend <.001). Among the various physical fitness components, a clear dose-response association with hearing loss incidence was observed in vertical jump height and single-leg balance (Ptrend <.001 for both). CONCLUSION: Higher muscular and performance fitness is associated with a lower incidence of hearing loss.

DOI： 10.1016/j.amjmed.2020.06.021

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AIMS: Little is known about the relationship between medication adherence for oral hypoglycemic agents (OHAs) and glycemic control after adjusting healthy adherer effect in large scale study. Thus, adjusting for health-related behaviors, we investigated the clinical variables associated with medication adherence and the relationship between medication adherence and glycemic control using a large claims database. METHODS: Analyzed were 8805 patients with diabetes whose medication records for OHA were available for at least 1year. Medication adherence was evaluated by the proportion of days covered (PDC). Multivariate logistic regression model was used to identify clinical variables significantly associated with non-adherence. Multiple regression analysis evaluated the relationship between PDC and HbA1c after adjusting for health-related behaviors. RESULTS: Mean PDC was 80.1% and 32.8% of patients were non-adherence. Logistic analysis indicated that older age and taking concomitant medications were significantly associated with adherence while skipping breakfast (odds ratio 0.66 [95% CI 0.57-0.76]), late-night eating (0.86 [0.75-0.98]), and current smoking (0.89 [0.80-0.99]) were significantly associated with non-adherence. CONCLUSIONS: Skipping breakfast, late-night eating and current smoking were significantly associated with medication adherence, suggesting that clinicians pay attention to those health-related behaviors to achieve good medication adherence.

DOI： 10.1016/j.pcd.2020.05.002

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Language：Japanese   Publisher：新潟医学会  

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AIMS: Obesity and hepatic fat accumulation diminish hepatic insulin clearance, which can cause hyperinsulinaemia. Sodium/glucose-cotransporter 2 inhibitors (SGLTis) improve insulin resistance and hyperinsulinaemia by weight loss via increased urinary glucose excretion in type 2 diabetes. However, there are few reports of the influence of SGLT2is on hepatic insulin clearance. We examined the impact of an SGLT2i on hepatic insulin clearance and explored the clinical influence associated with changes in hepatic insulin clearance via an SGLT2i and the mechanism of the effects of SGLT2i. MATERIALS AND METHODS: Data were analysed from 419 patients with type 2 diabetes controlled by diet and exercise. Patients received a placebo or the SGLT2i tofogliflozin (TOFO) (placebo: n = 56; TOFO: n = 363) orally once daily for ≥24 weeks. Hepatic insulin clearance was calculated from the ratio of areas under the curve (AUC) of C-peptide and insulin levels derived from oral meal tolerance test data (C-peptide AUC0-120 min /insulin AUC0-120 min : HICCIR ). The correlation of HICCIR via the SGLT2i with other clinical variables was analysed using multivariate analysis. RESULTS: HICCIR was significantly increased via TOFO at week 24. Furthermore, with TOFO insulin and triglyceride (TG) levels were significantly reduced (P <0.001) and β-hydroxybutyrate (BHB) was significantly elevated (P <0.001). Changes in HICCIR were significantly correlated with changes in TG and BHB via TOFO. CONCLUSIONS: Increased HICCIR was significantly associated with reduced TG via TOFO and contributed to the greater increase in BHB compared with placebo in addition to the correction of hyperinsulinaemia.

DOI： 10.1111/dom.13980

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

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OBJECTIVE: Declining healthy life expectancy due to functional disability is relevant and urgent because of its association with decreased quality of life and also for its enormous socioeconomic impact. The aim of this study is to examine the impact of diabetes, hypertension, dyslipidemia and physical activity habits on functional disability among community-dwelling Japanese adults. RESEARCH DESIGN AND METHODS: This is a population-based retrospective cohort study including 9673 people aged 39-98 years in Japan (4420, men). Functional disability was defined as a condition meeting Japan's new long-term care insurance certification requirements for the need of assistance in the activities of daily living whether by caregivers or assistive devices. Cox proportional-hazards regression model identified variables related to functional disability. RESULTS: Median follow-up was 3.7 years. During the study period, 165 disabilities occurred in the overall study population. Multivariate analysis showed that diabetes (HR 1.74 (95% CI 1.12 to 2.68)) and no physical activity habit (HR 1.83 (1.27 to 2.65)) presented increased risks for disability. HR for disability increased with the number of risk factors (HR of individuals with four conditions, 3.96 (1.59 to 9.99) vs individuals with none of those conditions as a reference). HR for disability among patients with diabetes with and without a physical activity habit was 1.68 (0.70 to 4.04) and 3.19 (1.79 to 5.70), respectively, compared with individuals without diabetes with a physical activity habit. CONCLUSIONS: The combination of diabetes and lack of habitual physical activity is predictive of functional disability in Japanese. Habitual physical activity attenuates the risk of functional disability in patients with diabetes.

