title: Screening for pre-diabetes to predict future diabetes using various cut-off points for HbA(1c)  and impaired fasting glucose: the Toranomon Hospital Health Management Center Study 4 (TOPICS 4).
abstract: OBJECTIVE
  To evaluate various screening criteria for pre-diabetes to identify which combination of impaired fasting glucose and elevated HbA(1c) values performs most effectively in predicting future diabetes in a large cohort of Japanese individuals.
  
  
  METHODS
  The study included 4670 men and 1571 women without diabetes (diabetes: fasting plasma glucose ≥ 7.0 mmol/l, HbA(1c) ≥ 48 mmol/mol (≥ 6.5%), or self-reported clinician-diagnosed diabetes). Pre-diabetes was diagnosed by a combination of impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/l or 6.1-6.9 mmol/l) and elevated HbA(1c) [39-46 mmol/mol (5.7-6.4%) or 42-46 mmol/mol (6.0-6.4%)].
  
  
  RESULTS
  During a 5-year follow-up, 338 incident cases of diabetes occurred. The combination of HbA(1c) 39-46 mmol/mol (5.7-6.4%) and fasting plasma glucose 5.6-6.9 mmol/l yielded the highest sensitivity (86%) and generated a large population-attributable per cent risk (78%) for predicting development of diabetes. Among individuals classified as having pre-diabetes by any of the four combined criteria, 20.5-32.0% reverted to the normoglycaemic state as having neither elevated HbA(1c) nor impaired fasting glucose at the last follow-up examination. At 5.6 years after the baseline examination, however, pre-diabetic individuals who fulfilled both HbA(1c) 42-46 mmol/mol (6.0-6.4%) and fasting plasma glucose 6.1-6.9 mmol/l had a 100% cumulative risk of developing diabetes.
  
  
  CONCLUSIONS
  The combination of HbA(1c) 39-46 mmol/mol (5.7-6.4%) and fasting plasma glucose 5.6-6.9 mmol/l would have the best performance in reducing the likelihood of missing future cases of diabetes. Identifying pre-diabetic individuals who strictly fulfil HbA(1c) 42-46 mmol/mol (6.0-6.4%) and fasting plasma glucose 6.1-6.9 mmol/l would predict definite progression to diabetes.
authors.affiliation: Department of Internal Medicine, University of Tsukuba Institute of Clinical Medicine, Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Heianza
authors.forename: Y
authors.initials: Y
authors.lastname: Arase
authors.forename: K
authors.initials: K
authors.lastname: Fujihara
authors.forename: H
authors.initials: H
authors.lastname: Tsuji
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: S D
authors.initials: SD
authors.lastname: Hsieh
authors.forename: S
authors.initials: S
authors.lastname: Kodama
authors.forename: H
authors.initials: H
authors.lastname: Shimano
authors.forename: N
authors.initials: N
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Hara
authors.forename: H
authors.initials: H
authors.lastname: Sone
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000453:epidemiology*; D005215:Fasting / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D015994:Incidence; D007564:Japan; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood* / Q000145:classification / Q000175:diagnosis*; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin