Insulin Analogues in Children and Teens with Type Diabetes Advantages and Caveats

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Marianna Rachmiel, MD, Kusiel Perlman, MD, FRCPC, Denis Daneman, MB, BCh, FRCPC*

Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8

Type 1 diabetes mellitus (T1D) is a chronic, metabolic disorder that most commonly presents during childhood and is characterized by absolute insulin deficiency. T1D is caused by selective immune-mediated autoreactive T-cell destruction of beta cells in the pancreatic islets of Langerhans [1]. Insulin deficiency leads to chronic hyperglycemia and other disturbances of intermediary metabolism. As a result, individuals who have diabetes are at risk of developing progressive long-term microvascular (eg, retinopathy, nephropathy, and neuropathy) and macrovascular (eg, cerebral, coronary, and peripheral vascular disease) complications [2]. The seminal trial in T1D, the Diabetes Control and Complications Trial, proved in adults and adolescents that the onset and progression of the microvascular complications can be prevented or delayed by tight control of blood glucose levels [2-4].

Although advanced complications are rare in youth, the demonstration of glycemic memory in follow-up studies of the Diabetes Control and Complications Trial cohort mandates the implementation of meticulous glycemic control in all individuals who have T1D as early as possible in the course of the disease [4]. This goal is particularly difficult to achieve in the pediatric population because of the increased risk for hazardous hypoglycemia [5-9], fluctuating insulin requirements caused by exercise, illness, and variable carbohydrate intake, and psychosocial and physiologic issues related to age, puberty, and weight gain [10,11]. Adolescents who have T1D have higher average HbA1c levels compared with adults [8,11,12], which is probably the result of a combination of biologic

T Corresponding author.

E-mail address: [email protected] (D. Daneman).

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