HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bolli, G. B. Articles by Rosenstock, J. Search for Related Content PubMed Articles by Bolli, G. B. Articles by Rosenstock, J. Social Bookmarking                What's this?

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

Response to Monnier et al., the Diabetes Research in Children Network (DirecNet) Study Group, and Irsch and Brownlee

¹ Section of Internal Medicine, Endocrinology and Metabolism, Department of Internal Medicine, University of Perugia, Perugia, Italy
² McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
³ Dallas Diabetes and Endocrine Center, Dallas, Texas

Address correspondence to Geremia B. Bolli, MD, Department of Internal Medicine, Section of Internal Medicine, Endocrinology and Metabolism, University of Perugia, Via E. Dal Pozzo, I-06126 Perugia, Italy. E-mail: bolli{at}unipg.it

In response to the recent article by Kilpatrick et al. (1) and the accompanying editorial (2), a number of letters to the editor have been published in Diabetes Care. Given the relevance of the topic, this is not surprising and actually is a good opportunity for additional comments to the article.

Monnier et al. (3), the Diabetes Research in Children Network (DirecNet) Study Group (4), and Irsch and Brownlee (5) all correctly point out that the seven-point blood glucose profile from which the calculations of Kilpatrick et al. (1) are based may not accurately reflect glucose variability. Therefore, they claim that the conclusion of Kilpatrick et al. (1) that glucose variability is not a risk factor for long-term microvascular complications is not valid (3–5).

No one can argue that the mean amplitude of glycemic excursion index is a more sophisticated assessment than the SD of the seven-point blood glucose profile and that, at least in theory, continuous glucose monitoring would be superior to single points of blood glucose measurements. However, it is important to remember that mean amplitude of glycemic excursions require continuous blood glucose monitoring. Moreover, there currently are limitations to measuring glucose continuously in the interstitial space. Factors such as poor knowledge of glucose dynamics in the interstitial versus vascular space and the unpredictable performance of the glucose sensor(s) and its limited ability to reliably transmit data of glucose reading make it unrealistic to use this approach to generate an extraordinarily large and solid database like the one used by Kilpatrick et al. (1) for their analysis, at least at the present time. Similarly, whereas the idea of additional studies in the area with more accurate assessment of glucose variability is acceptable in principle, it is unrealistic to think that a second Diabetes Control and Complications Trial study will be planned to assess the role of glucose variability on the development of microangiopathy.

Their critical comments (3–5) may also discount the simple finding by Kilpatrick et al. (1) that glucose variability did not correlate with the appearance of microangiopathy. Moreover, the limited value of the SD of glucose in the seven-point blood glucose profile is counter-balanced by the fact that: 1) the database of blood glucose readings in hundreds of subjects with type 1 diabetes is extraordinarily large, which makes it unlikely that important spikes of hyperglycemia were missed; 2) many subjects were followed-up for many years in their real life conditions; 3) real blood measurements, not interstitial glucose approximations, were done; and 4) blood glucose measurements correlated with "hard" end points, i.e., microangiopathy (1), and not surrogate markers such as oxidative stress (3). The limitations of the observation (1), including the fact that it is confined to type 1 diabetes and microangiopathy and does not allow extrapolation to type 2 diabetes and/or to macroangiopathy, have already been made clear (2).

The study of Kilpatrick et al. (1) clearly does not diminish the importance of insulin substitution and glycemic control in type 1 diabetes targeting an A1C <7.0%. However, the average risk for severe hypoglycemia in the intensively treated group of the Diabetes Control and Complications Trial was high, and at present, it is possible to use more precise modes of insulin delivery including either continuous subcutaneous insulin infusion (6) or multiple daily injections (7) based on insulin analogs to achieve an A1C <7.0% and at the same time limit hypoglycemia. These approaches also reduce large glycemic excursions. However, the Kilpatrick et al. article (1) suggests that these excursions alone do not translate into risk for microangiopathy.

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 29:1707–1710, 2006[Free Full Text]
   
3. Monnier L, Colette C, Leiter L, Ceriello A, Hanefeld M, Owens D, Tajima N, Toumiletho J, Davidson J: The effect of glucose variability on the risk of microvascular complications in type 1 diabetes (Letter). Diabetes Care 30:185–186, 2007[Free Full Text]
   
4. The Diabetes Research in Children Network (DirecNet) Study Group: The effect of glucose variability on the risk of microvascular complications in type 1 diabetes (Letter). Diabetes Care 30:185, 2007[Free Full Text]
   
5. Hirsch IB, Brownlee M: The effect of glucose variability on the risk of microvascular complications in type 1 diabetes (Letter). Diabetes Care 30:186–187, 2007[Free Full Text]
   
6. Hoogma R, Hammond PJ, Gomis R, Kerr D, Bruttomesso D, Bouter KP, Wiefels KJ, De la Calle H, Schweitzer DH, Pfohl M, Torlone E, Krinelke LG, Bolli GB, the 5-Nations Study Group: Comparison of continuous subcutaneous insulin infusion (CSII) vs. NPH-based multiple daily insulin injections (MDI) in regard to metabolic control and quality of life: results of the 5-Nations trial. Diabet Med 23:141–147, 2006[Medline]
   
7. Porcellati F, Rossetti P, Pampanelli S, Fanelli CG, Torlone E, Scionti L, Perriello G, Bolli GB: Better long-term glycaemic control with the basal insulin glargine as compared with NPH in patients with type 1 diabetes mellitus given meal-time lispro insulin. Diabet Med 21:1213–1220, 2004[Medline]
   

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bolli, G. B. Articles by Rosenstock, J. Search for Related Content PubMed Articles by Bolli, G. B. Articles by Rosenstock, J. Social Bookmarking                What's this?