ReviewThe evaluation and management of childhood type 2 diabetes mellitus
Introduction
Abdominal obesity and a propensity toward upper body fat play a prominent role in the development of insulin resistance and/or type 2 diabetes in adults [1] and in children. Tight glucose control as a mediator to complication prevention in the population with type 2 diabetes is promoted based on the findings of the hallmark United Kingdom Prospective Diabetes Study [2]. Many treatment approaches paradoxically contribute to the obesity epidemic through relative increases in circulating insulin levels or improved insulin sensitivity by promoting adiposity. The adiposity that results from enhanced insulin function and availability place individuals at risk for further insulin resistance and obesity. The paradoxical phenomenon of worsening insulin resistance through treatment-induced weight gain can be termed metabolic-lock-in syndrome. The purpose of this article is to provide an introduction to current treatment paradigms and a multidisciplinary approach to care.
Section snippets
Epidemiology and risk factors
Diabetes is a global problem, expected to reach pandemic proportions by 2030, with most noticeable impact in third world countries [3]. Generally, children with type 2 diabetes are between the ages of 10 and 19 years of age, obese, insulin resistant, have a strong family history for type 2 diabetes, and have glycosylated hemoglobin (HbA1c) levels between 10% and 12% good control is defined as below 7% by the American Diabetes Association (2010) [4] indicating poor control [5]. Currently, in the
Diagnostic criteria
Type 2 diabetes is hallmarked by a main component referred to as insulin resistance. Insulin resistance can be described as impairment in the way glucose, lipids, protein metabolism, and vascular endothelium respond to the physiologic effects of insulin [10]. Insulin resistance eventually results in pancreatic beta cell loss that results in an actual insulin deficiency. According to the World Health Organization (WHO), diabetes is an inherited and/or acquired-deficiency in pancreatic insulin
Pathophysiology of type 2 diabetes and insulin resistance
Abdominal obesity results in hepatic visceral adiposity, the primary culprit in the insulin resistance syndrome. Hepatic fat deposits enter the portal blood stream resulting in circulating free fatty acids non-esterified fatty acids (NEFAs) that impair musculoskeletal insulin receptor function [12], [13]. NEFAs are essential for adequate glucose-stimulated insulin secretion in lean, non-diabetic individuals. However, increased plasma free fatty acid (FFA) levels reduce skeletal muscle and
Assessment and identification of insulin resistance
Although the “classic” symptoms are recognizable, yet also insidious in the adult population, early detection in children is ever more challenging. The hallmark symptom of diabetes, glycosuria-induced polyuria [4] may present as nocturia, bedwetting, or regression to incontinence in a previously diaper trained toddler. Other shared symptoms include fatigue and polyphagia [4]. Fatigue may present as irritability or behavior change. For example, school performance or athletic performance may
Pharmacologic treatment paradigms
Two mainstream treatment paradigms have emerged, the traditional glucocentric paradigm, in which hyperglycemia is viewed as a disease of primarily impaired glucose metabolism or the lipocentric paradigm in which hyperglycemia is viewed as secondary to metabolic damage caused by lipotoxicity [29]. Under the lipocentric treatment paradigm, insulin treatment is viewed largely as insulting the insulin resistant state as opposed to improving it [20]. The competing contemporary treatment paradigms
Treatment paradigms and obesity
Treatment approaches that optimize HbA1c control to below 7% almost always lead to significant weight gain of 2–5 kg on average [31], [32]. Multiple studies have demonstrated that the following therapeutic agents promote weight gain in the context of reducing HbA1c: (1) insulin [33], [34], [35]; (2) thiazoldindiones (TZD) [36], [37] and; (3) sulfonylureas [38]. The conventional glucocentric treatment approach paradoxically plays a role in furthering the obesity-induced insulin resistance. The
Tailoring adult-treatment regimens to children
Most diabetes treatment trials in children focus on the obese adolescent population. The prevalence of type 2 diabetes in children is quickly emerging, but drug studies designed to treat children are rare or inadequately powered to detect a high probability of efficacy. It is difficult to recruit the needed number of children to demonstrate treatment effectiveness. Finding a large enough sample of children affected by the disease in order to conduct between subjects comparisons is challenging.
Home blood glucose monitoring
Although home self-monitoring of blood glucose using a hand-held device remains the mainstay of monitoring, continuous blood glucose monitors (CBMG) are rapidly becoming available. CBMG offers continuous real-time assessment of glucose alterations which makes it ideal for earlier intervention for hypoglycemia management. It is especially useful in patient populations that experience hypoglycemia unawareness either because of their developmental status or neurologic impairment (i.e. autonomic
Psychosocial and behavioral considerations
Every chronic disease affecting a child has a unique impact on children and their families. Diabetes is made ever more challenging because even if ideal multidisciplinary approached care can be full-filled, self-empowered care requires a high degree of self advocacy, health literacy, and numeracy [63], [64]. Caregivers should be screened for potential limitations in health literacy and numeracy using validated measures. The intrusive nature of diabetes as a chronic illness [65] may affect
Translating adult weight loss options to children
Weight loss with medication or surgery are emerging as viable options for adolescents who have attained the bulk of their skeletal maturity (i.e. girls aged over 13; boys aged over 15) [74]. Medications such as Orlistat are effective in adolescents and result in weight loss through malabsorption of fatty acids in the gut [75]. The primary limitation for adolescents is the co-malabsorption of fat soluble vitamins (Vitamins A, D, E, and K) [76]. Malabsorption of fat soluble vitamins will affect
Conclusion
In conclusion, insulin resistant type 2 diabetes is a complex condition. Knowledge from effective adult treatment approaches needs to be translated and adapted to children. Much of the evidence regarding metabolic outcomes of treatment approaches and coping and psychological well-being come from adult studies. Although easily translatable to older adolescents, clinicians are often times left feeling uncertain about how to manage and treat very young children and adolescents with type 2
Conflict of interest
The authors state that they have no conflict of interest.
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