The joint association of diabetes distress and depressive symptoms with all-cause mortality in Japanese individuals with type 2 diabetes: a prospective cohort study (Diabetes Distress and Care Registry in Tenri [DDCRT 20]).

AIMS/HYPOTHESIS: The independent association of depressive symptoms and diabetes distress with mortality risk in individuals with diabetes has not been evaluated. We examined the temporal joint association of diabetes distress and depressive symptoms at baseline and the subsequent risk of all-cause mortality. METHODS: The longitudinal data of 3118 individuals with type 2 diabetes were obtained from a large Japanese diabetes registry. To assess the joint association of diabetes distress and depressive symptoms at baseline with the subsequent risk of all-cause mortality, the Cox proportional hazards model was used with adjustment for potential confounders. RESULTS: The mean age, BMI and HbA1c levels were 64.7 years, 24.6 kg/m2 and 58.6 mmol/mol (7.5%), respectively, and 38.1% of the participants were women. In the multivariable-adjusted models evaluating the diabetes distress and depressive symptoms separately, the HRs for all-cause mortality were 1.67 (95% CI 1.14, 2.43; p = 0.008) and 1.40 (95% CI 1.05, 1.85; p = 0.020), respectively. In such models evaluating the joint association of diabetes distress and depressive symptoms, compared with individuals without diabetes distress or depressive symptoms (DD-/DS-), the HRs for all-cause mortality for the group without diabetes distress but with depressive symptoms (DD-/DS+), with diabetes distress but without depressive symptoms (DD+/DS-), and with diabetes distress and depressive symptoms (DD+/DS+) were 1.34 (95% CI 0.99, 1.86; p = 0.056), 1.96 (95% CI 1.10, 3.50; p = 0.023) and 1.71 (95% CI 1.06, 2.77; p = 0.029), respectively. We did not observe a significant interaction between diabetes distress and depressive symptoms with all-cause mortality risk (p = 0.2636). In the stratified analysis by sex, a significant joint association of diabetes distress and depressive symptoms with the risk of all-cause mortality was observed only in men. CONCLUSIONS/INTERPRETATION: Diabetes distress and depressive symptoms were independently associated with all-cause mortality risk in male participants with type 2 diabetes, but we did not observe a significant interaction between diabetes distress and depressive symptoms in relation to all-cause mortality. Graphical abstract.

Effects of dapagliflozin on renin-angiotensin-aldosterone system under renin-angiotensin system inhibitor administration.

Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are reported to prevent cardiovascular events by a mechanism possibly including diuresis and sodium excretion. In this respect, diuresis-induced compensatory upregulation of the renin-angiotensin-aldosterone (RAA) system should be clarified and we performed a randomized controlled trial using dapagliflozin, an SGLT2I. Hypertensive diabetic patients taking angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were randomly assigned to a dapagliflozin group (DAPA) or a control group (CTRL) with the difference in the changes in plasma renin activity (PRA) after 24 weeks of the treatment as the primary outcome. PRA, plasma aldosterone concentration (PAC), age, sex, BMI, blood pressure, pulse rate, eGFRcys, and HbA1c were not different between the groups at baseline. After 24 weeks, the changes in the PRA from the baseline of the DAPA (n = 44) and CTRL (n = 39) groups were 6.30 ± 15.55 and 1.42 ± 11.43 ng/mL/h, respectively (p = 0.11) although the power of detection was too small. However, post hoc nonparametric analyses revealed that there was a definite increase in the PRA and PAC in the DAPA group (p < 0.0001 and p = 0.00025, respectively) but not in the CTRL group. The PRA in the DAPA group after 24 weeks treatment was significantly elevated compared to the CTRL group (p = 0.013) but not for the PAC. Accordingly, it would be suggested that dapagliflozin may not induce a profound increase, if any, in PAC after 24 weeks of treatment in hypertensive type 2 diabetic patients under RAA suppression.

Association between diabetes distress and all-cause mortality in Japanese individuals with type 2 diabetes: a prospective cohort study (Diabetes Distress and Care Registry in Tenri [DDCRT 18]).

