Japanese Diabetic Patients Research Articles

Analysis of thyroid autoantibodies and the risk of insulin depletion after the clinical onset of acute-onset type 1 diabetes in Japanese patients: the TIDE-J study

Analysis of thyroid autoantibodies and the risk of insulin depletion after the clinical onset of acute-onset type 1 diabetes in Japanese patients: the TIDE-J study

Retrospective Longitudinal Observational Study on the Long-Term Effects of Sodium-Glucose Cotransporter-2 Inhibitors on the Development of Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetic Japanese Patients.

Background/Objectives: The health burden of metabolic dysfunction-associated fatty liver disease (MASLD) has been increasing lately. Cardiovascular disease (CVD) is the main cause of death in MASLD patients; therefore, the treatments for MASLD should improve both CV risk factors such as obesity, diabetes, and dyslipidemia, in addition to an improvement in liver function. The evidence on the long-term effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on the progression of MASLD in Asian populations is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at our institute. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between 1 April 2014 and 31 March 2018. We collected the data on metabolic parameters, including laboratory data and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. Three-year SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein cholesterol, triglyceride, and non-high-density lipoprotein cholesterol (non-HDL-C). Such favorable changes in serum lipids were remarkable in patients with statins. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

Nilotinib-induced Diabetes in Japanese Patients with Chronic Myeloid Leukemia.

Objective This study aimed to examine the risk of diabetes mellitus induced by nilotinib, a second-generation tyrosine kinase inhibitor. Methods This retrospective study included 25 patients with chronic myeloid leukemia (CML) treated with nilotinib at our hospital. Four patients had diabetes mellitus at the start of nilotinib administration (prior DM group), and five patients were newly diagnosed with diabetes mellitus after the start of nilotinib administration (new DM group). Sixteen patients who were not diagnosed with diabetes mellitus were classified into the non-DM group. Changes in the blood glucose and HbA1c levels were evaluated in each group at the time of nilotinib administration and two years later. Results Molecular genetic remission of CML was achieved in 81.8% of patients with diabetes and 72.2% of patients without non-DM group. There were no cases in this study in which nilotinib was changed or discontinued owing to hyperglycemia. There was no difference in the blood glucose levels at the start of nilotinib treatment among the groups. Two years after starting nilotinib, the blood glucose levels in the new DM group (232 (186-296) mg/dL) and prior DM group (168 (123-269) mg/dL) were significantly higher than those in the non-DM group (100 (91-115) mg/dL). ΔHbA1c levels in the new DM group (1.3 (0.9-2.2) %) and prior DM group (1.6 (0.7-1.7) %) were significantly higher than those in the non-DM group (-0.2 (-0.3-0.1) %). Conclusion Nilotinib caused diabetes in 23.8% of the participants, but there were no hyperglycemia-related severe adverse events. Therefore, nilotinib may be safely continued with regular monitoring for the development of diabetes after nilotinib administration.

Sex Differences in the Association Between AST/ALT and Incidence of Type 2 Diabetes in Japanese Patients with Nonalcoholic Fatty Liver Disease: A Retrospective Cohort Study

ABSTRACT Objectives/Introduction The purpose of the current study was to investigate the association between Aspartate Transaminase (AST)/Alanine transaminase(ALT) and type 2 diabetes (T2DM) in nonalcoholic fatty liver disease (NAFLD) patients and to determine whether there were sex differences. Methods In the retrospective study, we collected data on NAFLD patients (1, 896 men and 465 women) at Murakami Memorial Hospital from 2004 to 2015. Data were stratified by sex to investigate the association between AST/ALT and T2DM incidence by sex. Multiple regression analysis, smooth curve fitting model and subgroup analysis were used to determine the correlation, non-linear relationship and threshold effect between AST/ALT and T2DM. Results In our study, 157 men and 40 women developed T2DM at follow-up. After adjusting for risk factors, AST/ALT was significantly associated with T2DM in men with NAFLD but not in women with NAFLD. The risk of T2DM increased as the AST/ALT ratio decreased. Besides, in male NAFLD patients, AST/ALT showed a non-linear relationship with T2DM, with an inflection point value of 0.964. When the AST to ALT ratio was below the threshold (AST/ALT <0.964), AST/ALT was significantly negatively associated with T2DM (HR = 0.177, 95% CI 0.055–0.568; P = 0.0036). In contrast, when AST/ALT >0.964, no significant association was found (HR = 3.174, 95% CI 0.345–29.167; P = 0.3074). Moreover, subgroup analysis showed that GGT could alter the relationship between AST/ALT and T2DM. In the group with GGT ≤ 40, AST/ALT was strongly associated with T2DM (HR = 0.24, 95% CI 0.09–0.66; P = 0.0059). Conclusions These results suggested that there were sex differences in the association between AST/ALT and T2DM in NAFLD participants. A non-linear association between AST/ALT and T2DM was observed in males. AST/ALT in the normal GGT group (GGT ≤40) might better facilitate the early screening of T2DM.

