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The Effect of Glucose Variability on the Risk of Microvascular Complications in Type 1 Diabetes

Response to Kilpatrick et al. and Bolli

Address correspondence to Darrell Wilson, MD, c/o DirecNet Coordinating Center, Jaeb Center for Health Research, 15310 Amberly Dr., Suite 350, Tampa, FL 33647. E-mail: direcnet{at}jaeb.org

The article by Kilpatrick et al. (1) used data from the Diabetes Control and Complication Trial to investigate the relationship between glycemic variability and the subsequent development of diabetes complications. They report that glucose variability, as measured by a quarterly eight-point glucose profile (excluding the 3 A.M. value because of limited data), was not associated with development or progression of retinopathy or nephropathy. An accompanying editorial by Bolli (2) highlights the potential clinical impact of this finding, stating that "the instant blood glucose at a given time of day is not important, and it does not matter if it is high or low either before or after meals (or vice versa) as long as A1C is at the target value <7.0%."

We believe that these results, and the clinical recommendations that have sprung from them, should be interpreted with caution. While the Diabetes Control and Complication Trial database is large and its data regarding complications extraordinary, quarterly seven-point glucose profiles are unlikely to fully reflect true glycemic variation in these subjects with type 1 diabetes.

Continuous glucose monitors provide the opportunity to capture the magnitude of glycemic variation far better than seven-point glucose profiles. The Diabetes Research in Children Network (DirecNet) Study Group (3) compared simultaneous eight-point glucose profiles over three days with near continuous glucose profiles (values every 5 min) using Medtronic-Minimed CGMS in 161 children and adolescents with type 1 diabetes. The eight-point glucose profiles were measured using One Touch UltraSmart (LifeScan) meter, a device shown to be quite accurate (4). The meal-related glucose excursion measured using eight-point testing was calculated by subtracting premeal from postmeal glucose. The analogous glucose excursion measured with continuous glucose self-monitoring (CGMS) was calculated as the difference between the premeal CGMS value (corresponding to the time of the eight-point test) and the peak value (within 3 h of the premeal eight-point test). Postprandial excursions were two to three times larger when measured by the CGMS than by eight-point testing. These findings are not surprising as it is unlikely a single glucose measurement would coincide with the postmeal peak. Moreover, a single measurement cannot measure the duration of the postmeal glucose rise.

Given that glucose profiles based on single point-in-time postprandial measurements are a suboptimal measure of glycemic variability, we believe it is premature to discount the potential clinical importance of reducing glycemic variability. Further studies using continuous glucose data will be needed to finally answer this important question.

References

1. Kilpatrick ES, Rigby AS, Atkin SL: The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care 29:1486–1490, 2006[Abstract/Free Full Text]
   
2. Bolli GB: Glucose variability and complications (Editorial). Diabetes Care 29:1707–1709, 2006[Free Full Text]
   
3. Diabetes Research in Children Network (DirecNet) Study Group: Eight-point glucose testing versus the continuous glucose monitoring system in evaluation of glycemic control in type 1 diabetes. J Clin Endocrinol Metab 90:3387–3391, 2005[Abstract/Free Full Text]
   
4. Diabetes Research in Children Network (DirecNet) Study Group: A multicenter study of the accuracy of the OneTouch Ultra home glucose meter in children with type 1 diabetes. Diabetes Technol Ther 5:933–941, 2003[Medline]
   

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