Complications In Japanese Patients Research Articles

6374 Prevalence and risk factor of complications in patients with adult growth hormone deficiency: A retrospective database study

Abstract Disclosure: H. Fukuoka: None. S. Fujio: None. T. Endo: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. S. Tsuboi: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. Though adult growth hormone deficiency (AGHD) is known to lead to increased prevalence of complications, large database studies on AGHD have not been conducted. We investigated the clinical characteristics and prevalence of AGHD-related complications in Japanese patients. We identified 8,809 GH-untreated patients with AGHD from Medical Data Vision claims database between April 2008 and September 2022. In 2020, 3,420 AGHD patients were identified, and their prevalence of complications adjusted for sex and age was higher than that of Japanese general population, 9.3% vs 3.6% for diabetes mellitus (DM), 4.8% vs 1.3% for osteoporosis, and especially 22.0% vs 3.9% for dyslipidemia. We explored the risk factors for the onset of complications using Cox proportional hazard model. Age was significant risk factor for most complications and being female was significant risk factor for osteoporosis. DM was a significant risk factor for dyslipidemia, ischemic heart disease, cerebrovascular disease, and all cause death. AGHD increases the overall risk of metabolic complications, risk factors of these complications were similar to those in general population. Comprehensive treatment approach needs to be considered to alleviate the risk of complications. Presentation: 6/3/2024

Exploring potential correlations between HLA class II and the risk of microvascular complications in Japanese patients with type 1 diabetes

Managing complications in Type 1 diabetes (T1D) remains challenging. HLA genes, particularly DR and DQ, are linked to T1D susceptibility. We studied 48 Japanese T1D inpatients and revealed associations between DRB1*04:05-DQB1*04:01 and DRB1*09:01-DQB1*03:03 haplotypes and complications, offering a new perspective for future research.

Geriatric 8 and Vulnerable Elders Survey-13 predict length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery

IntroductionThe Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) are established screening tools for assessing vulnerability in older patients. Here we investigated their usefulness as predictors of length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery. Materials and MethodsThis study included 643 patients who underwent urological surgery (74% were for malignancy) at our institute from 2017 to 2020. G8 and VES-13 scores were routinely recorded upon admission. These indices and other clinical data were obtained through chart review. The correlation between G8 group (high, >14; intermediate, 11–14; low, <11) or VES-13 group (normal, <3; high, ≥3) and length of total hospital stay (LOS), postoperative hospital stay (pLOS), and postoperative complications including delirium were analyzed. ResultsThe median patient age was 69 years. A total of 44%, 45%, and 11% of patients were classified into high, intermediate, and low G8 groups, respectively, while 77% and 23% were classified into normal and high VES-13 groups, respectively. Univariate analyses revealed that low G8 scores were associated with prolonged LOS (vs. intermediate, odds ratio [OR] 2.87, P < 0.001; vs. high, OR 3.87, P < 0.001), prolonged pLOS (vs. intermediate, OR 2.37, P = 0.005; vs. high, OR 3.06, P < 0.001), and delirium (vs. intermediate, OR 3.23, P = 0.007; vs. high, OR 5.38, P < 0.001), and high VES-13 scores were associated with prolonged LOS (OR 2.85, P < 0.001), prolonged pLOS (OR 2.97, P < 0.001), and Clavien-Dindo grade ≥ 2 complications (OR 1.74, P = 0.044), and delirium (OR 3.18, P = 0.001). Furthermore, multivariate analyses revealed that low G8 and high VES-13 scores were independent factors which predicted prolonged LOS (low G8; vs. intermediate, OR 2.96, P < 0.001; vs. high, OR 3.94, P < 0.001; high VES-13; OR 2.98, P < 0.001) and prolonged pLOS (low G8; vs. intermediate, OR 2.41, P = 0.008; vs. high, OR 3.18, P = 0.002; high VES-13; OR 3.47, P < 0.001), respectively. DiscussionThe G8 and VES-13 may be effective tools for predicting prolonged LOS/pLOS and postoperative complications in Japanese patients who undergo urological surgery.

