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

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

BackgroundChronic kidney disease (CKD) is characterized by a decreased glomerular filtration rate or renal injury (especially proteinuria) for at least 3 months. The early detection and treatment of CKD, a major global public health concern, before the onset of symptoms is important. This study aimed to develop machine learning models to predict the risk of developing CKD within 1 and 5 years using health examination data.MethodsData were collected from patients who underwent annual health examinations between 2017 and 2022. Among the 30,273 participants included in the study, 1,372 had CKD. Demographic characteristics, body mass index, blood pressure, blood and urine test results, and questionnaire responses were used to predict the risk of CKD development at 1 and 5 years. This study examined three outcomes: incident estimated glomerular filtration rate (eGFR) 0.8 for predicting the onset of CKD in 1 year when the outcome was eGFR 0.9. With LR and a neural network, the specificities were 0.749 and 0.739 and AUROCs were 0.889 and 0.890, respectively, for predicting onset within 5 years. The AUROCs of most models were approximately 0.65 when the outcome was eGFR

Metabolic compromise is crucial in aggravating age-associated chronic inflammation, oxidative stress, mitochondrial damage, increased LDL and triglycerides, and elevated blood pressure. Excessive adiposity, hyperglycemia, and insulin resistance due to aging are associated with elevated levels of damaging free radicals, inducing a proinflammatory state and hampering immune cell activity, leading to a malfunctioning cardiometabolic condition. The age-associated oxidative load and redox imbalance are contributing factors for cardiometabolic morbidities via vascular remodelling and endothelial damage. Recent evidence has claimed the importance of gut microbiota in maintaining regular metabolic activity, which declines with chronological aging and cardiometabolic comorbidities. Genetic mutations, polymorphic changes, and environmental factors strongly correlate with increased vulnerability to aberrant cardiometabolic changes by affecting key physiological pathways. Numerous studies have reported a robust link between biological aging and cardiometabolic dysfunction. This review outlines the scientific evidence exploring potential mechanisms behind the onset and development of cardiovascular and metabolic issues, particularly exacerbated with aging.

The association between screen time (ST), including that for smartphones, and overweight/obesity in children was examined separately for boys and girls, considering the influence of lifestyle factors. A cross-sectional study was conducted in 2,242 Japanese children (1,278 girls) aged 10–14 years. Overweight/obesity was defined by the International Obesity Task Force. Logistic regression analysis showed that only for girls, total ST (≥4 h), smartphone ST (≥3 h), and non-smartphone ST (≥2 h) were all independently and significantly associated with overweight/obesity compared to

Abstract We examined the impact of a history of coronary artery disease (CAD) or cerebrovascular disease (CVD) and physical activity habits on functional disability among community-dwelling Japanese adults. This population-based retrospective cohort study included 10,661 people aged 39–98 years in Japan (5054, men). Median follow-up was 3.7 years. During the study period, 209 functional disabilities occurred in the overall study population. In multivariable analysis, a history of CVD (hazard ratio [HR] 1.57 [95% CI: 1.00–2.45]) and no physical activity habit (HR 1.74 [1.27–2.39]) presented increased risks for functional disability. HRs for functional disability among patients with a CVD history with and without a physical activity habit were 1.68 (0.75–3.74) and 2.65 (1.49–4.71), respectively, compared with individuals without a history of CVD with a physical activity habit. Similar results were observed for CAD. We found no significant difference in the incidence of functional disability between the group with a history of CAD or CVD and physical activity habits and the group with no history of CAD or CVD and without physical activity habits. Physical activity habits had a favorable influence on avoiding functional disability regardless of a history of CAD or CVD. Future prospective studies are needed to clarify these associations.

Objective: To analyze the association between the dietary protein/energy ratio and percentages of dietary animal and plant protein and obesity in Japanese patients with type 2 diabetes. Design: This was a cross-sectional study. Obesity was defined as BMI ≥25 kg/m2. Data were collected for all study participants and stratified according to age and sex. Diet was assessed via a food frequency questionnaire. Setting: 26 clinics participating in the Japan Diabetes Clinical Data Management Study Group (JDDM) from December 2014 to December 2019. Participants: 1567 Japanese out patients with type 2 diabetes (63.1% men; mean age 62.3 ± 11.6 years). Results: In all participants, multivariate analysis with adjustment by major confounders showed a significant inverse association in those in the highest quartile of the protein/energy ratio (mean 17.7%) with obesity (OR = 0.588, 95% CI = 0.435-0.794; p trend = 00.007), but after the addition of vegetable intake it became non-significant. In the age- and sex-stratified analysis, a high protein/energy ratio (mean 15.6%) was inversely associated with obesity in older women only (OR = 0.280, 95% CI = 0.123-0.638), which remained significant after adjustment of individual food groups correlated with protein. No association between percentages of dietary animal or plant protein and obesity was found. Conclusions: In older women only, a higher dietary protein/energy ratio was associated with lower obesity after adjustment by confounders and individual food groups correlated with protein intake. Future longitudinal research that includes data on food groups as well as age- and sex-stratification of participants is recommended to further clarify this relationship.

Globally, the number of people with diabetes mellitus has quadrupled in the past three decades, and approximately one in 11 adults worldwide have diabetes mellitus. Since both microvascular and macrovascular diseases in patients with diabetes predispose them to a lower quality of life as well as higher rates of mortality, managing blood glucose levels is of clinical relevance in diabetes care. Many classes of antihyperglycemic drugs are currently approved to treat hyperglycemia in patients with type 2 diabetes mellitus, with several new drugs having been developed during the last decade. Diabetes-related complications have been reduced substantially worldwide. Prioritization of therapeutic agents varies according to national guidelines. However, since the characteristics of participants in clinical trials differ from patients in actual clinical practice, it is difficult to apply the results of such trials to clinical practice. Machine learning approaches became highly topical issues in medicine along with rapid technological innovations in the fields of information and communication in the 1990s. However, adopting these technologies to support decision-making regarding drug treatment strategies for diabetes care has been slow. This review summarizes data from recent studies on the choice of drugs for type 2 diabetes mellitus focusing on machine learning approaches.

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.

Abstract 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.

Abstract Aims/Introduction Recently, an increasing number of cohort studies have suggested using machine learning (ML) to predict type 2 diabetes mellitus. However, its predictive ability remains inconclusive. This meta‐analysis evaluated the current ability of ML algorithms for predicting incident type 2 diabetes mellitus. Materials and Methods We systematically searched longitudinal studies published from 1 January 1950 to 17 May 2020 using MEDLINE and EMBASE. Included studies had to compare ML’s classification with the actual incidence of type 2 diabetes mellitus, and present data on the number of true positives, false positives, true negatives and false negatives. The dataset for these four values was pooled with a hierarchical summary receiver operating characteristic and a bivariate random effects model. Results There were 12 eligible studies. The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 0.81 (95% confidence interval [CI] 0.67–0.90), 0.82 [95% CI 0.74–0.88], 4.55 [95% CI 3.07–6.75] and 0.23 [95% CI 0.13–0.42], respectively. The area under the summarized receiver operating characteristic curve was 0.88 (95% CI 0.85–0.91). Conclusions Current ML algorithms have sufficient ability to help clinicians determine whether individuals will develop type 2 diabetes mellitus in the future. However, persons should be cautious before changing their attitude toward future diabetes risk after learning the result of the diabetes prediction test using ML algorithms.

BackgroundObesity is an established risk factor for non-communicable diseases such as type 2 diabetes mellitus, hypertension and cardiovascular disease. Thus, weight control is a key factor in the prevention of non-communicable diseases. A simple and quick method to predict weight change over a few years could be helpful for weight management in clinical settings.MethodsWe examined the ability of a machine learning model that we constructed to predict changes in future body weight over 3 years using big data. Input in the machine learning model were three-year data on 50,000 Japanese persons (32,977 men) aged 19–91 years who underwent annual health examinations. The predictive formulas that used heterogeneous mixture learning technology (HMLT) to predict body weight in the subsequent 3 years were validated for 5,000 persons. The root mean square error (RMSE) was used to evaluate accuracy compared with multiple regression.ResultsThe machine learning model utilizing HMLT automatically generated five predictive formulas. The influence of lifestyle on body weight was found to be large in people with a high body mass index (BMI) at baseline (BMI ≥29.93 kg/m2) and in young people (

