Diabetes Mellitus in Children-Some Basics-

Anamaria Manea, MDPediatric Endocrinology

01/10/2020

Objectives Identify the symptoms of diabetes mellitus across the lifespan Review type 1 DM and type 2 DM Describe pertinent physical exam findings Review the labs used to confirm the diagnosis Discuss complications and screening labs Review management options

Diabetes Classification Type 1

– failure of beta cells resulting in insulin deficiency Type 2

– Insulin resistance + failure of beta cells to compensate – ‘relative’ insulin deficiency

Genetic defects in beta cell function– MODY (maturity onset diabetes of youth)

• AD; Single gene defect (MODY 1- 6)– Mitochondrial

Drug induced – Glucocorticoids– L-Asparaginase– Newer antipsychotics

Diseases affecting pancreatic function– CF, pancreatitis, hemolytic uremic sydrome

Genetic syndromes

Normal Fasting Blood Sugar <100

Impaired Glucose Tolerance >100 but <126 Fasting

Diabetes Fasting >126Random >2002 hr postprandial glucose>200HbA1c >=6.5%

Defining diabetes

Type I DM

Autoimmune destruction of pancreatic beta cells Insulin deficiency

– Deficient glucose utilization– Cells use alternate sources of fuel (fats ketones)– Hyperglycemia glucosuria polyuria

polydipsia

Type I DM: Epidemiology Most common cause of diabetes in children

– 80% of all diabetes 9 yrs old and younger

Incidence increasing– ~1-2 per 10,000 per year– Peak incidence is early adolescence

More common in Caucasian Less common in Asian and African American

Type I DM: Epidemiology

New onset T1DM: 30% in DKA at presentation - age 0–4: 37.5%- age 15-19: 14.7%

Type I DM: Etiology

Genetic susceptibility– monozygotic twins 40% risk– Siblings 5% risk

Environmental trigger– Infectious trigger? Incidence more common in

fall and winter– Possibly multiple potential triggers in early

infancy: viruses, cow’s milk, toxins

T1DM Management

Glucose Monitoring:

Check blood sugars 4 times/day– before breakfast, lunch, dinner, and bedtime – +/- in the middle of the night

Types of insulinInsulin

Onset(min)

Peak(hr)

Duration(hr)

Lispro/Humalog5 1 ½ 3

Aspart/Novolog 5 1 ½ 3Apidra 5 1- 1 ½ 3Regular 30 1-5 6-10NPH 120 6-8 8-20Levemir/Detemir 120 Dose

dependentDose

dependentGlargine/Lantus 180 No peak 24

Fast acting

Long acting

Glargine/Lantus

Bed timeB L D

Basal bolus insulin regimenLispro/Humalog or Aspart/Novolog and Glargine/Lantus

Hypoglycemia

Symptoms– Shaky, sweaty, hungry, weak, mood and

behavior changes– Waking up with HA, nightmares, restless sleeper

Treat with fast acting sugars– Recheck blood sugar in 15 minutes

Basal Insulin Typically lasts 24 hours in the body Important to give at the same time every

day Approx 50% of TDD (total daily dose) Given with or without food Same dose everyday – not dependent on

food intake or blood sugars

Bolus insulin

Used to cover the carbohydrate in food consumed

Utilize an insulin:carb ratio Correction doses used at meals and often

during illness and when ketones are present

Challenges for families Set doses

Hypoglycemia

After exercise, extra insulin doses If severe: seizures or altered mental status,

brain damage AMS/LOC: Glucagon IM, Basqimi Nasal

Glucagon

Sick Day Management

Sick Day Management cont

Sick Day Management cont

Surveillance:

DIABETES KETOACIDOSIS (DKA)

Missed insulin doses Missed warning signs Triggers: acute illness (URI, gastroenteritis, etc) High metabolic demand, not enough insulin, hyperglycemia, ketones Vomiting, abdominal pain, polyuria, Kussmaul breathing, AMS Dehydration, acidosis, electrolytes imbalance Admission (PICU) Treatment: NPO+IVF + insulin drip

Type 2 DM

Primary defect: – insulin resistance --- hyperglycemia ---

glucose toxicity to beta cells

ß Cell Function

Type 2 Diabetes Random blood sugar over 200 Fasting AM glucose >126 OGTT 2 hour glucose >200 Impaired Glucose Tolerance

