Additional markers of risk for diabetic microvascular complications beyond Hemoglobin A1c needed

The "gold standard" diabetes test, Hemoglobin A1c (A1C), explains much less about the risk of cardiovascular complications in patients with diabetes than originally thought, according to an article in the June 9 issue of the Journal of the American Medical Association (JAMA).  The article entitled, "Beyond HbA1c: Need for Additional Markers of Risk for Diabetic Microvascular Complications," was co-authored by Irl Hirsch, M.D., of the University of Washington Medical School (Seattle, WA) and Michael Brownlee, M.D., of the Albert Einstein College of Medicine (New York, NY).

The authors contend that the A1C test and duration of diabetes (glycemic exposure) explain only 11% of the risk of microvascular complications in the Diabetes Control and Complications Trial (DCCT), a major landmark study in diabetes care.  They then suggest that fluctuations of blood glucose levels ("glycemic variability" or "glucose peaks and valleys") may be a significant factor in explaining the remaining 89% of microvascular complication risk.  As the A1C test represents an average of glucose levels over a two to three-month period, it provides no information on glucose fluctuations.

The 1,5-anhydroglucitol test (GlycoMark) and/or continuous glucose monitoring (CGM) are advocated as clinical monitoring tools which provide a "definitive examination of the impact of glycemic variability on clinical endpoints." New therapeutic approaches which address glycemic variability are also recommended.  These include faster prandial insulins, pramlintide, and incretins.

According to co-author Irl Hirsch, "A1C is helpful in tracking broad glucose targets, but it provides virtually no information on glycemic variability. 1,5-anhydroglucitol is a simple blood test which provides an index of postprandial hyperglycemia and glycemic variability over the past 2-3 weeks and can be used in routine clinical practice."

Hirsch and Brownlee conclude the article by indicating that "it is important for physicians to realize that much remains to be done in identifying important factors contributing to microvascular complications risk which are not captured by A1C.  The future identification of these factors will have important implications for devising additional markers and for designing better treatment methods."