Searching for glycemic control in pediatric type 1 diabetes: A long way to go

Abstract

See related article, p 197. There is a unique impact of type 1 diabetes on affected children and their families.1Kaufman FR Halvorson M New trends in managing type 1 diabetes.Contemp Pediatr. 1999; 16: 112-123Google Scholar Their daily lives are governed by a regimen that requires frequent blood glucose monitoring, multiple insulin injections or insulin pump therapy and insulin dosage adjustment, the appropriate intake of food, and the balancing of activity level. Despite the attention paid to diabetes management, children and families live with the fear of the acute complications of diabetes, severe hypoglycemia and ketoacidosis, and the long-term micro- and macro-circulatory complications that lead to morbidity and death. In addition to coping with the rigors of the diabetes regimen and the many issues that surround their disease, these children must still reach the normal developmental milestones of childhood and adolescence and strive to succeed in school and develop autonomy. To accomplish this, they must receive support from a multidisciplinary team of diabetes specialists, diabetes educators, and primary care providers to coordinate pediatric care and to address medical, developmental, psychologic, recreational, and nutritional needs.2American Diabetes Association Standards of medical care for patients with diabetes mellitus.Diabetes Care. 2001; 24: S33-S43PubMed Google Scholar, 3Kaufman FR Diabetes mellitus.Pediatr Rev. 1997; 18: 383-392PubMed Google Scholar The ultimate success is the attainment of the target glucose and glycosylated hemoglobin (HbA1c) levels, reduction in severe hypoglycemia and ketoacidosis, avoidance of hospitalizations and emergency department visits, normalization of physical and psychologic development, and minimization of long-term diabetes complications. Multiple reports have shown that children and youth have poorer glycemic outcome as assessed by HbA1c levels than do adults with this disease.4DCCT Research Group The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.N Engl J Med. 1993; 329: 986-997Google Scholar, 5DCCT Research Group Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus.J Pediatr. 1994; 125: 177-188Abstract Full Text Full Text PDF PubMed Scopus (1462) Google Scholar, 6Scottish Study Groups for the Care of the Young Diabetic Factors influencing glycemic control in young people with type 1 diabetes in Scotland.Diabetes Care. 2001; 24: 239-244Crossref PubMed Scopus (130) Google Scholar The Diabetes Control and Complications Trial5DCCT Research Group Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus.J Pediatr. 1994; 125: 177-188Abstract Full Text Full Text PDF PubMed Scopus (1462) Google Scholar indicated that the adolescent cohort, regardless of whether they were in the intensive or conventional diabetes treatment groups, had higher mean HbA1c levels compared with adults and more acute complications, such as ketoacidosis and severe hypoglycemia. The goal of the study in this issue of The Journal of Pediatrics by Levine et al7Levine B-S Anderson BJ Butler DA Antisdel JE Brackett J Laffel LMB Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetes.J Pediatr. 2001; 139: 197-203Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar was to explore the predictors of glycemic control and short-term adverse outcomes in pediatric subjects with type 1 disease. The authors’ prospective, 1-year study, which involved 300 subjects, 7 to 16 years of age (85% clinic participation rate), showed that the mean HbA1c level of the group (all of whom were receiving insulin injections) was unacceptably high at 8.7% at the beginning of the study and 8.9% at the end. The authors validated the findings of others8Rosilio M Cotton JB Wieliczko MC Gendrault B Carel JC Couvaras O et al.Factors associated with glycemic control. A cross-sectional nationwide study in 2,579 French children with type 1 diabetes. The French Pediatric Diabetes Group.Diabetes Care. 1998; 21: 1146-1153Crossref PubMed Scopus (187) Google Scholar, 9Chase HP Kim LM Owen SL MacKenzie TA Klingensmith GJ Murtfeldt R et al.Continuous subcutaneous glucose monitoring in children with type 1 diabetes.Pediatrics. 2001; 107: 222-226Crossref PubMed Scopus (190) Google Scholar and revealed that the subject’s HbA1c tertile was highly predicted by the frequency of blood glucose monitoring, which ranged from 1 to 5 or more times per day. Although testing blood glucose levels more frequently may just be a proxy measure for greater adherence to the diabetes regimen, with more glucose values obtained, more adjustments can be made in insulin dosages, food intake, and activity patterns to improve glycemic control. Despite advances in technology that have increased the speed with which glucose levels can be determined (5-45 seconds) and that have allowed for easier10D’Arrigo T New products.Diabetes Forecast. 