Log in

Do high blood glucose peaks contribute to higher HbA1c? Results from repeated continuous glucose measurements in children

  • Original Article
  • Published:
World Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Background

HbA1c levels are infl uenced by the glycemic control of previous 2–3 months. Sometimes patients have surprisingly low HbA1c in spite of many correctly measured high blood glucose values, which is diffi cult to explain. As glucose sensors give an objective picture based on glucose readings several times per minute over 24 hours, we used the area under the curve (AUC) of such subcutaneous glucose profi les to evaluate their relationship with HbA1c.

Methods

Thirty-two patients were randomized into two study arms, one open and the other blinded. Both arms had 8 pump users and 8 patients with multiple daily injections (MDI). After three months the two arms crossed over. Both study arms wore a continuous glucose monitoring system (CGMS) for 3 days every 2 weeks. HbA1c was determined before and after each 3-month study period.

Results

There was no relationship between HbA1c and s.c. glucose AUC or between HbA1c and the number of peaks >15.0 mmol/L when all CGMS profi les during the 6 months were taken together. Children on MDI showed a positive relationship between HbA1c and AUC (P<0.01) as well as the number of peaks (P<0.01). Children with a negative relationship between HbA1c and AUC generally had fewer fluctuations in blood glucose values, whereas children with a positive relationship had wide fluctuations.

Conclusions

Although there was no relationship between s.c. glucose AUC and HbA1c, the results indicate that wide blood glucose fluctuations may be related to high HbA1c values. Therefore, complications and therapeutic interventions should aim at reducing such fluctuations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977–986.

  2. Bojestig M, Arnqvist HJ, Hermansson G, Karlberg BE, Ludvigsson J. Declining incidence of nephropathy in insulindependent diabetes mellitus. N Engl J 1994;330:15–18.

    Article  CAS  Google Scholar 

  3. Nordwall M, Bojestig M, Arnqvist HJ, Ludvigsson J. Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of Type 1 diabetes-the Linkö** Diabetes Complications Study. Diabetologia 2004;47:1266–1272.

    Article  PubMed  CAS  Google Scholar 

  4. Hovind P, Tarnow L, Rossing K, Rossing P, Eising S, Larsen N, et al. Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care 2003;26:1258–1264.

    Article  PubMed  Google Scholar 

  5. Mortensen HB, Hougaard P. Comparison of metabolic control in a cross-sectional study of 2,873 children and adolescents with IDDM from 18 countries. The Hvidøre Study Group on Childhood Diabetes. Diabetes Care 1997;20:714–720.

    Article  PubMed  CAS  Google Scholar 

  6. Danne T, Mortensen HB, Hougaard P, Lynggaard H, Aanstoot HJ, Chiarelli F, et al. Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidore Study Group. Diabetes Care 2001;24:1342–1347.

    Article  PubMed  CAS  Google Scholar 

  7. Lindblad B, Nordin G, SWEDIABKIDS. The Swedish childhood diabetes registry. 0–18 years. Experiences with HbA1c from the first years. Pediatr Diabetes 2004;5(Suppl 1):15.

    Google Scholar 

  8. Danne T, Mortensen HB, Hougaard P, Lynggaard H, Aanstoot HJ, Chiarelli F, et al. Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidore Study Group. Diabetes Care 2001;24:1342–1347.

    Article  PubMed  CAS  Google Scholar 

  9. Gabbay KH, Hasty K, Breslow JL, Ellison RC, Bunn HF, Gallop PM. Glycosylated hemoglobins and long-term blood glucose control in diabetes mellitus. J Clin Endocrinol Metab 1977;44:859–864.

    Article  PubMed  CAS  Google Scholar 

  10. Mayer TK, Freedman ZR. Protein glycosylation in diabetes mellitus: a review of laboratory measurements and of their clinical utility. Clin Chim Acta 1983;127:147–184.

    Article  PubMed  CAS  Google Scholar 

  11. Davie SJ, Gould BJ, Yudkin JS. Effect of vitamin C on glycosylation of proteins. Diabetes 1992;41:167–173.

    Article  PubMed  CAS  Google Scholar 

  12. van Heyningen C, Hanid TK, Hopkinson I. Glycosylated haemoglobin by affi nity chromatography in diabetic and nondiabetic children. Ann Clin Biochem 1986;23:425–428.

    PubMed  Google Scholar 

  13. Kilpatrick ES, Dominiczak MH, Small M. The effects of ageing on glycation and the interpretation of glycaemic control in Type 2 diabetes. QJM 1996;89:307–312.

    PubMed  CAS  Google Scholar 

  14. Lowrey CH, Lyness SJ, Soeldner JS. The effect of hemoglobin ligands on the kinetics of human hemoglobin A1c formation. J Biol Chem 1985;260:11611–11618.

    PubMed  CAS  Google Scholar 

  15. Kilpatrick ES, Maylor PW, Keevil BG. Biological variation of glycated hemoglobin. Implications for diabetes screening and monitoring. Diabetes Care 1998;21:261–264.

    Article  PubMed  CAS  Google Scholar 

  16. Gross TM, Bode BW, Einhorn D, Kayne DM, Reed JH, White NH, et al. Performance evaluation of the MiniMed continuous glucose monitoring system during patient home use. Diabetes Technol Ther 2000;2:49–56.

    Article  PubMed  CAS  Google Scholar 

  17. Mastrototaro J. The MiniMed Continuous Glucose Monitoring System (CGMS). J Pediatr Endocrinol Metab 1999;12Suppl 3:751–758.

