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EASD: Elevated Glucose Appears Years before Diabetes Diagnosis

Posted: Monday, September 26, 2011

In patients diagnosed with type 2 diabetes, elevations in blood levels of glucose and glycated hemoglobin (HbA1c) can be seen as much as 10 years prior to diagnosis.

Esther van 't Riet, PhD, from the Department of Epidemiology and Biostatistics at the VU University Medical Center in Amsterdam, the Netherlands, stated during a poster session, that after moderate increases, the levels rise rapidly during the few years leading up to the diagnosis, often with an increase in HbA1c preceding a rise in glucose.

Dr. van 't Riet and coworkers analyzed data from the Hoorn Study, a Dutch population-based cohort of people 50 to 75 years of age at baseline in 1989, with follow-up encounters in 1996 and 2000. The analysis consisted of 565 participants without diabetes at baseline.

At follow-up, incident diabetes was diagnosed according to World Health Organization/American Diabetes Association 2011 criteria of a fasting blood glucose of 126.1 mg/dL ( 7.0 mmol/L) or greater or a postload glucose of 200 mg/dL (11.1 mmol/L) or greater, and/or HbA1c of 6.5% or greater. Participants were categorized as no diabetes at baseline or follow-up, incident diabetes in 1996, or incident diabetes in 2000.

By 1996, 99 participants had developed incident diabetes and by 2000, 48 more had; 418 remained free of the disease. "Those who developed diabetes already had elevated levels of glucose and A1c in 1989. So up to 10 years before diagnosis, we already see an elevation of all 3 glycemic measures," Dr. van 't Riet reported. (The third measure is the postload glucose level, obtained 2 hours into an oral glucose tolerance test.)

"When we look at changes in time, we first compared those who never developed diabetes with those who had insulin diabetes in 1996. We see that all 3 glycemic measures show a steep increase from 1989 to 1996. After the diagnosis in 1996, they stabilize," she said.

Finally, the investigators compared people who never developed diabetes with those who developed diabetes in 2000. The increase in fasting glucose and postload glucose between 1989 and 1996 "is almost comparable for those who developed diabetes and those who never developed diabetes," Dr. van 't Riet reported, with no significant increase for either group. But after 1996, about 4 years before the diagnosis of diabetes, "a steep increase is observed, which was not seen in those who never developed diabetes."

The picture was somewhat different for HbA1c in people who were diagnosed with diabetes in 2000; it showed a significant increase between 1989 and 1996. "This might indicate that A1c increases earlier than glucose," she said.

In light of changes in diagnostic criteria for diabetes, the investigators performed further analyses on people with incident diabetes in 2000 who had elevated HbA1c but low glucose (n = 17) and in those with high glucose but normal HbA1c (n = 20).

"In those with diabetes based on high glucose, A1c levels tend to increase also. But in those with diabetes based on high A1c, glucose levels tend to stabilize in the follow-up period.... It might indicate that there are different developmental patterns according to the type of criteria you use," Dr. van 't Riet suggested.

Moderator Francisco Javier Novoa, MD, professor of endocrinology at Universidad de Las Palmas de Gran Canaria, stated that the only feasible intervention is lifestyle changes when rising blood glucose and HbA1c are detected in the absence of a diagnosis of diabetes.

Dr. Novoa added that metformin is his drug of choice for patients with diabetes for whom lifestyle changes do not produce sufficient results, but "I think there is no evidence" for using drugs before a diagnosis of diabetes. He said he would need to see further trial results before he would recommend drug therapy in the years leading up to a possible diagnosis.

Source:, European Association for the Study of Diabetes (EASD) 47th Annual Meeting: Abstract 335. Presented September 13, 2011.

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