Fasting AM glucose 100-126

OGTT 2hr glucose 140-200

The Path to Type 2 Diabetes

Type 2with DKA

↑ Glucose

Obesity-related insulin resistanceGlucose may be normal Asymptomatic

Epidemiology Increasing in incidence, particularly in the teenage years

– Mean age of diagnosis 13.5 yrs– Puberty: peak of insulin resistance

More common in non-Caucasian (African American, Hispanic, Native American)

Stronger (poly)genetic basis than type 1 – Almost 100% concordance in monozygotic twins– >75% of cases in youth have 1st or 2nd degree relative with T2DM

Diagnosis of T2DM Fasting plasma glucose ≥ 126 mg/dl

2-hr oral Glucose tolerance test– 75g glucose load– Plasma glucose 2 hrs later ≥ 200 mg/dl

Symptoms of DM + random plasma glucose ≥ 200 mg/dl – Symptoms: polyuria, polydipsia, weight loss,

glucosuria

Presentation of T2DM in Children Incidental finding Screening due to obesity or family history

of type 2 DM Polydipsia/polyuria Diabetic Ketoacidosis!!!

Typical Physical Exam in Childhood type 2 DM

Overweight or obeseAcanthosis nigricans +/- Hypertension

Management

Promote lifestyle changes – Weight loss, increased exercise

Oral hypoglycemic agents– Metformin

Insulin may be necessary – High doses needed due to insulin resistance

Goal for home glucose monitoring

Check at least twice a day– Morning and 1-2 hours after a meal– Check more often if on insulin– Check during symptoms of low blood sugar

The insulin resistance syndrome

Type II Diabetes Obesity Nephropathy Hypertension Dyslipidemia Polycystic Ovary Syndrome Non-alcoholic fatty liver disease Systemic inflammation

Metformin

Insulin sensitizer– Liver: ↓ gluconeogenesis ↓ hepatic

glucose production– muscle, fat tissue: ↑ glucose uptake– May help with ovulatory abnormalities in

girls with PCOS

Metformin: side effects

GI– Abdominal pain, diarrhea, nausea– Slow dosage titration over 3-4 weeks

• 500 mg daily 1000 mg bid

Lactic acidosis: extremely rare– Don’t use in renal impairment, liver

disease, cardiac/respiratory insufficiency

Insulin

Ketosis/ketoacidosis Oral agents inadequate (persistently

elevated HbA1c despite oral therapy) May be able to use Lantus only

Surveillance:

At diagnosis and yearly:- Lipids- Urine Alb/creatinine ratio- Dilated eye exam- Periodontal examination- Foot examination- Depression screening- BP every visit

15-25% of newly diagnosed T1DM may be obese

Many children with T2DM have ketonuria or DKA at diagnosis

Type 1 vs Type 2 DM: not always easy

Distinguishing Type 1 from Type 2

May be clinically obvious

Look for markers of islet cell autoimmunity– 80% - Anti GAD (glutamic acid decarboxylase) Ab– Islet cell antibodies– 5-10% of adults with Type 2 have one or more positive

antibody

Look for residual islet cell function– Serum insulin or C-peptide

Look at subsequent clinical course on insulin– Type 1 kids -“honeymoon” period– Type 2 kids- larger per kg insulin doses

Distinguishing Type 1 from Type 2

Presentation of Type 1 vs. Type 2

Type 1 Slender Weight loss Almost always symptomatic School age Caucasian No acanthosis nigricans Ketonuria usual Often presents with ketoacidosis

Type 2 Obese Often no weight loss Often asymptomatic Unusual in preteen Non-Caucasian Acanthosis nigricans Ketonuria less typical Ketoacidosis less frequent

Summary Type 1 and type 2 DM increasing in

incidence Helpful to distinguish between the two If ketonuria admit to the hospital and

start insulin If obese or signs of insulin resistance

lifestyle modification and metformin Monitor for comorbidities

References Insel RA et al. Staging Presymptomatic Type 1 Diabetes: A Scientific Statement of

JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care 2015 Oct; 38(10):1964-1974

Standards of medical care in Diabetes 2019. ADA Chaing JL et al. Type 1 Diabetes in Children and Adolescents: A Position Statement

by the American Diabetes Association. Diabetes Care 2018 Sept; 41(9): 2026-2044 Arslanian S. Evaluation and Management of Youth-Onset Type 2 Diabetes: A

Position Statement by the American Diabetes Association. Diabetes Care 2018 Dec; 41(12): 2648-2668