Patients who have been diagnosed with Type 2 diabetes can demonstrate elevated levels of glucose and glycated hemoglobin (HbA1c) even 10 years before their actual diagnosis, according to Esther van’t Riet, Ph.D., with the Department of Epidemiology and Biostatistics at VU University Medical Center in Amsterdam. Dr. van’t Riet presented the information at a poster session at the 47th annual meeting of the European Association for the Study of Diabetes (EASD). According to Dr. van’t Riet, individuals demonstrate moderate increases and then rapid increases in the few years prior to the diagnosis of diabetes, with increases in Hba1c often preceding elevated glucose.

Dr. van’t Riet and her research team used data from the Hoorn Study, a cohort of 565 Dutch participants, aged 50 to 75 at baseline in 1989 and with follow-ups in 1996 and 2000. None of the 565 participants had been diagnosed with diabetes at the beginning of the study.

At follow-up meetings, incident diabetes was diagnosed with the World Health Organization and American Diabetes Association’s 2011 criteria for the disease: fasting blood glucose levels of 7.0 mmol/L (126.1 mg/dL) or greater, or post-load glucose levels of 11.1 mmol/L (200mg/dL) or higher; and/or HbA1c levels of 6.5% or higher. Participants were categorized according to the status of their development of diabetes at baseline and follow-up.

At the 1996 follow-up, 99 of the study participants had developed incident diabetes; by 2000, an additional 48 had developed the disease. At the 2000 follow-up, 418 participants had still not developed diabetes. According to van’t Riet, the development of diabetes was preceded by elevated glucose and HbA1c levels in the years leading up to the diagnosis. “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,” she said. The third measure that the study analyzed was post-load glucose levels, which were obtained two 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,” said Dr. van’t Riet.

The researchers also compared study participants who didn’t develop diabetes throughout the course of the investigation with those who had developed the disease in 2000. Those who developed diabetes saw increases in fasting glucose and post-load glucose between 1989 and 1996 that was “almost comparable for those who developed diabetes and those who never developed diabetes.” However, by 1996, those levels increased in the group that developed diabetes: “A steep increase is observed, which was not seen in those who never developed diabetes,” said dr. van’t Riet.

Unlike blood glucose levels, HbA1c levels did increase between 1989 and 1996 for those who later developed diabetes. “This might indicate that A1c increases earlier than glucose,” said Dr. van’t Riet.

The researchers performed further analysis on study participants with incident diabetes in 2000 who had increased HbA1c levels but lower glucose, and on those who had high glucose and normal HbA1c due to changes in the diagnostic criteria for diabetes.

“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,” continued van’t Riet.