Dipeptidyl peptidase-4 inhibitors reduce the incidence of first cardiovascular events in Japanese diabetic patients.

Dipeptidyl Peptidase-4 (DPP-4) inhibitors do not suppress cardiovascular events in diabetic patients with a history of cardiovascular disease. However, the effect of DPP-4 inhibitors on cardiovascular events in Japanese diabetic patients is unclear. Therefore, we investigated whether DPP-4 inhibitors alter the incidence of cardiovascular events in Japanese diabetic patients without a history of cardiovascular events. The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study conducted from 2002 to 2008. After completion of the JPAD trial, we followed up the patients until 2019. Patients who had had a cardiovascular event by the 2013 follow-up were excluded from the study. JPAD patients were divided into a DPP-4 group and a non-DPP-4 group based on whether they were taking DPP-4 inhibitors at the 2013 follow-up because few patients took DPP-4 inhibitors before 2013. We investigated the incidence of cardiovascular events consisting of coronary events, cerebrovascular events, heart failure requiring hospitalization, and aortic and peripheral vascular disease in 1099 JPAD patients until 2019. During the observation period from 2013 to 2019, 37 (7%) first cardiovascular events occurred in the DPP-4 group (n = 518) and 66 (11%) in the non-DPP-4 group (n = 581). The incidence of cardiovascular events was significantly lower in the DPP-4 group than in the non-DPP-4 group (Log-Rank P = 0.0065). Cox proportional hazards model analysis revealed that the use of DPP-4 inhibitors (hazard ratio 0.65; 95% confidence interval 0.43-0.98; P = 0.038) was an independent factor after adjustment for age ≥ 65years, hypertension, statin usage, and insulin usage. Our findings have demonstrated that the use of DPP-4 inhibitors may be associated with a reduced incidence of first cardiovascular events in Japanese diabetic patients. The results require confirmation in randomized controlled trials.

Attention-Based UNet Deep Learning Model for Plaque Segmentation in Carotid Ultrasound for Stroke Risk Stratification: An Artificial Intelligence Paradigm.

Stroke and cardiovascular diseases (CVD) significantly affect the world population. The early detection of such events may prevent the burden of death and costly surgery. Conventional methods are neither automated nor clinically accurate. Artificial Intelligence-based methods of automatically detecting and predicting the severity of CVD and stroke in their early stages are of prime importance. This study proposes an attention-channel-based UNet deep learning (DL) model that identifies the carotid plaques in the internal carotid artery (ICA) and common carotid artery (CCA) images. Our experiments consist of 970 ICA images from the UK, 379 CCA images from diabetic Japanese patients, and 300 CCA images from post-menopausal women from Hong Kong. We combined both CCA images to form an integrated database of 679 images. A rotation transformation technique was applied to 679 CCA images, doubling the database for the experiments. The cross-validation K5 (80% training: 20% testing) protocol was applied for accuracy determination. The results of the Attention-UNet model are benchmarked against UNet, UNet++, and UNet3P models. Visual plaque segmentation showed improvement in the Attention-UNet results compared to the other three models. The correlation coefficient (CC) value for Attention-UNet is 0.96, compared to 0.93, 0.96, and 0.92 for UNet, UNet++, and UNet3P models. Similarly, the AUC value for Attention-UNet is 0.97, compared to 0.964, 0.966, and 0.965 for other models. Conclusively, the Attention-UNet model is beneficial in segmenting very bright and fuzzy plaque images that are hard to diagnose using other methods. Further, we present a multi-ethnic, multi-center, racial bias-free study of stroke risk assessment.

