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British Medical Journal

Clinical Articles, Lead Article

Pre-diabetes increases likelihood of stroke

Millions of people suffering from pre-diabetes may be at a higher risk of stroke, according to a study published recently on

A team of researchers from the University of California looked at the relationship between pre-diabetes and risk of stroke whilst taking into consideration other cardiovascular risk factors such as an unhealthy weight and lifestyle. The authors analysed the results of 15 studies involving 760,925 participants.

They found that the relationship between pre-diabetes and risk of stroke appears to depend on the definition of pre-diabetes.
  Pre-diabetes is generally defined as impaired fasting glucose (raised blood glucose levels after a 12-hour fast). A range of 70.2 to 100 mg/dl is normal, while a level of 100 to 126 mg/dl is considered a sign of pre-diabetes.

The researchers found that pre-diabetes based on the 1997 American Diabetes Association (ADA) definition of 110 to 125 mg/dl carried a 21% higher chance of stroke.
 However, in 2003 the ADA redefined pre-diabetes as an impaired fasting glucose of 100 to 125 mg/dl and no risk was found in studies using this current, less stringent definition.

Urine SampleThis suggests that there may be a ‘threshold effect’ with regard to the relationship between impaired fasting glucose and future stroke risk to the extent that the risk of a stroke only begins to rise at or above a fasting glucose level of 110 mg/dL.

The authors stress the possibility that some other confounding factor may explain these results, and that the quality of evidence was variable. 

The authors conclude that people with pre-diabetes (with a fasting glucose 110 to 125 mg/dl) were at a “modestly higher risk of future stroke”. They do add however that those with the 2003 ADA’s definition (100 to 125 mg/dl) do not have an increased risk of stroke.

The authors suggest that those with pre-diabetes “should be aware that they are at increased risk of future stroke” and that the condition is associated with the presence of one or more other cardiovascular risk factors. They recommend that weight be kept under control and that healthy lifestyle changes should be adopted to decrease this risk.

In an accompanying editorial,2 Dr Jonathan Treadwell, from the ECRI Institute in Philadelphia, suggests that due to unmeasured factors such as age, obesity and hypertension, it is impossible to know the exact size of the association between pre-diabetes and stroke. He also argues that Lee’s study only takes into consideration two of the overall four categories that define pre-diabetes.

He concludes that it is “too simple” to categorise whether someone has diabetes, pre-diabetes, and not diabetes, but commends Lee’s study for thinking “outside of the box of what meta-analysis can achieve” adding that the “clinical question must drive the research methods”.


1. Lee M, Saver JL, Hong KS, Song S, Chang KH, Ovbiagele B. Effect of pre-diabetes on future risk of stroke: meta-analysis. BMJ 2012;344:e3564. doi: 10.1136/bmj.e3564

2. Treadwell JR. Pre-diabetes as a contributor to stroke. BMJ 2012;344:e3285. doi: 10.1136/bmj.e3285

Published on: June 25, 2012

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