    PubMed  Google Scholar 

  18. Boyne MS, Silver DM, Kaplan J, Saudek CD. Timing of changes in interstitial and venous blood glucose measured with a continuous subcutaneous glucose sensor. Diabetes 2003;52:2790–2794.

    Article  PubMed  CAS  Google Scholar 

  19. Ludvigsson J, Hanas R. Continuous subcutaneous glucose monitoring improved metabolic control in pediatric patients with type 1 diabetes: a controlled crossover study. Pediatrics 2003;111:933–938.

    Article  PubMed  Google Scholar 

  20. Kullberg CE, Bergström A, Dinesen B, Larsson L, Little RR, Goldstein DE, et al. Comparisons of studies on diabetic complications hampered by differences in GHb measurements. Diabetes Care 1996;19:726–729.

    Article  PubMed  CAS  Google Scholar 

  21. Arnqvist H, Wallensteen M, Jeppson JO. Standards for longterm measures of blood sugar are established. Lakartidningen 1997;94:4789–4790.

    PubMed  CAS  Google Scholar 

  22. Kovatchev BP, Cox DJ, Gonder-Frederick LA, Young-Hyman D, Schlundt D, Clarke W. Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index. Diabetes Care 1998;21:1870–1875.

    Article  PubMed  CAS  Google Scholar 

  23. Hermansson G, Ludvigsson J, Larsson Y. Home blood glucose monitoring in diabetic children and adolescents. A 3-year feasibility study. Acta Paediatr Scand 1986;75:98–105.

    Article  PubMed  CAS  Google Scholar 

  24. The DCCT Research group. Diabetes Control and Complications Trial (DCCT): results of feasibility study. The DCCT Research Group. Diabetes Care 1987;10:1–19.

    Article  Google Scholar 

  25. McCarter RJ, Hempe JM, Gomez R, Chalew SA. Biological variation in HbA1c predicts risk of retinopathy and nephropathy in type 1 diabetes. Diabetes Care 2004;27:1259–1264.

    Article  PubMed  CAS  Google Scholar 

  26. Deiss D, Hartmann R, Hoeffe J, Kordonouri O. Assessment of glycemic control by continuous glucose monitoring system in 50 children with type 1 diabetes starting on insulin pump therapy. Pediatr Diabetes 2004;5:117–121.

    Article  PubMed  Google Scholar 

  27. Alemzadeh R, Loppnow C, Parton E, Kirby M. Glucose sensor evaluation of glycemic instability in pediatric type 1 diabetes mellitus. Diabetes Technol Ther 2003;5:167–173.

    Article  PubMed  CAS  Google Scholar 

  28. Fiallo-Scharer R; Diabetes Research in Children Network 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 2005;90:3387–3391.

    Article  PubMed  CAS  Google Scholar 

  29. Sachedina N, Pickup JC. Performance assessment of the Medtronic-MiniMed Continuous Glucose Monitoring System and its use for measurement of glycaemic control in Type 1 diabetic subjects. Diabet Med 2003;20:1012–1015.

    Article  PubMed  CAS  Google Scholar 

  30. Kilpatrick ES, Rigby AS, Atkin SL. The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care 2006;29:1486–1490.

    Article  PubMed  CAS  Google Scholar 

  31. Snieder H, Sawtell PA, Ross L, Walker J, Spector TD, Leslie RD. HbA(1c) levels are genetically determined even in type 1 diabetes: evidence from healthy and diabetic twins. Diabetes 2001;50:2858–2863.

    Article  PubMed  CAS  Google Scholar 

  32. Hempe JM, Gomez R, McCarter RJ Jr, Chalew SA. High and low hemoglobin glycation phenotypes in type 1 diabetes: a challenge for interpretation of glycemic control. J Diabetes Complications 2002;16:313–320.

    Article  PubMed  Google Scholar 

  33. Polhill TS, Saad S, Poronnik P, Fulcher GR, Pollock CA. Short-term peaks in glucose promote renal fi brogenesis independently of total glucose exposure. Am J Physiol Am J Physiol Renal Physiol 2004;287:F268–273.

    Article  CAS  Google Scholar 

  34. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes 1995;44:968–983.

  35. McCarter RJ, Hempe JM, Chalew SA. Mean blood glucose and biological variation have greater infl uence on HbA1c levels than glucose instability: an analysis of data from the Diabetes Control and Complications Trial. Diabetes Care 2006;29:352–355.

    Article  PubMed  Google Scholar 

  36. Derr R, Garrett E, Stacy GA, Saudek CD. Is HbA1c affected by glycemic instability? Diabetes Care 2003;26:2728–2733.

    Article  PubMed  Google Scholar 

  37. Pickup JC, Kidd J, Burmiston S, Yemane N. Determinants of glycaemic control in type 1 diabetes during intensifi ed therapy with multiple daily insulin injections or continuous subcutaneous insulin infusion: importance of blood glucose variability. Diabetes Metab Res Rev 2006;22:232–237.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ulf Samuelsson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Samuelsson, U., Hanas, R., Whiss, P.A. et al. Do high blood glucose peaks contribute to higher HbA1c? Results from repeated continuous glucose measurements in children. World J Pediatr 4, 215–221 (2008). https://doi.org/10.1007/s12519-008-0040-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12519-008-0040-8

Key words

Navigation