Pediatric Type 2 Diabetes Mellitus


Article Author:
Cara Tillotson


Article Editor:
Sameh Boktor


Editors In Chief:
Chaddie Doerr


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
3/19/2019 1:33:01 AM

Introduction

Type 2 diabetes mellitus 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 increasing in prevalence in children. Risk factors for children are similar to those in adults: ethnicity, family history, obesity, and 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 of the disease. Early recognition, screening, and treatment of children with type 2 diabetes mellitus are important for prevention of long-term complications from the disease. 

Etiology

Hyperglycemia results when there is a relative lack of insulin compared to glucose in the blood. In type 2 diabetes mellitus, insulin resistance first leads to increased insulin production by the beta cells of the pancreas. When the beta cells are unable to produce enough insulin to maintain euglycemia, hyperglycemia results. Hyperglycemia has damaging effects to multiple organs, including kidneys, eyes, heart, and nerves. Further, hyperglycemia puts children at risk for other electrolyte disturbances.[4]

Comparatively, type 1 diabetes mellitus is characterized by autoimmune destruction of beta cells in the pancreas leading to a lack of insulin production. 

Epidemiology

Type 1 diabetes remains the most prevalent form of diabetes in children. However, type 2 diabetes mellitus is estimated to occur in one in three (20% to 33%) of new diagnoses of diabetes in children today. The rate of type 2 diabetes mellitus in children continues to rise even as the obesity rates have plateaued in these age groups. Risk factors include high-risk ethnicity (African American, Hispanic, Native Americans, Pacific Islanders, Asian Americans), a positive first-degree relative with the disorder, obesity, low birth weight, 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. [5][6]

Pathophysiology

Obesity leads to peripheral insulin resistance, which in turn leads to hyperglycemia as discussed. Independent of obesity, certain ethnicities have higher risks of insulin resistance and beta cell dysfunction. Hyperglycemia leads to an osmotic diuresis (polyuria), which increases thirst (polydipsia). This diuresis causes moderate to severe dehydration. Prolonged hyperglycemia can produce two distinct emergent states in type 2 diabetes mellitus in children:[7]

Diabetic ketoacidosis: much more common in children with type 2 diabetes mellitus compared to 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 type 2 diabetes mellitus most often present during symptomatic screening.

Children may have the typical symptoms of polyuria, polydipsia, polyphagia, and weight loss. Children with type 2 diabetes mellitus 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 type 2 diabetes mellitus may also present in Hyperosmolar Hyperglycemic State (HHS). 

Physical exam findings can include acanthosis nigricans (dark, velvety rash present in the axillae and neck). The American Diabetes Association 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 two risk factors. These factors can be positive family history, high-risk ethnicity, signs of insulin resistance (polycystic ovary syndrome (PCOS), acanthosis, symptoms), or history of maternal gestational diabetes mellitus.

Evaluation

The American Diabetes Association recommends screening for type 2 diabetes mellitus  every three years starting at age ten years (or at the onset of puberty) for patients who are:[8][9][10]

  • Obese (body mass index (BMI) greater than or equal to the 95th percentile for age)
  • Overweight (BMI greater than or equal to the 85thpercentile) and have at lease two risk factors (positive family history, higher risk race or ethnicity, signs of insulin resistance, maternal history of gestational DM). 

Diagnostic criteria:

  • Random plasma blood glucose 200 mg/dl or greater with symptoms of polyuria, polydipsia, or weight loss.
  • Fasting blood glucose of 126 mg/dl or higher in an asymptomatic patient. 
  • Oral glucose tolerance test with blood sugar 200 mg/dl or greater at two hours post ingestion.
  • Hemoglobin A1c > 6.5%. 

If the diagnosis between type 1 and type 2 diabetes mellitus is not clear, helpful labs include fasting insulin or c peptide (both usually high or normal in type 2 diabetes mellitus, low in type 1 diabetes mellitus ), and autoantibodies for type 1 diabetes mellitus.

Treatment / Management

The American Academy of Pediatrics recommends lifestyle modifications and Metformin as the first line therapy. Lifestyle changes include moderate to vigorous exercise for 60 minutes per day, limiting screen time to less than two hours per day, and a dietary referral.[11][12][13][14]

Metformin and/or insulin should be started at diagnosis. Metformin is first line and available as a liquid. Start at 500 mg/day and increase by 500 mg every one to two weeks to a maximum of 2000 mg twice a day. The gradual increase of the medication and taking it with food helps to prevent gastrointestinal side effects.

