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Canadian Pharmacists Association
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Chapter 35: Type 2 Diabetes in Children and Adolescents

Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada

Introduction   
  • Type 2 diabetes in children has increased in frequency around the world over the past 2 decades.
  • Children from ethnic groups at high risk for type 2 diabetes, including Aboriginal, African, Arabic, Hispanic or Asian descent, are disproportionally affected.
  • A recent Canadian national surveillance study demonstrated a minimum incidence of type 2 diabetes in children and adolescents <18 years of age of 1.54 per 100 000 children per year.
Prevention
  • Breastfeeding has been shown to reduce the risk of youth-onset type 2 diabetes in some populations.

  • Anticipatory guidance promoting healthy eating, maintenance of a healthy weight and regular physical activity is recommended as part of routine pediatric care [Grade D, Consensus].

  • Obesity is a major modifiable risk factor for the development of type 2 diabetes. In obese children, dietary modifications and regular clinic visits have been shown to have little benefit for weight reduction. While data are limited, family-based lifestyle interventions with a behavioral component aimed at changes in diet and physical activity patterns have been shown to result in significant weight reduction in both children and adolescents.

  • Health Canada-endorsed recommendations for physical activity and nutrition in children can be accessed on the Canadian Society Exercise Physiology and Health Canada websites.

  • Intensive lifestyle intervention, including dietary and exercise interventions, family counselling and family-oriented behaviour therapy, should be undertaken for obese children in order to achieve and maintain a healthy body weight [Grade D, Consensus].

  • Several studies suggest that lifestyle changes plus pharmacotherapy may act synergistically when lifestyle intervention is aggressively pursued.

    • While both metformin and orlistat have potential for short-term positive effects on weight, glycemic control, insulin sensitivity and/or lipids, no pediatric studies have been performed to assess the prevention of diabetes or long-term complications.
    • As such, the use of antiobesity drugs in children should only be considered in this population within the context of a supervised clinical trial.

Screening and Diagnosis

  • The microvascular complications of type 2 diabetes have been identified at diagnosis, implying long-term, unrecognized hyperglycemia.
  • Children may also present with acute decompensation in diabetic ketoacidosis (DKA) and/or hyperosmolar coma. This argues for a systematic screening program aimed to identify children with type 2 diabetes in order to prevent acute, life-threatening presentation and to decrease the development of chronic complications.
  • Thus, consideration should be given for screening at a younger age in high-risk individuals.
  • Screening for type 2 diabetes should be performed every 2 years using an FPG test in children with any of the following:
    • ≥3 risk factors in nonpubertal or ≥2 risk factors in pubertal children [Grade D, Consensus]
      • Obesity (BMI ≥95th percentile for age and gender) [Grade D, Level 4]
      • Member of a high-risk ethnic group (e.g. Aboriginal, African, Asian, Hispanic or South Asian descent) [Grade D, Level 4]
      • Family history of type 2 diabetes and/or exposure to hyperglycemia in utero [Grade D, Level 4]
      • Signs or symptoms of insulin resistance (including acanthosis nigricans, hypertension, dyslipidemia, NAFLD [ALT >3X upper limit of normal or fatty liver on ultrasound], PCOS) [Grade D, Level 4]
    • Impaired fasting glucose or impaired glucose tolerance [Grade D, Consensus]
    • Use of atypical antipsychotic medications [Grade D, Consensus]
  • An oral glucose tolerance test (1.75 g/kg; maximum 75 g) may be used as a screening test in very obese children (BMI ≥99th percentile for age and gender) or those with multiple risk factors who meet the criteria in recommendation 3 [Grade D, Consensus].
  • Glycated hemoglobin (A1C) is not recommended as a method to diagnose type 2 diabetes in children. Otherwise, the diagnostic criteria for diabetes in children are the same as for adults.
Classification
  • In most children, the presence of clinical risk factors, mode of presentation and early course of the disease indicate whether the child has type 1 or type 2 diabetes. However, differentiation may be difficult in some.

  • Children with type 2 diabetes can present with DKA.

  • Testing for the absence of islet autoantibodies may be useful.

  • Fasting insulin levels are not helpful at diagnosis, as levels may be low due to glucose toxicity.

