title: Patterns of obesity development before the diagnosis of type 2 diabetes: the Whitehall II cohort study.
abstract: BACKGROUND
  Patients with type 2 diabetes vary greatly with respect to degree of obesity at time of diagnosis. To address the heterogeneity of type 2 diabetes, we characterised patterns of change in body mass index (BMI) and other cardiometabolic risk factors before type 2 diabetes diagnosis.
  
  
  RESULTS
  We studied 6,705 participants from the Whitehall II study, an observational prospective cohort study of civil servants based in London. White men and women, initially free of diabetes, were followed with 5-yearly clinical examinations from 1991-2009 for a median of 14.1 years (interquartile range [IQR]: 8.7-16.2 years). Type 2 diabetes developed in 645 (1,209 person-examinations) and 6,060 remained free of diabetes during follow-up (14,060 person-examinations). Latent class trajectory analysis of incident diabetes cases was used to identify patterns of pre-disease BMI. Associated trajectories of cardiometabolic risk factors were studied using adjusted mixed-effects models. Three patterns of BMI changes were identified. Most participants belonged to the "stable overweight" group (n = 604, 94%) with a relatively constant BMI level within the overweight category throughout follow-up. They experienced slightly worsening of beta cell function and insulin sensitivity from 5 years prior to diagnosis. A small group of "progressive weight gainers" (n = 15) exhibited a pattern of consistent weight gain before diagnosis. Linear increases in blood pressure and an exponential increase in insulin resistance a few years before diagnosis accompanied the weight gain. The "persistently obese" (n = 26) were severely obese throughout the whole 18 years before diabetes diagnosis. They experienced an initial beta cell compensation followed by loss of beta cell function, whereas insulin sensitivity was relatively stable. Since the generalizability of these findings is limited, the results need confirmation in other study populations.
  
  
  CONCLUSIONS
  Three patterns of obesity changes prior to diabetes diagnosis were accompanied by distinct trajectories of insulin resistance and other cardiometabolic risk factors in a white, British population. While these results should be verified independently, the great majority of patients had modest weight gain prior to diagnosis. These results suggest that strategies focusing on small weight reductions for the entire population may be more beneficial than predominantly focusing on weight loss for high-risk individuals.
authors: Steno Diabetes Center, Gentofte, Denmark.
authors: Dorte
authors: D
authors: Vistisen
authors: Centre de Recherche Public de la Santé, Strassen, Luxembourg.
authors: Daniel R
authors: DR
authors: Witte
authors: Department of Epidemiology and Public Health, University College London, London, United Kingdom ; 1st Department of Medicine, Semmelweis University, Faculty of Medicine, Budapest, Hungary.
authors: Adam G
authors: AG
authors: Tabák
authors: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors: Christian
authors: C
authors: Herder
authors: Department of Epidemiology and Public Health, University College London, London, United Kingdom.
authors: Eric J
authors: EJ
authors: Brunner
authors: Department of Epidemiology and Public Health, University College London, London, United Kingdom.
authors: Mika
authors: M
authors: Kivimäki
authors: Steno Diabetes Center, Gentofte, Denmark.
authors: Kristine
authors: K
authors: Færch
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism; D016014:Linear Models; D008055:Lipids / Q000097:blood; D008131:London / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000503:physiopathology; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D015430:Weight Gain; D044465:White People
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids