Hidetoshi Yamashita

Yamagata University, Ямагата, Yamagata, Japan

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Publications (143)392.05 Total impact

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    ABSTRACT: Obesity is associated with environmental factors; however, information about gene–environment interactions is lacking. We aimed to elucidate the effects of gene–environment interactions on obesity, specifically between genetic predisposition and various obesity-related lifestyle factors, using data from a population-based prospective cohort study. The genetic risk score (GRS) calculated from East Asian ancestry single-nucleotide polymorphisms was significantly associated with the body mass index (BMI) at baseline (P<0.001). Significant gene–environment interactions were observed for six nutritional factors, alcohol intake, metabolic equivalents-hour per day and the homeostasis model assessment ratio. The GRS altered the effects of lifestyle factors on BMI. Increases in the BMI at baseline per unit intake for each nutritional factor differed depending on the GRS. However, we did not observe significant correlations between the GRS and annual changes in BMI during the follow-up period. This study suggests that the effects of lifestyle factors on obesity differ depending on the genetic risk factors. The approach used to evaluate gene–environment interaction in this study may be applicable to the practice of preventive medicine.
    Full-text · Article · Dec 2015 · Journal of Human Genetics
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    ABSTRACT: The number of cancer survivors is increasing; however, optimal health management of cancer survivors remains unclear due to limited knowledge. To elucidate the risk of non-communicable diseases, and the effect of lifestyle habits on risk of non-communicable diseases, we compared cancer survivors and those who never had cancer (non-cancer controls) using a population-based prospective cohort study. The baseline survey of 2,292 participants was conducted from 2004–2006, and the follow-up survey of 2,124 participants was performed in 2011. We compared the baseline characteristics and the risk of non-communicable diseases between cancer survivors and non-cancer controls. Analyzed participants included 124 cancer survivors (men/women; 57/67), and 2,168 non-cancer controls (939/1229). Several lifestyle factors and nutritional intake significantly differed between survivors and non-cancer controls, although smoking status did not differ between the groups (P = 0.30). Univariate logistic regression analysis showed increased risk of death (odds ratio [OR] 3.64, 95% confidence interval [CI] 2.19–6.05) and heart disease (OR 2.60, 95% CI 1.06–6.39) in cancer survivors. Increased risk of heart disease was also significant (OR 2.95, 95% CI 1.05–8.26, P = 0.04) in the multivariate analysis of the smoking-related cancer subgroup. Current smoking significantly increased risk of death (OR 2.42, 95% CI 1.13–5.18). Specific management should be implemented for cancer survivors. More intense management against smoking is necessary, as continued smoking in cancer survivors may increase the risk of second primary cancer. Moreover, cancer survivors are at a high risk of heart disease; thus, additional care should be taken.This article is protected by copyright. All rights reserved.
    Full-text · Article · Sep 2015 · Cancer Science
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    ABSTRACT: To evaluate the effects of treatment for hyperlipidemia on total mortality, we examined the association with adjustments for multiple factors, including those related to general health, such as blood hemoglobin and serum levels of albumin, adiponectin, brain natriuretic peptide, and lipids, using a prospective cohort study of a general Japanese population. The population-based, longitudinal Takahata study enrolled 3,291 Japanese individuals (1515 male, 1776 female; age: 62.5±10.3 years) between 2004 and 2006. The incidence and causes of death were annually monitored until January 10, 2012 (median follow-up period: 2,655 days). During the follow-up period, there were 169 deaths. The Cox proportional hazard regression model analysis used to adjust for factors related to general health condition, cardiovascular disease risks, and serum lipid levels showed a significant association between treatment for hyperlipidemia and decreased total mortality compared with no treatment for hyperlipidemia [hazard ratio (HR): 0.24; 95% confidence interval (CI): 0.08-0.69) and subjects without hyperlipidemia (HR: 0.34;95%CI: 0.12-0.96). The Cox proportional hazard regression model analysis with adjustments for factors related to general health conditions showed a significantly lower total mortality in subjects without hyperlipidemia than that in subjects with untreated hyperlipidemia (HR: 0.70; 95%CI: 0.50-0.99). Not only antihyperlipidemic drugs used but also selection bias and non-evaluated factors, such as socio-economic status, educational level, health literacy, and daily nutrition, affected the results. Subjects taking treatment for hyperlipidemia were found to have reduced total mortality, which was independent of serum lipid levels.
    Full-text · Article · May 2015 · Journal of atherosclerosis and thrombosis
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    ABSTRACT: Data envelopment analysis (DEA) is a method of operations research that has not yet been applied in the field of obesity research. However, DEA might be used to evaluate individuals' susceptibility to obesity, which could help establish effective risk models for the onset of obesity. Therefore, we conducted this study to evaluate the feasibility of applying DEA to predict obesity, by calculating efficiency scores and evaluating the usefulness of risk models. In this study, we evaluated data from the Takahata study, which was a population-based cohort study (with a follow-up study) of Japanese people who are >40 years old. For our analysis, we used the input-oriented Charnes-Cooper-Rhodes model of DEA, and defined the decision-making units (DMUs) as individual subjects. The inputs were defined as (1) exercise (measured as calories expended) and (2) the inverse of food intake (measured as calories ingested). The output was defined as the inverse of body mass index (BMI). Using the β coefficients for the participants' single nucleotide polymorphisms, we then calculated their genetic predisposition score (GPS). Both efficiency scores and GPS were available for 1,620 participants from the baseline survey, and for 708 participants from the follow-up survey. To compare the strengths of the associations, we used models of multiple linear regressions. To evaluate the effects of genetic factors and efficiency score on body mass index (BMI), we used multiple linear regression analysis, with BMI as the dependent variable, GPS and efficiency scores as the explanatory variables, and several demographic controls, including age and sex. Our results indicated that all factors were statistically significant (p < 0.05), with an adjusted R2 value of 0.66. Therefore, it is possible to use DEA to predict environmentally driven obesity, and thus to establish a well-fitted model for risk of obesity.
    Full-text · Article · May 2015 · PLoS ONE
  • Mari Narumi · Koichi Nishitsuka · Mitsunori Yamakawa · Hidetoshi Yamashita
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    ABSTRACT: To confirm the efficacy of liquid-based cytology (LBC) method in the observation of vitreous cells in various vitreoretinal diseases in human. Vitreous fluid samples from 30 eyes were obtained by 23-gauge 3-port pars plana vitrectomy. After making three ports, we collected vitreous specimen from the core vitreous cavity without infusion. We divided the samples into a quiescent group and an active group based on clinical signs of inflammation. To confirm availability of LBC preparation slides for immunostaining, we also performed immunocytochemistry (ICC) for CD68, RPE65 and DEC-205 (CD205) using LBC slides of 10 cell-rich cases including retinal detachment and endophthalmitis. Using LBC method, small amounts of vitreous cells were observed efficiently. Vitreous cells were observed in inflammatory quiescent cases including macular pucker and macular hole. The number of vitreous cells increased significantly in the cases with clinically active inflammation (2297 versus 207 cells/ml, respectively, p < 0.01, Mann-Whitney U-test). The ICC results showed the presence of CD68(+) cells in all 10 cases. Large numbers of DEC-205(+) cells were observed in one case with infectious endophthalmitis. In the cases with retinal detachment, the predominant cell type was RPE65(+) . Neutrophils and lymphocytes were also observed. The LBC method makes it possible to examine vitreous specimens easily and efficiently, facilitating the expedient diagnosis of vitreoretinal diseases, and the preparation slides are available for immunocytochemistry. This study also showed that vitreoretinal disease involves the migration of various types of cells including macrophages, neutrophils, lymphocytes, RPE65(+) pigmented cells and DEC-205(+) cells. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
    No preview · Article · Mar 2015 · Acta ophthalmologica
