OBJECTIVE -The aim of this study is to clarify the conflicting results of the ⑀2/⑀3/⑀4 APOE polymorphism as a risk factor on diabetic nephropathy by a cohort study. RESEARCH DESIGN AND METHODS-A total of 429 Japanese subjects with type 2 diabetes and with normoalbuminuria (n ϭ 299) or with microalbuminuria (n ϭ 130) were enrolled in a prospective observational follow-up study during 1995-1998 and followed until 2001 (for at least 3 years). The endpoint was the occurrence of a renal event defined as the progression to a higher stage of diabetic nephropathy.RESULTS -During the study (the mean follow-up period: 4.4 Ϯ 1.0 years), 31 of 429 subjects progressed: 21 from normoalbuminuria to microalbuminuria and 10 from microalbuminuria to overt proteinuria. The allele frequency of the APOE polymorphism was significantly different between the progressors and the nonprogressors. Eight of 42 ⑀2 carriers (19%) progressed, whereas 23 of 387 noncarriers (6%) progressed with a relative risk of 3.2 (95% CI 1.5-6.7). When subjects were stratified by renal status at baseline, each relative risk for the progression in the ⑀2 carriers was 2.7 (0.99 -7.4) in those with normoalbuminuria and 4.2 (1.3-13.3) in those with microalbuminuria. Furthermore, when analyzed only in subjects with normoalbuminuria and short duration of diabetes (Ͻ15 years) at baseline, the risk in the ⑀2 carriers became higher to 3.2 (1.2-8.8).CONCLUSIONS -Our follow-up study indicates that the ⑀2 allele of the APOE polymorphism is a prognostic risk factor for both the onset and the progression of diabetic nephropathy in Japanese type 2 diabetes. Diabetes Care 26:2416 -2420, 2003D iabetic nephropathy (DN) associated with type 2 diabetes is a leading cause of end-stage renal disease (ESRD) in Japan and the U.S. (1,2). Although long-standing hyperglycemia is an important risk factor for the development of DN, epidemiologic and family studies suggest that genetic susceptibility to this complication is also required (3). The abnormalities of lipid metabolism have been proposed as one plausible mechanism in the pathogenesis of the development of DN (4). Thus, the genes encoding components of this pathway that regulate lipid metabolism can be considered as candidate genes susceptible to DN (5).Apolipoprotein E (apoE) is a 299-amino acid glycoprotein that plays a central role in lipid metabolism. ApoE is well known to consist of three common isoforms (E2, E3, E4) encoded by three alleles (⑀2, ⑀3, ⑀4) in exon 4 of the apoE gene (APOE) (6). The lipid profiles or atherogenic factors are, in part, determined by this genetic variation of APOE (6). Carriers of apoE4 have higher plasma levels of total cholesterol and low-density lipoprotein cholesterol than carriers of apoE2 or apoE3 homozygotes (6). On the other hand, the binding of apoE2 to lipoprotein receptors is defective in comparison with that of E3 or E4 and results in delayed clearance of triglyceride (TG)-rich lipoprotein.Recently, this ⑀2/⑀3/⑀4 polymorphism of APOE has been investigated for the association with DN ...

tion. Magnetic resonance imaging revealed bilateral temporal lesions (Figure, B). The lesions slowly expanded to the parieto-occipital region. He developed akinetic mutism and became bedridden. During this course, patient 2 experienced a sudden cardiac arrest in his early 50s. He died of congestive heart failure 2 years later. These patients grew up separately without knowing each other. Their mother and another sibling did not have diabetes, deafness, short stature, or cardiac disease.

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Glycated albumin (GA) is considered a more reliable marker than glycated hemoglobin (HbA1c) for monitoring glycemic control, particularly in diabetic hemodialysis patients. We investigated the associations of GA, HbA1c, and random serum glucose levels with survival, and evaluated possible targets for improving survival in diabetic hemodialysis patients. In this prospective, longitudinal, observational study, we enrolled 90 diabetic hemodialysis patients across six dialysis centers in Japan. The median duration of follow-up was 36.0 months (mean follow-up, 29.8 months; range, 3-36 months). There were 11 deaths during the observation period. GA was a significant predictor for mortality (hazard ratio, 1.143 per 1% increase in GA; 95% confidence interval, 1.011-1.292; P = 0.033), whereas HbA1c and random glucose levels were not predictors for mortality. Receiver operating characteristics curve analysis showed that the cutoff value of GA for predicting the risk of mortality was 25%. In the Kaplan-Meier analysis, the cumulative survival rate was significantly greater in patients with GA ≤ 25% than in patients with GA >25%. GA predicted the risk of all-cause and cardiovascular mortality in diabetic hemodialysis patients. Our results suggest that GA ≤ 25% is an appropriate target for improving survival in diabetic hemodialysis patients.

Objective The Mini-Z 2.0 is a new, simple, and nonproprietary tool for assessing physician well-being and burnout. To date, a non-English version of the Mini-Z 2.0 survey has not been validated. Therefore, we aimed to develop a Japanese version of the Mini-Z 2.0 and to evaluate its validity and reliability using survey data from physicians affiliated with an internal medicine academic society. Methods The Mini-Z 2.0 survey was translated into Japanese using a forward-backward translation method. The participants belonged to the American College of Physicians' Japan Chapter. The translated version of the Mini-Z 2.0 survey was distributed to participants using an electronic mailing list. Convergent validity was assessed between burnout and other items using Pearson's product-moment statistic. Structural validity was evaluated using an exploratory factor analysis and confirmatory factor analysis, and reliability was assessed using internal consistency. Results Of the 1,255 physicians and medical residents contacted, 283 responded (22.5%). Burnout was present in 34.6% of the participants, with 48.8% reporting high stress levels. Convergent validity was demonstrated, with satisfactory correlations between burnout and satisfaction, value alignment, work control, and stress. An exploratory factor analysis identified two factors (i.e. Well-Being and Relationships and Work-Related Stressors); however, the three models evaluated using the confirmatory factor analysis revealed a poor fit. Cronbach's alpha for the sample was 0.80. ConclusionThe Japanese version of the Mini-Z 2.0 demonstrated good internal consistency and convergent validity. Despite its inadequate structural validity, it can be used to measure physician well-being and related workplace conditions in Japan.