Abstract 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

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

Background: Grip strength reflects systemic muscle strength and mass and is reportedly associated with various metabolic variables. However, its prognostic association with dyslipidemia is unknown. We examined the association of grip strength and other physical fitness markers with the incidence of dyslipidemia among Japanese adults. Methods: A total of 16,149 Japanese (6,208 women) individuals aged 20–92 years who underwent a physical fitness test between April 2001 and March 2002 were included in this cohort study. Grip strength, vertical jump, single-leg balance with eyes closed, forward bending, and whole-body reaction time were evaluated at baseline. Dyslipidemia was annually determined based on fasting serum lipid profiles and self-reported dyslipidemia from April 2001 to March 2008. Results: During the follow-up period, 4,458 (44.9%) men and 2,461 (39.6%) women developed dyslipidemia. A higher relative grip strength (grip strength/body mass index) was associated with a lower incidence of dyslipidemia among both men and women (P for trend

Background: Endothelial dysfunction is an early pathophysiological feature and independent predictor of a poor prognosis in most forms of cardiovascular disease. We evaluated the effect of brown rice crackers (BR-C) on endothelial function. Methods: Effect of heat-moisture treated (HMT) -BR-C on postprandial flow-mediated dilation (FMD) in adults with mild endothelial dysfunction was compared with that of BR-C and white rice crackers (WR-C) in 12 adults with mild endothelial dysfunction (less than 7.0% of FMD) by a randomized, single-blind, three-treatment three-period crossover trial (UMIN 000034898). Since we considered that the FMD increase was associated with the treatment of HMT-BR-C, we examined the effect of three possible factors: postprandial glucose levels, polyphenol content, and polyphenol release from the food matrix. Results: Mean pre-intake baseline FMD values of HMT-BR-C, BR-C, and WR-C were 4.9%, 5.1%, and 4.9%, respectively, and those values 1 h post-intake were 6.3%, 5.1%, and 4.8%, respectively. There was no difference in intergroup comparisons of FMD using Dunnett's multiple comparison test. There was a significant increase in FMD only in HMT-BR-C in intragroup comparisons (P = 0.042 by paired-t test). In comparison with BR-C, no significant difference was noted in the postprandial glucose level nor in the content of total polyphenols and ferulic acid derivatives in HMT-BR-C. However, the 70% ethanol extracted from HMT-BR-C contained a significantly larger amount of free and bound ferulic acids than from BR-C. Conclusion: HMT-BR-C intake increased the postprandial FMD response.

Abstract Despite mounting evidence of the positive relationship between diabetes mellitus (DM) and heart failure (HF), the entire context of the magnitude of risk for HF in relation to DM remains insufficiently understood. The principal reason is because new‐onset HF (HF occurring in participants without a history of HF) and recurrent HF (HF re‐occurring in patients with a history of HF) are not discriminated. This meta‐analysis aims to comprehensively and separately assess the risk of new‐onset and recurrent HF depending on the presence or absence of DM. We systematically searched cohort studies that examined the relationship between DM and new‐onset or recurrent HF using EMBASE and MEDLINE (from 1 Jan 1950 to 28 Jul 2019). The risk ratio (RR) for HF in individuals with DM compared with those without DM was pooled with a random‐effects model. Seventy‐four and 38 eligible studies presented data on RRs for new‐onset and recurrent HF, respectively. For new‐onset HF, the pooled RR [95% confidence interval (CI)] of 69 studies that examined HF as a whole [i.e. combining HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF)] was 2.14 (1.96–2.34). The large between‐study heterogeneity (I2 = 99.7%, P

Objectives It has been hypothesised that smoking intensity may be related to occupational stress. This study aimed to investigate whether stress, including problems with superiors or co-workers, is a driver of smoking.Design Cross-sectional study.Setting and participants 59 355 employees (34 865 men and 24 490 women) across multiple occupations who completed a self-reported questionnaire-based occupational stress survey between April 2016 and March 2017 in Niigata Prefecture.Main outcome measures Stress scores for the Brief Job Stress Questionnaire subscales summed up after assigning high points for high stress and converted to Z-scores based on the mean of all participants. Heavy smokers (HS) smoked ≥15 cigarettes/day and light smokers (LS) smoked