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    ABSTRACT: To develop a classification and grading system for myopic maculopathy. Development and evaluation of a classification system for myopic maculopathy based on observational case series. A comprehensive set of myopic macular lesions was defined via literature review and through consensus meetings among retinal specialists and clinician scientists. A classification of myopic maculopathy was formulated based on fundus photographs and a modified Delphi process and consensus. Inter- and intra-observer reproducibility, assessed as agreement (%) and weighted kappa values, were evaluated. One-hundred retinal photographs with myopia and myopic macular lesions were selected from case series at the High Myopia Clinic of the Tokyo Medical and Dental University, Tokyo Japan. We defined 5 categories of myopic maculopathy including "no myopic retinal degenerative lesion" (Category 0), "tessellated fundus" (Category 1), "diffuse chorioretinal atrophy" (Category 2), "patchy chorioretinal atrophy" (Category 3), and "macular atrophy" (Category 4). Three additional features to supplement these categories were defined as "plus" lesions, namely, lacquer cracks, myopic choroidal neovascularization, Fuchs' spot. Posterior staphyloma was considered as a further important, sign of myopic retinopathy. The intra-observer agreement was ≥85% and the corresponding weighted kappa statistic was ≥0.6 between observations. After a brief training session, inter-observer kappa statistics reached the predefined satisfactory level (≥0.4), considered as above moderate agreement. We propose a classification system for myopic maculopathy which was found to be reproducible. Applying a uniform classification in different studies will facilitate communication and comparison of findings from clinical trials and epidemiological studies. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · American Journal of Ophthalmology
  • Shion Hayashi · Miho Sato · Hitomi Miura · Akira Sugano · Mai Yamazaki · Hidetoshi Yamashita
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    ABSTRACT: To analyze the relationship between changes in the intraocular pressure (IOP) and dislocation angle in highly myopic strabismus patients who had undergone muscle union surgery. Medical data were examined of eight eyes of seven consecutive patients with highly myopic strabismus, who had some limitation in abduction, received muscle union surgery and undergone pre- and postoperative IOP evaluation with a noncontact tonometer, and were retrospectively reviewed. In addition, 15 eyes of 15 patients with comitant horizontal strabismus who underwent unilateral recess-resect procedure as well as pre- and postoperative IOP evaluation were also included. The correlation between IOP changes after strabismus surgery and the dislocation angle of the globe was analyzed. The IOP was significantly reduced in the highly myopic strabismus group (-5.6 mmHg) but not in the fellow eye or in comitant horizontal strabismus patients. The decrease in IOP after surgery was significantly correlated with the preoperative dislocation angle of the globe (r = -0.725, p = 0.042). IOP is often higher in highly myopic strabismus patients than perceived, and it may indicate abnormal anatomy of the orbit rather than glaucoma. In that case, muscle union surgery can improve eye position and normalizes the IOP.
    No preview · Article · Dec 2014 · Japanese Journal of Ophthalmology
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    ABSTRACT: Purpose: To investigate the relationship between age and ocular higher-order wavefront aberrations (HOAs) in an adult Japanese population, as well as factors associated with HOA variations. Methods: In the Yamagata Study (Funagata) cohort, 227 adult Japanese participants (aged 37-86 years) were recruited, and they underwent systemic and ophthalmologic examinations in 2012. Ocular, corneal, and internal HOAs were measured. From the Zernike coefficients, we calculated the root mean square of the total HOA, coma, and spherical aberration for a pupil diameter of 4 mm. Linear regression analyses were used to determine whether HOAs were associated with age or other factors. Results: Multiple adjusted linear regression analyses demonstrated that all components of logarithmic HOAs increase with age. Ocular, corneal, and internal HOAs increased by 0.012/year (P < 0.001), 0.007/year (P = 0.010), and 0.014/year (P < 0.001), respectively. Ocular coma also significantly increased with age (0.010/ year, P = 0.007), but corneal (P = 0.963) and internal (P = 0.476) coma did not. Age-related spherical aberration increased only in the internal component (0.019/year, P = 0.001). In addition to age, ocular and corneal HOAs were mainly affected by corneal indexes. Conclusion: Age is associated with increases in ocular HOAs, independent of other possible confounding factors. Associations of ocular HOAs with corneal parameters indicate that ocular HOAs are mainly generated by the cornea. Internal HOAs, supposedly generated from cataract progression, may be associated with systemic factors, including serum creatinine and blood pressure. Copyright © 2014 by Association for Research in Vision and Ophthalmology.
