title: Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes: a prospective cohort study.
abstract: BACKGROUND
  Data are scarce for the lifetime risk of developing impaired glucose metabolism, including prediabetes, as are data for the risk of eventual progression from prediabetes to diabetes and for initiation of insulin treatment in previously untreated patients with diabetes. We aimed to calculate the lifetime risk of the full range of glucose impairments, from normoglycaemia to prediabetes, type 2 diabetes, and eventual insulin use.
  
  
  METHODS
  In this prospective population-based cohort analysis, we used data from the population-based Rotterdam Study. We identified diagnostic events by use of general practitioners' records, hospital discharge letters, pharmacy dispensing data, and serum fasting glucose measurements taken at the study centre (Rotterdam, Netherlands) visits. Normoglycaemia, prediabetes, and diabetes were defined on the basis of WHO criteria for fasting glucose (normoglycaemia: ≤6·0 mmol/L; prediabetes: >6·0 mmol/L and <7·0 mmol/L; and diabetes ≥7·0 mmol/L or use of glucose-lowering drug). We calculated lifetime risk using a modified version of survival analysis adjusted for the competing risk of death. We also estimated the lifetime risk of progression from prediabetes to overt diabetes and from diabetes free of insulin treatment to insulin use. Additionally, we calculated years lived with healthy glucose metabolism.
  
  
  RESULTS
  We used data from 10 050 participants from the Rotterdam Study. During a follow-up of up to 14·7 years (between April 1, 1997, and Jan 1, 2012), 1148 participants developed prediabetes, 828 developed diabetes, and 237 started insulin treatment. At age 45 years, the remaining lifetime risk was 48·7% (95% CI 46·2-51·3) for prediabetes, 31·3% (29·3-33·3) for diabetes, and 9·1% (7·8-10·3) for insulin use. In individuals aged 45 years, the lifetime risk to progress from prediabetes to diabetes was 74·0% (95% CI 67·6-80·5), and 49·1% (38·2-60·0) of the individuals with overt diabetes at this age started insulin treatment. The lifetime risks attenuated with advancing age, but increased with increasing BMI and waist circumference. On average, individuals with severe obesity lived 10 fewer years without glucose impairment compared with normal-weight individuals.
  
  
  CONCLUSIONS
  Impaired glucose metabolism is a substantial burden on population health, and our findings emphasise the need for more effective prevention strategies, which should be implemented as soon in a person's life as possible. The substantial lifetime risk of prediabetes and diabetes in lean individuals also supports risk factor control in non-obese individuals.
  
  
  BACKGROUND
  Erasmus MC and Erasmus University Rotterdam; Netherlands Organisation for Scientific Research; Netherlands Organisation for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomics Initiative; Netherlands Ministry of Education, Culture and Science; Netherlands Ministry of Health, Welfare and Sports; European Commission; and Municipality of Rotterdam.
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Symen
authors.initials: S
authors.lastname: Ligthart
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Thijs T W
authors.initials: TT
authors.lastname: van Herpt
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Cardiology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Maarten J G
authors.initials: MJ
authors.lastname: Leening
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kavousi
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands; Inspectorate for Health Care, Utrecht, Netherlands.
authors.forename: Bruno H C
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Mandy
authors.initials: M
authors.lastname: van Hoek
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands. Electronic address: a.dehghan@erasmusmc.nl.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000453:epidemiology* / Q000378:metabolism; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D005947:Glucose