Continuing Education Activity

Type 2 diabetes mellitus is a metabolic disorder characterized by peripheral insulin resistance, leading to hyperglycemia. Once considered a predominantly adult disease, it has become a pressing concern in the field of pediatrics due to its rising incidence, mainly attributable to lifestyle factors and childhood obesity. This condition presents unique challenges in diagnosis, management, and long-term care compared to its type 1 counterpart, emphasizing the need for specialized knowledge and a patient-centered approach. Early screening, recognition, and treatment of children with type 2 diabetes are crucial for preventing long-term complications. This activity delves into the key aspects of pediatric type 2 diabetes, shedding light on its causes, diagnostic criteria, management strategies, and its broader impact on the health and well-being of affected children and adolescents. It also highlights the role of interprofessional team members in collaborating to provide well-coordinated care and enhance outcomes for affected patients.

Objectives:

• Identify children at risk for type 2 diabetes mellitus.
• Assess glycemic control, complications, and psychosocial needs in pediatric patients with type 2 diabetes mellitus.
• Implement evidence-based interventions for managing pediatric type 2 diabetes mellitus, including lifestyle modifications, pharmacological therapies, and behavioral support.
• Coordinate amongst an interprofessional team to enhance care for children and adolescents affected by type 2 diabetes mellitus.

Introduction

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by peripheral insulin resistance and a failure of beta cells to compensate, leading to hyperglycemia.[1][2][3] While once considered an adult pathology, it is increasingly prevalent in children.[4] Risk factors for children are similar to those in adults: ethnicity, family history, obesity, and a sedentary lifestyle. However, presentation and management differ from adults with the disorder. Children with diabetes of any kind are at an increased risk of many complications. Early recognition, screening, and treatment of children and adolescents with T2DM are important for preventing long-term complications from the disease.[5]

Etiology

Hyperglycemia results when there is a relative lack of insulin compared to glucose in the blood. In T2DM, insulin resistance first leads to increased insulin production by the beta cells of the pancreas.[5] Hyperglycemia results when the beta cells cannot produce enough insulin to maintain euglycemia. Hyperglycemia damages multiple organs, including kidneys, eyes, heart, and nerves. Further, hyperglycemia puts children at risk for other electrolyte disturbances.[6]. Compared to adults, children with T2DM develop complications earlier and are often more challenging to manage.[7]

There has been an increase in the diagnosis of T2DM secondary to the ever-increasing rates of obesity.[8][9] The general cause of adult and T2DM is similar, with some pathophysiological differences as mentioned below.[5]

Epidemiology

Type 1 diabetes mellitus (T1DM) remains the most prevalent form of diabetes in children. However, T2DM is estimated to occur in 1 in 3 (20% to 33%) of new diagnoses of diabetes in children today. The rate of T2DM in children continues to rise even as the obesity rates have plateaued in these age groups.[10][11][12] Girls are more affected than boys.[12] Risk factors include high-risk ethnicity (African American, Hispanic, Native American, Pacific Islanders, Asian Americans), a positive first-degree relative with the disorder, obesity, low birth weight, a mother with gestational diabetes, and female sex. It is more likely to be diagnosed during adolescence when insulin resistance is common due to multiple factors, including hormonal changes. [10][11] 

Pathophysiology

Obesity leads to peripheral insulin resistance, which in turn leads to hyperglycemia. Insulin resistance occurs in multiple organs and tissues, eventually leading to beta-cell failure.[7] Generally speaking, insulin resistance can be present for a significant period of time before the diagnosis of T2DM.[7] It is important to note that visceral obesity, rather than BMI, may be a better predictor for the complications of insulin resistance, including T2DM and hypertension.[7] Independent of obesity, certain ethnicities have higher risks of insulin resistance and beta cell dysfunction. In addition, hormonal changes at puberty result in temporary insulin resistance, leading to hyperglycemia and the risk of developing T2DM.[13] Hyperglycemia leads to an osmotic diuresis (polyuria), which increases thirst (polydipsia). This diuresis causes moderate to severe dehydration.

Prolonged hyperglycemia can produce 2 distinct emergent states in T2DM in children: [14]

• Diabetic Ketoacidosis (DKA): much more common in children with T2DM than adults. Lack of insulin inhibits the body's ability to use glucose for energy and reverts to breaking down fat for energy. This leads to ketosis, acidosis, and electrolyte abnormalities and may lead to coma and death.                                               
• Hyperglycemic Hyperosmolar State (HHS): characterized by hypertonicity, extreme hyperglycemia (>600 mg/dl), and severe dehydration. The profound hyperglycemia results in continued osmotic diuresis and intravascular depletion. 

