Stepped Introduction Ex. 2





The prevalence of type 2 diabetes is rapidly increasing worldwide. The International Diabetes Federation (IDF) estimates that between 2003 and 2025, the worldwide prevalence of diabetes among persons aged 20 years and older will increase from 5.1% to 6.3%{Federation, 2003 #699}. 



For primary prevention, the identification of persons at high risk for developing diabetes is essential. Major variables predictive of the development of diabetes were plasma glucose at fasting{Dinneen, 1998 #2}{Chou, 1998 #455}, and postload {Edelstein, 1997 #401}{Chou, 1998 #455}, glycated hemoglobin(ref), late insulin response at postload{Nagi, 1995 #62} in addition to other risks such as obesity{Chou, 1998 #455}{Edelstein, 1997 #401}, and physical inactivity{Hu, 1999 #707}.14 Recently, triglycerides {Dotevall, 2004 #855}, liver enzymes {Wannamethee, 2005 #757; Sattar, 2004 #758}, white blood cell count {Vozarova, 2002 #515; Nakanishi, 2002 #516}, high blood pressure{Dotevall, 2004 #855}  and C-reactive protein have been reported to predict the development of type 2 diabetes.(Diab Med, modify!) 



Among these, fasiting plasma glucose (FPG) levels is less expensive, more convenient, and more reproducible than performing an oral glucose tolerance test [8]; consequently, FPG is recommended in the guideline published by the American Diabetes Association (ADA) as the preferred test for screening and diagnosing diabetes [9]. Recently, even FPG within normal range has been reported to be associated with a gradient risk of diabetes{Dinneen, 1998 #2}{Takahashi, 2001 #703}{Meigs, 2003 #523}{Tirosh, 2005 #742}. Based upon recently published data, the lower limit for 'impaired fasting glucose (IFG)' was reduced in the ADA guideline from a FPG level of 6.11 to 5.56 mmol/l [10]. 


新しいImpaired fasting glucoseの診断基準ではより多くの人が含まれてしまう。

The revised criteria of IFG naturally cost of classifying more individuals as having IFG.{Vaccaro, 2005 #1038}{Schriger, 2004 #1045; Davidson, 2003 #1044} and majority of individuals with IFG will not develop diabetes. A lower threshold for IFG will produce a more heterogenous population with regard to diabetes risk than a higher classical threshold, because the lower threshold  inveitably has higher sensitivity at the expense of lower specificity for predicting future diabetes.(DC comment Reviwer 3 No 7) Thus, use of additional tests to better define diabetes risk when the lower IFG threshold is used, may be even more important than with the higher IFG threshhold. 



Recently, the autors have reported the combined usefulness of one fasting plasma glucose and a hemoglobin A1c level  at baseline to predict the progression to diabetes in a Japanese large population {Diab Med, Inoue}. Measuring FPG has been recommended and widely accepted as a  screening tool for diabetes{WHO, 2003 #818; American Diabetes, 2006 #826}, which promted us the following reseach question; can the combination of twice FPG measurements effectively predict individuals who develop diabetes more than once FPG? Using this cohort data, the authors had the opportunity to address the likelihood of this possibility, since some subjects had more than one FPG measurement during the baseline period (DC comment Reviewer 3 No 2) and subsequently test the optimum cut-off point for twice FPG to predict diabetes. So far, few is known about the clinical significance of twice FPG measurements in identifying individuals with future risk of diabetes. これまでのところ、2回空腹時血糖測定の発症予測における有用性は調べられていない。


In this study, therefore, we compared the incidence of diabetes, with adjustments for diabetic risk factors,among subjects classified into four groups according to the results of FPG measured twice. よって我々は、危険因子の調整をしたうえで2回空腹時血糖測定の結果で4群に分けた対象者で、糖尿病発症率を比較した。