RWD150 Cost of Illness: Estimating Direct Healthcare Costs Related to Obesity in a Japanese Clinical Setting

Obesity or overweight is associated with diabetes, cardiovascular complications, cancer, and knee replacement surgery. This study aimed to estimate direct healthcare costs of obesity-related complications in Japanese patients.

Infrequent Thrombotic Complications in Japanese Patients with Warm Autoimmune Hemolytic Anemia.

Objective Patients with autoimmune hemolytic anemia (AIHA) are considered to be at an increased risk of thrombosis, and prophylaxis for venous thromboembolism (VTE) is often recommended. However, the occurrence of thrombosis in Asian patients has not been specifically studied. Thrombotic complications and features of Japanese warm AIHA (WAIHA) patients were studied to see if Japanese patients were at an increased risk of thrombosis and should receive prophylaxis for VTE. Patients and Methods Forty-seven consecutive patients with warm WAIHA were retrospectively studied. Twenty-nine patients were diagnosed as primary cases and 18 as secondary cases, and 10 patients were diagnosed with Evans syndrome. Results No patient presented with thrombosis, and over a median observation period of 15 months, 3 patients had ischemic cerebral vascular accidents. However, all three of those patients had other known risks for thrombosis, with only one taking thrombotic prophylaxis. No venous thrombosis occurred in any patients during the follow-up period. There was no mortality associated with thrombosis. D-dimer levels were often elevated in patients with WAIHA, indicating that the coagulation was activated in a considerable number of patients, but not to such a level as to be associated with clinically overt thrombosis. Conclusion Thrombotic complications occur infrequently in Japanese WAIHA patients, and these individuals do not appear to be at a particularly increased risk of thrombosis because of WAIHA. The indication of VTE prophylaxis should be determined individually, considering other risks.

ACUTE PULMONARY HYPERTENSION AFTER BORTEZOMIB THERAPY

ACUTE PULMONARY HYPERTENSION AFTER BORTEZOMIB THERAPY

Comparison of continuous subcutaneous insulin infusion treatment and multiple daily injection treatment on the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.

ABSTRACTTo evaluate whether continuous subcutaneous insulin infusion attenuates the progression of diabetic complications, we retrospectively extracted data from 35 individuals who had developed type 1 diabetes mellitus aged ≤20 years and whose treatment had been changed from multiple daily injections to continuous subcutaneous insulin infusion. The annual changes in estimated glomerular filtration rate, urinary albumin excretion rate, carotid intima‐media thickness and brachial‐ankle pulse wave velocity during each treatment period were calculated. Although mean glycated hemoglobin under the continuous subcutaneous insulin infusion treatment was lower than that under the multiple daily injection treatment, there were no significant differences in annual changes in diabetic nephropathy and atherosclerosis between the two treatment periods. This pilot study showed that, in Japanese patients with juvenile‐onset type 1 diabetes mellitus, there was no significant difference in the progression of diabetic nephropathy and atherosclerosis, at least in the early stage, between the two treatments.

Cervical lateral mass screw length analysis in men versus women.

Posterior fixations with lateral mass screws have become popular. The Roy-Camille and the Magerl techniques have been established and screw length was identified as a particularly important element. Sex and ethnicity are significant factors in cervical spine morphology, but few studies have been performed for screw length. We performed measurements using computed tomography (CT) images of adult patients hospitalized for surgery of the cervical spine, with targeted 3D data analysis. The final number of patients was 47 (33 men, 14 women) and 235 vertebrae. With the Roy-Camille technique, the screw length was longest at C3 (men: 13.0 mm ± 1.9 mm, women: 13.0 mm ± 1.9 mm) and smallest at C7 (men: 10.8 mm ± 1.8 mm, women: 9.4 mm ± 1.2 mm). With the Magerl technique, the screw length was smallest at C3 (men: 14.8 mm ± 1.6 mm, women: 14.3 mm ± 1.6 mm) and longest at C7 for men (16.8 mm ± 2.8 mm), and at C6 for women (15.4 mm ± 3.0 mm). To differ from spinal canal or pedicle, cervical lateral mass showed no obvious morphological differences from that of subjects of other ethnicity. The placement of a standard lateral mass screw would not cause complications in Japanese patients, even with the use of devices designed in North America or Europe. However, the anatomical background is essential because it is important to optimize the selection for each patient to avoid complications considering sex and individual differences.

PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD

BackgroundReliable noninvasive predictors of the top three causes of death [cardiovascular diseases (CVDs), malignancies, and liver-related events in patients with non-alcoholic fatty liver disease (NAFLD)] have not yet been determined.MethodsWe retrospectively investigated the incidence of three complications [CVDs, malignancy (except for liver cancer), and liver-related events] in 477 Japanese patients with histo-pathologically confirmed NAFLD for a median follow-up of 5.9 years. In addition to histological findings, we also investigated noninvasive predictors.ResultsA score of ≥ 2.67 for the noninvasive diagnosis of stage 4 fibrosis based on the Fibrosis-4 (FIB-4) index indicated a high level area under the receiver operating characteristic (AUROC) curve (0.90), sensitivity (82.9%), specificity (86.4%), and negative predictive value [(NPV) of 98.5%]. The yearly incidence rates of CVDs, malignancies, and liver-related events were found to be 1.04%, 0.83%, and 0.30%, respectively. Multivariate analysis identified a FIB-4 index ≥ 2.67 score as a significant and independent, noninvasive predictor of these three complications. Furthermore, the cumulative incidence rates of CVDs were significantly different among the three genotypes of PNPLA3. PNPLA3 genotype CC, chronic kidney disease (CKD), and FIB-4 index ≥ 2.67 was could be attributed to these three significant CVD risk factors. The rates of CVDs were significantly different among the three subgroups based on the combination of risk factors. In malignancy (except for liver cancer), the incidence rate of colon cancer was 25.0%; in particular, the rate in females was 53.8%.ConclusionsOur results highlighted the importance of the PNPLA3 genotype and FIB-4 index ≥ 2.67 on the incidence of complications in Japanese patients with NAFLD, especially the incidence of CVDs. Early diagnosis, based on the presence of one or more risk factors, and early treatment might improve the prognosis for NAFLD patients.

Comorbidities and complications in Japanese patients with type 2 diabetes mellitus: Retrospective analyses of J-DREAMS, an advanced electronic medical records database

AimsTo investigate the prevalence of comorbid conditions/complications among Japanese patients with type 2 diabetes mellitus (T2DM) in a real-world setting. MethodsWe performed retrospective analyses of a large-scale database directly linked to electronic medical records, J-DREAMS (Japan Diabetes compREhensive database project based on an Advanced electronic Medical record System), to determine the prevalence of clinically significant comorbid conditions/complications among Japanese patients with T2DM aged ≥ 20 years with ≥ 1 clinical encounter at a referral center between April 1, 2017 and March 31, 2019. ResultsData were available for 10,151 patients (39.2% female). The mean age and T2DM duration were 66.0 years and 16.1 years, respectively. Only 0.5% had isolated T2DM, 6.6% had one comorbid condition/complication, and the remainder had multiple comorbid conditions/complications. Dyslipidemia (84.7%) and hypertension (75.1%) were the most common, followed by chronic kidney disease (35.4%), retinopathy (23.1%), and cardiovascular diseases (22.1%). Overall, 36.0% of patients were overweight/obese (body mass index ≥ 25 kg/m2) and 18.6% had a history of neoplasms. The prevalence of comorbid conditions/complications tended to increase with advancing age and duration of T2DM. ConclusionsWe revealed a high prevalence of comorbid conditions/complications, including chronic kidney and cardiovascular diseases, in Japanese patients with T2DM.

