Jury Still Out on Proposed Long Term Blood Glucose Markers, UC Researcher Writes

CINCINNATI—It's too soon to tell how well two new tests or markers for measuring long-term blood glucose control will work for diagnosing diabetes and determining diabetes complications risk, says a University of Cincinnati researcher who co-authored a commentary on research about the tests in an international medical journal.

Robert Cohen, MD, professor in UC’s endocrinology, diabetes and metabolism division, co-authored the commentary in The Lancet Diabetes & Endocrinology with William Herman, MD, professor in the department of internal medicine at the University of Michigan. It appears in today’s edition.

The commentary reviews findings presented by researcher Elizabeth Selvin, PhD, associate professor of epidemiology at Johns Hopkins University. Selvin and her colleagues ask whether fructosamine or glycated albumin can be substituted for hemoglobin A1C as an alternative indirect measure of average glycemia for predicting the diagnosis of diabetes and of microvascular complications.

Fructosamine is the generic name for plasma protein ketoamines - proteins that have a glucose molecule attached.  Albumin is the most abundant protein in serum and fructosamine is predominantly a measure of glycated albumin, according to Cohen and Herman.

During an interview Cohen said testing hemoglobin A1C concentration is a primary measure of long-term blood sugar control, but some researchers have raised concerns about misleading information the test can provide in a subset of patients. The problem is it is difficult to figure out who belongs to that subset.

"People have been looking for other tests that may overcome limitations with hemoglobin A1C in certain circumstances,” said Cohen. "We make decisions on treating people with diabetes based on whether they are at the right level. If their control is too tight then they may have hypoglycemic spells which may be dangerous. If the control isn’t tight enough they may develop complications of diabetes.”

Selvin’s study is useful, but its methodology may limit the ability to apply some findings to individual patients with diabetes, said Cohen.

The study was essentially a "freezer study,” meaning the investigators went back and ran blood tests on frozen samples collected during an earlier prospective study, said Cohen.

"The investigators drew inferences about test performance for the diagnosis of diabetes using fasting glucose levels and patient report, but without a true gold standard,” wrote Cohen and Herman. "There was an interval between the baseline assessment of glycemia and the retinopathy assessments, meaning the measures of glycaemia were not truly a measure of prevalent diabetic retinopathy.”

In their commentary, Cohen and Herman explained the analyses by Selvin and her colleagues did produce some new and potentially unexpected findings which suggest that combination testing for glycated albumin, fructosamine and hemoglobin A1C may be better in diagnosing diabetes than examining hemoglobin A1C alone.

"All three tests seem to work well in populations, especially for predicting complications, but it remains to be seen how well they perform in individuals, especially for the diagnosis of diabetes,” wrote Cohen and Herman. "And although all three measures might work well for most patients, it will not always be obvious for whom these indirect measures of average glycaemia do not work. Research should focus on rigorously defining where there is discordance among the direct and indirect measures of glycaemia.”

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