Background: Simple physical fitness test can be a useful potential predictor of type 2 diabetes (T2DM). We examined the association between performances on simple physical fitness tests and the incidence of T2DM. Methods: This longitudinal study was conducted in 21,802 nondiabetic Japanese (6,649 women) aged 20 to 92 years, who underwent all physical fitness tests at baseline (April 2001 to March 2002). From April 2001 to March 2008, physical fitness tests, including grip strength, vertical jump, single-leg balance with eyes closed, forward bending, whole-body reaction time, and supine legs-up, were performed every year. Participants had physical fitness tests at least two times during the period. T2DM was also annually determined based on fasting blood glucose, glycated hemoglobin, and self-reported diabetes during the period. Discrete-time logit models were used to examine the influence of the serial level of each physical fitness test on the incidence of T2DM. Results: During the entire study period, 972 participants developed diabetes. Lower relative grip strength (grip strength/body weight) and single-leg balance performance were associated with a higher incidence of T2DM. For relative grip strength, as compared with the fourth quartile group, the odds ratios for other groups ranged from 1.16 to 1.56 (P for trend < 0.001). For single-leg balance, the odds ratios ranged from 1.03 to 1.49 (P for trend < 0.001). Conclusion: The performance of a simple single-leg balance test as well as that of a grip strength test were negatively associated with the risk of T2DM among Japanese.

Introduction Cost-effectiveness analyses are becoming increasingly important in Japan following the introduction of a health technology assessment scheme. The study objective was to develop an economic model to evaluate the cost-effectiveness of two interventions for type 2 diabetes in a Japanese population.Research design and methods The Japan Diabetes Complications Study/Japanese Elderly Diabetes Intervention Trial risk engine (JJRE) Cost-Effectiveness Model (JJCEM) was developed, incorporating validated risk equations in Japanese patients with type 2 diabetes from the JJRE. Weibull regression models were developed for progression of the model outcomes, and a targeted literature review was performed to inform default values for utilities and costs. To illustrate outcomes, two simulated analyses were performed in younger (aged 40 years) and older (aged 80 years) Japanese populations, comparing a hypothetical treatment with placebo.Results The model considers a population based on user-defined values for 11 baseline characteristic parameters and simulates rates of diabetic complications over a defined time horizon. Costs, quality-adjusted life years, and an incremental cost-effectiveness ratio are estimated. The model provides disaggregated results for two competing interventions, allowing visualization of the key drivers of cost and utility. A scatterplot of simulations and cost-effectiveness acceptability curve are generated for each analysis.Conclusions This is the first cost-effectiveness model for East Asian patients with type 2 diabetes, developed using Japan-specific risk equations. This population constitutes the largest share of the global population with diabetes, making this model highly relevant. The model can be used to evaluate the cost-effectiveness of anti-diabetic interventions in patients with type 2 diabetes in Japan and other East Asian populations.

Abstract 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

IntroductionThe incidence of type 2 diabetes mellitus (T2DM) is increasing, in parallel with the epidemic of obesity. Although bariatric surgery, which profoundly affects T2DM, has increased 10-fold since the millennium, only a fraction of diabetics is offered this treatment option.ObjectiveTo investigate the association between clinical and socioeconomic factors in selecting patients with T2DM for bariatric surgery in a publicly financed healthcare system.Research design and methodsCohort study using prospectively registered data from two nationwide quality registers, the Scandinavian Obesity Surgery Registry (SOReg) and the Swedish National Diabetes Register (NDR), and data from two government agencies. An age, gender and body mass index-matched case-control analysis containing 10 642 patients with T2DM was performed.ResultsPatients with T2DM having bariatric surgery had a higher education level (upper secondary school or college level, OR 1.42% and 95% CI (1.29 to 1.57) and 1.33 (1.18 to 1.51), respectively) as well as a higher income (OR 1.37 (1.22 to 1.53) to 1.94 (1.72 to 2.18) for quartile 2–4) than non-operated patients. Operated patients were more often married or had been married (OR 1.51 (1.37 to 1.66) and 1.65 (1.46 to 1.86), respectively) as well as natives (OR 0.84 (0.73 to 0.95) if born in the rest of Europe). Groups did not differ regarding relevant laboratory data and present medication, nor in former in-patient diagnoses.ConclusionDespite similar clinical data, superior socioeconomic status was associated with increased rate of bariatric surgery in patients with T2DM. We believe that this warrants actions, for example concerning referral patterns.