History and Physical

Children with T2DM most often present during asymptomatic screening.

Children may have the typical symptoms of polyuria, polydipsia, polyphagia, and weight loss. Children with T2DM are more likely than adults with the disorder to present in DKA (5% to 13%), especially if they are of ethnic minority descent. Adolescents with T2DM may also present in HHS. 

Physical examination findings may include acanthosis nigricans (a dark, velvety rash on the axillae and/or neck). The American Diabetes Association (ADA) recommends screening children at 10 years old or at the start of puberty in children who are obese (>95th percentile BMI for age) or are overweight (BMI >85th percentile for age or >120% ideal body weight) and have 2 risk factors. These factors include a positive family history, high-risk ethnicity, signs of insulin resistance (polycystic ovary syndrome (PCOS), acanthosis nigricans,  diabetic symptoms), or a history of maternal gestational diabetes mellitus.

Evaluation

The American Diabetes Association (ADA) recommends screening for T2DM  every 3 years starting at age 10 years (or at the onset of puberty) for patients who are: [15][16][17]

• Obese (BMI ≥95th percentile for age)                                                                                                     
• Overweight (BMI ≥ 85th percentile for age) and have at least 2 risk factors (positive family history, high-risk race or ethnicity, signs of insulin resistance, maternal history of gestational diabetes). 

Diagnostic Criteria:

• Random plasma blood glucose ≥200 mg/dl with symptoms of polyuria, polydipsia, or weight loss

• Fasting blood glucose ≥126 mg/dl in an asymptomatic patient. 

• Oral glucose tolerance test (GTT) with blood sugar ≥ 200 mg/dl at 2 hours post-ingestion.

• Hemoglobin A1c >6.5%

If the diagnosis between T1DM and T2DM is unclear, helpful labs include fasting insulin or C-peptide (both usually high or normal in T2DM, low in T1DM) and autoantibodies for T1DM.

Treatment / Management

The American Academy of Pediatrics (AAP) recommends lifestyle modifications and metformin as the first-line therapy. Lifestyle changes include moderate to vigorous exercise for 60 minutes daily, limiting screen time to less than 2 hours per day, and a dietary referral.[18][19][20][21]

Metformin and/or insulin should be started at diagnosis. Metformin is first-line and available as a liquid. It can be started at 500 mg/day and increased by 500 mg every 1 to 2 weeks to a maximum of 2000 mg twice per day. The gradual increase of the medication and taking it with food helps to prevent adverse gastrointestinal effects.

Insulin should be started for patients who are ketotic or in DKA, have a random blood glucose >250 mg/dl, a hemoglobin A1c >8.5%, or in whom the diagnosis of T1DM versus T2DM is unclear. A basal/bolus regimen like in T1DM may be used, but typically, T2DM patients require higher doses (2 units/kg/day to 3 units/kg/day). Insulin should be initiated and managed by pediatric endocrinologists. Insulin takers have a risk of hypoglycemia; therefore, frequent monitoring is required.[13]

Home glucose monitoring is recommended for those who take insulin, have not met glucose control goals, are changing medications, or are sick.

Hemoglobin A1c test goals vary by association. The ADA and AAP list an A1c test goal of <7%, while the American Association of Clinical Endocrinologists places the goal at <6.5%.

Differential Diagnosis

The differential diagnosis for pediatric T2DM includes the following:

• Atypical diabetes mellitus (ADM)

• Maturity-onset diabetes of the young (MODY)

• Diabetes secondary to mutations in DNA

• Diseases of the exocrine pancreas

• Drug or chemical-induced diabetes

• Diabetic ketoacidosis (DKA)

• Endocrinopathies

• Genetic defects of beta cells 

• Genetic defects in insulin action 

• Type 1 diabetes mellitus (T1DM)

Prognosis

There have been no long-term prognosis studies for pediatric T2DM. The prognosis is of great concern in the medical community, primarily due to its potential for long-term complications. Many children and adolescents can achieve good glycemic control and lead healthy lives with proper treatment, lifestyle modifications, and regular monitoring. While the condition is manageable, it can lead to significant health challenges if not well-controlled. The risk of complications, including cardiovascular disease, kidney problems, and retinopathy, remains a real and persistent threat. The long-term prognosis is intricately tied to the child's ability to adhere to treatment plans, maintain a healthy lifestyle, and receive consistent medical care. Early diagnosis, comprehensive education, and robust support systems are crucial for improving the prognosis and minimizing the risk of severe complications in pediatric patients with T2DM.

