Protein glycosylation in diabetes mellitus: a review of laboratory measurements and of their clinical utility

Summary The major utility of the glycosylated hemoglobin assay continues to be as a monitor for the effectiveness of diet/insulin or oral agent therapy in the normalization of serum glucose concentrations. During periods of poor glycemic control, as assessed by frequent positive urine glucose determinations, or by elevated fasting or postprandial blood glucose concentrations, or by episodes of ketoacidosis, the use of the glycosylated hemoglobin assay adds little information. Rather, it is most useful during periods of stable control, to assess the effectiveness of the combined therapy of diet, activity, and insulin or oral agents. As the glycosylated hemoglobin concentrations tend to reflect the metabolic control during the previous four to eight weeks, little is to be gained from more frequent use of this assay. An isolated elevated serum glucose concentration obtained in the office or hospital laboratory, associated with a near-normal serum glycosylated hemoglobin concentration need not demand drastic rearrangement of the patient's therapuetic regimen. The normal hemoglobin A 1c concentration reflects good blood glucose control over the past one to two months. The elevated blood glucose concentration may reflect a transient aberration secondary to stress, diet, or other factors. If, however, actual deterioration in the patient's metabolic control is occurring, this may not be reflected in the hemoglobin A 1c concentration for several weeks or months. Likewise, during a period of stable control, a normal office or lab glucose concentration associated with an elevated glycosylated hemoglobin concentration may indicate poor control, the normal glucose resulting from the peak effectiveness of either short- or intermediate-acting insulin. In this situation, more frequent glucose determinations would reveal elevation of blood glucose concentrations. Whereas the glycosylated hemoglobin assay may help the physician and patient to assess glycemic control, this alone cannot lead to improved control. In this regard the use of home glucose monitoring with or without insulin infusion pumps has led to near-normalization of blood glucose concentrations in Type I and in pregnant diabetic patients [105, 175, 176]. The frequent determination of blood glucose concentrations on a daily basis can allow for optimum use of dietary and insulin therapy. Moreover, the reported variability in glycosylated hemoglobin after periods of poor control may reflect the time relation between blood glucose and hemoglobin A 1c concentrations, or the stability of the glycosylated hemoglobin, and may diminish the clinical utility of the glycosylated hemoglobin concentration in the individual patient. The clinical utility of the glycosylated albumin or protein assay in diabetes management remains to be established [211]. At this time the combined use of multiple daily home blood glucose determinations, coupled with several well-spaced hemoglobin A 1 determinations may be the most sensitive indicators of the state of metabolic control. Thus, protein glycosylation provides an indication of glycemic regulation. Protein glycosylation may also contribute to the complications of diabetes mellitus, but such relationships, for the most part, remain to be established.