    Full-text · Article · Dec 2014 · Investigative Ophthalmology & Visual Science
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    ABSTRACT: Compared with the peripheral corneal limbus, the human central cornea lacks blood vessels, which is responsible for its immunologically privileged status and high transparency. Dendritic cells (DCs) are present in the central avascular area of inflamed corneas, but the mechanisms of their migration to this location are poorly understood. Here, we investigated the contribution of vessel formation to DC migration into the central cornea, and analyzed the DC chemotactic factors produced by human corneal epithelial (HCE) cells. Using human eyes obtained from surgical procedures, we then assessed vessel formation, DC distribution, and activin A expression immunohistochemically. The results demonstrated increased numbers of vessels and DCs in the central area of inflamed corneas, and a positive correlation between the number of vessels and DCs. Activin A was expressed in the subepithelial space and the endothelium of newly formed blood vessels in the inflamed cornea. In infected corneas, DCs were present in the central area but no vascularization was observed, suggesting the presence of chemotactic factors that induced DC migration from the limbal vessels. To test this hypothesis, we assessed the migration of monocyte-derived DCs toward HCE cell supernatants with or without lipopolysaccharide (LPS) stimulation of HCE cells and inflammatory cytokines (released by HCE cells). DCs migrated toward tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and activin A, as well as LPS-stimulated HCE cell supernatants. The supernatant contained elevated TNF-α, IL-6, and activin A levels, suggesting that they were produced by HCE cells after LPS stimulation. Therefore, vessels in the central cornea might constitute a DC migration route, and activin A expressed in the endothelium of newly formed vessels might contribute to corneal vascularization. Activin A also functions as a chemotactic factor, similar to HCE-produced TNF-α and IL-6. These findings enhance our understanding of the pathophysiology of corneal inflammation during infection.
    Full-text · Article · Oct 2014 · PLoS ONE
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    ABSTRACT: ObjectiveA higher plasma aldosterone-renin ratio (ARR) is an established marker for screening for primary aldosteronism (PA). The association between higher ARR and mortality in a general population has not been fully explored. We here examined whether higher ARR is a risk factor for total and cause-specific mortality in a Japanese population.Subjects and MethodsA population-based, longitudinal study of 1,310 Japanese individuals (age: 63·9 ± 9·8 years) enrolled in the Takahata study between 2004 and 2006 and followed for up to 8 years. The incidence and causes of death were monitored annually until 10 January 2012 (median follow-up: 2691 days).ResultsDuring the follow-up period, 64 subjects died. Kaplan-Meier analysis showed a significantly increased risk for total and cancer mortality in subjects with lower ARR (log-rank P < 0·001). Cox's proportional hazard model analyses with adjustment for age and gender showed that lower ARR was associated with increased total and cancer mortality in subjects with low (≦72) vs high (>72) ARR (hazard ratios and 95% confidential intervals: 2·56, 1·44-4·56 and 2·78, 1·16-6·65, respectively).Conclusions Lower ARR was a significant and independent risk factor for increased total and cancer mortality in this Japanese population. Subjects with higher ARR were not-at-risk for total death in general. These findings increase the necessity for identifying people with PA from those with higher ARR. People with higher ARR without PA may be at very low risk for total and cancer death.
    No preview · Article · Oct 2014 · Clinical Endocrinology
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    ABSTRACT: Purpose: Indocyanine green (ICG), an adjuvant used for peeling of the internal limiting membrane (ILM) during vitreous surgery for idiopathic macular hole (MH), has been reported to be toxic, possibly affecting postoperative visual acuity. We compared the long-term outcomes (within 2 years) of brilliant blue G (BBG), ICG, and triamcinolone acetonide (TA). Patients and methods: This study involved 97 eyes of 94 patients who underwent vitreous surgery for MH at the Yamagata University Hospital between June 2002 and November 2010. The surgical adjuvants used were BBG for 15 eyes, ICG for 61 eyes, and TA for 21 eyes. We compared the postoperative visual acuities, initial closure rates, final closure rates, and complications of the 3 groups. Results: In all 3 groups, the visual acuity significantly improved after surgery. The magnitude of the improvement at 2 years after surgery was significantly better in the BBG group than in the ICG group (Mann-Whitney test, P = 0.020). The postoperative visual acuity did not significantly differ between the BBG and TA groups (P = 0.627) or between the ICG and TA groups (P =0 .137). Thus, the surgery using BBG resulted in a significantly better outcome in visual acuity than did the surgery using ICG. The 3 groups did not differ in initial or final closure rates or in incidence of complications. Conclusion: Analysis of the long-term outcomes of vitreous surgeries provided evidence that BBG is a useful adjuvant for ILM peeling.
    No preview · Article · Sep 2014 · Japanese Journal of Ophthalmology
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    ABSTRACT: To facilitate personalized health care for multifactorial diseases, risks of genetic and clinical/environmental factors should be assessed together for each individual in an integrated fashion. This approach is possible with the likelihood ratio (LR)-based risk assessment system, as this system can incorporate manifold tests. We examined the usefulness of this system for assessing type 2 diabetes (T2D). Our system employed 29 genetic susceptibility variants, body mass index (BMI), and hypertension as risk factors whose LRs can be estimated from openly available T2D association data for the Japanese population. The pretest probability was set at a sex- and age-appropriate population average of diabetes prevalence. The classification performance of our LR-based risk assessment was compared to that of a non-invasive screening test for diabetes called TOPICS (with score based on age, sex, family history, smoking, BMI, and hypertension) using receiver operating characteristic analysis with a community cohort (n = 1263). The area under the receiver operating characteristic curve (AUC) for the LR-based assessment and TOPICS was 0.707 (95% CI 0.665-0.750) and 0.719 (0.675-0.762), respectively. These AUCs were much higher than that of a genetic risk score constructed using the same genetic susceptibility variants, 0.624 (0.574-0.674). The use of ethnically matched LRs is necessary for proper personal risk assessment. In conclusion, although LR-based integrated risk assessment for T2D still requires additional tests that evaluate other factors, such as risks involved in missing heritability, our results indicate the potential usability of LR-based assessment system and stress the importance of stratified epidemiological investigations in personalized medicine.
    Full-text · Article · Jul 2014 · Endocrine Journal
  • Koichi Nishitsuka · Hidetoshi Yamashita
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    ABSTRACT: Background and objective: To evaluate a novel surgical technique for IOL fixation using a newly designed suture thread inserter. Patients and methods: Scleral fixation of an IOL combined with 25-gauge vitrectomy was performed in 13 patients (eight aphakic eyes and five with IOL dislocation). Conjunctival peritomy was performed and scleral tunnels were created at the 2- and 8-o'clock positions. An infusion cannula was inserted through the inferotemporal sclera, and two cannulas were inserted through the scleral tunnels 1.5 or 2.0 mm posterior to the corneal limbus. After vitrectomy, the loop of the 10-0 polypropylene suture was inserted into the ports with a suture thread inserter. The haptics of the foldable IOL were sutured via the cow-hitch method. Haptic externalization was performed in eyes with IOL dislocation. After removing the infusion cannulas, the 10-0 polypropylene sutures were tied to scleral tunnels. Results: In all cases, the IOL was fixed stably and visual acuity was improved. There were no intraoperative or postoperative complications. Conclusion: Scleral IOL fixation with a suture thread inserter combined with 25-gauge vitrectomy appears to be safe and minimally invasive for aphakic eyes and cases of IOL dislocation. The thread inserter mitigates the risk of hemorrhage. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:xxx-xxx.].
    No preview · Article · Jun 2014 · Ophthalmic Surgery Lasers and Imaging Retina
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    ABSTRACT: The aim of this study was to examine the efficacy and surgical success rates of amniotic membrane (AM) transplantation performed for corneal perforation closure using a novel technique. This study included 6 eyes from 6 patients with corneal perforation who had received AM transplantation between May 2011 and April 2012. The AM was collected from human placenta shortly after cesarean section. In surgery, the AM was folded into pleats and used to plug the wound using 10-0 nylon suture. The wound was then covered with an AM seal. After reepithelialization and AM scarring, sutures were removed. All 6 patients had successful wound closure with 1 surgery. One patient underwent optical keratoplasty later, and 1 patient required combined preserved sclera transplantation. The absolute value of astigmatism decreased to <3.50 diopters (D) 3 months after surgery and to <3.00 D 6 months after surgery in patients with peripheral AM transplants. The visual acuity gradually improved over the first 3 months after surgery, and visual acuity gains were maintained at the 6-month postoperative mark. The AM transplantation procedure may be an effective option for treating corneal perforations when the wound is circular or irregular, except for incised wounds. Our "Pleats Fold" AM transplantation technique can achieve definite closure and effectively repair wounds of various sizes. Postoperative astigmatic values were acceptable. Therefore, we recommend this procedure for repairing lesions <3 mm in diameter that do not involve the central cornea and that are infection free.