AIMS/HYPOTHESIS: The absence of data on the direct association between diabetes-specific distress and all-cause mortality in individuals with diabetes prompted us to examine the temporal association between Problem Areas in Diabetes (PAID) survey scores and the subsequent risk of all-cause mortality in a cohort of individuals with type 2 diabetes. METHODS: Longitudinal data from 3305 individuals with diabetes were obtained from a large Japanese diabetes registry. Independent correlations between quintiles of PAID total scores or PAID scores of ≥40 and all-cause mortality (median follow-up of 6.1 years) were examined using Cox proportional hazards models with adjustment for potential confounders. RESULTS: The study population included 1280 women and 2025 men with a mean age of 64.9 years, BMI of 24.6 kg/m2 and HbA1c level of 58.7 mmol/mol (7.5%). In the multivariable-adjusted model, compared with the first quintile of PAID scores, the multivariable-adjusted HRs (95% CIs) for all-cause mortality for the second to fifth quintiles were 1.11 (0.77, 1.60; p = 0.56), 0.87 (0.56, 1.35; p = 0.524), 0.95 (0.63, 1.46; p = 0.802) and 1.60 (1.09, 2.36; p = 0.016), respectively. Compared with a PAID score of <40, the multivariable-adjusted HR for all-cause mortality of those with a score of ≥10 was 1.56 (95% CI 1.17, 2.08; p = 0.002). In subgroup analyses, the association between PAID score and all-cause mortality was found in men (HR 1.76; 95% CI 1.26, 2.46) but not in women (HR 1.09; 95% CI 0.60, 2.00), with a significant interaction between diabetes distress and sex (p = 0.0336). CONCLUSIONS/INTERPRETATION: We observed a significant positive association between high diabetes distress and all-cause mortality in men with diabetes.

Serum uric acid levels are associated with increased risk of newly developed diabetic retinopathy among Japanese male patients with type 2 diabetes: A prospective cohort study (diabetes distress and care registry at Tenri [DDCRT 13]).

OBJECTIVE: We assessed the prospective association between baseline serum uric acid levels and consequent risk of developing diabetic retinopathy. RESEARCH DESIGN AND METHODS: Data for 1839 type 2 diabetes patients without diabetic retinopathy were obtained from a Japanese diabetes registry. A Cox proportional hazards model with time-varying exposure information by sex was used and adjusted for potential confounders to assess the independent correlations between baseline serum uric acid levels and incidence rate of diabetic retinopathy. RESULTS: Newly developed diabetic retinopathy was recognized in 188 patients (10.2%) during the observation period of 2 years. Compared to the first serum uric acid quartile level, the multivariate adjusted hazards ratio for diabetic retinopathy development in male patients was 1.97 (95% CI, 1.14-3.41; P = .015), 1.92 (95% CI, 1.18-3.13; P = .008), and 2.17 (95% CI, 1.40-3.37; P = .001) for the second, third, and fourth serum uric acid quartile levels, respectively. But this was not the case with female patients. CONCLUSION: Higher serum uric acid levels were associated with increased risk of developing diabetic retinopathy in male patients with type 2 diabetes, but not in female patients. Serum uric acid may be a useful biomarker for predicting the future risk of developing diabetic retinopathy in male patients with type 2 diabetes.

Revisiting Interdialytic Weight Gain and Mortality Association With Serum Albumin Interactions: The Japanese Dialysis Outcomes and Practice Pattern Study.

BACKGROUND: The dialysis practice guideline in Japan sets a limit on the allowed interdialytic weight gain (IDWG) <6%. However, the effects of relative gain of fluid volume to body weight may differ in presence of morbid conditions. Here, we examined whether or not the associations between IDWG and mortality differ by serum albumin (sAlb), a nutritional and illness marker. DESIGN: The study type used was prospective cohort study. SUBJECTS: Patients who participated in the Japan Dialysis Outcomes and Practice Pattern Study (phase 1-4 [1999-2011]) and received thrice-weekly hemodialysis. METHODS: IDWG was the exposure of interest and was collected every 4 months, divided into 7 categories as follows: <2%, 2% to 3%, 3% to 4% (reference), 4% to 5%, 5% to 6%, 6% to 7%, and >7%. sAlb was treated as both an effect modifier and confounder and dichotomized into ≥3.8 g/dL and <3.8 g/dL segments, according to the protein-energy wasting criteria proposed by the International Society of Renal Nutrition and Metabolism. MAIN OUTCOME MEASURE: The outcome in this study was all-cause mortality. RESULTS: A total of 8,661 patients were analyzed. Time-varying Cox regression analyses revealed that, when sAlb was ≥3.8 g/dL, an IDWG >7% was associated with greater risk of mortality (adjusted hazard ratio [AHR] 2.74; 95% confidence interval [CI], 1.49-5.05). When sAlb was <3.8 g/dL, however, IDWGs <2% (AHR 1.89; 95% CI, 1.50-2.39) and 4% to 5% (AHR 0.75; 95% CI, 0.58-0.96) were associated with mortality (P for interaction = .001). Cubic spline analyses showed that the mortality increased when IDWG exceeded 6% for patients with sAlb ≥3.8 g/dL; in contrast, for patients with sAlb <3.8 g/dL, the mortality increased when IDWG was <3% and decreased when IDWG was between 4% and 6%. LIMITATION: The main limitation was possible residual confounding. CONCLUSIONS: The direction and magnitude of the associations between IDWG and mortality were modified by sAlb. Dialysis experts should take these results into account when revising the clinical practice guidelines.

Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction.

OBJECTIVES: To examine the prospective associations between consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice with type 2 diabetes before and after adjustment for adiposity, and to estimate the population attributable fraction for type 2 diabetes from consumption of sugar sweetened beverages in the United States and United Kingdom. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND ELIGIBILITY: PubMed, Embase, Ovid, and Web of Knowledge for prospective studies of adults without diabetes, published until February 2014. The population attributable fraction was estimated in national surveys in the USA, 2009-10 (n=4729 representing 189.1 million adults without diabetes) and the UK, 2008-12 (n=1932 representing 44.7 million). SYNTHESIS METHODS: Random effects meta-analysis and survey analysis for population attributable fraction associated with consumption of sugar sweetened beverages. RESULTS: Prespecified information was extracted from 17 cohorts (38,253 cases/10,126,754 person years). Higher consumption of sugar sweetened beverages was associated with a greater incidence of type 2 diabetes, by 18% per one serving/day (95% confidence interval 9% to 28%, I(2) for heterogeneity=89%) and 13% (6% to 21%, I(2)=79%) before and after adjustment for adiposity; for artificially sweetened beverages, 25% (18% to 33%, I(2)=70%) and 8% (2% to 15%, I(2)=64%); and for fruit juice, 5% (-1% to 11%, I(2)=58%) and 7% (1% to 14%, I(2)=51%). Potential sources of heterogeneity or bias were not evident for sugar sweetened beverages. For artificially sweetened beverages, publication bias and residual confounding were indicated. For fruit juice the finding was non-significant in studies ascertaining type 2 diabetes objectively (P for heterogeneity=0.008). Under specified assumptions for population attributable fraction, of 20.9 million events of type 2 diabetes predicted to occur over 10 years in the USA (absolute event rate 11.0%), 1.8 million would be attributable to consumption of sugar sweetened beverages (population attributable fraction 8.7%, 95% confidence interval 3.9% to 12.9%); and of 2.6 million events in the UK (absolute event rate 5.8%), 79,000 would be attributable to consumption of sugar sweetened beverages (population attributable fraction 3.6%, 1.7% to 5.6%). CONCLUSIONS: Habitual consumption of sugar sweetened beverages was associated with a greater incidence of type 2 diabetes, independently of adiposity. Although artificially sweetened beverages and fruit juice also showed positive associations with incidence of type 2 diabetes, the findings were likely to involve bias. None the less, both artificially sweetened beverages and fruit juice were unlikely to be healthy alternatives to sugar sweetened beverages for the prevention of type 2 diabetes. Under assumption of causality, consumption of sugar sweetened beverages over years may be related to a substantial number of cases of new onset diabetes.

Glycated hemoglobin and risk of death in diabetic patients treated with hemodialysis: a meta-analysis.

BACKGROUND: Studies investigating the association between glycated hemoglobin (HbA1c) level and mortality risk in diabetic patients receiving hemodialysis have shown conflicting results. STUDY DESIGN: We conducted a systematic review and meta-analysis using MEDLINE, EMBASE, Web of Science, and the Cochrane Library. SETTING & POPULATION: Diabetic patients on maintenance hemodialysis therapy. SELECTION CRITERIA FOR STUDIES: Observational studies or randomized controlled trials investigating the association between HbA1c values and mortality risk. Study authors were asked to provide anonymized individual patient data or reanalyze results according to a standard template. PREDICTOR: Single measurement or mean HbA1c values. Mean HbA1c values were calculated using all individual-patient HbA1c values during the follow-up period of contributing studies. OUTCOME: HR for mortality risk. RESULTS: 10 studies (83,684 participants) were included: 9 observational studies and one secondary analysis of a randomized trial. After adjustment for confounders, patients with baseline HbA1c levels ≥ 8.5% (≥ 69 mmol/mol) had increased mortality (7 studies; HR, 1.14; 95% CI, 1.09-1.19) compared with patients with HbA1c levels of 6.5%-7.4% (48-57mmol/mol). Likewise, patients with a mean HbA1c value ≥ 8.5% also had a higher adjusted risk of mortality (6 studies; HR,1.29; 95% CI, 1.23-1.35). There was a small but nonsignificant increase in mortality associated with mean HbA1c levels ≤ 5.4% (≤ 36 mmol/mol; 6 studies; HR, 1.09; 95% CI, 0.89-1.34). Sensitivity analyses in incident (≤ 90 days of hemodialysis) and prevalent patients (>90 days of hemodialysis) showed a similar pattern. In incident patients, mean HbA1c levels ≤ 5.4% also were associated with increased mortality risk (4 studies; HR, 1.29; 95% CI, 1.23-1.35). LIMITATIONS: Observational study data and inability to adjust for diabetes type in all studies. CONCLUSIONS: Despite concerns about the utility of HbA1c measurement in hemodialysis patients, high levels (≥ 8.5%) are associated with increased mortality risk. Very low HbA1c levels (≤ 5.4%) also may be associated with increased mortality risk.