Complications

There are significant long-term complications for children with T2DM, and they often occur earlier in the disease course than their adult counterparts.[7] Evidence shows that these patients begin to experience renal and neurological complications within 10 years of the disease, including the need for dialysis, amputation, and blindness.[22] Compared with children who do not have diabetes, those with diabetes increase their risk of dialysis almost 40-fold.[23] 

For adult patients with T2DM, there is a significant reduction in life expectancy compared to patients without T2DM.[24] Given the recent increase in pediatric T2DM amongst the general population, no data on life expectancy associated with pediatric T2DM exists.

There is also data to suggest that having adult T2DM puts patients at higher risk of further complications such as cancers and other non-vascular causes[25]. In pediatric patients, approximately a quarter of children with T2DM will have hypertension, and slightly over 20% have albuminuria.[26]

Consultations

The specialties often consulted for patients with pediatric T2DM include the following:

• Pediatric Endocrinology                                                                              
• Pediatric Opthalmology
• Pediatric Nephrology
• Registered Dietician
• Child and Adolescent Psychiatry

Deterrence and Patient Education

There is a sizeable familial component to pediatric T2DM.[27] Preventing T2DM in children primarily involves addressing modifiable risk factors, such as obesity and a sedentary lifestyle. Encouraging healthy eating habits, regular physical activity, and weight management can significantly reduce the risk of developing the condition.[28] Public health campaigns, school programs, and community initiatives promoting a healthy lifestyle are essential for deterrence.

Educating pediatric patients and their caregivers about T2DM is paramount. They should understand the importance of dietary choices, portion control, and the significance of regular exercise in managing the condition. Patients need to learn self-monitoring techniques, such as blood glucose testing and the proper administration of medications if prescribed. Patient education should be ongoing and tailored to the child's age and comprehension level.

Incorporating both deterrence strategies and comprehensive patient education into clinical practice can lead to better outcomes and a reduced incidence of pediatric T2DM. By empowering children and their families with the knowledge and the tools to make healthy choices, the medical community can help mitigate the impact of this growing health concern.

Pearls and Other Issues

Complications of T2DM in children are similar to those of adults. Complications tend to occur after a patient has had the disease for many years. Those who are diagnosed in childhood have the disease for longer periods of time. Therefore, strict control and management of blood glucose are crucial to help prevent these complications. All people with diabetes should have regular dilated eye exams (to examine for diabetic retinopathy), urine microalbumin screening at appropriate intervals (to evaluate for renal involvement), hyperlipidemia screens/treatment, hypertension screening/treatment, and regular monitoring.[29]

Enhancing Healthcare Team Outcomes

T2DM in children is best managed by an interprofessional team that includes a pediatrician or primary care provider, endocrinologist, pharmacist, diabetic nurse, dietician, and relevant specialists. It is vital to ensure that these children are also evaluated by an ophthalmologist, nephrologist, cardiologist, and dental surgeon. 

Physicians should have proficiency in diagnosis, medication management, and complication prevention. Nurses play a crucial role in patient education and ongoing monitoring. Pharmacists ensure appropriate medication selection and dosing. Open, transparent communication among team members is essential to meet the patient's needs. Regular case discussions and updates are crucial for optimal care. Efficient care coordination is vital, including aligning appointments and services to provide holistic, patient-centered care.

A cohesive strategy should encompass regular patient education, dietary guidance, medication management, and exercise plans. Monitoring blood glucose levels and identifying early signs of complications is pivotal. An interprofessional team approach ensures that the patient receives well-rounded, evidence-based care and significantly improves outcomes in managing pediatric T2DM.

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Disclosure: Cara Tillotson declares no relevant financial relationships with ineligible companies.

Disclosure: Sasigarn Bowden declares no relevant financial relationships with ineligible companies.

Disclosure: Manan Shah declares no relevant financial relationships with ineligible companies.

Disclosure: Sameh Boktor declares no relevant financial relationships with ineligible companies.