    No preview · Article · Apr 2014 · Cornea
  • Tatsumi Moriya · Ryo Kawasaki · Hidetoshi Yamashita · Shigehiro Katayama

    No preview · Article · Apr 2014 · Nihon Naika Gakkai Zasshi
  • Koichi Nishitsuka · Hidetoshi Yamashita
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    ABSTRACT: The world's population is aging, and simultaneously, the prevalence of diabetes mellitus worldwide is rapidly increasing. Therefore, the clinical management of diabetic retinopathy and diabetic maculopathy in elderly patients with diabetes is increasingly becoming more important. Therefore, collaboration between ophthalmologists and physicians is mandatory. The international clinical diabetic retinopathy and macular edema disease severity scales are very useful for information sharing between ophthalmologists and diabetologists. This review describes a strategy to assess symptoms of diabetes, including the clinical course of retinopathy and maculopathy, pathological changes, and pathogenesis, as well as details an updated treatment modality. Elderly patients tend to present with multiple complications that should be considered by the management team.
    No preview · Article · Nov 2013 · Nippon rinsho. Japanese journal of clinical medicine
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    ABSTRACT: To report the findings of fine folds on the retina obtained by spectral-domain optical coherence tomography (OCT). A retrospective non-comparative case series; 26 eyes of diabetic macular edema (DME) patients who underwent vitrectomy were observed using three-dimensional (3D) images of OCT preoperatively and postoperatively. The specimens were investigated immunohistochemically. Using only tomography, non-tractional vitreoretinal interfaces were observed in 15 eyes and tractional vitreoretinal interfaces in the other 11 eyes. Using 3D imaging, we observed fine folds in 11 eyes among 15 cases showing non-tractional interfaces. Based on these findings, the state of the vitreoretinal interface was classified into 3 patterns. Group 1, both tomography and 3D imaging showed smooth retinal surfaces. Group 2, tomography showed a smooth retinal surface, but 3D imaging showed fine folds on the retina. Group 3, both tomography and 3D imaging showed a tractional vitreoretinal interface with an obvious epiretinal membrane and/or taut posterior vitreous cortex. The fine folds in group 2 disappeared and macular edema improved after inner limiting membrane (ILM) peeling, and the CRT of groups 2 and 3 reduced significantly. The fine folds were confirmed to involve the ILM because type IV collagen expression was detected in the surgically obtained specimens. We observed tangential fine folds of the ILM. These were detected by using only 3D imaging, and might be useful for investigating the optimal indication of vitrectomy for DME.
    No preview · Article · Oct 2013 · Japanese Journal of Ophthalmology
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    ABSTRACT: To describe the pathophysiological findings of a patient with pemphigus vulgaris (PV) showing giant conjunctival papillae. A 64-year-old man who had mucosal-dominant PV with giant conjunctival papillae, resembling those of vernal keratoconjunctivitis (VKC), underwent an ophthalmological workup. The clinical and pathological findings were investigated. Ophthalmic interventions were unable to provide the desired beneficial effects, and multiple excisions were necessary to remove the proliferative conjunctival lesions. Histopathological investigations of the excised tissues demonstrated acantholysis and a subconjunctival infiltration with numerous inflammatory cells such as lymphocytes, plasma cells, and neutrophils. However, in contrast to typical VKC, mast cells and eosinophils were rarely found in the subconjunctival tissues. Direct immunofluorescent staining showed a significant deposition of immunoglobulin G and complement component 3 in the epithelial intercellular substance, consistent with mucosal-dominant PV. Then, the patient was hospitalized because of oral erosion exacerbation and malnutrition. Because of the patient's declining general condition, we administered an increasing dose of a systemic steroid with an intravenous immunoglobulin, after which his ocular lesions and symptoms improved. The histological conjunctival papilla findings were quite different from those of VKC papillae. If PV causes a lesion in a patient, systemic immunosuppression might be more effective than topical ophthalmic treatment because of overall immunological involvement.