Dipeptidyl peptidase-4 inhibitors reduced long-term cardiovascular risk in diabetic patients after percutaneous coronary intervention via insulin-like growth factor-1 axis

Dipeptidyl-peptidase-4 inhibitors (DPP4i) have been the most used antidiabetic medications worldwide due to their good safety profiles and tolerability with a low risk of hypoglycemia, however, large cardiovascular outcome trials (CVOTs) have not shown any significant the prognostic superiority. On the contrary, since observational studies have suggested the effects of DPP4i are enhanced some populations, such as Asians and those who without overweight, their prognostic benefit is still under debate. The aim of this study was thus to assess the prognostic impact of DPP4i in patients with both diabetes and coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) through the insulin-like growth factor-1 (IGF-1) axis, a substrate of DPP4. This single-center analysis involved consecutive Japanese diabetic patients who underwent PCI for the first time between 2008 and 2018 (n = 885). Primary and secondary endpoints were set as cardiovascular (CV) death and the composite of CV death, non-fatal myocardial infarction and ischemic stroke (3P-MACE). Serum levels of IGF-1 and its main binding protein (insulin-like growth factor binding protein-3: IGFBP-3) were measured. In consequences, unadjusted Kaplan–Meier analyses revealed reduced incidences of CV-death and 3P-MACE by DPP4i, which was particularly enhanced in patients who were not overweight (BMI ≤ 25). Multivariate Cox hazard analyses consistently indicated reduced risks of CV death by DPP4i at PCI (hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.16–0.82, p = 0.01) and 3P-MACE (HR 0.47, 95% CI 0.25–0.84, p = 0.01), respectively. Moreover, elevated IGF-1 activity indicated by the IGF-1/IGFBP-3 ratio was associated with decreased risks of both endpoints and it was significantly higher in patients with DPP4i (p < 0.0001). In conclusion, the findings of the present study indicate beneficial effects of DPP4i to improve outcomes in Japanese diabetic patients following PCI, which might be mediated by DPP4–IGF-1 axis.

Therapeutic effect of laparoscopic sleeve gastrectomy on obstructive sleep apnea and relationship of type 2 diabetes in Japanese patients with severe obesity.

Aims/IntroductionObstructive sleep apnea (OSA) is among the most important obesity‐related diseases, and offers the potential for accelerated the early onset and progression of type 2 diabetes. The aim of the present study was to clarify the therapeutic effect of laparoscopic sleeve gastrectomy on OSA in severely obese Japanese patients, and to find correlations between OSA improvements and β‐cell function (BCF).Materials and MethodsBetween September 2013 and December 2019, 61 patients who underwent laparoscopic sleeve gastrectomy were enrolled. The apnea–hypopnea index (AHI) was used to diagnose OSA. The tongue area, uvula area and other parameters were measured using cone‐beam computed tomography. Regarding BCF parameters, the homeostasis model assessment of β‐cell function, insulinogenic, Matsuda and disposition indexes were used to evaluate the improvement in BCF. Improvement of OSA was defined as AHI <15.ResultsThe improvement rate of OSA was 51.8% (29/56). The change in AHI was significantly correlated with the excess weight loss percentage (ρ = 0.501), changes in tongue area (ρ = 0.350) and uvula area (ρ = 0.341). Multivariate analysis showed that preoperative AHI and postoperative hemoglobin A1c were independent prognostic factors of OSA non‐improvement. The homeostasis model assessment of β‐cell function (P < 0.001), the insulinogenic index (P < 0.001) and the disposition index (P = 0.019) of patients with AHI of <15 were significantly higher than those in patients with AHI of ≥15.ConclusionsLaparoscopic sleeve gastrectomy is a promising procedure for severely obese patients with OSA. BCF recovery was found to be significantly higher in patients with OSA improvement.

Analysis of HLA class II genes associated with susceptibility to type 1 diabetes in Japanese patients with autoimmune thyroid disease

Analysis of HLA class II genes associated with susceptibility to type 1 diabetes in Japanese patients with autoimmune thyroid disease

A Comparison of the Renal Composite Outcome Between Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide 1 Receptor Agonists in Japanese Diabetes Patients

A Comparison of the Renal Composite Outcome Between Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide 1 Receptor Agonists in Japanese Diabetes Patients

Translational research on human pancreatic β-cell mass expansion for the treatment of diabetes.

The structural, functional, and pathological differences between human islets and rodent islets, such as mouse or rat islets, have been clarified, and research using human islets is becoming more important for elucidating the pathophysiology of diabetes and developing therapeutic strategies for diabetes. Increasing the functional human β-cell mass is a feasible method for the treatment of both type 1 and type 2 diabetes. The glucokinase-mediated glucose signaling pathway is known to promote β-cell proliferation not only in rodent models but also in humans. However, little is known about the signaling components of glucose- or glucokinase-mediated signaling pathways. Studies have gradually revealed the involvement of ER stress-related molecules, cell cycle regulators, inflammatory proteins, extracellular matrix proteins, and neurotransmitters in the glucokinase-mediated signaling pathway in β-cells. Unraveling the mechanisms of those molecules in the regulation of human β-cell mass will provide new insights into how the functional β-cell mass can be increased. The human islet distribution program is essential for human islet research. However, human islets for research are only available by import from Europe and America into Japan or Asia. Since Japanese or Asian diabetes patients possibly show different features compared with European or American diabetes patients, studies using human islets from Japanese or Asian populations have become important for the elucidation of pathophysiology in these specific population groups. This review outlines new pathways important for the regulation of human pancreatic β-cell mass and expectations regarding the establishment of a human islet distribution program in Japan.

Diabetes management by either telemedicine or clinic visit improved glycemic control during the coronavirus disease 2019 pandemic state of emergency in Japan.

The purpose of this retrospective cohort study at a Tokyo diabetes clinic was to evaluate the effect of telemedicine and clinic visit on glycated hemoglobin (HbA1c) during the coronavirus disease 2019 state of emergency. The effect of telemedicine and clinic visit during the emergency period on the post‐emergency measured HbA1c was evaluated by multiple regression models and logistic regression models adjusted for age, sex, type of diabetes, pre‐emergency HbA1c and body mass index, and body mass index change during the emergency period. Among 2,727 patients who visited the clinic before and after the emergency period, the interval between clinic visits during the emergency period was significantly associated with HbA1c improvement. Telemedicine and clinic visit were independently associated with HbA1c improvement when pre‐emergency HbA1c was ≥7%. In conclusion, clinic visit and telemedicine during the coronavirus disease 2019 emergency period were both independently effective in HbA1c improvement in Japanese diabetes patients who had insufficient HbA1c control.

Body mass index and γ-glutamyltransferase are associated with serum lactate levels in Japanese diabetic patients under metformin therapy

Body mass index and γ-glutamyltransferase are associated with serum lactate levels in Japanese diabetic patients under metformin therapy

2166-PUB: Surprisingly High Prevalence of Vitamin D Deficiency in Japanese Diabetic Patients

Vitamin D is known to regulate many cellular functions such as insulin secretion, cardiac function, immune system, skeletal muscle in addition to bone mineral metabolism. With respect to diabetes, diabetes prevention trials by vitamin D supplementation and reports showing an association between low levels of blood vitamin D and cardiovascular events, bone fractures, falls and most recently the life prognosis have been published. However, reports on Japanese diabetic patients and vitamin D is scarce. We measured serum 25 (OH) D concentration (ECLIA) in 133 patients (M/F: 85/48) with type 1 (n=15) and type 2 diabetes patients (118). Age, sex, BMI and biochemical indicators (serum Ca, P, Alb, HbA1c, LDL-C, TG, CPR and atherosclerosis indices (urinary albumin, NT-proBNP, baPWV and max IMT) were investigated. The subjects mean age was 59.1±14.0 years (mean±SD) and HbA1c9.1 ±2.6%, and BMI25.0±4.3. Serum 25 (OH) D concentration state was only 3% in sufficient group(&amp;gt;30ng/ml), 11% insufficient group and 86% was in deficiency (&amp;lt;20ng/ml). This was the same regardless of type 1 or type 2. Correlations with the aforementioned indicators including HbA1c was not observed. However, serum 25 (OH) D concentration and max IMT in HbA1c above 8% group had a weak but significant reverse correlation, which was consistent with the previous metaanalysis. The limitation of this study is a single center based, and it does not include data on dieting status, or exposure to sunlight. However, subjects have a history of medical nutritional education and they are residents of urban areas with adequate ADL, it is unlikely that they are particularly biased diabetes populations. In an aging society, it is important to prevent sarcopenia, and fractures in diabetes. The present results shed a new insight in Japanese medical nutritional therapy. For vitamin D deficiency cohort, interventions and bone salt quantification are going to be carried out and osteoporosis, fractures, and cardiovascular risk are evaluated in a prospective manner. Disclosure N. Kashima: None. K. Hamano: None.