  • DNA diagnostic testing for genetic defects in beta cell function should be considered in children who have a strong family history suggestive of autosomal dominant inheritance and who are lacking features of insulin resistance. This may be helpful when diabetes classification is unclear and may lead to more appropriate management.

Management
  • Commencing at the time of diagnosis of type 2 diabetes, all children should receive ongoing intensive counseling, including lifestyle modification, from an interdisciplinary pediatric healthcare team [Grade D, Level 4].

  • The target A1C for most children with type 2 diabetes should be ≤7.0% [Grade D, Consensus].

  • To be effective, treatment programs for adolescents with type 2 diabetes need to address the lifestyle and health habits of the entire family, emphasizing healthy eating and physical activity.
  • Children with type 2 diabetes should strive to achieve the same activity level recommended for children in general: 60 minutes daily of moderate-to-vigorous physical activity and limiting sedentary screen time to no more than 2 hours per day.
  • In children with type 2 diabetes and A1C ≥9.0% and in those with severe metabolic decompensation (e.g. DKA), insulin therapy should be initiated but may be successfully weaned once glycemic targets are achieved, particularly if lifestyle changes are effectively adopted [Grade D, Level 4].
  • In children with type 2 diabetes, if glycemic targets are not achieved within 3–6 months using lifestyle modifications alone, one of the following should be initiated:
    • Metformin [Grade B, Level 2] OR
    • Glimepiride [Grade B, Level 2] OR
    • Insulin [Grade D, Consensus]
  • There are limited data about the safety or efficacy of oral antihyperglycemic agents in the pediatric population, and none of the oral antidiabetic agents have been approved by Health Canada for use in children.
    • Metformin has been shown to be safe in adolescents for up to 16 weeks, reducing A1C by 1.0% to 2.0% and lowering FPG with similar side effects as seen in adults.
    • Glimepiride has also been shown to be safe and effective in adolescents for up to 24 weeks, reducing A1C to a similar extent as metformin but resulting in a significant weight increase of 1.3 kg.
  • If the decision is made to use an oral antihyperglycemic agent, metformin should be used over glimepiride [Grade D, Consensus]. Metformin may be used at diagnosis in those children presenting with A1C >7.0% [Grade B, Level 2].
  • Insulin is required in those with severe metabolic decompensation at diagnosis (e.g. DKA, glycated hemoglobin A1C ≥9.0%, symptoms of severe hyperglycemia) but may be successfully weaned once glycemic targets are achieved, particularly if lifestyle changes are effectively adopted
  • The experience of bariatric surgery in adolescents with type 2 diabetes is very limited with specific eligibility criteria (BMI >35 kg/m2, Tanner stage IV or V, and skeletal maturity). A single retrospective case series of 11 postpubertal adolescents with type 2 diabetes who underwent roux-en-Y gastric bypass demonstrated significant improvements in BMI, glycemic control, serum lipid levels and blood pressure (BP) compared to 67 adolescents who were medically managed over 1 year (47) . Notably, 10 of the 11 surgically treated youth experienced remission of their diabetes without the need for medication.

Table 1: Screening for Diabetes Complications and Comorbidities in Children with Type 2 Diabetes

Compluication/ Comorbid condition

Indications and intervals for screening

Screening test

Dyslipidemia

Screening should commence at diagnosis of diabetes and every 1-3 years thereafter as clinically indicated

Fasting TC, HDL-C, TG, calculated LDL-C

Hypertension

At diagnosis of diabetes and every diabetes-related clinical encounter thereafter (at least twice annually)

BP measurement using appropriately sized cuff

NAFLD

 

 

Nephropathy

Yearly screening commencing at diagnosis of diabetes

Yearly screening commencing at diagnosis of diabetes

ALT

  • First morning (preferred) or random ACR
  • Abnormal ACR requires confirmation at least 1 month later with either a first morning ACR or timed overnight urine collection for ACR
  • Repeated sampling should be done every 3 to 4 months over a 6- to 12-month period to demonstrate persistence

Neuropathy

Yearly screening commencing at diagnosis of diabetes

Questioned and examined for:

  • Symptoms of numbness, pain, cramps, and paresthesia
  • Vibration sence
  • Light touch and ankle reflexes

PCOS

Yearly screening commencing at diagnosis of diabetes in pubertal females

Clincial assessment on history and physical exam for olgio/amenorrhea, acne, and/or hirsutism

  • Seven-standard fielt, stereoscopic colour fundus photography with interpretation by a trained reader (gold standard); or
  • Direct ophthalmoscopy or indirect slit-lamp funduscopy through dilated pupil; or
  • Digital fundus photography

Retinopathy

Yearly screening commencing at diagnosis of diabetes

ACR albumin to creatinine ratio; ALT, alanine aminotransferase; BP, blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; NAFLD, non-alcoholic fatty liver disease; PCOS, polycycstic ovary syndrome; TC, total cholesterol; TG, triglycerides.

