The Journal of Pediatrics
Volume 155, Issue 3 , Pages 308-309, September 2009

Pramlintide in Pediatric Type 1 Diabetes

  • Ilene Fennoy, MD, MPH

      Affiliations

    • Corresponding Author InformationReprint requests: Ilene Fennoy, MD, MPH, Department of Pediatrics, Columbia University, 630 W. 168th St, PH5E-522, New York, NY 10032.

Division of Pediatric Endocrinology, Department of Pediatrics, Columbia University, 630 W. 168th St, PH5E-522, New York, NY

Article Outline

 

See related article, p 369

Blood glucose control to near-normal glycemia remains the goal of treatment in type 1 diabetes.1, 2 Yet achieving this goal without undue side effects is often difficult. Insulin therapy with multiple insulins each with a different action profile and with multiple regimens, including basal-bolus administration, continuous pump therapy, and inhaled insulin have all attempted to overcome this issue,3, 4, 5 not always with success. Weight gain, hypoglycemia, and suboptimal reduction of hemoglobin A1c have all been limitations of insulin therapy.4 Adjunct therapies to improve glycemic control are needed.

Normally, insulin is cosecreted with amylin, a 37–amino acid protein produced in the β-cells of the pancreas and stored there in secretory granules.6 The pathophysiological process of the β-cell in type 1 diabetes includes not only loss of insulin release, but also loss of amylin and alterations in α-cell release of glucagon.7 Indeed, glucose homeostasis is not only the result of insulin action, but a function of the interplay of multiple hormones. Amylin is cosecreted with insulin, decreased in type 1 diabetes, increased in early type 2 diabetes, and decreased in end-stage type 2 diabetes.8 In animal models, amylin delays gastric emptying9, 10 and amylin receptor blockade accelerates gastric emptying.11 It also inhibits glucagon secretion.12

Human amylin is unfortunately a fibrillar protein that tends to aggregate, making it unsuitable for therapeutic administration.13 Pramlintide, a synthetic analogue of amylin, was developed to overcome this obstacle. Pramlintide demonstrates the same spectrum of activities, as does amylin with delayed gastric emptying and inhibition of glucagon secretion.7, 14, 15 It was approved for use in adult patients with type 1 and type 2 diabetes in 2005 as a subcutaneous injectible medication. Data demonstrate that use of this agent is associated with improved blood glucose control in adult patients with both type 1 diabetes16 and type 2 diabetes and is associated with a small amount of weight loss.15 However, pramlintide injection has been associated with nausea, anorexia, and hypoglycemia, although the hypoglycemia was at no greater frequency than that seen with insulin therapy.17

In adolescents with type 1 diabetes, as seen in adults, pramlintide injection has resulted in inhibition of glucagon secretion, delayed gastric emptying and improved postprandial blood glucose control.18 Hypoglycemia also occurred, raising concerns about appropriate dosing regimens and safety in the adolescent age group. In this issue of The Journal, Chase et al19 studied adolescents in a single-blind, randomized controlled, crossover trial to establish the pharmacokinetics and safety profile of pramlintide in adolescents. They have been able to provide needed evidence for the development of appropriate dosing regimens to allow for the safe use of this medication in the adolescent population. On the basis of its ability to improve blood glucose profiles, reduce weight, and increase hypoglycemic events, pramlintide offers benefits to patients with fluctuating blood glucose control who are investing significant effort to limit excursions. More studies with greater numbers of children and over a longer period of time will be needed before pramlintide can be routinely included in the diabetic pediatric population.

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References 

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  19. Chase P, Lutz K, Pencek R, Zhang B, Porter L. Pramlintide lowered glucose excursions and was well-tolerated in adolescents with type 1 diabetes: results from a randomized, single-blind, placebo-controlled, crossover study. J Pediatr. 2009;155:369–373

PII: S0022-3476(09)00471-5

doi:10.1016/j.jpeds.2009.04.065

Refers to article:

  • Pramlintide Lowered Glucose Excursions and Was Well-Tolerated in Adolescents with Type 1 Diabetes: Results from a Randomized, Single-Blind, Placebo-Controlled, Crossover Study , 22 May 2009

    H. Peter Chase, Karen Lutz, Richard Pencek, Bei Zhang, Lisa Porter
    The Journal of Pediatrics September 2009 (Vol. 155, Issue 3, Pages 369-373)

The Journal of Pediatrics
Volume 155, Issue 3 , Pages 308-309, September 2009

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