2001; 54: 42-45Google Scholar and alternate-site sampling (forearm, upper arm, thigh, and calf), many children and teens still do not obtain the requisite number of tests to be able to effectively manage their disease. Determining ways to increase the frequency of blood glucose monitoring should continue to be a focus of research. The widespread use of continuous glucose monitoring systems that can determine interstitial glucose levels (Continuous Glucose Monitoring System; MiniMed, Northridge, Calif)9Chase HP Kim LM Owen SL MacKenzie TA Klingensmith GJ Murtfeldt R et al.Continuous subcutaneous glucose monitoring in children with type 1 diabetes.Pediatrics. 2001; 107: 222-226Crossref PubMed Scopus (190) Google Scholar, 11Mastortotoro J Levy R Georges L-P White N Mestman J Clinical results from a continuous glucose sensor multi-center study [abstract].Diabetes. 1998; 47: A61Google Scholar or frequent glucose monitoring devices, such as those that use reverse iontophoresis to measure glucose values (GlucoWatch Biographer; Cygnus Inc, Redwood City, Calif),12Kaufman FR Role of continuous glucose monitoring in pediatric patients.Diabetes Technol Ther. 2000; 2: S49-S52Crossref PubMed Scopus (24) Google Scholar, 13Garg SK Potts RO Ackerman NR Fermi SJ Tamada JA Chase HP Correlation of fingerstick blood glucose measurements with GlucoWatch Biographer glucose results in young subjects with type 1 diabetes.Diabetes Care. 1999; 22: 1708-1714Crossref PubMed Scopus (181) Google Scholar should enable pediatric subjects to more easily obtain multiple glucose measurements per day in the very near future. These systems have already been shown to reduce HbA1c values over the short term.9Chase HP Kim LM Owen SL MacKenzie TA Klingensmith GJ Murtfeldt R et al.Continuous subcutaneous glucose monitoring in children with type 1 diabetes.Pediatrics. 2001; 107: 222-226Crossref PubMed Scopus (190) Google Scholar, 14Bode BW Gross TM Thronton KR Mastrototoro JM Continuous glucose monitoring used to adjust diabetes therapy improves glycosylated hemoglobin. A pilot study.Diabetes Res Clin Pract. 1999; 46: 183-190Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar It is hoped that these systems will enable patients to reach HbA1c targets and improve the outcome of this disease. Levine et al7Levine B-S Anderson BJ Butler DA Antisdel JE Brackett J Laffel LMB Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetes.J Pediatr. 2001; 139: 197-203Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar described other factors associated with higher HbA1c levels that have been well established by previous studies including older age,15Mortensen HB Hougaard P Comparison of metabolic control in a cross-sectional study of 1,873 children and adolescents with IDDM from 18 countries.Diabetes Care. 1997; 20: 714-720Crossref PubMed Scopus (379) Google Scholar more advanced pubertal stage,16Grey M Boland EA Davidson M Yu C Sullivan-Bolyai S Tamborlane WV Short-term effects of coping skills training as an adjunct to intensive therapy in adolescents.Diabetes Care. 1998; 21: 902-908Crossref PubMed Scopus (177) Google Scholar and being members of single-mother families17Thompson SJ Auslander WE White NH Comparison of single-mother and two-parent families on metabolic control of children with diabetes.Diabetes Care. 2001; 24: 234-238Crossref PubMed Scopus (103) Google Scholar but not the number of insulin injections. With no patients using an insulin pump in this study, the previously described benefits involving HbA1c values and frequency of hypoglycemia were not addressed by the authors.18Kaufman FR Halvorson M Carpenter S Devoe D Pitukcheewanont P Insulin therapy in young children with diabetes.Diabetes Spectrum. 2001; 14: 84-89Crossref Google Scholar Levine et al7Levine B-S Anderson BJ Butler DA Antisdel JE Brackett J Laffel LMB Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetes.J Pediatr. 2001; 139: 197-203Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar did not find a correlation between HbA1c values and number of clinic visits. It had previously been reported that subjects with 1 to 2 clinic visits per year (approximately 25% of the sample), compared with those with 3 to 4 visits per year (75% of the sample), had significantly higher HbA1c values.19Kaufman FR Halvorson M Carpenter S Association between diabetes control and visits to a multidisciplinary pediatric diabetes clinic.Pediatrics. 1999; 103: 984-1951Crossref Scopus (121) Google Scholar The difference in findings might be due to the relatively short duration of this study (1 year) or to other factors. Because of the study design, these findings should not lead to the conclusion that 1 or 2 visits with the diabetes team will be as effective as 3 or more visits. The hypoglycemia event rate for this study was 62 events per 100 person-years. Of interest, there was a high incidence of hypoglycemia in those with poor metabolic control. This differs from the finding of the Diabetes Control and Complications Trial4DCCT Research Group The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.N Engl J Med. 1993; 329: 986-997Google Scholar, 5DCCT Research Group Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus.J Pediatr. 