A fact-finding survey on self-efficacy of foot care behaviour in patients with diabetes: Analysis using the Diabetes Study from the Center of Tokyo Women's Medical University 2017 (DIACET 2017).

AimWe aimed to determine the association between self‐efficacy of foot care behaviour and chronic complications in Japanese patients with diabetes.MethodsWe conducted a cross‐sectional study based on a questionnaire survey of 4571 patients with type 1 and type 2 diabetes who had (a) given consent to participate in the Diabetes Study from the Center of Tokyo Women's Medical University: DIACET 2017, and (b) completed all the questions of the Japanese Version of Foot Care Confidence Scale (J‐FCCS), consisting of 12 statements.ResultsA greater proportion of respondents answered that they were not confident in determining the condition of corns and/or calluses and the condition of toenails. The J‐FCCS total scores of the patients with retinopathy (p <.001) and numbness or pain in the feet (p <.001) were significantly lower than those of the patients without these complications. In both the multiple regression analysis and logistic regression analysis, lower J‐FCCS was significantly associated with retinopathy and numbness or pain in the feet.ConclusionFoot care education that emphasizes a psychological approach in improving confidence associated with foot self‐care is important for patients with advanced complications of diabetes.

Clinical experience of the use of reamer irrigator aspirator in Japanese patients: A report of the first 42 cases

BackgroundA reamer irrigator aspirator (RIA) can be used to harvest substantial amounts of autologous bone and debride the intramedullary canal. Clinical experience using reamer irrigator aspirators in Japan is very limited. The applicability of the reamer irrigator aspirator head with a minimum diameter of 12 mm for Japanese people is often questioned as the Japanese are smaller than Americans and Europeans. There are no reports of complications in Japanese patients. This study aimed to retrospectively review clinical cases and describe reamer irrigator aspirator use in Japanese patients. MethodsAll patients for whom a reamer irrigator aspirator was used during surgery at our hospital between January 2014 and September 2018 were included. The patients’ clinical and radiographic data were retrospectively reviewed. ResultsData of 40 patients (42 cases) were collected. The reamer irrigator aspirator was used for bone graft harvesting in 32 cases, intramedullary debridement and irrigation in 9 cases, and reaming for exchange nailing in 1 case. The diameter of the reamer irrigator aspirator reamer head was 12 mm in 22 cases (53.7%), 12.5 mm in 4 cases (9.8%), 13 mm in 9 cases (22.0%), 13.5 mm in 1 case (2.4%), 14.0 mm in 1 case (2.4%), 14.5 mm in 1 case (2.4%), and 15 mm in 4 cases (9.8%). Mean intraoperative bleeding volume was 1158.6 mL (range, 100–3800 mL). We experienced no difficulty inserting the reamer irrigator aspirator into the intramedullary canals and no cases of insertion-related intraoperative fracture. Five cortical perforations (11.9%) were observed on postoperative computed tomography scans, although no patient was symptomatic. One case (2.4%) of postoperative femur fracture occurred. ConclusionsReamer irrigator aspirators can be used in Japanese patients. Smaller reamer head sizes were mainly used in our experience. We should manage complications as in previous reports from Western countries.

Questionnaire survey of angiogenesis inhibitor-related oral complications based on a nation-wide study in Japan

Background/purposeThe prevalence of oral adverse events and dental treatments related complications during the molecular targeted drugs therapy remains unclear. The purpose of this study was to investigate the contents of dental treatment-related complications in Japanese patients during molecular targeted therapy. Materials and methodsThe nation-wide survey of dental treatment related complications was performed by the Japanese Society of Dentistry for Medically Compromised Patient as retrospective cohort study. ResultsAmong 212 dentists, 87.3% recognized the possibility of dental treatments related complications in patients with angiogenesis inhibitors. The oral adverse events including dental treatment-related complications associated with angiogenesis inhibitors were 79 cases. In patients with angiogenesis inhibitors, 73.4% of patients were administrated with bevacizumab. The average administration period of angiogenesis inhibitors was 14.0 ± 10.0 months. As the dental treatment related complications, delayed wound healing was most commonly seen in 45 patients (57.0%), followed by osteonecrosis of the jaw in 25 (31.6%). The triggered factor of complications was tooth extraction in 51 cases (96.2%). ConclusionThe extraction of the tooth with pre-existing inflammation may be suggested as one of risk factors for angiogenesis inhibitor-related dental treatment complications.

