It is a common notion that type 2 diabetes is precipitated by substantial progressive weight gain, but a study published this week in PLOS Medicine suggests that this might not be true.
Dorte Vistisen and Kristine Færch, from the Steno Diabetes Center in Gentofte, Denmark, and colleagues analyzed data from participants of the Whitehall II cohort, a group of London-based civil servants who have been followed for more than a decade, to see what changes in body weight and other parameters had occurred in people in the years before they were diagnosed with diabetes.
6,705 participants were free of diabetes when they entered the study and are included in the analysis here. They were tested for diabetes every 5 years, and 645 of them were subsequently diagnosed with the disease. Going back to measurements of body mass index (or BMI, calculated using height and weight) which were recorded regularly, the researchers used a statistical method to identify patterns of change in BMI among individuals who went on to develop diabetes.
They identified three groups: by far the largest (comprising 606 individuals) were "stably overweight", and showed little change in their BMI over the years before they were diagnosed with diabetes. A second, much smaller group (15 participants) had gained weight continuously in the years before diagnosis. The remaining 26 participants were persistently obese for the entire time they participated in the study, in some cases for 18 years before they developed diabetes.
Because the three distinct patterns of obesity development were accompanied by different changes over time in insulin resistance and other risk factors for heart disease and diabetes, the authors conclude that "type 2 diabetes is a not a single disease entity, but rather a heterogeneous disease with different pathophysiological pathways depending on the level and development of obesity."
This study is the first one to apply this methodology to the question of how weight changes relate to the development of diabetes, and it used data from a homogeneous group of all-white civil servants. Before drawing firm conclusions on the process of diabetes development, it will be important to confirm the results in additional and more diverse populations.
Nonetheless, the results are provocative and should stimulate debate on how best to identify people at risk for diabetes and how to prevent the disease or delay its onset. The authors 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."
Funding: The Whitehall II study is supported by the following bodies: Medical Research Council (K013351), Economic and Social Research Council (ESRC), British Heart Foundation, Health and Safety Executive, and Department of Health (UK), National Heart Lung and Blood Institute (HL36310), National Institute on Aging (AG13196), Agency for Health Care Policy Research (HS06516), and The John D and Catherine T MacArthur Foundation (USA). MK is supported by a professorial fellowship from the ESRC. Serum adiponectin and IL-1Ra was measured at the German Diabetes Center, which is funded by the German Federal Ministry of Health and the Ministry of School, Science and Research of the State of North-Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.). AGT is supported by TA´MOP 4.2.4.A/1-11-1-2012-0001 National Excellence Program - research fellowship co-financed by the European Union and the European Social Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: Steno Diabetes Center A/S receives part of its core funding from unrestricted grants from the Novo Nordisk Foundation and Novo Nordisk A/S. KF and DV are employed by Steno Diabetes Center A/S, a research hospital working in the Danish National Health Service and owned by Novo Nordisk A/S. KF, DV, and DRW own shares in Novo Nordisk A/S.
Citation: Vistisen D, Witte DR, Taba´k AG, Herder C, Brunner EJ, et al. (2014) Patterns of Obesity Development before the Diagnosis of Type 2 Diabetes: The Whitehall II Cohort Study. PLoS Med 11(2): e1001602. doi:10.1371/journal.pmed.1001602
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