SAN DIEGO – Based on their analysis of a cohort of more than half a million people, Swedish researchers now believe that mildly elevated fasting plasma glucose and triglyceride levels could indicate an increased risk for type 2 diabetes a quarter-century before diagnosis.
“Previous studies have shown that risk factors for type 2 diabetes, including obesity and elevated fasting glucose, may be present up to 10 years before disease onset. Our study extends this period to more than 20 years before diagnosis,” said the study’s lead author Håkan Malmström, PhD, an epidemiologist with the Karolinska Institute, Stockholm. “Even small elevations in subjects over time early in life may be important to recognize, in particular for people who are overweight or obese.” The study findings were presented in an oral presentation at the scientific sessions of the American Diabetes Association.
The researchers identified 47,997 new type 2 diabetes cases in a Swedish cohort of 537,119 people tracked from 1985-2012. For each case, they compared risk factors from clinical examinations performed from 1985-1996 with those of five matched controls.
They found that on average, several risk factors were more common among individuals with type 2 diabetes, compared with the matched controls “many years before the diagnosis,” Dr. Malmström said. “In particular, BMI [body mass index], fasting triglycerides, fasting glucose, the apo B/apo A-I ratio and inflammatory markers were increased up to 25 years before the diagnosis.”
For example, 25 years before diagnosis, mean fasting plasma glucose in the type 2 diabetes group was higher than controls at 90 mg/dL vs. 86 mg/dL, respectively. By 10 years before diagnosis, that gap had widened to 98 mg/dL vs. 88 mg/dL. At 1 year before diagnosis, the levels were 106 mg/dl vs. 90 mg/dL.
As for fasting triglycerides, high levels earlier in life appeared to be especially risky: Individuals with levels over 124 mg/dL were more likely to develop type 2 diabetes 20 years later, even if they weren’t overweight or had elevated mean fasting glucose levels.
At 25 years before diagnosis, the type 2 diabetes group had mean fasting triglyceride levels of 120 mg/dL vs. 89 mg/dL in the control group. And at 1 year before diagnosis, the difference had widened to 146 mg/dL vs. 106 mg/dL.
Researchers found signs of higher levels of fructosamine – a marker of glycemic levels over an extended period of time (2-3 weeks) – at about 15 years before diagnosis. According to Dr. Malmström, this finding suggests that “glucose metabolism was starting to become more disturbed later than the changes in fasting glucose, but still many years before the type 2 diabetes diagnosis.”
He speculated that early signs of type 2 diabetes revealed by the study are related to genetic predisposition. “The risk of developing the disease presents early with increased BMI and dyslipidemia, which in turn leads to successively decreased insulin sensitivity,” he said.
One step for future research, he added, would be to “elaborate on these early changes in risk factors and create a risk score based on a few easily available factors in clinical settings.”
The study was funded by Sweden’s Gunnar and Ingmar Jungner Foundation for Laboratory Medicine. Dr. Malmström reported no relevant disclosures.