Association between mean platelet volume in the pathogenesis of type2 diabetes mellitus and diabetic macrovascular complications in Japanese patients.

Aims/IntroductionMean platelet volume (MPV) is a widely used biological marker of platelet function and activity. Increased MPV is associated with accelerated thrombopoiesis and an elevated risk of cardiovascular disease. However, it is not known whether higher MPV is related to the pathogenesis of type 2 diabetes and diabetic macrovascular complications in Japanese patients. Therefore, we analyzed MPV and its correlation with atherosclerosis in Japanese patients with type 2 diabetes and those who had prediabetes.Materials and MethodsWe divided the patients into three groups: normoglycemic patients (n = 56), prediabetes patients (n = 44) and type 2 diabetes patients group, (n = 115). We measured platelet parameters and evaluated arterial stiffness in the three groups.ResultsSignificantly higher MPV was found in the type 2 diabetes mellitus and prediabetes patients compared with normoglycemic patients. MPV was significantly correlated with fasting blood glucose and glycated hemoglobin levels. Multiple linear regression analysis showed that MPV was positively correlated with HbA1c, even after adjustment for confounding factors. In the evaluation of arterial stiffness by measuring the cardio‐ankle vascular index and maximum intima‐media thickness, MPV showed a positive correlation with these parameters.ConclusionsThese findings suggest that MPV was significantly increased in the early stage of type 2 diabetes. We showed positive correlations between MPV and HbA1c levels, and between MPV and arterial stiffness in Japanese patients with type 2 diabetes.

1579-P: Higher Calcium Intake Is Associated with Lower Incidence of Diabetic Nephropathy in Japanese Patients with Type 2 Diabetes

Evidence for optimal dietary intake of calcium for prevention of diabetic complications is sparse although population-based cohort studies showed that calcium intake reduces the risk of type 2 diabetes (T2D). We aimed to investigate the relationship between calcium intake and the incidence of diabetes complications in Japanese patients with T2D aged 40-70 years with HbA1c ≥6.5%. This analysis was conducted as a multicenter prospective study of the incidence of and risk factors for macro- and microvascular complications among 2205 Japanese patients with T2D from outpatient clinics in 59 university and general hospitals in Japan. Analyzed were 1588 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups or a dietary record. Primary outcome was the 8-year risk of nephropathy, retinopathy, and cardiovascular disease (CVD). Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, BMI, HbA1c, smoking, energy intake, and other confounders. Mean calcium intake in quartiles ranged from 487.5 to 751 mg/day, and more than half of participants had calcium intake below the recommended daily dietary allowance in Japan (men 700 mg/d; women 650 mg/d). After adjusting for confounders, HRs of diabetic nephropathy in the 2nd, 3rd, and 4th quartiles for calcium intake compared with the 1st quartile were 1.20 (95% confidence interval 0.67-2.18, p=0.540), 0.60 (0.28-1.28, p=0.185), and 0.42 (0.18-0.97, p=0.024), respectively. There were no significant associations of calcium intake with retinopathy and CVD in the 2nd to 4th quartiles relative to the 1st quartile (retinopathy: 1.15 (0.81-1.64, p=0.441), 1.14 (0.78-1.68, p=0.491), and 0.93 (0.59-1.46, p=0.809); CVD: 0.86 (0.51-1.44, p=0.558), 0.92 (0.53-1.61, p=0.763), and 0.81 (0.42-1.53, p=0.508). Findings suggested an association of high calcium intake with a lower incidence of diabetes nephropathy in Japanese patients with T2D. Disclosure C. Horikawa: None. R. Aida: None. S. Tanaka: None. S. Tanaka: None. C. Kamada: None. Y. Yoshimura: None. A. Araki: Speaker's Bureau; Self; Dainippon Sumitomo Parma Co. Ltd., Merck &amp; Co., Inc., Tanabe Mitsubishi Pharma Corporation. T. Moriya: None. S. Katayama: None. Y. Akanuma: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Funding Japan Society for the Promotion of Science; Japan Ministry of Health, Labour and Welfare