The Japanese version of Problem Areas in Diabetes Scale: a clinical and research tool to assess emotional functioning among people with diabetes.

Introduction: The purpose of this study was to develop the Japanese version of the Problem Areas in Diabetes (PAID) scale, a measure of emotional adjustment to diabetes that has been translated into Japanese by our group. Materials and methods: A total of 418 Japanese people with diabetes attending our outpatient clinic participated (n = 65 type 1 and n = 353 type 2). We assessed the internal reliability of the PAID, examined correlations of the PAID with conceptually related psychosocial constructs, evaluated mean differences in the PAID between diabetes treatment groups, and examined correlations of the PAID with diabetes self-care behaviours and selected treatment outcomes. Results: Results showed that the PAID had excellent reliability (Cronbach alpha = 0.934). The PAID correlated significantly with the Diabetes Treatment Satisfaction Questionnaire (r = -0.593, p < 0.0001) and the positive wellbeing (r = -0.396, p < 0.0001), negative wellbeing (r = -0.640, p < 0.0001) and energy (r = -0.444, p < 0.0001) subscales of the Wellbeing Questionnaire. Adherence to diet was negatively correlated with PAID score (r = -0.263, p < 0.0001). The frequency of recent hypoglycemia and number of chronic complications (retinopathy, nephropathy and neuropathy) were positively correlated with PAID scores. PAID was weakly correlated with HbA1c (r = 0.13, p = 0.01). Conclusions: In conclusion, the Japanese version of the PAID demonstrated good internal reliability and evidence of concurrent and discriminant validity. The PAID measures the impact of diabetes, diabetes treatment and treatment outcomes on the emotions of people with diabetes. The results provide encouraging evidence for the clinical utility of the PAID in Japanese people with diabetes.

Clinical usefulness of the two-question assessment tool for depressive symptoms in Japanese patients with chronic obstructive pulmonary disease.

PURPOSE: Depressive symptoms are highly prevalent in patients with chronic obstructive pulmonary disease (COPD) and have been associated with poor outcomes. Developing a concise questionnaire to measure depressive symptoms in COPD patients is needed in outpatient settings. We evaluated the clinical usefulness of a concise two-question instrument to assess depressive symptoms in patients with COPD. METHODS: The study was conducted as a cross-sectional analysis in patients with COPD. All patients completed a self-reported questionnaire consisting of the two-question instrument, as well as a shortened version of the Center for Epidemiologic Studies Depression Scale (CESD-10) to measure depressive symptoms. Performance of the two-question instrument was evaluated using the results for CESD-10 as standard. We also measured patients' health-related quality of life using the Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8) to determine whether the instrument was related to SF-8. RESULTS: Sensitivity of the two-question instrument in the detection of depressive symptoms was 73.3 % (95 % confidence interval [CI] 51-95.7), specificity was 73 % (95 % CI 58.7-87.3), and area under the receiver operating characteristics curve was 0.73 (95 % CI 0.59-0.87). When study patients were divided into two groups with a cutoff of 1 point on the two-question instrument, scores for all subscales of the SF-8 except "bodily pain" were significantly lower in patients with than without depressive symptoms. CONCLUSIONS: This concise two-question instrument is useful as assessment of depressive symptom in patients with COPD in busy outpatient settings.

Risk factors predicting the outcome of salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy.