Health Inequalities Among Elderly Type 2 Diabetes Mellitus Patients in Japan.

The influence of socioeconomic status (SES) on health inequalities has received much attention worldwide. This study examined the effect of SES on the following older type 2 diabetes mellitus patient health outcomes: oral hypoglycemic agent (OHA) medication adherence (proportion of days covered, PDC), risk of hospitalization for diabetic macrovascular complications, and in-hospital death. A retrospective cohort design using 2013–2016 claims data was used. Subjects were 58,349 diabetes patients aged >74 years in 2013. Age, sex, residential area, and comorbidities were controlled for. Logistic regression was conducted to assess the effects of income on PDC; survival analysis was used to assess the effects on hospitalization and in-hospital death. Regressions were conducted separately by sex. Compared with the lowest income group, adjusted PDC odds ratios for medium- and high-income males, respectively, were 1.35 (95% CI: 1.27–1.43) and 1.41 (95% CI: 1.30–1.54); females: 1.17 (95% CI: 1.11–1.23) and 1.24 (95% CI: 1.13–1.35). Adjusted hazard ratios (AHRs) for male hospitalization were 0.88 (95% CI: 0.80–0.96) and 0.88 (95% CI: 0.79–0.99); females: 1.00 (95% CI: 0.93–1.07) and 0.95 (95% CI: 0.83–1.08). AHRs for male in-hospital death were 0.83 (95% CI: 0.75–0.91) and 0.62 (95% CI: 0.54–0.70); females: 0.94 (95% CI: 0.87–1.02) and 0.77 (95% CI: 0.65–0.92). Results revealed sex-specific health inequalities among older Japanese diabetes patients. Subjects with worse SES had significantly poorer OHA medication adherence (both sexes), higher hospitalization risk for diabetes complications (males), and higher in-hospital death risk (both sexes).

Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial

Given the unique phenotype of type 2 diabetes in Japanese patients, novel therapies such as oral semaglutide require evaluation in this population. PIONEER 9 aimed to assess the dose-response of oral semaglutide and to compare the efficacy and safety of oral semaglutide with placebo and a subcutaneous GLP-1 receptor agonist in a Japanese population. PIONEER 9 was a 52-week, phase 2/3a, randomised, controlled trial done at 16 sites (clinics and university hospitals) in Japan. Japanese patients aged 20 years or older with uncontrolled type 2 diabetes managed by diet or exercise or with oral glucose-lowering drug monotherapy (washed out) were randomly assigned (1:1:1:1:1) to receive double-blind once-daily oral semaglutide (3 mg, 7 mg, or 14 mg) or placebo, or open-label subcutaneous once-daily liraglutide 0·9 mg. The primary endpoint was change in HbA1c from baseline to week 26 with the trial product (primary) estimand (which assumes all patients remained on trial product without rescue medication use) in all randomly assigned patients. This trial is registered with ClinicalTrials.gov, NCT03018028. Between Jan 10, and July 11, 2017, 243 patients were randomly assigned to oral semaglutide 3 mg (n=49), 7 mg (n=49), or 14 mg (n=48), or placebo (n=49), or to liraglutide 0·9 mg (n=48). Changes in HbA1c from baseline (mean 8·2%) to week 26 were dose-dependent with oral semaglutide (mean change -1·1% [SE 0·1] for oral semaglutide 3 mg, -1·5% [0·1] for 7 mg, and -1·7% [0·1] for 14 mg), -0·1% (0·1) with placebo, and -1·4% (0·1) with liraglutide 0·9 mg. Estimated treatment differences for change in HbA1c compared with placebo were -1·1 percentage points (95% CI -1·4 to -0·8; p<0·0001) for oral semaglutide 3 mg, -1·5 percentage points (-1·7 to -1·2; p<0·0001) for oral semaglutide 7 mg, and -1·7 percentage points (-2·0 to -1·4; p<0·0001) for oral semaglutide 14 mg. Estimated treatment differences for change in HbA1c compared with liraglutide 0·9 mg were 0·3 percentage points (95% CI -0·0 to 0·6; p=0·0799) for oral semaglutide 3 mg, -0·1 percentage points (-0·4 to 0·2; p=0·3942) for oral semaglutide 7 mg, and -0·3 percentage points (-0·6 to -0·0; p=0·0272) for oral semaglutide 14 mg. Gastrointestinal events, predominantly of mild or moderate severity, were the most frequently reported class of adverse event with oral semaglutide: constipation was most common, occurring in five to six (10-13%) patients with oral semaglutide, three (6%) with placebo, and nine (19%) with liraglutide 0·9 mg. This study showed that oral semaglutide provides significant reductions in HbA1c compared with placebo in a dose-dependent manner in Japanese patients with type 2 diabetes, and has a safety profile consistent with that of GLP-1 receptor agonists. Novo Nordisk.

