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Insulin Changes Occur Years Before Diabetes

Study Reveals Timeline of Prediabetes

By Salynn Boyles
WebMD Health News

Reviewed By Louise Chang, MD

June 9, 2009 -- Evidence of insulin resistance and changes in blood sugar linked to type 2 diabetes can be measured more than a decade before the disease occurs, new research confirms.

The findings suggest that diabetes prevention efforts that focus on people with prediabetes may come too late to make a big difference.

The findings were presented today at the 69th Scientific Sessions of the American Diabetes Association in New Orleans, and they also appear in the latest online issue of the journal The Lancet.

Researchers followed more than 6,500 British civil servants without diabetes for up to 13 years, during which time they repeatedly measured insulin sensitivity and fasting and non-fasting glucose levels.

During an average follow-up of 10 years, 505 of the study participants developed type 2 diabetes.

The study showed a steady upward trajectory in metabolic changes in participants who did not develop diabetes. In contrast, these changes tended to occur at different periods in those who did go on to have diabetes, and these changes were often abrupt.

Timeline to Type 2 Diabetes

Specifically, the findings revealed:

  • A steady trend in fasting glucose as early as 13 years prior to the diagnosis of type 2 diabetes, with fasting glucose levels rising rapidly three years before diagnosis
  • Glucose levels after eating (post-meal glucose) began to increase rapidly starting three years prior to diagnosis
  • Insulin sensitivity began to decline steeply five years before diagnosis
  • Beta-cell function -- a measure of insulin production -- began to increase three to four years prior to diagnosis, as the pancreas tried to compensate for increases in blood glucose by producing more insulin. Insulin production dropped precipitously in the three years prior to a diagnosis of type 2 diabetes.

"The main addition of this study is that it shows for the first time a clear picture of the timeline to diabetes," study co-author Daniel R. Witte, MD, of the University College London tells WebMD.

Witte says the timeline suggests three distinct phases in the progression to diabetes, which may require different disease prevention strategies.

During the first phase, which occurs six or more years before diagnosis, glucose levels remain relatively stable but insulin resistance increases along with insulin secretion.

"This is the time when relatively straightforward lifestyle changes, like increasing physical activity, changing diet, and reducing obesity, could have the biggest impact," he says.

The second phase of progression to disease is characterized by increased beta-cell activity as the pancreas produces more insulin to compensate for insulin resistance.

Witte says prevention efforts during this period may require more aggressive lifestyle intervention along with blood-sugar regulating medications like metformin.

During the final phase toward progression, which Witte refers to as the unstable phase, insulin production drops and blood glucose levels rise dramatically and rapidly.

The study suggests that people who are generally considered to have prediabetes are in this final phase or close to it.

"We hypothesize that prevention would be more effective before this unstable period, but more research is needed to identify people at this stage of disease development."

Early Intervention Is Key

Diabetes specialist Sue Kirkman, MD, tells WebMD that the research confirms that the progression to diabetes occurs over many years and not just a few.

Kirkman serves as vice president of clinical affairs for the American Diabetes Association.

"The earlier we can identify people at risk and intervene, the better off they are likely to be," she says.

But the new study may not help find at-risk patients any earlier, an accompanying editorial in The Lancet suggests.

David Matthews, MD, and Jonathan Levy, MD, of the U.K.'s Oxford Center for Diabetes write that the prediction model is not specific or sensitive enough to identify patients years before they have clinically recognized disease.

"Does this mean that we can find those who are about to get diabetes -- perhaps even 3 or 4 years ahead?" We fear not," they write. "... However, we might at last begin to use insulin concentrations interpreted into beta-cell function and insulin resistance as another marker of risk -- and we know that we have proven advice and therapies that we can give."

SOURCES: Tabak, A.G., The Lancet, June 8, 2009; online edition. Daniel R. Witte, MD, department of epidemiology and public health, University College London, England. Sue Kirkman, MD, vice president of clinical affairs, American Diabetes Association.

©2009 WebMD, LLC. All Rights Reserved.





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