OBJECTIVES: Salvage radiotherapy is the only curative treatment for patients with prostate cancer showing biochemical progression after radical prostatectomy. In this study, we evaluated the clinicopathological parameters that influence the outcome of salvage radiotherapy. METHODS: Medical records of 49 patients who underwent salvage radiotherapy after radical prostatectomy from 1997 to 2008 at the Graduate School of Medicine, Kyoto University, were retrospectively reviewed. Radiotherapy was carried out with 66 Gy on the prostatic bed. RESULTS: Biochemical progression-free survival after salvage radiotherapy at 2, 5 and 7 years was 51.0%, 42.2% and 42.2%, respectively. Significant parameters predicting biochemical progression after salvage radiotherapy by Cox regression analysis were prostatectomy Gleason score sum ≥ 8 (hazard ratio 0.08; 95% confidence interval 0.03-0.22; P=0.001), prostate-specific antigen nadir after radical prostatectomy ≥ 0.04 ng/mL (hazard ratio 0.30; 95% confidence interval 0.13-0.69; P=0.005) and negative surgical margin (hazard ratio 0.28; 95% confidence interval 0.12-0.70; P=0.006). When the patients were subgrouped by these risk factors, the 5-year progression-free survival rates after salvage radiotherapy were 77.8%, 50.0% and 6.7% in patients with 0, 1 and ≥ 2 predictors, respectively. CONCLUSION: In order to discriminate favorable candidates for salvage radiotherapy, Gleason score of prostatectomy, prostate-specific antigen nadir after prostatectomy and positive surgical margin represent independent predictors. Thus, progression-free survival might be more precisely predicted according to the presence/absence of these risk factors. The significance of this risk classification should be confirmed by large prospective studies.

Diabetes Distress Is Associated With Future Risk of Progression of Diabetic Nephropathy in Adults With Type 2 Diabetes: A Prospective Cohort Study (Diabetes Distress and Care Registry at Tenri [DDCRT23]).

OBJECTIVES: Our aim in this study was to investigate the prospective association between diabetes distress assessed with Problem Areas in Diabetes (PAID) survey scores at baseline and the subsequent risk of development or progression of diabetic nephropathy in people with type 2 diabetes. METHODS: Longitudinal data were acquired from 2,845 individuals with type 2 diabetes registered in a Japanese diabetes registry. A Cox proportional hazards model was used to adjust for possible confounders to examine the prospective association between baseline diabetes distress (PAID score ≥40) and the development or progression of albuminuria. RESULTS: Mean patient age, body mass index, and glycated hemoglobin level were 64.8 years, 24.5 kg/m2, and 57.4 mmol/mol (7.5%), respectively. We did not observe a significant association between diabetes distress and the subsequent risk of diabetic nephropathy development from normoalbuminuria to microalbuminuria/macroalbuminuria (multivariable-adjusted hazard ratio [HR]=0.95 over 4.2 years, 95% confidence interval [CI] 0.77 to 1.17, p=0.640); however, we identified a significant association for progression from microalbuminuria to macroalbuminuria (multivariable-adjusted HR=1.34 over 7.0 years, 95% CI 1.01 to 1.80, p=0.045). Stratification by sex revealed a significant association between diabetes distress and the subsequent risk of progressing diabetic nephropathy (HR=1.45, 95% CI 1.06 to 1.98, p=0.019) in males, but not females (HR=1.42, 95% CI 0.95 to 2.14, p=0.087). CONCLUSIONS: Diabetes distress at baseline, assessed using the PAID survey, was associated with a subsequent risk of progressing diabetic nephropathy independent of possible confounders in males, but not females, with type 2 diabetes.

Causes of death in Japanese people with type 2 diabetes and factors associated with all-cause mortality from a large registry in Japan: the Japan Diabetes Complication and its prevention prospective (JDCP) study-9.

Aims: We aimed to estimate the causes of death and their incidence rates and risk factors for all-cause mortality in Japanese people with type 2 diabetes using baseline data from the Japan Diabetes Complication and its Prevention (JDCP) prospective study. Methods: We analyzed a multicenter prospective cohort of 5944 Japanese people with diabetes aged 40-74 years. Causes of death were categorized as cardiac or cerebrovascular disease, malignancy, infectious disease, accident or suicide, sudden death of unknown cause, and other unknown causes. The Cox proportional hazards model was used to estimate the hazard ratio of all-cause mortality risk factors. Results: The mean age was 61.4 years, and 39.9% of the population was female. Overall, the mortality ratio per 100,000 person-years (95% confidence interval [CI]) was 515.3 (95% CI 445.1-596.9). Malignancies are the most common cause of death among people with type 2 diabetes, accounting for 46.9% of all deaths, followed by cardiac and cerebrovascular diseases at 11.7% and infectious diseases at 3.9%. Higher mortality risk was significantly associated with older age, lower body-mass index, alcohol intake, history of hypertension, and acute myocardial infarction (AMI). Conclusions: The frequency of causes of death in people with type 2 diabetes identified in this study was similar to that from a recent survey on causes of death conducted by the Japan Diabetes Society. A lower body-mass index, alcohol intake, history of hypertension, and AMI were found to be associated with an increased total risk of type 2 diabetes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00628-y.