ObjectiveDeclining 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 methodsThis 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.ResultsMedian 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.ConclusionsThe 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.

Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13–1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08–1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution.

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.

Aims. To elucidate the levels of malondialdehyde-modified LDL (MDA-LDL)-related variables for predicting coronary artery stenosis (CAS) by coronary CT angiography (CCTA) in asymptomatic patients with type 2 diabetes (T2DM). Methods. Enrolled were 36 Japanese patients with T2DM who underwent CCTA and in whom MDA-LDL levels were measured. Definition of CAS was luminal narrowing of ≥50%. Trends through tertiles of each MDA-LDL-related variable were analyzed with a general linear model. The ability of each MDA-LDL-related variable to predict CAS was compared to areas under the curve (AUCs) in receiver operating characteristic curve (ROC) analysis. Results. Seventeen patients had CAS. Each MDA-LDL-related variable was an independent predictor of CAS (P=0.039 for MDALDL, P=0.013 for MDA-LDL/LDL-C, P=0.047 for MDA-LDL/HDL-C, and P=0.013 for (MDA-LDL/LDL-C)/HDL-C). AUCs of MDA-LDL, MDA-LDL/LDL-C, MDA-LDL/HDL-C, and (MDA-LDL/LDL-C)/HDL-C were 0.675 (95% CI 0.496–0.854), 0.765 (0.602–0.927), 0.752 (0.592–0.913), and 0.799 (0.643–0.955), respectively, for predicting CAS. Trends throughout the tertiles showed significant associations between MDA-LDL/LDL-C, MDA-LDL/HDL-C, or (MDALDL/LDL-C)/HDL-C and CAS (P=0.003 for MDA-LDL/LDL-C, P=0.042 for MDA-LDL/HDL-C, and P=0.001 for (MDA-LDL/LDL-C)/HDL-C). Conclusions. Data suggest that measurements of MDA-LDL/LDL-C, MDA-LDL/HDLC, and (MDA-LDL/LDL-C)/HDL-C are useful for predicting CAS.

Objective. To assess the association between Helicobacter pylori (HP) infection and glycemic control in patients with diabetes through a meta-analytic approach. Research Design and Methods. Electronic literature searches were conducted for cross-sectional studies that examined the hemoglobin A1c (A1C) level by whether patients with diabetes were or were not carriers of HP. Mean differences in A1C between groups with and without HP infection were pooled with a random-effects model. Results. Thirteen eligible studies were included in this meta-analysis. Overall, the HP carriers did not have significantly higher A1C levels compared with HP noncarriers (mean difference (95% CI), 0.19% (−0.18 to 0.46), P = 0.16). When the analysis was limited to studies targeting patients with type 1 diabetes, there was also no significant difference in A1C (0.69% (−0.31 to 1.68), P = 0.18). Conclusions. There was insufficient evidence that HP infection worsened glycemic control in patients with diabetes.

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

Metabolic compromise is crucial in aggravating age-associated chronic inflammation, oxidative stress, mitochondrial damage, increased LDL and triglycerides, and elevated blood pressure. Excessive adiposity, hyperglycemia, and insulin resistance due to aging are associated with elevated levels of damaging free radicals, inducing a proinflammatory state and hampering immune cell activity, leading to a malfunctioning cardiometabolic condition. The age-associated oxidative load and redox imbalance are contributing factors for cardiometabolic morbidities via vascular remodelling and endothelial damage. Recent evidence has claimed the importance of gut microbiota in maintaining regular metabolic activity, which declines with chronological aging and cardiometabolic comorbidities. Genetic mutations, polymorphic changes, and environmental factors strongly correlate with increased vulnerability to aberrant cardiometabolic changes by affecting key physiological pathways. Numerous studies have reported a robust link between biological aging and cardiometabolic dysfunction. This review outlines the scientific evidence exploring potential mechanisms behind the onset and development of cardiovascular and metabolic issues, particularly exacerbated with aging. [ABSTRACT FROM AUTHOR]