The Journal of Pediatrics
Volume 155, Issue 2 , Pages 161-162, August 2009

In Pursuit Of Lower A1c

  • Michael J. Haller, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Michael Haller, MD, University of Florida, Department of Pediatric Endocrinology, PO Box 10296, Gainesville, FL 32610.
    • ,
  • Janet H. Silverstein, MD

Department of Pediatric Endocrinology University of Florida, Gainesville, Florida

Article Outline

DCCT, Diabetes Control and Complications Trial, SMBG, Self-monitoring of blood glucose, T1D, Type 1 diabetes

 

See related article, p 183

With the discovery of insulin by Banting et al1 in 1921, type 1 diabetes (T1D) was transformed from a uniformly fatal diagnosis to a chronic disease characterized by complications driven by long-term hyperglycemia. Since the discovery of the “thick brown muck” initially used to treat Leonard Thompson, great strides have been made in the day-to-day management of T1D. Undoubtedly, the development of recombinant human insulin, insulin analogues, insulin pumps, and devices for performing self-monitoring of blood glucose (SMBG) has improved the quality of life of many patients with T1D. Nevertheless, patients of all ages, and especially children, continue to struggle with the challenges of trying to maintain normoglycemia.

Until the late 1980s, debate raged over an association between glycemic control and the development of complications of diabetes. The Diabetes Control and Complications Trial (DCCT) unequivocally answered this question, firmly establishing that intensive diabetes management, including frequent glucose monitoring, frequent injections or insulin pump use, frequent phone contact, and education regarding self-insulin dose adjustments, was associated with improved glycemic control.2 This in turn was associated with decreased progression of long-term microvascular and macrovascular complications of T1D.3, 4 Notably, the adolescents in the DCCT failed to achieve the level of glycemic control attained by adults in the study despite being a highly compliant population. Thus, the question is no longer whether glycemic control matters, but how best to achieve this control? Since the DCCT, there have been many advances in diabetes care, including the development of insulin analogues with more physiological action profiles, improved blood glucose monitoring devices, and widespread use of basal-bolus insulin regimens, including insulin pump technology. Nevertheless, the goal of achieving near-normal glycemia while avoiding hypoglycemia remains a lofty one, because the large majority of children with T1D in 2009 still fail to achieve the A1c goals known to reduce long-term complication risks.5

Why children with T1D are unable to achieve A1c goals associated with reduced risk of complications has been widely discussed. The effect of the growth hormone surge on insulin resistance during adolescence, fear of hypoglycemia causing discomfort with normal blood glucose concentrations, and the feeling of invulnerability and risk-taking behaviors typical of adolescence are all thought to be contributing factors. But definitively identifying the factors affecting metabolic control in this age group has been difficult. The SEARCH for Diabetes in Youth study is a multicenter collaborative effort encompassing 6 clinical centers across the United States. Designed to perform a population-based observational study of diabetes in children (under age 20 years) in each clinical center, SEARCH is well situated to explore many of the complex issues that drive diabetes management in children.6

In this issue of The Journal, Paris et al7 present data on 2743 SEARCH participants with T1D in an attempt to better explain the factors that drive the choice of insulin regimen, clinical outcomes, and glycemic control. Although this particular analysis is limited by its cross-sectional design and descriptive nature, the sheer size of the SEARCH cohort provides considerable power to examine these complex issues. Not surprisingly, the majority of children (75.6%) receive their diabetes care from a pediatric endocrinologist, and nearly half (46.8%) are managed with basal-bolus therapy. Comparing patients receiving 1 or 2 injections per day with those receiving all other insulin regimens confirmed the well-established perception that sociodemographic factors predict insulin regimen. Specifically, age, sex, ethnicity, family income, and education all were found to predict insulin regimen, with younger African-American boys from low-income families most likely to use a 1- or 2-injection-per-day regimen and older non-Hispanic white females from high-education and high-income families most likely to use an insulin pump.