Association between urinary C-megalin levels and progressive kidney dysfunction: a cohort study based on the diabetes distress and care registry at Tenri (DDCRT 24).

AIMS: The aim of this cohort study was to evaluate the association between urinary levels of C-megalin, a full-length form of megalin, and kidney dysfunction progression and its dependence on the urinary albumin-creatinine ratio (UACR) in individuals with diabetes. METHODS: We enrolled 1,547 individuals with diabetes who visited the ambulatory clinic at Tenri Hospital, a regional tertiary-care hospital in Tenri City, Nara Prefecture, Japan, with an estimated glomerular filtration (eGFR) of ≥ 30 mL/min/1.73 m2. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox proportional hazard models to examine the association between urinary C-megalin levels and eGFR decline by ≥ 40% from baseline. RESULTS: Urinary C-megalin level was not associated with ≥ 40% eGFR decline in an age-, sex-, eGFR-, systolic blood pressure-, hemoglobin-, and UACR-adjusted model in the 1,547 patients enrolled in the study. However, urinary C-megalin levels were associated with a ≥ 40% decline in eGFR when accounting for the relationship between urinary C-megalin levels and UACR in the model. This association was UACR-dependent. CONCLUSIONS: High urinary C-megalin levels were associated with progressive kidney dysfunction in individuals with diabetes, and this association was attenuated by high UACRs.

Behavioral change stage might moderate the impact of multifaceted interventions on non-attendance from medical care among patients with type 2 diabetes: The Japan Diabetes Outcome Intervention Trial-2 Large-Scale Trial 007 (J-DOIT2-LT007).

AIMS/INTRODUCTION: Non-attendance from regular medical care is a major problem in diabetes patients. This study aimed to examine the impact of a multifaceted lifestyle intervention by face-to-face approach (FFA) on non-attendance from regular medical care in comparison with that by telephone from the technical support center (TSC). MATERIALS AND METHODS: This was secondary analysis from a 1-year, prospective, cluster randomized, intervention study. Patients with type 2 diabetes, who were regularly visiting primary care physicians cluster-randomized into the control or intervention (TSC or FFA according to resource availability of the district medical associations) groups, were consecutively recruited. The primary end-point was non-attendance from regular medical care. The interaction between the type of intervention (TSC vs FFA) and behavioral change stage (pre- vs post-action stage) in diet and exercise for the dropout rate was assessed. RESULTS: Among the 1,915 participants (mean age 56 ± 6 years; 36% women) enrolled, 828, 564 and 264 patients belonged to the control, TSC and FFA groups, respectively. We found evidence suggestive of an interaction between the intervention type and behavioral change stage in diet (P = 0.042) and exercise (P = 0.038) after adjusting for covariates. The hazard ratios (95% confidence interval) of FFA to TSC were 0.21 (0.05-0.93) and 7.69 (0.50-117.78) in the pre-action and post-action stages for diet, respectively, whereas they were 0.20 (0.05-0.92) and 4.75 (0.29-73.70) in the pre-action and post-action stages for exercise. CONCLUSIONS: Among diabetes patients, the impact of multifaceted intervention on non-attendance from medical care might differ by the behavioral change stage.

Disappearance of association in diabetic patients on hemodialysis between anemia and mortality risk: the Japan dialysis outcomes and practice pattern study.

We previously demonstrated that anemia was not associated with mortality in hemodialysis patients with cardiovascular disease (CVD). Since diabetes mellitus (DM) accelerates CVD, the influence of DM on the relationship between anemia and mortality was examined using the data obtained from 1,385 DM patients and 2,583 non-DM hemodialysis patients recruited into the Dialysis Outcomes Practice Pattern Study in Japan (J-DOPPS). When all patients were stratified into four groups on their hematocrit levels, mortality rate was significantly and steadily lower in the subgroups with the higher levels of hematocrit by the Kaplan-Meier method (p = 0.0003 by log-rank test). When DM and non-DM patients were analyzed separately, a significant association of lower hematocrit levels with higher mortality disappeared in DM patients (p = 0.6280), in contrast with its retention in non-DM counterparts (p < 0.0001). Multivariable-adjusted Cox proportional hazards models demonstrated a significant association between hematocrit with all-cause mortality in non-DM patients after adjustment for age, gender, BMI, hemodialysis duration, SBP, DBP, albumin, total cholesterol, calcium, phosphorus, and intact PTH (p = 0.046), whereas this association disappeared in DM patients in the same model (p = 0.583). In conclusion, these results suggested that the association between anemia and higher mortality disappeared in DM hemodialysis patients, in contrast with non-DM counterparts.

