Yasuaki Hayashino

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%, I2 for heterogeneity=89%) and 13% (6% to 21%, I2=79%) before and after adjustment for adiposity; for artificially sweetened beverages, 25% (18% to 33%, I2=70%) and 8% (2% to 15%, I2=64%); and for fruit juice, 5% (−1% to 11%, I2=58%) and 7% (1% to 14%, I2=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 showd 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.

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.

Diagnostic accuracy of cerebrospinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis: A meta-analysis

OBJECTIVES Cerebrospinal fluid (CSF) lactate is produced by bacterial anaerobic metabolism and is not affected by blood lactate concentration, an advantage over CSF glucose in differentiating bacterial meningitis from aseptic meningitis. However, the previous investigations have shown mixed results of the sensitivity and specificity. Our studys purpose was to assess the utility of CSF lactate in differentiating bacterial meningitis from aseptic meningitis. METHODS We searched MEDLINE and EMBASE for clinical studies that included CSF lactate measurement in bacterial meningitis and aseptic meningitis. Test characteristics were pooled using hierarchical summary ROC curve and random effects model. RESULTS Thirty three studies were included. The pooled test characteristics of CSF lactate were sensitivity 0.93 (95% CI: 0.89-0.96), specificity 0.96 (95% CI: 0.93-0.98), likelihood ratio positive 22.9 (95% CI: 12.6-41.9), likelihood ratio negative 0.07 (95% CI: 0.05-0.12), and diagnostic odds ratio 313 (95% CI: 141-698). Pretreatment with antibiotics lowered the sensitivity 0.49 (95% CI: 0.23-0.75). CSF lactate of around 35 mg/dl (34-36 mg/dl) had higher sensitivity and specificity than those of around 27 mg/dl (26-28 mg/dl). CONCLUSIONS CSF lactates high negative likelihood ratio may make it useful for ruling out bacterial meningitis though pretreatment with antibiotics reduces clinical accuracy. CSF lactate of 35 mg/dl could be optimal cut-off value for distinguishing bacterial meningitis from aseptic meningitis.

Relation between sleep quality and quantity, quality of life, and risk of developing diabetes in healthy workers in Japan: The High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study

BackgroundThe effect of sleep on the risk of developing diabetes has not been explored in an Asian population. The objective of this study is to investigate the effect of self-reported sleep duration and sleep quality on the risk of developing diabetes in a prospective cohort in Japan.MethodsData were analyzed from the cohort of participants in a High-risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP), conducted in Japan from the year 1999 until 2004. A Cox proportional hazard model was used to evaluate the association between sleep duration or sleep quality and the risk of diabetes.ResultsOf 6509 participants (26.1% of women, 19–69 years of age), a total of 230 type 2 diabetes cases were reported over a median 4.2 years of follow-up. For participants who often experienced difficulty in initiating sleep, the multivariate-adjusted hazard ratios for diabetes were 1.42 (95%CI, 1.05–1.91) in participants with a medium frequency of difficulty initiating sleep, and 1.61 (95%CI, 1.00–2.58) for those with a high frequency, with a statistically significant linear trend. Significant association was not observed in the association between difficulty of maintaining sleep or duration of sleep, and risk of diabetes.ConclusionMedium and high frequencies of difficulty initiating sleep, but not difficulty in maintaining sleep or in sleep duration, are associated with higher risks of diabetes in relatively healthy Asian workers, even after adjusting for a large number of possible further factors.

Effects of exercise on C-reactive protein, inflammatory cytokine and adipokine in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

OBJECTIVE C-reactive protein (CRP), inflammatory cytokines, and adipokines contribute to atherosclerosis, insulin resistance, and development of late-onset complication in patients with type 2 diabetes. We performed a systematic review to assess effects of exercise interventions on inflammatory markers/cytokines and adipokines. MATERIALS/METHODS We searched electronic databases (MEDLINE, EMBASE, and Cochrane Controlled Trials Registry) and reference lists in relevant papers for articles published in 1966-2013. We selected studies that evaluated the effects of exercise intervention on inflammatory markers/cytokines and adipokines in adult patients with type 2 diabetes. Weighted mean differences of exercise on outcomes were derived using fixed or random effect models; factors influencing heterogeneity were identified using meta-regression analysis. RESULTS Fourteen randomized controlled trials (824 patients) were included in our meta-analysis. Exercise was associated with a significant in CRP=-0.66mg/l (95% CI, -1.09 to -0.23mg/l; -14% from baseline) and interleukin-6 (IL-6)=-0.88pg/ml (95% CI, -1.44 to -0.32pg/ml; -18% from baseline) but did not alter adiponectin or resistin levels; aerobic exercise program was associated with a significant change in leptin=-3.72ng/ml (95% CI, -6.26 to -1.18ng/ml; -24% from baseline). For IL-6, exercise was more effective in those with a longer duration in the program and larger number of sessions during study (p=0.001). CONCLUSIONS Exercise decreases inflammatory cytokine (CRP and IL-6) in patients with type 2 diabetes. Exercise could be a therapeutic option for improving abnormalities in inflammation levels in patients with diabetes.