1994; 125: 177-188Abstract Full Text Full Text PDF PubMed Scopus (1462) Google Scholar of a 3-fold increase in severe hypoglycemia in those in the intensively managed group. This observation led to the dictum that intensive management of the pediatric patient, with its risk of hypoglycemia, is the limiting factor to lowering the HbA1c value. However, others have shown that the hypoglycemia rate is not correlated with HbA1c values. Cox et al20Cox DJ Kovatchev BP Julian DM Gonder-Frederick LA Polonsky WH Schlundt DG et al.Frequency of severe hypoglycemia in insulin-dependent diabetes mellitus can be predicted from self-monitoring of blood glucose data.J Clin Endocrinol Metab. 1994; 79: 1659-1662PubMed Google Scholar showed no association between glycated hemoglobin levels and the risk that the 78 pediatric subjects in their study would have a severe hypoglycemic episode. The lack of association between glycated hemoglobin levels and severe symptomatic hypoglycemia was also found by Bhatia and Wolfsdorf.21Bhatia V Wolfsdorf JI Severe hypoglycemia in youth with insulin-dependent diabetes mellitus: frequency and causative factors.Pediatrics. 1991; 88: 1187-1193PubMed Google Scholar They reported an incidence of 0.12 episodes of severe hypoglycemia per patient-year in 196 subjects with a markedly elevated mean HbA1c level of 11.4%. Nordfeldt and Ludvigsson22Nordfedlt S Ludvigsson J Severe hypoglycemia in children with IDDM: a prospective population study, 1992-1994.Diabetes Care. 1997; 20: 487-503Crossref PubMed Scopus (18) Google Scholar showed that 146 children managed with intensive therapy had no increase in severe hypoglycemia. Beregszaszi et al,23Beregszaszi M Tubiana-Rufi N Benali K Noel M Bloch J Czernichow P Nocturnal hypoglycemia in children and adolescents with insulin-dependent diabetes mellitus. Prevalence and risk factors.J Pediatr. 1997; 131: 27-33Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar studying nocturnal hypoglycemia, noted no difference in the mean HbA1c value in the groups with and without hypoglycemia (mean HbA1c 8.4% vs 8.9%, respectively). In a study from my center,24Kaufman FR Epport K Engilman R Halvorson M Neurocognitive functioning in children diagnosed with diabetes before age 10 years.J Diabetes Complications. 1999; 13: 31-38Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar there was no relationship between HbA1c value and severe hypoglycemia or hypoglycemic seizures. Levine et al7Levine B-S Anderson BJ Butler DA Antisdel JE Brackett J Laffel LMB Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetes.J Pediatr. 2001; 139: 197-203Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar confirm that the risk of moderate to severe hypoglycemia in children and teens is independent of HbA1c value. The authors’ findings of the association between poor glycemic control and increased hospitalization rate brings home the importance of achieving glucose targets as a means to reduce the morbidity and expense of this disease. The overall hospitalization rate was greater than 3 times the rate seen in the same age population, with those in the highest HbA1c tertile having a rate 2 times greater than the other study subjects. As pointed out by Levine et al,7Levine B-S Anderson BJ Butler DA Antisdel JE Brackett J Laffel LMB Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetes.J Pediatr. 2001; 139: 197-203Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar the overall hospitalization rate for children with diabetes does not appear to be decreasing over time. The stark message of this article is that despite the advances in diabetes care and the reduction in adverse events appreciated by those with optimal HbA1c levels compared with those with poor glycemic control, there remains an unacceptably high incidence of short-term complications in children and youth with diabetes secondary to the inability to achieve glycemic targets. We must continue to develop technical and behavioral strategies to promote better health for pediatric subjects affected by diabetes. Although the focus is on finding the cure for this devastating disease, diabetes care providers, patients, and families cannot ignore that what we need now are effective ways to reach high-risk populations. We must get all children and youth with diabetes to monitor their glucose levels effectively so that glycemic control improves and short-term adverse outcomes begin to disappear. Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetesThe Journal of PediatricsVol. 139Issue 2PreviewObjectives: To examine predictors of glycemic control and to assess how glycemic control affects the incidence of short-term adverse outcomes in a pediatric population with type 1 diabetes. Study design: Three hundred youth, aged 7 to 16 years, with type 1 diabetes who were receiving diabetes specialty care were followed up prospectively for 1 year. Treatment plans and frequency of adverse outcomes were ascertained by questionnaires and medical record review. Incidence rates of adverse outcomes were compared among 3 strata of the population, representing tertiles of baseline glycosylated hemoglobin (HbA1c). Full-Text PDF