Although both adjusted and unadjusted analyses demonstrated that youth using insulin pumps achieved the lowest A1c, far too many children (including many using a pump) failed to achieve even the modest age-adjusted A1c goals specified by the American Diabetes Association.8 As such, determining which modifiable factors are associated with A1c is perhaps the most important task in determining how to help more children achieve their A1c goal. The complexity of this issue should not be underestimated; unadjusted analyses demonstrated significant A1c differences between centers, and analyses adjusted for sociodemographic variables, fasting C-peptide level, duration of diabetes, and frequency of SMBG eliminated any such differences. Although not a major focus of this analysis, the SEARCH data clearly show that frequency of SMBG is in and of itself a strong predictor of A1c regardless of insulin regimen used. Given the large size of the SEARCH database, additional analyses can and should be designed to better document the frequency of SMBG most closely associated with achieving A1c goals. Furthermore, analyses to determine which parental factors predict control and which factors predict success and failure with insulin pump use would be extremely valuable.

T1D is a chronic disease commonly diagnosed in childhood. Affecting nearly 1 in every 300 US children,9 T1D is associated with a life-long increased risk for complications that is difficult for children to comprehend. Until the dream of a prevention or cure for T1D is realized, continued efforts to better understand the complex sociodemographic factors that predict glycemic control are needed to develop more effective strategies for treating children with T1D and preventing or reducing their risk of complications.

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References 

  1. Bliss M. The Discovery of Insulin. 25th anniversary ed. Chicago: University of Chicago Press; 2007;
  2. Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus. Diabetes Control and Complications Trial. J Pediatr. 1994;125:177–188
  3. Cleary PA, Orchard TJ, Genuth S, Wong ND, Detrano R, Backlund JY, et al. The effect of intensive glycemic treatment on coronary artery calcification in type 1 diabetic participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC). Study. Diabetes. 2006;55:3556–3565
  4. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353:2643–2653
  5. Gerstl EM, Rabl W, Rosenbauer J, Grobe H, Hofer SE, Krause U, et al. Metabolic control as reflected by HbA1c in children, adolescents and young adults with type 1 diabetes mellitus: combined longitudinal analysis including 27,035 patients from 207 centers in Germany and Austria during the last decade. Eur J Pediatr. 2008;167:447–453
  6. SEARCH for Diabetes in Youth: a multicenter study of the prevalence, incidence and classification of diabetes mellitus in youth. Control Clin Trials. 2004;25:458–471
  7. Paris CA, Klingensmith G, Petiti D, Rodriguez B, Anderson AM, Schwarz D, et al. Predictors of insulin regimens and impact on outcomes in youth with type 1 diabetes: the SEARCH for Diabetes in Youth Study. J Pediatr. 2009;155:183–189
  8. Standards of medical care in diabetes—2009. Diabetes Care. 2009;32(Suppl 1):S13–S61
  9. Vehik K, Hamman RF, Lezotte D, Norris JM, Klingensmith G, Bloch C, et al. Increasing incidence of type 1 diabetes in 0- to 17-year-old Colorado youth. Diabetes Care. 2007;30:503–509

PII: S0022-3476(09)00219-4

doi:10.1016/j.jpeds.2009.03.006

Refers to article:

  • Predictors of Insulin Regimens and Impact on Outcomes in Youth with Type 1 Diabetes: The SEARCH for Diabetes in Youth Study , 27 April 2009

    Carolyn A. Paris, Giuseppina Imperatore, Georgeanna Klingensmith, Diana Petitti, Beatriz Rodriguez, Andrea M. Anderson, I. David Schwartz, Debra A. Standiford, Catherine Pihoker
    The Journal of Pediatrics August 2009 (Vol. 155, Issue 2, Pages 183-189.e1)

The Journal of Pediatrics
Volume 155, Issue 2 , Pages 161-162, August 2009

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