Immunization
  • There are no recommendations for influenza and pneumococcal immunization in Canada for children with type 2 diabetes, and there are no studies evaluating the usefulness of the influenza or pneumococcal vaccine in this population.
  • These children should be managed in a similar fashion to those with type 1 diabetes in whom influenza immunization is recommended to avoid an intercurrent illness that could complicate diabetes management.
Complications
  • Short-term complications of type 2 diabetes in children include DKA and hyperglycemic hyperosmolar state (HHS); 10% of Canadian youth present with DKA at the time of diagnosis.
  • Children with type 2 diabetes should be screened annually for microvascular complications (nephropathy, neuropathy, retinopathy) beginning at diagnosis of diabetes [Grade D, Level 4].
    • Evidence suggests that early-onset type 2 diabetes in adolescence is associated with severe and early-onset microvascular complications, including retinopathy, neuropathy and nephropathy. Although neither retinopathy nor neuropathy has been described in adolescents with type 2 diabetes at diagnosis, 1 study found that 1 in 5 youth with type 2 diabetes had peripheral nerve abnormalities, and more than half had autonomic neuropathy after a median duration of diabetes of 1.3 years.
  • Children with type 2 diabetes should be screened for microalbuminuria with a first morning urine ACR (preferred) [Grade B, Level 2] or a random ACR [Grade D, Consensus]. Abnormal results should be confirmed [Grade B, Level 2] at least 1 month later with a first morning ACR and, if abnormal, followed by timed, overnight urine collection for albumin excretion rate [Grade D, Consensus]. Microalbuminuria [ACR > 2.5 mg/mmol] should not be diagnosed in adolescents unless it is persistent as demonstrated by 2 consecutive first morning ACR or timed collections obtained at 3- to 4-month intervals over a 6- to 12-month period [Grade D, Consensus]. Those with persistent albuminuria should be referred to a pediatric nephrologist for assessment of etiology and treatment [Grade D, Level 4].
    • Micro- or macroalbuminuria has been noted in 14.2% of Canadian youth at diagnosis and in up to 22.2% of US youth with a mean diabetes duration of 1.9 years.
Comorbid Conditions
  • Children with type 2 diabetes have an increased prevalence of dyslipidemia, with 44.8% of Canadian children reported to have dyslipidemia at the time of diagnosis. Children with type 2 diabetes should have a fasting lipid profile measured at diagnosis of diabetes and every 1–3 years thereafter, as clinically indicated [Grade D, Consensus].
    • In children with familial dyslipidemia and a positive family history of early cardiovascular events, a statin should be started if the low-density lipoprotein cholesterol level remains >4.1 mmol/L after a 3- to 6-month trial of dietary intervention. A similar approach seems reasonable in the absence of evidence to recommend a specific intervention in children with type 2 diabetes.
  • Children with type 2 diabetes should be screened for hypertension beginning at diagnosis of diabetes and at every diabetes-related clinical encounter thereafter (at least biannually) [Grade D, Consensus].

    • Up to 36% of adolescents with type 2 diabetes have hypertension.
  • Children with type 2 diabetes should be screened at diagnosis for comorbid conditions associated with insulin resistance, including NAFLD [Grade D, Level 4] and PCOS in pubertal females [Grade D, Level 4], and yearly thereafter as clinically indicated [Grade D, Consensus].

    • PCOS was reported in 12.1% and NAFLD (defined as alanine aminotransferase [ALT] >3× the upper limit of normal or fatty liver on ultrasound) in 22.2% of children and youth at diagnosis of type 2 diabetes.


For definitions of the levels of evidence cited in this chapter, please refer to the Guideline Recommendations: Levels of Evidence.

If you would like more details on this topic, please visit the Canadian Diabetes Association Clinical Practice Guidelines: Chapter 35.