Prevalence of diabetes in Japanese patients with cancer.

Cancer patients with diabetes experience a poorer prognosis, yet the population burden of this multimorbidity remains unknown. This study aimed to estimate the latest incidence and prevalence of cancer with diabetes mellitus in Japan. We used projection of cancer incidence and latest survival data from population‐based cancer registries. The incidence of cancer associated with diabetes was estimated separately for patients with pre‐existing diabetes and those without diabetes, and used to estimate the 5‐year cancer prevalence for those with and without diabetes. The prevalence of pre‐existing diabetes in cancer patients at any cancer site was estimated to be 20.7% (647,160 men and women). Among cancer sites, diabetes prevalence was high in patients with liver and pancreatic cancers in both sexes. In conclusion, our study shows a large burden of diabetes in cancer patients in Japan, which warrants further attention by health practitioners and policy‐makers.

Fasting and Non-Fasting Triglycerides and Risk of Cardiovascular Events in Diabetic Patients Under Statin Therapy.

Few data specifically investigate associations between fasting/non-fasting triglycerides (TG) and cardiovascular (CV) events under statin therapy among Japanese diabetic patients. We recruited 4,988 participants with diabetes from the EMPATHY study. Median follow-up was 3 years. We evaluated associations between serum fasting/non-fasting TG and first CV events in Cox-regression hazard models adjusted by classical risk factors. CV events were defined as (1) major adverse cardiac events (MACE) including myocardial infarction, stroke, or cardiac death; and (2) CV diseases (CVD) including myocardial infarction, unstable angina, ischemic stroke, or large artery disease or peripheral arterial disease. Fasting as well as non-fasting TG were associated with MACE (adjusted hazard ratio [HR]: 1.017 per 10 mg/dL; 95% confidence interval [CI]: 1.000-1.037; P=0.046, adjusted HR: 1.028 per 10 mg/dL; 95% CI: 1.006-1.050; P=0.0091) and CVD (adjusted HR: 1.024 per 10 mg/dL; 95% CI: 1.011-1.038; P=4.4×10-3, adjusted HR: 1.028 per 10 mg/dL; 95% CI: 1.010-1.046; P=4.9×10-3). Comparing the top quartile with the bottom quartile of non-fasting TG, adjusted HR significantly increased 5.18 (95% CI: 1.38-18.3, P=0.014) for MACE, and 2.40 (95% CI: 1.11-4.75, P=0.021) for CVD, while adjusted HR did not change when divided into quartile of fasting TG. Non-fasting TG could be considered as a substitute for fasting TG as a risk stratification for future CV events among Japanese diabetic patients.

Increased risk of cardiovascular mortality by strict glycemic control (pre-procedural HbA1c\u2009