Effects of supervised exercise on lipid profiles and blood pressure control in people with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials

AIMS Our studys purpose was to perform a systematic review to assess the effect of supervised exercise interventions on lipid profiles and blood pressure control. METHODS We searched electronic databases and selected studies that evaluated the effect of supervised exercise intervention on cardiovascular risk factors in adult people with type 2 diabetes. We used random effect models to derive weighted mean differences of exercise on lipid profiles and blood pressure control. RESULTS Forty-two RCTs (2808 subjects) met inclusion criteria and are included in our meta-analysis. Structured exercise was associated with a change in systolic blood pressure (SBP) of -2.42 mmHg (95% CI, -4.39 to -0.45 mmHg), diastolic blood pressure (DBP) of -2.23 mmHg (95% CI, -3.21 to -1.25 mmHg), high-density lipoprotein cholesterol (HDL-C) of 0.04 mmol/L (95% CI, 0.02-0.07 mmol/L), and low-density lipoprotein cholesterol (LDL-C) of -0.16 mmol/L (95% CI, -0.30 to -0.01 mmol/L). Heterogeneity was partially explained by age, dietary co-intervention and the duration and intensity of the exercise. CONCLUSIONS Supervised exercise is effective in improving blood pressure control, lowering LDL-C, and elevating HDL-C levels in people with diabetes. Physicians should recommend exercise for their adult patients with diabetes who can safely do so.

Outcome and risk factors of de novo autoimmune hepatitis in living-donor liver transplantation.

Background. Graft dysfunction mimicking autoimmune hepatitis (AIH) develops only rarely after liver transplantation for nonautoimmune liver disease. The long-term prognosis and risk factors of de novo AIH after living-donor liver transplantation (LDLT) are unknown. Methods. We review our LDLT series to investigate the incidence and outcome of this form of graft dysfunction, focusing on follow-up histology. Results. Of 633 patients who underwent LDLT at Kyoto University from 1990 to 2002, 13 (2.1%) developed graft dysfunction with interface hepatitis resembling AIH (2 males, 11 females). The median age at LDLT of these 13 patients was 10 years (8 months to 26 years). All received tacrolimus-based immunosuppression. The dysfunction presented at a median interval of 3.1 (0.7–9.5) years after LDLT. Nine had definite AIH, and four had probable AIH at the onset of hepatitis. Patients were followed after a median of 3.5 (0.1–8) years from the onset of de novo AIH. Of 11 patients who underwent follow-up histologic evaluation, 3 underwent retransplantation, and 8 continued to have similar findings on subsequent biopsies, with fluctuations in the amount of necroinflammatory activity and an increase in fibrosis despite treatment. In a multivariate analysis, acute rejection episodes and recipient age between 11 and 15 years at LDLT independently had predictive value for the development of de novo AIH. Human leukocyte antigen-A, B, and DR mismatches and sex mismatch did not influence the occurrence of de novo AIH. Conclusion. This series highlights the more severe histologic outcome of de novo AIH with longer follow-up despite immunosuppressive treatment. De novo AIH may arise from alloimmunologic injury, marked by clinically obvious episodes of acute rejection.

Association between number of comorbid conditions, depression, and sleep quality using the Pittsburgh Sleep Quality Index: results from a population-based survey.

