Type 2 Diabetes in Children Lindsey Nicol, MD Doernbecher Children’s Hospital Oregon Health & Science University Division of Pediatric Endocrinology and Diabetes

By the end of this talk you should be able to… Identify children at risk for type 2 diabetes Initiate the work-up Triage those who need medical intervention or referral to a pediatric endocrinologist

Prevalence(/1000) Type 1 DiabetesType 2 Diabetes Total NHW Black Hispanic ASPI AIAN Prevalence of Diabetes in U.S. Youth in 2009: The SEARCH for Diabetes in Youth StudyDiabetes Care February 2014 vol. 37 no

Proportion of type 1 and type 2 diabetes among 15–19 year olds by race/ethnicity. Who is at higher risk? Prevalence of Diabetes in U.S. Youth in 2009: The SEARCH for Diabetes in Youth StudyDiabetes Care February 2014 vol. 37 no

Case 1 Hispanic male 15 years old BMI > 85% Polyuria/polydipsia Glucosuria Hemoglobin A1C 9.8%

Is this type 1 or type 2 diabetes? Family history Prenatal history Physical exam

Definition of Obesity in Pediatrics Depends on your age/development Depends on your sex

Family History: Stronger link in type 2 Type1 DiabetesType 2 Diabetes One parentMother: 1 in 25 to 1:100 Father: 1 in 17 1 in 7 Both parents 1 in 10 to 1:41 in 2 Identical twins < 50% concordance70% concordance Dean L, McEntyre J. The Genetic Landscape of Diabetes

Prenatal History High Prevalence of Type 2 Diabetes and Pre- Diabetes in Adult Offspring of Women With Gestational Diabetes Mellitus or Type 1 Diabetes The role of intrauterine hyperglycemia Diabetes Care February 2008 vol. 31 no

Physical Exam

The work-up: Will additional tests help? Antibodies C-peptide Insulin levels

Interventions: Starting insulin Diabetic ketoacidosis Distinction between type 1 and type unclear – Random Blood glucose > 250 mg/dL – HbA1c > 9%

Why it is not the end of the world to start insulin. Many can be weaned May allow beta cells to “rest and recover” Families understand the seriousness

Case 1 Does he meet criteria to start insulin? If he has type 2 diabetes can he go into diabetic ketoacidosis? Should he be referred to a pediatric endocrinologist?

Interventions: “The Cornerstone” Lifestyle changes metformin

Case 2 16 year old African American girl 140kg Asymptomatic/acanthosis nigricans Mother has type 2 diabetes

What is going on inside this girl’s body? A continuum of disease Pathophysiology of insulin resistance Inflammatory state

ß Cell Function Type 2 Diabetes Random blood sugar over 200 Fasting AM glucose >126 Oral GTT 2 hour glucose >200 A1C ≤ 6.5% Impaired Glucose Tolerance Fasting AM glucose Oral GTT 2hr glucose A1C ≤ 5.9% The Path to Type 2 Diabetes - continuum Type 2 with DKA ↑ Glucose Obesity-related insulin resistance

Other signs of insulin resistance Dyslipidemia: –  Triglycerides –  LDL –  HDL Fatty liver (non-alcoholic steatohepatitis)

Insulin is important in fat metabolism  Triglycerides  LDL  HDL LPL STORED FAT LDL Insulin HDL

What is fatty liver (non-alcoholic steatohepatitis)?  AST and ALT

Case 2 16 year old African American girl 140kg Asymptomatic/acanthosis nigricans Mother has type 2 diabetes

Would additional labs help? What is her glucose homeostasis? What is the status of her lipid metabolism? Is there evidence of organ inflammation from her obesity? Is there any evidence of type 1 diabetes? – A1C% 7.2 – Triglycerides 205 (<150) – LDL 132 (<100) – HDL 38 (>40) – AST 67 (<36) – ALT 85 (<40) – Negative antibodies – Detectable c-peptide

Interventions: “The Cornerstone” Lifestyle changes Metformin

Metformin – Does it help? Does it improve insulin resistance? Does it improve BMI? What is the safety profile in children?

Case 2 16 year old African American girl 140kg Asymptomatic/acanthosis nigricans Mother has type 2 diabetes

Case 2 – So far we have… Identified her as high risk group for type 2 diabetes Worked her case up to assess her metabolic profile What is your intervention? Should she be referred to a pediatric endocrinologist?

Summary Type 2 diabetes is becoming more prevalent in pediatrics and identifying those at risk is important in preventing disease progression Differentiating between type 1 and 2 helps can be difficult, both should still be considered even in high risk groups Life-style intervention is still the cornerstone of prevention and treatment of type 2 diabetes

Meeting our objectives Identify children at risk for type 2 diabetes Initiate the work-up Triage those who need medical intervention or referral to a pediatric endocrinologist