DOI： 10.1136/bmjdrc-2019-000901

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Publishing type：Research paper (scientific journal)   Publisher：Japan Epidemiological Association  

DOI： 10.2188/jea.je20200034

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DOI： 10.2337/DB20-449-P

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DOI： 10.2337/DB20-1485-P

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DOI： 10.2337/DB20-1903-P

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DOI： 10.2337/DB20-663-P

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DOI： 10.2337/DB20-6-OR

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DOI： 10.2337/DB20-1988-P

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DOI： 10.2337/DB20-1125-P

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DOI： 10.2337/DB20-518-P

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DOI： 10.2337/DB20-389-P

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

OBJECTIVE: Although glucose abnormality status (GAS), prior coronary artery disease (CAD), and other traditional risk factors affect the incidence of subsequent CAD, their impact in the same cohort has been scantly studied. RESEARCH DESIGN AND METHODS: We analyzed data from a nationwide claims database in Japan that was accumulated during 2008-2016 involving 138,162 men aged 18-72 years. Participants were classified as having normoglycemia, borderline glycemia, or diabetes mellitus (DM) with prior CAD (CAD+) or without prior CAD (CAD-). Cox regression model identified variables related to the incidence of CAD. RESULTS: Among CAD-, management of traditional risks differed from those with and without subsequent CAD events. On the other hand, such differences were weaker in borderline glycemia and DM CAD+, and the influence of traditional risk factors on subsequent CAD was not observed. Cox regression model showed that borderline glycemia and DM confer approximately 1.2- and 2.8-fold excess risks of CAD, respectively, compared with CAD- with normoglycemia. CAD+ confers approximately a 5- to 8-fold increased risk. The impacts of DM and prior CAD additively reached a hazard ratio (HR) of 15.74 (95% confidence interval [CI]: 11.82-21.00). However, the HR in those with borderline glycemia and CAD+ was 7.20 (95% CI: 5.01-10.34), which was not different from those with normoglycemia and CAD+. CONCLUSION: Control status of traditional risk factors and impact on subsequent CAD differ among categories of glycemic status with and without prior CAD. Individualizing treatment strategies is needed in consideration of risk factors, such as GAS and CAD+.

DOI： 10.1016/j.metabol.2019.153991

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PURPOSE: To determine the degree of control of multiple risk factors under real-world conditions for coronary artery disease (CAD) according to the presence or absence of diabetes mellitus (DM) and to determine whether reaching multifactorial targets for blood pressure (BP), low-density lipoprotein-cholesterol (LDL-C), HbA1c, and current smoking is associated with lower risks for CAD. METHODS: We investigated the effects on subsequent CAD of the number of controlled risk factors among BP, LDL-C, HbA1c, and current smoking in a prospective cohort study using a nationwide claims database of 220,894 individuals in Japan. Cox regression examined risks over a 4.8-year follow-up. RESULTS: The largest percentage of participants had two risk factors at target in patients with DM (39.6%) and subjects without DM (36.4%). Compared with those who had two targets achieved, the risks of CAD among those who had any one and no target achieved were two and four times greater, respectively, regardless of the presence of DM. The effect of composite control was sufficient to bring CAD risk in patients with DM below that for subjects without DM with any two targets achieved, whereas the risk of CAD in the DM group with all four risk factors uncontrolled was 9.4 times more than in the non-DM group who had achieved two targets. CONCLUSIONS: These findings show that composite control of modifiable risk factors has a large effect in patients with and without DM. The effect was sufficient to bring CAD risk in patients with DM below that in the non-DM group who had two targets achieved.