Real-World Data on the Incidence of Macrovascular Complications in Japanese Patients with Type 2 Diabetes: The Sitagliptin Registration Type 2 Diabetes-Juntendo Collaborating Project.

IntroductionType 2 diabetes is associated with vascular complications that deteriorate the quality of life and decrease the life expectancy of individuals. We previously reported the efficacy of sitagliptin for glucose control in patients with type 2 diabetes in the Sitagliptin Registration Type 2 Diabetes-Juntendo Collaborating Project (SPIRITS-J). Through the results of the SPIRITS-J study, we expected that optimal comprehensive management of type 2 diabetes according to current clinical practice guidelines in addition to achieving individualized glycemic goals would reduce macrovascular complications and all-cause mortality in Japan. The aim of this study was to evaluate this hypothesis.MethodsWe investigated the clinical outcomes prospectively in the extended SPIRITS-J study and compared these to previous Japanese cohort studies in the era before widespread use of guidelines. The primary clinical outcome was a composite of myocardial infarction (MI), stroke, and all-cause mortality.ResultsMean duration of follow-up was 3.5 ± 1.3 years. The crude incidence of the primary outcome per 1000 person-years was 13.9 (non-fatal MI 1.44, non-fatal stroke 4.22, all-cause mortality 8.79 per 1000 person-years, respectively). It is noteworthy that the incidence of MI in the SPIRITS-J study was very much lower than that in a previous Japanese cohort study. In multivariate analysis, both the history of coronary artery disease and low-density lipoprotein cholesterol (LDL-C) were independently associated with incidence of primary clinical outcome.ConclusionThe extended SPIRITS-J study demonstrated that optimal comprehensive management in patients with type 2 diabetes according to the recent practice guidelines has succeeded in preventing macrovascular complications in Japan. This study suggests that more intensive LDL-C-lowering therapy is important for further prevention of macrovascular complications even in Japanese patients with type 2 diabetes (UMIN 000004121).Electronic supplementary materialThe online version of this article (10.1007/s13300-019-0626-2) contains supplementary material, which is available to authorized users.

Incidence of catheter-related complications among Japanese patients with central venous catheters as well as patients with short bowel syndrome.

PurposeShort bowel syndrome (SBS) is a serious rare disorder that is usually managed with parenteral nutrition. Central venous catheter (CVC)-related complications are known to occur, but their incidence rates (IRs) in Japan are unknown. The aim of this study was to estimate the incidence of complications in Japanese patients with CVCs, including patients with SBS using CVCs.Patients and methodsA retrospective cohort study in 64,817 patients with CVCs, including 81 patients with SBS, between April 2008 and October 2016 using a claims database in Japan was conducted. IRs of complications were calculated as total events divided by total catheter-days among all patients with CVCs and among patients with SBS.ResultsThe majority (>90%) of patients in the CVC and SBS cohorts were ≥18 years old. Overall, IRs of any type of complication were numerically higher in patients with SBS compared with all patients with CVCs (2.68 vs 1.95 cases per 1,000 catheter-days, respectively). Among patients with SBS, septicemia, infection, and inflammatory reaction were the only complications observed. The complications with the highest incidence were catheter-related bloodstream infections (CRBSIs) in both the overall CVC cohort and the SBS cohort with IRs of 1.35 and 2.68 cases per 1,000 catheter-days, respectively. The IR of any CVC-related complication was numerically higher in patients with SBS with cancer vs without cancer (3.44 vs 1.86 cases per 1,000 catheter-days, respectively).ConclusionOur study quantifies the incidence of complications in patients with CVCs, including those with SBS, in Japan.

