Retrospective cohort study to examine the association between serum amylase and the incidence of type 2 diabetes mellitus, Toranomon Hospital Health Management Center Study 23 (TOPICS 23).

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.

Developing a health economic model for Asians with type 2 diabetes based on the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial.

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.

Refinement of the Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation.

The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) is a widely used tool for pre-transplant risk assessment. Allogeneic hematopoietic cell transplantation (HCT) is performed on patients with diverse backgrounds, highlighting the need for other predictors to complement the HCT-CI and support bedside decision-making. There is a strong body of evidence supporting the use of pre-transplant serum ferritin (SF) in risk assessments of allogeneic HCT. We additionally found that the Glasgow Prognostic Score (GPS), which assesses inflammatory biomarkers and predicts survival of patients with solid organ malignancies, is a useful predictive marker for overall survival (OS) and non-relapse mortality (NRM) in allogeneic HCT, independent of HCT-CI and SF. In this study, we refined the GPS by adding pre-transplant SF to improve its prognostic ability and enable better stratification; we call this revised index the HCT-specific revised Glasgow Prognostic Score (HCT-GPS). We observed that the HCT-GPS more accurately predicted NRM and early-term OS than the GPS. Moreover, the HCT-GPS provides an independent prognostic factor adjusted for the HCT-CI and disease status, and stratifies patients into four risk groups by OS and NRM. Thus, the HCT-GPS is a useful index for predicting early-term complications after allogeneic HCT in patients with hematopoietic diseases.

The Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation.

Evaluation methods, such as scoring systems for predicting complications in advance, are necessary for determining the adaptation of allogeneic hematopoietic cell transplantation (HCT) and selecting appropriate conditioning regimens. The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), which is based on functions of main organs, is a useful tool for pre-transplant risk assessments and has been widely applied in determining treatment strategies for patients with hematological diseases. However, as allogeneic HCT is performed on patients with diverse backgrounds, another factor, which reinforces the HCT-CI, is required to evaluate pre-transplant risk assessments. The Glasgow Prognostic Score (GPS), which assesses the combined C-reactive protein and albumin, was reported to predict survival of patients with solid-organ malignancies independently of receiving chemo/radiotherapy and stages of cancer. In this study, we applied the GPS for pre-transplant risk assessments for allogeneic HCT. The GPS successfully stratified the patients into three risk groups of overall survival (OS) and non-relapse mortality (NRM). Moreover, the GPS could predict outcomes independently of the HCT-CI for OS and NRM in multivariate analysis. The GPS is considered to be a useful tool and reinforces the HCT-CI for determining adaptation of allogeneic HCT for patients with hematopoietic neoplasms.

Impact of individual components and their combinations within a family history of hypertension on the incidence of hypertension: Toranomon hospital health management center study 22.

Although a family history (FH) of hypertension is a risk factor for the development of hypertension, only a few studies have investigated in detail the impact of individual components of an FH on incident hypertension. We investigated the impact of individual components and their combinations on the presence or development of hypertension considering obesity, smoking habits, physical activity, and other metabolic parameters.Studied were 12,222 Japanese individuals without hypertension (n = 9,766) and with hypertension (n = 2,456) at the baseline examination. The presence or incidence of hypertension during 5 years after a baseline examination was assessed by the presence of systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or a self-reported history of clinician-diagnosed hypertension. In this prospective study, the odds ratio for incident hypertension was 1.39 (95% confidence interval [CI], 1.22, 1.59) for individuals with any FH of hypertension compared with those without such an FH. Individuals with an FH of hypertension in both parents and one or more grandparents had an odds ratio of 3.05 (95% CI 1.74, 5.36) for hypertension compared with those without an FH of hypertension. FH was associated with incident hypertension independently of other modifiable risk factors such as obesity, smoking, physical inactivity, hyperglycemia, hyperuricemia, and hypertriglyceridemia.A parental history of hypertension was an essential component within an FH for incident hypertension. FH of hypertension over two generations with both parents affected was the most important risk factor for incident hypertension. Although an FH is not a modifiable risk factor, modifying other risk factors could contribute to reducing the risk of hypertension even among individuals with a family history of hypertension.

Utility of nonblood-based risk assessment for predicting type 2 diabetes mellitus: A meta-analysis.

