Elsevier

Primary Care Diabetes

Volume 5, Issue 3, October 2011, Pages 151-158
Primary Care Diabetes

Review
The evaluation and management of childhood type 2 diabetes mellitus

https://doi.org/10.1016/j.pcd.2011.04.002Get rights and content

Abstract

Diabetes in children is increasing in prevalence with obesity-associated insulin resistance being a major contributing factor. This report contains a comprehensive review of treatment paradigms regarding the management of diabetes in children. The information provided was collected from an extensive literature review on type 2 diabetes, and children and/or adolescents with diabetes and/or obesity treatment. There is a wide array of contributing factors to the development of diabetes and consequences that indicate the need to tailor treatment plans with reducing obesity as a primary outcome. Lipocentric treatment paradigms offer opportunity to reduce the impact of obesity.

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.

References (80)

  • Centers for Disease Control and Prevention, Children and Diabetes-More Information,...
  • G.E. Duncan

    Prevalence of diabetes and impaired fasting glucose levels among US adults. National health and Examination Survey, 1999–2002

    Arch. Pediatr. Adolesc. Med.

    (2006)
  • International Diabetes Federation, Children and type 2 diabetes, 2004, http://www.idf.org/children-and-type-2-diabetes...
  • CDC Press Release, CDC funds registries for childhood diabetes, http://www.cdc.gov/media/pressrel/r2k1226.htm (accessed...
  • H.E. Lebovitz

    Insulin resistance: definition and consequences

    Exp. Clin. Endocrinol. Diabetes

    (2001)
  • World Health Organization, Diabetes, http://www.who.int/diabetes/en/ (accessed...
  • L.R. Roust et al.

    Postprandial free fatty acid kinetics are abnormal in upper body obesity

    Diabetes

    (1993)
  • J.D. McGarry et al.

    Fatty acids, lipotoxicity and insulin secretion

    Diabetologia

    (1999)
  • G. Boden et al.

    Mechanisms of fatty acid-induced inhibition of glucose uptake

    J. Clin. Invest.

    (1994)
  • G. Boden et al.

    Effects of fat on insulin-stimulated carbohydrate metabolism in normal men

    J. Clin. Invest.

    (1991)
  • P.J. Turnbaugh et al.

    An obesity-associated gut microbiome with increased capacity for energy harvest

    Nature

    (2006)
  • M. Kolak et al.

    Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity

    Diabetes

    (2007)
  • K.F. Petersen et al.

    The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome

    Proc. Natl. Acad. Sci. U.S.A.

    (2007)
  • E. Fabbrini et al.

    Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease

    Gastroenterology

    (2008)
  • R.H. Unger

    Reinventing type 2 diabetes. Pathogenesis, treatment, and prevention

    JAMA

    (2008)
  • M. Shimabukuro et al.

    Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes

    Proc. Natl. Acad. Sci. U.S.A.

    (1998)
  • B.C. Martin et al.

    Familial clustering of insulin sensitivity

    Diabetes

    (1992)
  • G. Schernthaner et al.

    Progress in the characterization of slowly progressive autoimmune diabetes in adult patients (LADA or type 1.5 diabetes)

    Exp. Clin. Endocrinol. Diabetes

    (2001)
  • M.J. Hepburn et al.

    The accuracy of the report of hepatic steatosis on ultrasonography in patients infected with hepatitis C in a clinical setting: a retrospective observational study

    BMC Gastroenterol.

    (2005)
  • R.D. Leslie et al.

    Clinical review: type 1 diabetes and latent autoimmune diabetes in adults: one end of the rainbow

    J. Clin. Endocrinol. Metab.

    (2006)
  • P. Dandona et al.

    Insulin therapy and lipid overload in type 2 diabetes

    JAMA

    (2008)
  • A.G. Mainous et al.

    Development of a measure to assess patient trust in medical researchers

    Ann. Fam. Med.

    (2006)
  • S.E. Kahn et al.

    Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy

    N. Engl. J. Med.

    (2006)
  • H.C. Gerstein et al.

    Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomized controlled trial

    Lancet

    (2006)
  • A. Salle et al.

    Effect of insulin treatment on the body composition of type 2 diabetic patients

    Diabet. Med.

    (2004)
  • A. Salle et al.

    ‘Glucose control-related’ and ‘non-glucose control-related’ effects of insulin on weight gain in newly insulin-treated type 2 diabetic patients

    Br. J. Nutr.

    (2005)
  • S. Makimattila et al.

    Causes of weight gain during insulin therapy with and without metformin in patients with type II diabetes mellitus

    Diabetologia

    (1999)
  • S.E. Kahn et al.

    Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy

    N. Engl. J. Med.

    (2006)
  • A. Basu et al.

    Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes

    Diabetes Care

    (2006)
  • D.S. Bell et al.

    Long-term glycaemic efficacy and weight changes associated with thiazolidinediones when added at an advanced stage of type 2 diabetes

    Diabetes Obes. Metab.

    (2006)
  • Cited by (0)

    View full text