Inhibition of the CD36 receptor reduces visceral fat accumulation and improves insulin resistance in obese mice carrying the BDNF-Val66Met variant

Obesity-induced metabolic dysfunctions increase the risk for vascular diseases, including type II diabetes and stroke. Managing obesity is of interest to address the worldwide health problem; however, the role of genetic variability in human obesity development and specific targets for obesity-related metabolic disease have not been thoroughly studied. A SNP in the brain-derived neurotropic factor (BDNF) gene that results in the substitution of a valine with a methionine at codon 66 (Val66Met) occurs with a high frequency in humans. This study addressed the effect of genetic variability in developing obesity and the efficacy of the inhibition of cluster of differentiation 36 (CD36), a multifunctional receptor implicated in obesity and insulin resistance, in WT mice and mice with the BDNF Val66Met variant. CD36 inhibition by salvionolic acid B (SAB) in diet-induced obese WT mice reduced visceral fat accumulation and improved insulin resistance. The benefit of SAB was abrogated in CD36 knockout mice, showing the specificity of SAB. In addition, mice with the Val66Met variant in both alleles (BDNFM/M) fed a high-fat diet exhibited extreme obesity with increased CD36 gene and protein levels in macrophages. Chronic SAB treatment in BDNFM/M mice significantly decreased visceral fat accumulation and improved insulin resistance. Notably, the effect of SAB was greater in the extremely obese BDNFM/M mice compared with the WT mice. The study demonstrated a link between BDNF Val66Met and elevated CD36 expression and suggested that CD36 inhibition may be a potential strategy to improve metabolic dysfunctions and to normalize risk factors for vascular diseases in the obese population.

Higher Dietary Intake of Vitamin D Is Associated with Lower Incidence of Diabetic Nephropathy in Japanese Patients with Type 2 Diabetes

Evidence for optimal dietary intake of vitamin D for prevention of diabetic complications is sparse although associations between low vitamin D intake and high incidence of diabetes and vitamin D supplementation and improvement in insulin resistance were reported. We aimed to investigate the relationship between vitamin D intake and the incidence of diabetes complications in Japanese patients with type 2 diabetes aged 40-70 years with HbA1c≥6.5%. The present analysis was conducted as a multicenter prospective study on the incidence of and risk factors for macro- and microvascular complications among 22Japanese patients with type 2 diabetes from outpatient clinics in 59 university and general hospitals in Japan.Analyzed were 1516 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 8-year risk of nephropathy, retinopathy, and cardiovascular disease (CVD). Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. Mean vitamin D intake in quartiles ranged from 5.4 to 18.7μg/day. After adjusting for confounders, HRs of diabetic nephropathy in the 2nd, 3rd, and 4th quartiles for vitamin D intake compared with the 1st quartile were 0.7 (95% confidence interval 0.4-1.3, p=0.29), 1.2 (0.6-2.2, p=0.61), and 0.33 (0.14-0.79, p=0.01), respectively. There was no significant associations of vitamin D intake with retinopathy and CVD in the 2nd to 4th quartiles relative to the first quartile (retinopathy: 1.2 (0.9-1.6, 0.4), 0.8 (0.5-1.2, p=0.23), and 0.7 (0.5-1.0, p=0.08); CVD: 1.1 (0.7-1.7, p=0.83), 1.2 (0.7-2.0, p=0.62), and 0.7 (0.4-1.3, p=0.22)). Findings suggested that high vitamin D intake was associated with a lower incidence of diabetes nephropathy among Japanese patients with type 2 diabetes. Disclosure C. Horikawa: None. R. Aida: None. S. Tanaka: None. S. Tanaka: None. C. Kamada: None. Y. Yoshimura: None. A. Araki: None. T. Moriya: None. S. Katayama: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..

Cardiovascular Protection in People With Diabetes.

Cardiovascular Protection in People With Diabetes.