Clinical features predict progression of type 2 diabetes

By MD Will Boggs

NEW YORK (Reuters Health) - The likelihood that type 2 diabetics will eventually need insulin is tied to several clinical features, but not to genetic factors, researchers have found.

Previous studies have suggested that a low body mass index (BMI), young age at diagnosis, and low beta-cell function are associated with faster progression of diabetes.

But no studies have investigated biomarkers of insulin resistance and inflammation or the possible effect of genetic variation on rates of diabetes progression, the researchers write in Diabetes Care, online November 1.

Dr. Ewan R. Pearson, from the University of Dundee in the UK, and his colleagues used data from 5,250 patients with type 2 diabetes in Tayside, Scotland, for their study. They defined insulin requirement as insulin treatment or hemoglobin (Hb)A1c of at least 8.5% (or 69 mmol/mol) treated with two or more non-insulin diabetes therapies.

The researchers used a weighted Genetic Risk Score (GRS) that covers 61 established type 2 diabetes risk variants. Each unit of the GRS corresponds to an expected genetic risk increase of 2.72 for type 2 diabetes.

BMI below 24 and over 30 were significantly associated with an increased risk of progression to insulin treatment, as was baseline HbA1c above 7% (53 mmol/mol).

Within the BMI and HbA1c strata, other features independently associated with a faster progression to insulin treatment included younger age at diagnosis of diabetes, earlier year of diagnosis, lower HDL cholesterol, and higher triglyceride level.

The type 2 diabetes GRS was not associated with time to requirement for insulin treatment, the team found. Increases in the GRS were, however, associated with younger age at diagnosis and younger age at requirement for insulin (but not with the interval between diagnosis and insulin requirement).

In a secondary analysis, there was no significant association of either the beta-cell GRS or the insulin resistance GRS with progression to insulin treatment after diabetes diagnosis.

"This lack of an association suggests that the biological factors captured by the diabetes risk variants do not play a large part in the biological mechanisms that result in progression of diabetes after diagnosis," the researchers say, "and there are certainly biological mechanisms that may explain this difference, e.g., gluco or lipotoxicity driving progression after development of hyperglycemia."

"While this paper is interesting, I would say it is largely hypothesis-generating and would not change how I manage my patients with type 2 diabetes," Dr. Christina Korownyk from University of Alberta, Edmonton, Alberta, Canada told Reuters Health by email.

"When we talk of reducing progression of type 2 diabetes, what our patients really care about is not their A1c level but rather reduction in cardiovascular outcomes," Dr. Korownyk, who was not involved in the new work, said. "Thus treatment should be based on overall risk -- not individual surrogate markers."

"Our ability to predict who will progress to poorer A1c values/insulin is very limited," Dr. Korownyk concluded. "We do have some tools to predict overall cardiovascular risk, which is ultimately what we want to prevent."

Dr. Pearson did not respond to a request for comment.


Diabetes Care 2013.

(c) Copyright Thomson Reuters 2013. Click For Restrictions -