The Detection Of Metabolic Changes Several Years Prior To The Diagnosis Of Diabetes Could Help Screening And Prevention (WHITEHALL II Study)

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Main Category: Diabetes
Article Date: 08 Jun 2009 - 16:00 PDT

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The results of the WHITEHALL II study are published in an article Online First and in a future edition of The Lancet. The findings are presented at the same time at the American Association of Diabetes meeting in New Orleans, USA. The study was funded by the UK Medical Research Council, as well as other organisations. They indicate that insulin sensitivity and blood glucose trends are altered a few years before the start of type 2 diabetes. Onset could be considerably postponed if people could identify the early stages of disease progress.

Dr Adam Tabák, of the University College London, and Dr Daniel Witte, of the University College London, UK, and the Steno Diabetes Center, Gentofte, Denmark, and collaborators studied 6,538 UK civil servants. None of them had type 2 diabetes at the beginning of the study, 71 percent were male and 91 percent were white. After an average monitoring of about ten years, 505 cases of diabetes were diagnosed. The researchers then evaluated data by looking back at the trajectories of blood glucose of pre-meal and after standard glucose test. They looked at insulin sensitivity which is the ability of tissues such as muscle and liver to respond sufficiently to insulin. They also assessed the function of the insulin-producing β-cells of the pancreas.

The results indicate that the metabolic changes followed linear trends in the participants without diabetes. The insulin secretion did not change during follow-up. In the participants that developed diabetes, a linear increase was seen in fasting glucose, followed by a sharp increase that started three years prior to the diagnosis of diabetes. In addition, post-meal glucose levels also showed a rapid increase, initiating three years before diagnosis. For the period of the five years prior to diagnosis, insulin sensitivity decreased abruptly. Between years four and three prior to diagnosis, β-cell function increased, as the participant´s body tried to compensate for the raised glucose levels. Then it decreased in the three years up to diagnosis.

The researchers explain: "The description of biomarker trajectories leading to diabetes diagnosis could contribute to future attempts of building more accurate risk-prediction models that use the wealth of repeated measures available for patients through regular check-ups. These models might give an indication of which trajectory best describes and individual's results. We anticipate that these models will have a better prediction than those that use only the most recent glucose measurements."

They write in conclusion: "Our findings show various opportunities for screening and prevention. Although most prevention studies focused on prediabetic people, our findings suggest that people with prediabetes are already on the steep part of the glucose trajectory. We hypothesise that prevention would be more effective before this unstable period, but more research is needed to successfully identify people at this stage of disease development. If a person could be kept on linear part of the fasting glucose (or post-load glucose) trajectory, the onset of diabetes might be substantially delayed. Further research is needed to confirm or refute these hypotheses."

In a supplementary note, Dr David Matthews and Dr Jonathan Levy, of the Oxford Centre for Diabetes Endocrinology and Metabolism, and of the University of Oxford, UK, remark: "Does this mean that we find those who are about to get diabetes - perhaps even three or four years ahead? We fear not. The sensitivity and specificity of the forward predictions would be poor...Now the hunt has to be intensified for the pathology that causes the decompensation that precipitates diabetes."

"Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study"
Adam G Tabák, Markus Jokela, Tasnime N Akbaraly, Eric J Brunner, Mika Kivimäki, Daniel R Witte
DOI: 10.1016/S0140-6736(09)60619-X
thelancet

Written by Stephanie Brunner (B.A.)
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