DOI： 10.1210/jc.2019-00168

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

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CONTEXT: Although calorie loss from increased urinary glucose excretion continues after long-term treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2is), the mechanisms of the attenuated weight loss due to SGLT2is are not well known. OBJECTIVE: To examine the mechanism of the attenuated weight loss during long-term treatment with an SGLT2i, tofogliflozin, focusing on the antilipolytic effect of insulin on adipose tissue. DESIGN AND PARTICIPANTS: An integrated analysis was performed using data from two phase 3 studies of 52 weeks of tofogliflozin administration. The antilipolytic effect was evaluated using adipose tissue insulin resistance (Adipo-IR) calculated from the product of the levels of fasting insulin (f-IRI) and fasting free fatty acids (f-FFAs). RESULTS: Data from 774 patients with type 2 diabetes (mean age, 58.5 years; glycosylated hemoglobin, 8.1%; body mass index, 25.6 kg/m2; estimated glomerular filtration rate, 83.9 mL/min/1.73m2; 66% men) were analyzed. Weight loss plateaued between weeks 24 and 52 after decreasing significantly. f-IRI levels decreased significantly from baseline to week 24, and the decrease was maintained until Week 52. f-FFA levels significantly increased, peaked at week 24, then declined from weeks 24 to 52. Adipo-IR levels declined progressively throughout the 52 weeks (-3.6 mmol/L·pmol/L and -6.2 mmol/L·pmol/L at weeks 24 and 52, respectively; P < 0.001 baseline vs weeks 24 and 52 and week 24 vs week 52). Higher baseline Adipo-IR levels were independently associated with greater weight loss at week 52. CONCLUSION: The improved antilipolytic effect in adipose tissue may attenuate progressive lipolysis, leading to attenuating future weight loss induced by an SGLT2i in patients with type 2 diabetes.

DOI： 10.1210/jc.2018-02254

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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)日本糖尿病学会  

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Purpose: Since the combined effects of proteinuria and a moderately decreased eGFR on incident severe eye complications in patients with diabetes are still largely unknown, these associations were determined in a large historical cohort of Japanese patients with diabetes mellitus. Methods: We evaluated the effects of overt proteinuria (OP) (dipstick 1+ and over) and/or moderately reduced estimated glomerular filtration rate (eGFR) (MG) (baseline eGFR 30.0-54.9 mL/min/1.73 m2) on the incidence of treatment-required diabetic eye diseases (TRDED). We divided 7709 patients into four groups according to the presence or absence of OP and MG: no OP without MG (NP[MG-]), OP without MG (OP[MG-]), no OP with MG (NP[MG+]), and OP with MG (OP[MG+]). Multivariate Cox analyses were performed to calculate hazard ratios (HRs) with 95% confidence intervals for combinations of the presence and/or absence of OP and MG on the risk of developing TRDED. Results: During the median follow-up period of 5.6 years, 168 patients developed TRDED. HRs for OP and MG for incident TRDED were 1.91 (95% confidence interval, 1.27-2.87) and 1.90 (1.11-3.23), respectively. HRs for incident TRDED were 1.73 (1.11-2.69) and 5.57 (2.40-12.94) for OP(MG-) and OP(MG+), respectively, in comparison with NP(MG-). Conclusions: In Japanese patients with diabetes, OP and MG were separately as well as additionally associated with higher risks of TRDED. Results indicate the necessity of the simultaneous assessment of proteinuria and eGFR for appropriate evaluation of risks of severe eye complications in patients with diabetes.

DOI： 10.1167/iovs.19-26749

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Background Evidence of the role of systolic blood pressure ( SBP ) in development of severe diabetic retinopathy is not strong, although the adverse effect of low diastolic blood pressure has been a partial explanation. We assessed the predictive ability of incident severe diabetic retinopathy between pulse pressure ( PP ) which considers both SBP and diastolic blood pressure, compared with SBP . Methods and Results Eligible patients (12 242, 83% men) aged 19 to 72 years from a nationwide claims database were analyzed for a median observational 4.8-year period. Severe diabetic retinopathy was defined as vision-threatening treatment-required diabetic eye diseases. Multivariate Cox regression analysis revealed that hazard ratios (95% CI ) of treatment-required diabetic eye diseases for 1 increment of standard deviation and the top tertile compared with the bottom tertile were 1.39 (1.21-1.60) and 1.72 (1.17-2.51), respectively, for PP and 1.22 (1.05-1.41) and 1.43 (0.97-2.11), respectively, for SBP adjusted for age, sex, body mass index, hemoglobin A1c, fasting plasma glucose, lipids, and smoking status. In a model with SBP and PP simultaneously as covariates, the hazard ratios of only PP (hazard ratios [95% CI ], 1.57 [1.26-1.96]) but not SBP (0.85 [0.68-1.07]) were statistically significant. Delong test revealed a significant difference in the area under the receiver operating characteristic curve between PP and SBP (area under the receiver operating characteristic curve [95% CI ], 0.58 [0.54-0.63] versus 0.54 [0.50-0.59]; P=0.03). The strongest predictor remained as hemoglobin A1c (area under the receiver operating characteristic curve [95% CI ], 0.80 [0.77-0.84]). Conclusions After excluding the significant impact of glycemic control, PP in comparison with SBP is a better predictor of severe diabetic retinopathy, suggesting a role of diastolic blood pressure and arterial stiffness in pathology.

DOI： 10.1161/JAHA.118.010627

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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)日本内分泌学会  

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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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AIMS: To determine incidence and predictors of starting dialysis in patients with diabetes emphasizing blood pressure variables. METHODS: A nationwide database with claim data on 18 935 people (15 789 men and 3146 women) with diabetes mellitus aged 19 to 72 years in Japan was used to elucidate predictors for starting dialysis. Initiation of dialysis was determined from claims using ICD-10 codes and medical procedures. Using multivariate Cox modelling, interactions between glycaemic and blood pressure values were determined. RESULTS: During a median follow-up of 5.3 years, incidence of dialysis was 0.81 per 1000 person-years. Multivariate analysis of a model involving systolic and diastolic blood pressure (SBP and DBP) simultaneously as covariates showed that hazard ratios (HRs) for starting dialysis for each 1-SD elevation in SBP and DBP were 2.05 (95% confidence interval 1.58-2.64) and 0.66 (0.50-0.88), respectively, implying that pulse pressure (PP) was a promising predictor. For confirmation, a model involving SBP and PP simultaneously as covariates demonstrated that HRs for each 1-SD elevation in SBP and PP were 1.09 (0.81-1.48) and 1.54 (1.14-2.08), respectively, with PP the more potent predictor. Compared with HbA1c <8% and PP <60 mmHg, the HR for those with HbA1c ≥8% and PP ≥60 mmHg was 6.32 (3.42-11.7). CONCLUSIONS: In our historical cohort analysis, SBP and PP were independent predictors for starting dialysis. PP was the more potent, suggesting the contribution of increased arterial stiffness to the incidence of dialysis. Future studies are needed to conclude the independent influence of PP and HbA1c on dialysis considering other risk factors.

DOI： 10.1002/dmrr.3120

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Language：Japanese   Publisher：新潟医学会  

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Language：Japanese   Publisher：新潟医学会  

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BACKGROUND & AIMS: High intake of fruit and vegetables is recommended for cardiovascular health. However, there have been persistent beliefs that fruits having high concentrations of fructose elevate the level of triglycerides (TG) in blood unlike vegetables. This meta-analysis aims to clarify the relationship between fruit intake and TG or hypertriglyceridemia. METHODS: Electronic literature searches were conducted for observational studies that investigated the relationship between fruit intake and hypertriglyceridemia or intervention studies that investigated the effect of increasing fruit intake on TG. Each effect size was pooled with an inverse-variance method. RESULTS: Five cross-sectional studies and only 2 intervention studies were eligible. The pooled odds ratio (OR) (95% confidence interval (CI)) of the 5 cross-sectional studies for the highest vs. the lowest fruit intake category was 0.79 (0.72-0.87). In these studies, the pooled OR for the highest vs. the lowest vegetable intake category was not significant (OR = 0.92; 95% CI, (0.82-1.03)). A linear dose-response association was observed between increases in fruit intake and ORs for hypertriglyceridemia; the OR (95% CI) for an incrementally increased intake of fruit by 1 serving/day was 0.91 (0.84-0.98). CONCLUSION: This meta-analysis suggests that high intake of fruit but not vegetables is inversely associated with hypertriglyceridemia. More trials are needed to clarify whether increasing fruit intake would reduce the level of TG and/or incident hypertriglyceridemia.

DOI： 10.1016/j.clnesp.2018.07.001

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AIM: To examine the association between treatment-achieved HbA1c values and incidence of both coronary artery disease (CAD) and severe eye disease with different diabetes treatments. METHODS: Associations of treatment-achieved HbA1c were investigated in various treatment groups [diet only; insulin; sulphonylurea (SU) alone; SU with glinides; and antihyperglycaemic agents other than glinides, SU or insulin] taken from a nationwide claims database of 14,633 Japanese diabetes patients. Cox's regression analysis examined risks over a 5.1-year follow-up. RESULTS: A significant linear trend was associated with HbA1c levels and CAD events in the diet-only group, and CAD risks were significantly higher in insulin and SU groups with HbA1c ≤ 7.0% and > 8.0% than in the diet-only group with HbA1c ≤ 7.0%. In contrast to CAD, a linear association was observed regardless of treatment modality between achieved HbA1c levels and risk of severe diabetic eye disease, but with no significant difference in eye disease risk between groups with HbA1c ≤ 7.0% and 7.1-8.0% in those treated with either SU alone, SU with glinides, or insulin. CONCLUSION: These findings suggest that the relationship between treatment-achieved HbA1c and incidence of both CAD and severe diabetic eye disease differed according to treatment, based on a large-scale real-life database. More research is now needed to confirm these findings and to further investigate the underlying mechanisms.

DOI： 10.1016/j.diabet.2018.08.009

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Language：Japanese   Publisher：日本糖尿病眼学会  

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

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Language：Japanese   Publisher：日本糖尿病眼学会  

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DOI： 10.1111/obr.12751

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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)日本動脈硬化学会  

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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：(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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AIM: Hepatic insulin clearance (HIC) is important in regulating plasma insulin levels. Diminished HIC causes inappropriate hyperinsulinaemia, and both obesity and fatty liver (FL), which are known to decrease HIC, can be found either together in the same patient or on their own. The mechanism by which obesity reduces HIC is presumed to be mediated by FL. However, few reports have examined the role of FL in the relationship between obesity and HIC in type 2 diabetes (T2D) patients. Therefore, our study investigated the association of HIC with clinical factors, including insulin sensitivity indices, focusing on the presence or absence of FL and obesity in T2D patients. METHOD: Baseline data from 419 patients with T2D (279 men, 140 women; mean age: 57.6 years; body mass index: 25.5kg/m2) controlled by diet and exercise were analyzed. HIC was calculated from the ratio of fasting c-peptide to fasting insulin levels (HICCIR). Correlation analyses between HICCIR and clinical variables were performed using Pearson's product-moment correlation coefficients and single regression analysis in all participants and in those with obesity and FL either alone or in combination. RESULTS: HICCIR was significantly correlated with whole-body insulin sensitivity indices and influenced by FL, but only in the FL group was obesity independently influenced HIC level. HICCIR decreased in those with both FL and obesity compared with those with only one such complication. CONCLUSION: HICCIR may be used to evaluate whole-body insulin sensitivity in T2D. Also, compared with obesity, the influence of FL strongly contributed to a reduced HIC. TRIAL REGISTRATION NUMBER: These trials were registered by the Japan Pharmaceutical Information Centre clinical trials information (JapicCTI) as 101349 and 101351.

DOI： 10.1016/j.diabet.2017.12.003

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DOI： 10.1016/j.diabet.2017.10.003

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OBJECTIVE: This study aimed to examine the impact of obesity, as defined by body mass index (BMI), and a metabolically unhealthy phenotype on the development of coronary artery disease (CAD) according to glucose tolerance status. METHODS: This population-based retrospective cohort study included 123,746 Japanese men aged 18-72years (normal glucose tolerance: 72,047; prediabetes: 39,633; diabetes: 12,066). Obesity was defined as a BMI≥25kg/m2. Metabolically unhealthy individuals were defined as those with one or more of the following conditions: hypertension, hypertriglyceridaemia and/or low HDL cholesterol. A Cox proportional hazards regression model identified variables related to CAD incidence. RESULTS: The prevalences of obese subjects with normal glucose tolerance, prediabetes and diabetes were 21%, 34% and 53%, whereas those for metabolically unhealthy people were 43%, 60% and 79%, respectively. Multivariate analysis showed that a metabolically unhealthy phenotype increases hazard ratios (HRs) for CAD compared with a metabolically healthy phenotype, regardless of glucose tolerance status (normal glucose tolerance: 1.98, 95% CI: 1.32-2.95; prediabetes: 2.91, 95% CI: 1.85-4.55; diabetes: 1.90, 95% CI: 1.18-3.06). HRs for CAD among metabolically unhealthy non-obese diabetes patients and obese diabetes patients with a metabolically unhealthy status were 6.14 (95% CI: 3.94-9.56) and 7.86 (95% CI: 5.21-11.9), respectively, compared with non-obese subjects with normal glucose tolerance and without a metabolically unhealthy status. CONCLUSION: A metabolically unhealthy state can associate with CAD independently of obesity across all glucose tolerance stages. Clinicians may need to consider those with at least one or more conditions indicating a metabolically unhealthy state as being at high risk for CAD regardless of glucose tolerance status.

