Response to Letter by Sacks

The response letter by Sacks (1) in this issue of Diabetes Care acknowledges that our study (2) was meticulous, but raises concerns as to the reliability of results, and reminds that hematocrit influences glucose values determined on whole blood. In this respect, some observations can be made.

First, the women involved in our study were absolutely free to leave the glucose profile monitoring program, which indeed was discontinued by a significant proportion of them (10%). This does not imply that the remainders were reliable but lends some credence to the fact that they performed and recorded the appropriate determinations at the right time. In addition, it is true that Accutrend α can only record the last nine values, but this allowed verification of determinations achieved in the night, which no doubt were those more likely to be skipped. Maybe hospitalization, as performed in previous studies, would positively contribute to obtaining precise plasma glucose determinations with reliable written results issued directly from the laboratory, but one may argue that the bias introduced by hospital stay in terms of lifestyle modifications (e.g., lack of physical activity) would in turn have some impact on the reliability of the results; also, the implications of hospitalization, in terms of both social costs and personal restrictions, would most probably limit, to a significant extent, the number of subjects available for such a study. More generally, if reliability of subjects enrolled in a study is questioned, then it would be tempting to suggest the absolute unreliability of many studies published thus far, as well as the fragility of most parameters on which clinical management relies, because it seems very difficult to achieve evidence that subjects enrolled in randomized controlled trials actually take their medications at the expected time with the expected continuity and, as for clinical practice, that pregnant women follow physicians’ advice and prescriptions.

Second, the influence of hematocrit on whole-blood glucose determinations is well known, but we believe that this criticism, despite formal correctness, is beside the point. In fact, the conversion in plasma glucose equivalents, assuming a hematocrit of 35%, still shows that glucose concentrations documented in our study are lower than those reported by others, although to a lesser extent. In addition, it is undeniable that glycemic normalization achieved in pregnant diabetic patients is commonly accomplished by following indications provided by capillary blood glucose determinations, without taking into account adjustments for hematocrit. It is important to realize that the aim of our study was to explore third-trimester glucose values in a group of nondiabetic pregnant women, because we felt the striking contrast of treating diabetes in pregnancy in an attempt to normalize glycemia without defining normoglycemia. This paradox could also explain the strange high rate of macrosomia found in some studies, despite apparent glycemic rectification. We contributed to this definition with a study involving 51 women who carefully followed our indications with high compliance; all pregnancies reported in our study were uneventful and had maternal cardiovascular adaptation with consequent changes in hematocrit values. In this context, the fact that capillary blood instead of plasma glucose was determined make the results more clinically useful, because the treatment of diabetic pregnant women is, in most instances, based on fingerstick measurements. For these reasons, we believe that glycemic values reported in our study, appropriately defined as unique, can be regarded as a point of reference.