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

Cluster-randomized trial to improve the quality of diabetes management: The study for the efficacy assessment of the standard diabetes manual (SEAS-DM).

AIMS/INTRODUCTION: 'The Standard Diabetes Manual' has been developed by clinical researchers from multiple major institutions in Japan, such as the National Center for Global Health and Medicine, as a comprehensive disease management program, including collaboration between primary care physicians (PCPs) and specialist services. The present study evaluated the efficacy of the manual as a quality improvement strategy in diabetes care by PCPs. MATERIALS AND METHODS: A total of 42 PCPs in eight domestic districts of the Japan Medical Association were allocated to either the intervention group or the control group in a cluster-randomized design. The PCPs in both groups were provided with a copy of the Diabetes Treatment Guide published by the Japan Diabetes Society, and the PCPs in the intervention group additionally received a copy of the manual and a 30-min relevant seminar at the inception of the intervention. The primary end-point was the adherence to the following performances as quality indicators: evaluation of retinopathy, and urinary albumin excretion measurements and serum creatinine measurements, as recommended by the Japan Medical Association. RESULTS: A total of 416 patients were enrolled by 36 PCPs. During the 1-year follow-up period, the proportion of PCPs who adhered to recommendation-concordant measurements of urinary albumin excretion was significantly higher in the intervention group than in the control group (adherence: 17.9% vs 5.3%, P = 0.016). The other parameters were not statistically different between the two groups. CONCLUSIONS: Implementation of 'The Standard Diabetes Manual' potentially leads to an improved quality of diabetes management by PCPs.

Assessment of kidney dysfunction with cystatin C- and creatinine-based estimated glomerular filtration rate and predicting type 2 diabetes: Toranomon Hospital Health Management Center Study 21.

OBJECTIVE: Whether early stages of kidney dysfunction assessed by the estimated glomerular filtration rate from cystatin C measurements (eGFRCysC) rather than from creatinine measurements (eGFRCr) would more precisely reflect the risk of developing type 2 diabetes (T2D) has not been clarified. We compared the risk of developing T2D associated with renal dysfunction indicated by eGFRCysC or eGFRCr measurements. METHODS: Studied were 2131 Japanese individuals without diabetes. Hazard ratios (HRs) for the development of T2D over 3-5 y were calculated across categories of eGFRCysC and eGFRCr, respectively. RESULTS: Reduced levels of eGFRCysC were associated with a step-wise increase in the cumulative incidence rate of T2D (p=0.007). In comparison with the eGFRCysC >85th percentile group (≥ 117.4 ml/min/1.73 m(2)), the lowest group, which was the eGFRCysC <15th percentile group (<86.2 ml/min/1.73 m(2)), had an adjusted HR of 2.30 (95% CI 1.13, 4.68) for T2D. Compared with the eGFRCr >85th percentile group, the lowest eGFRCr group (<15th percentile) had an HR of 1.19 (0.63, 2.24) for T2D. However, individuals with eGFRCr <60 ml/min/1.73 m(2) had a significantly increased risk of T2D. Clustering of both low eGFRCysC and low eGFRCr further elevated the HR for T2D compared with the presence of either. CONCLUSIONS: Although eGFRCr in ranges indicating chronic kidney disease reflected an elevated risk of developing diabetes, earlier stages of kidney dysfunction indicated by reduced eGFRCysC, which could not be captured by reduced eGFRCr, would be a marker for an elevated risk of developing T2D.

Quality and accuracy of Internet information concerning a healthy diet.

The Internet is used by many consumers interested in healthy living. The aim of the present study was to explore the variations among Internet information concerning a healthy diet and to evaluate the potential for misleading information. To conduct a descriptive analysis, the search term "healthy diet" was entered into three search engines and the first 100 results were examined. Of the evaluated 48 websites, 5, 26 and 11, respectively, gave references, date when information was updated and cautioned users. For assessment of accuracy, six dietary guidelines were used as references and the website was scored according to the number of recommended dietary features that matched the guidelines. Websites that specified their objectives scored significantly higher when matched with each guideline than the websites that did not state four guidelines (p < 0.05). Internet information on a "healthy diet" was likely to only partially follow recommendations of the guidelines.

Nutrition education in Japanese medical schools: a follow-up survey.

A questionnaire survey was used to determine the status of nutrition education in Japanese medical schools in 2009. A similar survey was conducted in 2004, at which time nutritional education was determined to be inadequate in Japanese medical schools. The current questionnaire was sent to the directors of Centers for Medical Education of 80 medical schools, who represented all medical schools in Japan. Sixty-seven medical schools (83.8%) responded, of which 25 schools (37.3%) offered dedicated nutrition courses and 36 schools (53.7%) did not offer dedicated nutrition courses but offered something related to nutrition in other courses; six schools (9.0%) did not offer any nutrition education. Overall, 61 schools (91.0%) offered at least some nutritional topics in their undergraduate education. Nevertheless, only 11 schools (16.4%) seem to dedicate more than 5 hours to substantial nutrition education as judged by their syllabi. Although the mean length of the course was 11 hours, substantial nutrition education accounted for only 4.2 hours. Of the 25 medical schools that offered dedicated nutrition courses, seven schools offered the nutrition course as a stand-alone course and 18 schools offered it as an integrated course. In conclusion, the status of nutrition education in Japan has improved slightly but is still inadequate.

Impact of introducing HbA1c into the diagnostic criteria on prevalence and cardiovascular risk profiles of individuals with newly diagnosed diabetes in Japan: the Toranomon Hospital Health Management Center Study 2 (TOPICS 2).

OBJECTIVE: To evaluate the impact of HbA1c for diagnosis of diabetes and investigate whether cardiovascular risks profiles differ among individuals with diabetes diagnosed by HbA1c or fasting plasma glucose (FPG). METHODS: This cross-sectional study involved 26,884 participants (30.6% women; aged 20-91 years) without known diabetes. Subjects were categorized into 4 groups according to the presence or absence of FPG ≥7.0 mmol/L and/or HbA1c ≥6.5%, which were American Diabetes Association criteria. Oral glucose tolerance test data were not available. RESULTS: Prevalence of undiagnosed diabetes was 3.6%. Of those individuals, 47.5% fulfilled both two criteria and 26.0% fulfilled only HbA1c criterion. Individuals with diabetes according to FPG ≥7.0 mmol/L alone were characterized as having poorly controlled hypertension while those with HbA1c ≥6.5% alone were characterized as older, female, and having lower blood pressure and γ-glutamyltransferase values. Persons with newly diagnosed diabetes by HbA1c had low HDL cholesterol and high LDL or non-HDL cholesterol levels. CONCLUSIONS: Introducing HbA1c into the diagnosis allowed detection of many previously undiagnosed cases of diabetes in Japanese individuals. Those diagnosed by FPG were characterized by hypertension and those diagnosed by HbA1c had unfavorable lipid profiles, reflecting an atherosclerotic trait.

Prevalence of albuminuria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes Clinical Data Management study (JDDM15).

BACKGROUND: Microalbuminuria is widely accepted as the first clinical sign of diabetic nephropathy. However, normoalbuminuric type 2 diabetic patients who have renal insufficiency (RI), i.e. low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2), exist. We explored the prevalence of such patients and associated clinical factors. METHODS: We investigated the distribution of patients when stratified by albuminuria stages and chronic kidney disease (CKD) stages in a large-scale population of Japanese type 2 diabetic patients (N = 3297), and the common and independent factors for albuminuria and low eGFR. RESULTS: The proportion of subjects with low eGFR was 15.3% (506/3297), which was 11.4% among those with normoalbuminuria (NA) (262/2298), 14.9% among those with microalbuminuria (105/705) and 47.3% among those with macroalbuminuria (139/294). There were 262 patients with NA and low eGFR, and 63.4% of them had neither diabetic retinopathy nor neuropathy. They were older and included a higher proportion of women and patients with hypertension, hyperlipidaemia and cardiovascular disease (CVD), and fewer smokers compared with those with NA and preserved eGFR. Multiple logistic regression analysis revealed that factors commonly associated with RI and albuminuria were hypertension, CVD and proliferative retinopathy. Factors independently associated with RI were age, duration of diabetes, A1C (negative), hyperlipidaemia, smoking (negative) and macroalbuminuria, whereas those associated with albuminuria were male sex, BMI, A1C, simple retinopathy and RI. CONCLUSIONS: A significant proportion of type 2 diabetic patients have normoalbuminuric RI. Renal disease in type 2 diabetes could be heterogeneous, implying the possibility of involvement of renal atherosclerosis and lipid toxicity.