DOI： 10.1016/j.diabet.2017.08.002

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DOI： 10.1016/j.diabet.2017.08.002

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Little is known about the relationships between patient factors and the antihyperglycemic agents that have been prescribed as initial therapy by diabetes specialists for patients with type 2 diabetes. Moreover, there has been little clarification of the subsequent usage patterns and related factors that influenced the continuation or discontinuation of the drug or the addition of another drug. To provide information on these issues, we evaluated the clinical characteristics of Japanese patients with type 2 diabetes for whom different types of oral hypoglycemic agents (i.e., either sulfonylureas, biguanides, or DPP-4 inhibitors (DPP-4Is)) were chosen as initial monotherapy by diabetes specialists and evaluated subsequent usage patterns.Prescription data on 3 different antidiabetic agents from December 2009 to March 2015 from diabetes specialists' patient registries were used to identify variables at baseline related to initial prescriptions; also, the addition of another hypoglycemic drug or discontinuation of the initial therapy was evaluated 1 year after the initial prescription. Analyzed were data on 2666 patients who received initial monotherapy with either a sulfonylurea (305 patients), biguanide (951 patients), or DPP-4I (1410 patients). Patients administered sulfonylureas were older, had a lower body mass index (BMI), longer duration of diabetes, and worse glycemic control than recipients of biguanides. Use of biguanides was related to younger age, short duration of diabetes, and obesity but was negatively associated with poor glycemic control. Older age but neither obesity nor poor glycemic control was associated with DPP-4Is. In all 3 groups a high HbA1c value was related to adding another hypoglycemic agent to the initial therapy. Moreover, adding another drug to a DPP-4I was related to a younger age and higher BMI.Patients' age, duration of diabetes, obesity, and glycemic control at baseline influenced the choice of hypoglycemic agents. Selection of a biguanide differs greatly from that of a sulfonylurea or DPP-4I with regard to age and obesity.

DOI： 10.1097/MD.0000000000006122

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OBJECTIVE: Nonblood-based risk assessment for type 2 diabetes mellitus (T2DM) that depends on data based on a questionnaire and anthropometry is expected to avoid unnecessary diagnostic testing and overdiagnosis due to blood testing. This meta-analysis aims to assess the predictive ability of nonblood-based risk assessment for future incident T2DM. METHODS: Electronic literature search was conducted using EMBASE and MEDLINE (from January 1, 1997 to October 1, 2014). Included studies had to use at least 3 predictors for T2DM risk assessment and allow reproduction of 2×2 contingency table data (i.e., true positive, true negative, false positive, false negative) to be pooled with a bivariate random-effects model and hierarchical summary receiver-operating characteristic model. Considering the importance of excluding individuals with a low likelihood of T2DM from diagnostic blood testing, we especially focused on specificity and LR-. RESULTS: Eighteen eligible studies consisting of 184,011 participants and 7038 cases were identified. The pooled estimates (95% confidence interval) were as follows: sensitivity=0.73 (0.66-0.79), specificity=0.66 (0.59-0.73), LR+=2.13 (1.81-2.50), and LR-=0.41 (0.34-0.50). CONCLUSIONS: Nonblood-based assessment of risk of T2DM could produce acceptable results although the feasibility of such a screener needs to be determined in future studies.