OBJECTIVES Although sleep problems are a serious public concern, it is not clear if the presence of depression or multiple comorbid conditions has an additive or multiplicative effect on sleep quality. METHODS We conducted a population-based, cross-sectional survey in a rural town in Japan. Multivariable-adjusted linear regression models were used to explore the association between the number of comorbid conditions and the Pittsburgh Sleep Quality Index (PSQI) global score. The association between the number of comorbid conditions and presence of depression, as defined by the five-item Mental Health Inventory (scores60), in those with poor quality sleep (PSQI global score>5) was determined using a non-parametric trend test. RESULTS Of 5107 respondents, 3403 (mean age: 51.0years, women: 52.6%) were used for the analysis after exclusion of missing PSQI data. The PSQI global score (mean: 4.9) increased as the number of comorbid conditions increased in a linear and statistically significant manner (p<0.0001). The PSQI global score increased by 0.374 for each additional comorbid condition (p<0.0001). Among those with poor sleep quality, the proportion with depression increased significantly and linearly (p<0.0001) as the number of comorbid conditions increased (37.5% for 0 vs. 59.9% for 4 comorbid conditions). CONCLUSION The number of comorbid conditions correlated positively with poor sleep quality, and as the number of comorbid conditions increased, the proportion of those also suffering from depression increased. Recognizing the signs of depression in patients with multiple comorbid conditions is important because of its exacerbation of poor sleep quality.

Diabetes, glycaemic control and mortality risk in patients on haemodialysis: the Japan Dialysis Outcomes and Practice Pattern Study

Aims/hypothesisThere are few data on the target level of glycaemic control among patients with diabetes on haemodialysis. We investigated the impact of glycaemic control on mortality risk among diabetic patients on haemodialysis.Subjects and methodsData were analysed from the Dialysis Outcomes Practice Pattern Study (DOPPS) for randomly selected patients on haemodialysis in Japan. The diagnosis of diabetes at baseline and information on clinical events during follow-up were abstracted from the medical records. A Cox proportional hazards model was used to evaluate the association between presence or absence of diabetes, glycaemic control (HbA1c quintiles) and mortality risk.ResultsData from 1,569 patients with and 3,342 patients without diabetes on haemodialysis were analysed. Among patients on haemodialysis, those with diabetes had a higher mortality risk than those without (multivariable hazard ratio 1.37, 95% CI 1.08–1.74). Compared with those in the bottom quintile of HbA1c level, the multivariable-adjusted hazard ratio for mortality was not increased in the bottom second to fourth quintiles of HbA1c (HbA1c 5.0–5.5% to 6.2–7.2%), but was significantly increased to 2.36 (95% CI 1.02–5.47) in the fifth quintile (HbA1c ≥ 7.3%). The effect of poor glycaemic control did not statistically correlate with baseline mortality risk (p = 0.27).Conclusions/interpretationAmong dialysis patients, poorer glycaemic control in those with diabetes was associated with higher mortality risk. This suggests a strong effect of poor glycaemic control above an HbA1c level of about 7.3% on mortality risk, and that this effect does not appear to be influenced by baseline comorbidity status.

Ramelteon for the treatment of insomnia in adults: a systematic review and meta-analysis.

Ramelteon is the first selective melatonin receptor agonist and currently is approved in the United States and Japan for the treatment of insomnia. Our meta-analysis assessed the efficacy and safety of ramelteon for the treatment of insomnia in adults. We included both published and unpublished data from randomized placebo-controlled trials evaluating the efficacy of ramelteon in adults with insomnia in the analysis. Our primary outcomes were sleep quality, subjective sleep latency (sSL), and subjective total sleep time (sTST). Secondary outcomes included latency to persistent sleep (LPS), total sleep time (TST), sleep efficiency (SE), proportion of rapid eye movement (REM) sleep, wakefulness after sleep onset (WASO), subjective WASO, number of nighttime awakenings (NAW), subjective NAW, and adverse events. Thirteen trials involving 5812 patients with insomnia or insomnia symptoms with a mean study duration of 38 days were pooled. Ramelteon was associated with reduced sSL (weighted mean difference [WMD], -4.30 min [95% confidence interval {CI}, -7.01 to -1.58]) and improved sleep quality (standardized mean differences, -0.074 [95% CI, -0.13 to -0.02]) but was not associated with increased sTST. Ramelteon also was associated with improvement in LPS, SE, and TST. The only significant adverse event was somnolence. Short-term use of ramelteon was associated with improvement in some sleep parameters in patients with insomnia, but its clinical impact is small. Long-term trials are needed before solid conclusions can be established.