BackgroundIn the secondary prevention of cardiovascular (CV) disease in patients with diabetes, an optimal level of HbA1c, the most widely-used glycemic control indicator, for favorable clinical consequences still remains to be established. This study assessed the association between preprocedural HbA1c level and CV mortality in Japanese diabetic patients undergoing percutaneous coronary intervention (PCI).MethodsThis is a retrospective observational study using a single-center prospective PCI database involving consecutive 4542 patients who underwent PCI between 2000 and 2016. Patients with any antidiabetic medication including insulin at PCI were included in the analysis (n = 1328). We divided the patients into 5 and 2 groups according to HbA1c level; HbA1c: < 6.5% (n = 267), 6.5–7.0% (n = 268), 7.0–7.5% (n = 262), 7.5–8.5% (n = 287) and ≥ 8.5% (n = 244), and 7.0% > and ≤ 7.0%, respectively. The primary outcome was CV mortality including sudden death. The median follow-up duration was 6.2 years.ResultsIn the follow-up period, CV and sudden death occurred in 81 and 23 patients, respectively. While unadjusted Kaplan–Meier analysis showed no difference in cumulative CV mortality rate between patients binarized by preprocedural HbA1c 7.0%, analysis of the 5 groups of HbA1c showed significantly higher cumulative CV death in patients with HbA1c < 6.5% compared with those with 7.0–7.5% (P = 0.042). Multivariate Cox hazard analysis revealed a U-shaped relationship between preprocedural HbA1c level and risk of CV death, and the lowest risk was in the HbA1c 7.0–7.5% group (Hazard ratio of HbA1c < 6.5% compared to 7.0–7.5%: 2.97, 95% confidence interval: 1.33–7.25, P = 0.007). Similarly, univariate analysis revealed the lowest risk of sudden death was in the HbA1c 7.0–7.5% group.ConclusionThe findings indicate an increased risk of CV mortality by strict glycemic control (HbA1c < 6.5%) in the secondary prevention of CV disease in Japanese patients with medically-treated diabetes.Trial registration This study reports the retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry UMIN-CTR 000035587).

P5663Impact of proteinuria on cardiovascular outcomes in Japanese diabetic patients with atrial fibrillation: the Fushimi AF Registry

Abstract Background Previous studies have suggested that proteinuria is independently associated with clinical outcomes in diabetic patients, irrespective of the presence of renal dysfunction. However, data regarding the impact of proteinuria on clinical outcomes in diabetic patients with atrial fibrillation (AF) are limited. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in our city in Japan. Follow-up data were available in 4,454 patients, and 634 diabetic patients with available data of proteinuria and estimated glomerular filtration rate (eGFR) were examined. We compared the clinical background and outcomes between patients with proteinuria (n=251) and those without (n=383). Then, we divided the patients into 4 subgroups according to the presence of proteinuria and renal dysfunction, and compared the clinical outcomes between groups; group 1 (without proteinuria, eGFR ≥60 ml/min/1.73 m2; n=203), group 2 (with proteinuria, eGFR ≥60; n=96), group 3 (without proteinuria, eGFR &lt;60; n=180), group 4 (with proteinuria, eGFR &lt;60; n=155). Results Age was comparable between patients with or without proteinuria. Patients with proteinuria had higher prevalences of previous heart failure (HF), stroke/systemic embolism, hypertension and renal dysfunction. The prevalences of previous myocardial infarction, and major bleeding were similar between two groups. During the median follow-up of 1,505 days, the incidence rates of HF hospitalization (4.1/100 person-years vs. 2.5/100 person-years; p&lt;0.01) and cardiovascular death (1.8/100 person-years vs. 0.4/100 person-years; p&lt;0.01) were higher in patients with proteinuria. When we divided patients into 4 subgroups, the incidences of HF hospitalization (group 1: 1.8/100 person-years vs. group 2: 3.4/100 person-years vs. group 3: 3.8/100 person-years vs. group 4: 4.9/100 person-years; p&lt;0.01) and cardiovascular death (group 1: 0.3/100 person-years vs. group 2: 1.8/100 person-years vs. group 3: 0.5/100 person-years vs. group 4: 2.2/100 person-years; p&lt;0.01) tended to be higher in not only group 3 and group 4 but also group 2 than group 1 (Figure). Multivariate Cox proportional hazards regression analysis including female gender, age (≥75 years), hypertension, pre-existing HF, renal dysfunction (eGFR &lt;60),low left ventricular ejection fraction (&lt;40%) and proteinuria revealed that proteinuria was an independent determinant of both of HF hospitalization (adjusted hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.05–2.34) and cardiovascular death (HR: 3.76, 95% CI: 1.59–8.88). Figure 1 Conclusion In Japanese diabetic patients with AF, proteinuria was associated with higher incidences of HF hospitalization and cardiovascular death, irrespective of the presence of renal dysfunction.