    Full-text · Article · Sep 2013 · Case Reports in Ophthalmology
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    ABSTRACT: OBJECTIVE To examine the interactive relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetic patients, and to elucidate the role of DR and microalbuminuria on the onset of macroalbuminuria and renal function decline.RESEARCH DESIGN AND METHODS We explored the effects of DR and microalbuminuria on the progression of DN from normoalbuminuria and low microalbuminuria (<150 mg/gCr) to macroalbuminuria or renal function decline in the Japan Diabetes Complications Study (JDCS), which is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification. Patients were divided into four groups according to presence or absence of DR and MA: normoalbuminuria without DR [NA(DR-)] (n = 773), normoalbuminuria with DR [NA(DR+)] (n = 279), microalbuminuria without DR [MA(DR-)] (n = 277), and microalbuminuria with DR [MA(DR+)] (n = 146). Basal urinary albumin-to-creatinine ratio and DR status were determined at baseline and followed for a median of 8.0 years.RESULTSAnnual incidence rates of macroalbuminuria were 1.6/1,000 person-years (9 incidences), 3.9/1,000 person-years (8 incidences), 18.4/1,000 person-years (34 incidences), and 22.1/1,000 person-years (22 incidences) in the four groups, respectively. Multivariate-adjusted hazard ratios of the progression to macroalbuminuria were 2.48 (95% CI 0.94-6.50; P = 0.07), 10.40 (4.91-22.03; P < 0.01), and 11.55 (5.24-25.45; P < 0.01) in NA(DR+), MA(DR-), and MA(DR+), respectively, in comparison with NA(DR-). Decline in estimated glomerular filtration rate (GFR) per year was two to three times faster in MA(DR+) (-1.92 mL/min/1.73 m(2)/year) than in the other groups.CONCLUSIONS In normo- and low microalbuminuric Japanese type 2 diabetic patients, presence of microalbuminuria at baseline was associated with higher risk of macroalbuminuria in 8 years. Patients with microalbuminuria and DR showed the fastest GFR decline. Albuminuria and DR should be considered as risk factors of renal prognosis in type 2 diabetic patients. An open sharing of information will benefit both ophthalmologists and diabetologists.
    Full-text · Article · Aug 2013 · Diabetes Care
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    ABSTRACT: The Japan Diabetes Complications Study, a randomised lifestyle intervention study of type 2 diabetes conducted at 59 institutes throughout Japan that enrolled 2033 eligible patients from January 1995 to March 1996, was directed at: (i) determining the incidence and progression rates of complications of diabetes; (ii) exploring clinical risk factors for complications of diabetes; and (iii) determining the association between lifestyle factors, including diet and physical activity, and complications of diabetes, in addition to comparing, in a randomised manner, the effects on type 2 diabetes of an extensive lifestyle intervention and conventional treatment. The protocol for the study originally specified four study populations according to primary outcomes, consisting of: (1) a macroangiopathy group (N = 1771); (ii) a nephropathy group (N = 1607); (iii) a retinopathy-incident group (N = 1221); and (iv) a retinopathy-progression group (N = 410). The primary outcomes were: (i) development of retinopathy; (ii) progression of retinopathy; (iii) development of overt nephropathy; and (iv) occurrence of macroangiopathic events including proven coronary heart disease and stroke. The study was originally planned to follow patients for 8 years, and an extended follow-up is ongoing. Information about primary outcomes, laboratory tests, and other clinical variables for each patient was collected at a central data centre through an annual report from each investigator. Additionally, extensive lifestyle surveys were conducted at baseline and 5 years after the beginning of the study intervention in both the intervention and conventional treatment groups. A description of the occurrence of complications of diabetes and of all-cause mortality, provided in this paper, demonstrated a clear gender-based difference in cardiovascular disease and all-cause mortality.
    Full-text · Article · Aug 2013 · International Journal of Epidemiology

Publication Stats

3k Citations
392.05 Total Impact Points

Institutions

  • 1999-2015
    • Yamagata University
      • • Department of Public Health
      • • Department of Ophthalmology and Visual Sciences
      • • School of Medicine
      Ямагата, Yamagata, Japan
  • 2011
    • Japan Society for the Promotion of Science
      Edo, Tōkyō, Japan
    • Kagoshima University
      • Department of Ophthalmology
      Kagosima, Kagoshima, Japan
  • 2003
    • Tokyo Medical University
      • Department of Ophthalmology
      Edo, Tōkyō, Japan
  • 2002-2003
    • Tokyo Women's Medical University
      • Department of Ophthalmology
      Tokyo, Tokyo-to, Japan
  • 1996-2000
    • The University of Tokyo
      • Faculty & Graduate School of Medicine
      Tōkyō, Japan
  • 1998
    • Japanese Foundation for Cancer Research
      Edo, Tōkyō, Japan
  • 1995
    • Ludwig Institute for Cancer Research Sweden
      Uppsala, Uppsala, Sweden
  • 1994
    • Tokyo Medical and Dental University
      Edo, Tōkyō, Japan