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Metabolic changes occur years before the onset of diabetes

Study suggests new screening and prevention opportunities

OnMedica Staff

Tuesday, 09 June 2009

Metabolic changes leading to diabetes occur several years before the onset of type 2 diabetes - giving new screening opportunities.

These are the findings of a Whitehall II study, reported in an article on Online First and in an upcoming edition of the Lancet, and presented at the American Association of Diabetes meeting in New Orleans, USA.

Blood glucose trends and insulin sensitivity change several years before onset of type 2 diabetes. If people can be successfully identified in these early stages of disease development, onset could be substantially delayed, explained researchers Dr Adam Tabák, of the University College London, UK, and Dr Daniel Witte, University College London, UK and Steno Diabetes Center, Gentofte, Denmark, and colleagues.

The team looked at 6538 UK civil servants (71% male and 91% white) without type 2 diabetes at the start of the study. During a median follow-up of almost ten years, 505 cases of diabetes were diagnosed. The authors then assessed retrospective trajectories of blood glucose both pre-meal (fasting) and after a standard glucose test, insulin sensitivity (the capacity of tissues such as muscle and liver to adequately respond to insulin), and the function of the insulin-producing β-cells of the pancreas.

The researcher showed that, in the participants without diabetes, the metabolic changes followed linear trends, except for insulin secretion that did not change during follow-up. In the diabetic group, a linear increase was seen in fasting glucose, followed by a steep increase starting three years before diagnosis of diabetes. Post-meal glucose levels also showed a rapid increase starting three years before diagnosis. Insulin sensitivity decreased steeply during the five years prior to diagnosis. Finally, β-cell function increased between years four and three prior to diagnosis (as the participant’s body tried to compensate for the raised glucose levels), but then decreased in the three years up to diagnosis.

The authors say: “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 an individual’s results. We anticipate that these models will have a better prediction than those that use only the most recent glucose measurements.”

They concluded that their findings showed opportunities for screening and prevention.

“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.”

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