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28-02-2011 | Diabetes | Article

High Type 2 diabetes prevalence in obese people could be evolutionary


Free abstract

MedWire News: An evolutionary mutation in the CMP-N-acetylneuraminic acid hydroxylase (CMAH) gene may be at least partly responsible for the high prevalence of Type 2 diabetes seen in obese humans, show study results.

Using a mouse model, Jane Kim (University of California, San Diego, USA) and colleagues show that Cmah-null mice, with a genetic mutation engineered to mimic the one seen in humans, have a significantly worse response to a high-fat diet than mice with a normal Cmah gene (controls).

The Cmah-null mice developed pancreatic β-cell failure, including a 65% reduction in pancreatic islet size and area, and a 50% decrease in functional pancreatic islet numbers, in addition to the insulin resistance also displayed by the control mice that consumed the same diet. Mice with the Cmah-null mutation also had a 40% reduction in response to insulin secretagogues in vivo in comparison to control mice.

Most mammals, including Old World primates, are able to produce two types of sialic acid: N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). Conversely, humans are unable to produce Neu5Gc due to the CMAH mutation, note the researchers.

They believe these results may explain why obese humans are prone to developing Type 2 diabetes. However, they caution that mammalian models may not accurately reflect the nature of the problem seen in humans.

"Our study for the first time links human-specific sialic acid changes to insulin and glucose metabolism and therefore opens up a new perspective in understanding the causes of diabetes," said Kim.

Writing in the FASEB Journal, the team concludes: "Given the high prevalence of Type 2 diabetes and its comorbidities, it is clear that further study is necessary to understand how the evolutionary loss of CMAH and changes in sialic acid composition affect the pathogenesis and prevention of metabolic disease in humans."

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Helen Albert

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