Impact of atherosclerosis on the relationship of glycemic control and mortality in diabetic patients on hemodialysis.

OBJECTIVE: The impact of preexisting cardiovascular disease (CVD) on glycemic control-improved survival in hemodialysis patients with diabetes mellitus (DM) was investigated. Glycoalbumin (GA) was used as a glycemic marker. METHODS: A single-center 4-year follow-up study was performed in an observational cohort of 178 DM hemodialysis patients to analyze the relationship between GA and all-cause mortality in patients with (n = 70) and without (n = 108) CVD. The subjects were divided into three categories based on GA value at the start of study. RESULTS: Baseline characteristics did not differ between the two groups of patients. During the 4-year follow-up, 24 of 108 (23.3%) CVD(-) patients and 30 of 70 (42.8%) CVD(+) patients died. The mortality was significantly higher in the CVD(+) group. Multivariate Cox analyses including GA, logCRP, age, gender, hemodialysis duration, albumin, hemoglobin, BMI, SBP, DBP, smoking habit, and SUN as independent variables showed that GA, in addition to logCRP and age, was independently associated with mortality in all patients. Kaplan-Meier analysis showed lower GA levels to be a significant predictor of lower mortality in the CVD(-) group, but not in the CVD(+) group. Multivariable-adjusted Cox proportional hazards models demonstrated a significant association between GA with allcause mortality risk in the CVD(-) group (p = 0.004), in contrast with the CVD(+) group in the same model (p = 0.842). CONCLUSION: These results demonstrate a beneficial effect of improved glycemic control on survival in DM hemodialysis patients, which might be attenuated by the presence of CVD.

Locomotor dysfunction and risk of cardiovascular disease, quality of life, and medical costs: design of the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) and baseline characteristics of the study population.

BACKGROUND: There is little evidence regarding long-term outcomes of locomotor dysfunction such as cardiovascular events, quality of life, and death. We are conducting a prospective cohort study to evaluate risk of cardiovascular disease, quality of life, medical costs, and mortality attributable to locomotor dysfunction. The present study determined baseline characteristics of participants in the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS). METHODS: Cohort participants were recruited from residents between 40 and 80 years old who received regular health check-ups conducted by local government each year between 2008 and 2010 in Minami-Aizu Town and Tadami Town in Fukushima Prefecture, Japan. Musculoskeletal examination included assessment of physical examination of the cervical and lumbar spine, and upper and lower extremities and of physical function, such as grasping power, one-leg standing time, and time for the 3-m timed up-and-go test. Cardiovascular risk factors, including blood pressure and biological parameters, were measured at annual health check-ups. We also conducted a self-administered questionnaire survey. RESULTS: LOHAS participants comprised 1,289 men (mean age 65.7 years) and 1,954 women (mean age 66.2 years) at the first year. The proportion of obese individuals (body mass index 25.0 kg/m(2)) was 31.9% in men and 34.3% in women, and 41.0% of participants reported being followed up for hypertension, 7.0% for diabetes, and 43.6% for hypercholesterolemia. Prevalence of lumbar spinal stenosis was 10.7% in men and 12.9% in women, while prevalence of low back pain was 15.8% in men and 17.6% in women. CONCLUSION: The LOHAS is a novel population-based prospective cohort study that will provide an opportunity to estimate the risk of cardiovascular disease, quality of life, medical costs, and mortality attributable to locomotor dysfunction, and to provide the epidemiological information required to develop policies for detection of locomotor dysfunction.

Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis.

CONTEXT: Botulinum toxin A is US Food and Drug Administration approved for prophylactic treatment for chronic migraines. OBJECTIVE: To assess botulinum toxin A for the prophylactic treatment of headaches in adults. DATA SOURCES: A search of MEDLINE, EMBASE, bibliographies of published systematic reviews, and the Cochrane trial registries between 1966 and March 15, 2012. Inclusion and exclusion criteria of each study were reviewed. Headaches were categorized as episodic (<15 headaches per month) or chronic (≥15 headaches per month) migraine and episodic or chronic daily or tension headaches. STUDY SELECTION: Randomized controlled trials comparing botulinum toxin A with placebo or other interventions for headaches among adults. DATA EXTRACTION: Data were abstracted and quality assessed independently by 2 reviewers. Outcomes were pooled using a random-effects model. DATA SYNTHESIS: Pooled analyses suggested that botulinum toxin A was associated with fewer headaches per month among patients with chronic daily headaches (1115 patients, -2.06 headaches per month; 95% CI, -3.56 to -0.56; 3 studies) and among patients with chronic migraine headaches (n = 1508, -2.30 headaches per month; 95% CI, -3.66 to -0.94; 5 studies). There was no significant association between use of botulinum toxin A and reduction in the number of episodic migraine (n = 1838, 0.05 headaches per month; 95% CI, -0.26 to 0.36; 9 studies) or chronic tension-type headaches (n = 675, -1.43 headaches per month; 95% CI, -3.13 to 0.27; 7 studies). In single trials, botulinum toxin A was not associated with fewer migraine headaches per month vs valproate (standardized mean difference [SMD], -0.20; 95% CI, -0.91 to 0.31), topiramate (SMD, 0.20; 95% CI, -0.36 to 0.76), or amitriptyline (SMD, 0.29; 95% CI, -0.17 to 0.76). Botulinum toxin A was associated with fewer chronic tension-type headaches per month vs methylprednisolone injections (SMD, -2.5; 95% CI, -3.5 to -1.5). Compared with placebo, botulinum toxin A was associated with a greater frequency of blepharoptosis, skin tightness, paresthesias, neck stiffness, muscle weakness, and neck pain. CONCLUSION: Botulinum toxin A compared with placebo was associated with a small to modest benefit for chronic daily headaches and chronic migraines but was not associated with fewer episodic migraine or chronic tension-type headaches per month.

Dietary intake and physical activity in Japanese patients with type 2 diabetes: the Japan Diabetes Complication and its Prevention prospective study (JDCP study 8).

Medical nutrition therapy and exercise therapy are the cornerstones of treatment for patients with type 2 diabetes; however, there has not been a nationwide study on the actual dietary intake and physical activity status of patients since the 2000s. We aimed to clarify this in Japanese patients with type 2 diabetes using data from the Japan Diabetes Complication and its Prevention prospective (JDCP), a nationwide study launched in 2007. A total of 1992 patients with type 2 diabetes, aged 40-75 years, completed either the Brief-type, self-administered Diet History Questionnaire (1643 patients) or International Physical Activity Questionnaire (1834 patients), and their data were analyzed in this study. Mean daily energy intake for all participants was 1686.8 kcal/day, and the mean proportions of carbohydrate, protein, and fat comprising total energy intake were 60.2, 16.2, and 23.6%, respectively. The patients in this study had similar energy and nutrient intake status to patients in the 1996 Japan Diabetes Complications Study; however, Japanese patients still had higher carbohydrate and lower fat consumption than patients with diabetes in Western countries. The physical activity questionnaire reported that 31.0% of patients did not have exercise habits; this was particularly noticeable in female patients and patients under the age of 65. BMI increased from 22.7 to 24.1 kg/m2 in men and 23.2 to 24.8 kg/m2 in women from 1996 to 2007, respectively. Further research is required to investigate how dietary intake and physical activity associates with the risk of developing complications in type 2 diabetes patients.

Employment status and diabetic outpatient appointment non-attendance in middle to senior working generation with type 2 diabetes: the Japan diabetes outcome intervention trial-2 large­scale trial 005 (J-DOIT2-LT005).

AIMS: Workplace demands, support, and relationships differ according to employment status (e.g., employment that is full-time, part-time, or self-employed) and may lead to unequal opportunities to keep diabetic appointments. We investigated the association between employment status and outpatient diabetic appointment non-attendance among working-age adults with type 2 diabetes. METHODS: This was a secondary analysis of a cluster-randomized trial (the Japan diabetes outcome intervention trial 2 large-scale trial). The analysis included 2010 trial participants (40-65 years old) with type 2 diabetes who were regularly followed by primary care physicians (PCPs). The outcome measure was the first non-attendance (defined as a failure to visit a PCP within 2 months of the original appointment) during the one-year follow-up. The association between baseline employment status and non-attendance was examined using Cox proportional hazard model in men and women. RESULTS: During the 1279 and 789 person-year follow-up periods, 90 men and 34 women, respectively, experienced their first appointment non-attendance. Among men, self-employed participants had a higher risk of non-attendance compared with full-time employees (adjusted HR, 1.84; 95% CI, 1.15, 2.95). The trial intervention (attendance promotion) was associated with a significantly reduced risk of non-attendance among self-employed participants (HR, 0.51; 95% CI, 0.26, 0.99). Among women, a significant association between employment status and non-attendance was not observed. CONCLUSIONS: Self-employed men with type 2 diabetes had a twofold increased risk of non-attendance than did full-time employees. Our study suggests that self-employed men with type 2 diabetes should be targeted for interventions promoting appointment adherence.