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Insulin Considerations and Comparisons for Pediatric and Adolescent Diabetic Populations

21 Jan 2021 6:15 PM | Anonymous

By: Hannah Michael, PharmD, PGY1 Pharmacy Resident – University of Missouri Health Care

Current guideline therapy provided by the American Diabetes Association and the International Society for Pediatric and Adolescent Diabetes (ISPAD) highlights that type 1 diabetes accounts for most diabetic diagnoses for children and adolescents.1-3 Due to the pharmacokinetic differences of the available types of insulins and highly variable pharmacodynamics in the pediatric population, data on these regimens are not transferable from the adult population to pediatric patients. Knowing this, it is important to highlight effective insulin treatment for this population as well as the differences in administration considerations to provide the most appropriate therapeutic regimens for all age groups with diabetes.

As in the adult population, glycemic goals and targets are just as essential in effectively assessing control of diabetes in children and adolescents to prevent acute and long-term complications, including microvascular and macrovascular complications. Diabetic nephropathy is a known major contributor to morbidity and mortality risk, and although the advanced stages of this occurrence are rare in children and adolescents, alterations in renal function develop quickly after diabetes diagnosis and often progress during puberty.4 In addition, it has been demonstrated that adolescents are at a higher risk of developing vision-threatening retinopathy when compared with adults. These examples of physiologic and developmental differences stress the importance of early identification of diabetes in this patient population as well as effective initial and lifelong insulin therapy.

Hemoglobin A1c levels remains an essential tool to assess long-term glycemic control and to prevent chronic complications of diabetes. A goal of <154 mg/dL (<7.0%) is recommended for many children, however, a less stringent goal of <168 mg/dL (<7.5%) may be appropriate depending on the presence of the following factors: the ability to articulate symptoms of hypoglycemia, individuals who have hypoglycemia unawareness, patients that cannot obtain/use analog insulins or lack access to insulin-delivery technologies, patients who cannot check blood glucose levels regularly, or patients who have nonglycemic factors that increase A1c.5 To achieve a goal of <7.5%, blood glucose targets include a pre-meal of 90-130 mg/dL, post-meal of 90-180 mg/dL, and pre-bed range of 90-150 mg/dL. Effective monitoring for these patients includes frequent blood glucose checks up to six to ten times per day, including before meals and snacks, at bedtime, and as needed for exercise, driving, and/or presence of hypoglycemia symptoms. Notably, better glucose control for pediatric and adolescent populations has been demonstrated with multiple daily injections and insulin pumps when compared to a twice daily regimen. Use of newer technologies for insulin delivery and monitoring, such as sensor-augmented and/or automated insulin pumps and continuous glucose monitoring (CGM), in conjunction with insulin analogs, have all been shown to reduce the risk of hypoglycemia with associated lower A1c targets.

Other necessary considerations for the pediatric and adolescent population include distinctions in insulin absorption and insulin requirements. Insulin activity has particular variability in children, as young children with less subcutaneous fat will have faster absorption, and, inversely, a higher percentage of subcutaneous fat will result in slower absorption. Absorption has shown to be quick (~15 minutes) when administered in the abdomen, intermediate (~20 minutes) with lateral arm injection, and slow (~30 minutes) for both front/lateral position of the thigh and the lateral upper quadrant of the buttocks. Insulin requirements evolve as these patients continue to grow: In the partial remission phase, or the honeymoon phase, where endogenous insulin is produced following the initial introduction of insulin treatment, a total daily dose of <0.5 units/kg/day may be required, whereas for prepubertal children, insulin dosing requirements may be between 0.7 to 1 units/kg/day, and during puberty, requirements may reach up to 2 units/kg/day. It is also interesting to note that the mechanisms which invoke the dawn phenomenon, or a rise in morning blood glucose levels, including increased nocturnal growth hormone secretion and increased resistance to insulin, are even more significant in puberty. Because of this, it may be appropriate to utilize an intermediate acting insulin later in the evening or longer acting basal insulin at bedtime for patients who do not utilize an insulin pump.

For a comprehensive comparison, the various insulins with considerations for pediatrics and adolescents is provided in the table below.1,2,3,6



Diabetes represents a complex disease state which requires extensive knowledge and practice in the individualization of treatment. These special considerations are made even more apparent in the pediatric and adolescent population as the continued growth and development of these patients provides multiple opportunities for adjustments in insulin treatment. Furthermore, understanding the intricacies of insulin therapy management is a crucial step in ensuring safe and effective therapy when optimizing each patient’s regimen.

Diabetes represents a complex disease state which requires extensive knowledge and practice in the individualization of treatment. These special considerations are made even more apparent in the pediatric and adolescent population as the continued growth and development of these patients provides multiple opportunities for adjustments in insulin treatment. Furthermore, understanding the intricacies of insulin therapy management is a crucial step in ensuring safe and effective therapy when optimizing each patient’s regimen. 

References:

  1. Danne T, Phillip M, Buckingham BA, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Insulin treatment in children and adolescents with diabetes. Pediatric Diabetes. 2018;19(Suppl. 27):115-135. DOI: 10.1111/pedi.12718
  2. American Diabetes Association. 13. Children and adolescents: Standards of Medical Care in Diabetes - 2021. Diabetes Care 2021;44(Suppl. 1):S180-S199. https://doi.org/10.2337/dc21-S013
  3. Children and Adolescents: Standards of Medical Care in Diabetes – 2020. Diabetes Care 2020;43(Suppl. 1):S163-2182. DOI: 10.2337/dc20-S013
  4. Donaghue KC, Marcovecchio ML, Wadwa RP, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Microvascular and macrovascular complications in children and adolescents. Pediatric Diabetes. 2018;19(Suppl. 27):262-274. DOI: 10.1111/pedi.12742
  5. DiMeglio LA, Acerini CL, Codner E, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatric Diabetes. 2018;19(Suppl. 27):105-114. DOI: 10.1111/pedi.12737
  6. Insulin NPH, Insulin Regular, Insulin Glargine, Insulin Detemir, Insulin Aspart, Insulin Degludec. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed December 10, 2020.
  7. Danne T, Phillip M, Buckingham BA, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Insulin treatment in children and adolescents with diabetes. Pediatric Diabetes. 2018;19(Suppl. 27):115-135. DOI: 10.1111/pedi.12718
  8. American Diabetes Association. 13. Children and adolescents: Standards of Medical Care in Diabetes - 2021. Diabetes Care 2021;44(Suppl. 1):S180-S199. https://doi.org/10.2337/dc21-S013
  9. Children and Adolescents: Standards of Medical Care in Diabetes – 2020. Diabetes Care 2020;43(Suppl. 1):S163-2182. DOI: 10.2337/dc20-S013
  10. Donaghue KC, Marcovecchio ML, Wadwa RP, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Microvascular and macrovascular complications in children and adolescents. Pediatric Diabetes. 2018;19(Suppl. 27):262-274. DOI: 10.1111/pedi.12742
  11. DiMeglio LA, Acerini CL, Codner E, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatric Diabetes. 2018;19(Suppl. 27):105-114. DOI: 10.1111/pedi.12737
  12. Insulin NPH, Insulin Regular, Insulin Glargine, Insulin Detemir, Insulin Aspart, Insulin Degludec. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed December 10, 2020.

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