Insulin should be started for patients who are ketotic or in diabetic ketoacidosis (DKA), have a random blood glucose > 250 mg/dl, an A1C > 9.0%, or in whom the diagnosis of type 1 vs. type 2 is not clear. May use a basal/bolus regimen like in type 1 diabetes mellitus, but typically type 2 diabetes mellitus patients require higher doses (2 unit/kg/day - 3 unit/kg/day). Insulin should be initiated and managed by pediatric endocrinologists. Insulin takers have a risk of hypoglycemia; therefore frequent monitoring is required.

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

A1C test goals vary by association. American Diabetes Association and the American Academy of Pediatrics list an A1C test goal of < 7%, while the American Association of Clinical Endocrinologists places the goal at < 6.5%.

Pearls and Other Issues

Complications of type 2 diabetes in children are similar to that of adults. Complications tend to occur after a person 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 (evaluated for renal involvement), hyperlipidemia screens/treatment, hypertension screening/treatment, and regular monitoring.

Enhancing Healthcare Team Outcomes

Type 2 diabetes in children is best managed by a multidisciplinary team that includes a pediatrician, priamry care provider, diabetic nurse, endocrinologist and relevant specialists. The American Academy of Pediatrics recommends lifestyle modifications and Metformin as the first line therapy. Lifestyle changes include moderate to vigorous exercise for 60 minutes per day, limiting screen time to less than two hours per day, and a dietary referral.

It is vital to ensure that these children are also evaluated by the ophthalmologist, nephrologist, cardiologist and dental surgeon. Complications of type 2 diabetes in children are similar to that of adults. Complications tend to occur after a person 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 (evaluated for renal involvement), hyperlipidemia screens/treatment, hypertension screening/treatment, and regular monitoring.[15]


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Pediatric Type 2 Diabetes Mellitus - Questions

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What is the first-line pharmaceutical agent for children with newly diagnosed type 2 diabetes?



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A 15-year-old African-American female presents to the clinic for a well adolescent exam. She complains of irregular and heavy periods. Her BMI is in the 85th percentile for age and she has acanthosis nigricans on exam. Which of the following is true of screening for type 2 diabetes mellitus in this patient?



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A 10-year-old male presents with polyuria and polydipsia. His BMI is in the 90th percentile for age, but he has lost 5 pounds in the last month. He has a positive family history of type 2 diabetes mellitus (DM) in his paternal grandmother. Labs show hyperglycemia with mild diabetic ketoacidosis (DKA)and glucosuria. He is admitted to the general pediatric floor for diabetes teaching. Does he have type 1 or type 2 diabetes?



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A 16-year-old female presents for a well child check. She is obese with BMI in the 95th percentile for age. She has never been screened for diabetes mellitus (DM). She denies any symptoms. Further workup to determine if she has diabetes mellitus are ordered. Which of the following would be diagnostic of diabetes in this patient?



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Pediatric Type 2 Diabetes Mellitus - References

References

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Winhusen T,Theobald J,Kaelber DC,Lewis D, Medical complications associated with substance use disorders in patients with type 2 diabetes and hypertension: Electronic health record findings. Addiction (Abingdon, England). 2019 Mar 9;     [PubMed]
Crawford R,Sims ED,Wang KW,Youssef M,Nadarajah A,Rivas A,Banfield L,Thabane L,Samaan MC, Traditional knowledge-based lifestyle interventions in the prevention of obesity and type 2 diabetes in Indigenous children in Canada: a systematic review protocol. Systematic reviews. 2019 Mar 6;     [PubMed]
Hernández-Montoya D,Soriano-Flores A,Esparza-Aguilar M,Benjet C,Llanes-Díaz N, Variation in incidence of type 2 diabetes mellitus: time series of Mexican adolescents. Annals of epidemiology. 2019 Feb;     [PubMed]
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Hagman E,Danielsson P,Brandt L,Ekbom A,Marcus C, Association between impaired fasting glycaemia in pediatric obesity and type 2 diabetes in young adulthood. Nutrition     [PubMed]
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Bhatt M,Nahari A,Wang PW,Kearsley E,Falzone N,Chen S,Fu E,Jeyakumar Y,Zukowski J,Banfield L,Thabane L,Samaan MC, The quality of clinical practice guidelines for management of pediatric type 2 diabetes mellitus: a systematic review using the AGREE II instrument. Systematic reviews. 2018 Nov 15;     [PubMed]
Albert Pérez E,Mateu Olivares V,Martínez-Espinosa RM,Molina Vila MD,Reig García-Galbis M, New Insights about How to Make an Intervention in Children and Adolescents with Metabolic Syndrome: Diet, Exercise vs. Changes in Body Composition. A Systematic Review of RCT. Nutrients. 2018 Jul 6;     [PubMed]
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