DOI： 10.1016/j.ypmed.2016.07.026

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Endogenous Cushing's syndrome is an endocrine disease resulting from chronic exposure to excessive glucocorticoids produced in the adrenal cortex. Although the ultimate outcome remains uncertain, functional and morphological brain changes are not uncommon in patients with this syndrome, and generally persist even after resolution of hypercortisolemia. We present an adolescent patient with Cushing's syndrome who exhibited cognitive impairment with brain atrophy. A 19-year-old Japanese male visited a local hospital following 5 days of behavioral abnormalities, such as money wasting or nighttime wandering. He had hypertension and a 1-year history of a rounded face. Magnetic resonance imaging (MRI) revealed apparently diffuse brain atrophy. Because of high random plasma cortisol levels (28.7 μg/dL) at 10 AM, he was referred to our hospital in August 2011. Endocrinological testing showed adrenocorticotropic hormone-independent hypercortisolemia, and abdominal computed tomography demonstrated a 2.7 cm tumor in the left adrenal gland. The patient underwent left adrenalectomy in September 2011, and the diagnosis of cortisol-secreting adenoma was confirmed histologically. His hypertension and Cushingoid features regressed. Behavioral abnormalities were no longer observed, and he was classified as cured of his cognitive disturbance caused by Cushing's syndrome in February 2012. MRI performed 8 months after surgery revealed reversal of brain atrophy, and his subsequent course has been uneventful. In summary, the young age at onset and the short duration of Cushing's syndrome probably contributed to the rapid recovery of both cognitive dysfunction and brain atrophy in our patient. Cushing's syndrome should be considered as a possible etiological factor in patients with cognitive impairment and brain atrophy that is atypical for their age.

DOI： 10.2147/NDT.S70611

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Endogenous Cushing's syndrome is an endocrine disease resulting from chronic exposure to excessive glucocorticoids produced in the adrenal cortex. Although the ultimate outcome remains uncertain, functional and morphological brain changes are not uncommon in patients with this syndrome, and generally persist even after resolution of hypercortisolemia. We present an adolescent patient with Cushing's syndrome who exhibited cognitive impairment with brain atrophy. A 19-year-old Japanese male visited a local hospital following 5 days of behavioral abnormalities, such as money wasting or nighttime wandering. He had hypertension and a 1-year history of a rounded face. Magnetic resonance imaging (MRI) revealed apparently diffuse brain atrophy. Because of high random plasma cortisol levels (28.7 mu g/dL) at 10 AM, he was referred to our hospital in August 2011. Endocrinological testing showed adrenocorticotropic hormone-independent hypercortisolemia, and abdominal computed tomography demonstrated a 2.7 cm tumor in the left adrenal gland. The patient underwent left adrenalectomy in September 2011, and the diagnosis of cortisol-secreting adenoma was confirmed histologically. His hypertension and Cushingoid features regressed. Behavioral abnormalities were no longer observed, and he was classified as cured of his cognitive disturbance caused by Cushing's syndrome in February 2012. MRI performed 8 months after surgery revealed reversal of brain atrophy, and his subsequent course has been uneventful. In summary, the young age at onset and the short duration of Cushing's syndrome probably contributed to the rapid recovery of both cognitive dysfunction and brain atrophy in our patient. Cushing's syndrome should be considered as a possible etiological factor in patients with cognitive impairment and brain atrophy that is atypical for their age.

DOI： 10.2147/NDT.S70611

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肥満関連高血圧は,交感神経活性の変化,インスリン抵抗性の増強など,さまざまな病態が複合して病態が形成されている.肥満症患者の高血圧は,心血管イベントとより強く関連するnon-dipperとなりやすくなることに留意が必要である.肥満は高血圧,脂質異常などのリスクの集積をもたらし,脳・心血管イベントを惹起するが,本邦においては,BMI増加が独立した危険因子として存在している可能性を示唆する報告もある.(著者抄録)

DOI： 10.15106/J00974.2016089660

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＜Point＞・2型糖尿病は「インスリン分泌低下を主体とするものと、インスリン抵抗性が主体で、それにインスリンの相対的不足を伴うものなどがある」と定義される。インスリン分泌不全とインスリン抵抗性それぞれの関与の程度は症例により異なる(これには人種差を含めた遺伝的背景も大きく関与する)・併存疾患や、患者さんがおかれている社会環境、治療介入に伴う副作用リスク等を包括的に判断し、治療目標を立てる必要がある・したがって、目標とする血糖管理値や治療方法は、個々の症例の病態を考慮し、個別化する必要がある(これは血圧、脂質にも共通するところがある)・日常診療における、欧米とわが国のおかれている状況との相違や、人種差、文化(食生活を含む)の相違、また、それらを背景とした疾病構造の相違等から、欧米のガイドラインをそのまま適用するのは決して望ましいとは言えない。ガイドラインを参照する際も、以上を踏まえたうえで解釈する必要がある(著者抄録)

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