Diabetes Mellitus in the Pediatric Patient William Bryant, M.D. Chief of Section Pediatric Endocrinology Children s Hospital at Scott & White Texas A&M University Temple, Texas
Disclosures None
Definitions to Know So you don t get stuck
Criteria for the Diagnosis of Diabetes Mellitus Symptoms of diabetes ( polyuria/polydipsia/weight loss) plus causal plasma glucose > 200 mg/dl or Fasting plasma glucose (FPG) > 126 mg/dl or 2 Hour PG > 200 mg/dl during an OGTT*
Impaired fasting glucose is defined by a plasma glucose: a. > 90 mg / dl b. 100 125 mg / dl c. 110 125 mg / dl d. > 125 mg / dl
Impaired fasting glucose is defined by a plasma glucose: a. > 90 mg / dl b. 100 125 mg / dl c. 110 125 mg / dl d. > 125 mg / dl
Diagnosis Impaired fasting glucose (IFG ) Fasting glucose 100 125 mg/dl Impaired glucose tolerance (IGT) 2 hr post prandial glucose 140 199 mg/dl
Simple Definition Diabetes = High BS 300 In a simple sense, diabetes is caused by either an absolute loss of insulin production (immune mediated beta cell destruction) - or - A relative insufficiency of insulin due to increased insulin needs beyond the ability of the pancreas to keep up.
Insulin Insufficiency & Diabetes Maximum insulin production capacity Insulin need less than insulin capacity Onset of symptoms 0 Type I Diabetes
Insulin Resistance & Diabetes Maximum insulin production capacity Insulin need less than insulin capacity Increasing insulin resistance Type II Diabetes Insulin need greater than insulin capacity
Insulin Resistance & Diabetes Maximum insulin production capacity Type II Diabetes The rise in insulin resistance and subsequent hyperglycemia often leads to a decline in beta cell function further worsening the insulin insufficiency
Diabetes Mellitus Basic Pathophysiology Type I - IDDM Insulin deficient Type II - NIDDM Insulin resistant +/- Insulin deficiency
Diabetes Mellitus Type 1 aka T1DM or IDDM
Epidemiology of IDDM Prevalence 1.2-1.9/1000 population IDDM affects males and females equally
Diagnosis of Type 1 DM Approximately 90% of white children will have autoantibodies at diagnosis. As many as 50% of children from other ethnic groups with new onset diabetes have type 2 diabetes.
Classification Type 1 1A Immune mediated 1B Nonimmune mediated Type 2 MODY Congenital Specific Genetic Syndromes
Comparison of the Common Forms of Youth Onset Diabetes Characteristic Type 1 Diabetes Congenital Diabetes MODY (monogenetic) Type 2 Diabetes Age at onset Peaks at 5 and 15 years old Predominant ethnic groups affected Birth <25 years old Teenage to young adult Caucasian None Caucasian Hispanic, African- American, Native American Islet autoimmunity Present Absent Absent Absent Insulin-dependent Yes Variable No No Percentage of probands with an affected firstdegree relative Mode of inheritance Pathogenesis <15% 100% Variable but common Sporadic Autoimmune betacell destruction: insulinopenia Autosomal dominant Sulfonylurea signaling Autosomal dominant Insulinopenia Strongly familial Insulin resistance plus relative insulinopenia
... Chromosome 6 C2B1TNF GLO DPDQDR B C T1DM related genes DR 3 DR 4 Account for 45% of genetic susceptibility for the disease Located within the HLA Class II region on chromosome 6p21
Genetics Relationship to proband Risk for IDDM (%) Mother 2 Father 6 Sibling 5 No HLA identity 1 HLA haploidentical 5 HLA identical 15 Monozygotic twin 33 HLA Genotypes Diabetes Mellitus Risk Potential DR 2 Protective DRB1*03/03;DQB1*0201/0201 1-2 DRB1*04/04;DQB1*0302/0302 1-5 DRB1*03/04;DQb1*0201/0302 6-10 DRB1*X/X;DQB1*0602/X 0.02-0.1 DR 3 / DR 4 Increased Risk
The most common cause of T1DM is: a. Autoimmunity b. Immunizations c. Early cow s milk feeding d. Cystic fibrosis e. Virus destruction of beta cells
The most common cause of T1DM is: a. Autoimmunity b. Immunizations c. Early cow s milk feeding d. Cystic fibrosis e. Virus destruction of beta cells
Type 1 Diabetes Mellitus Etiology Toxins Autoimmunity Pancreatic Destruction (Cystic Fibrosis)
Immune Mimicry T cell T cell T cell T cell T cell Virus Pancreas Coxsackie, mumps, etc. T cell T cell T cell Macrophage Autoimmune Diabetes Mellitus
Associated autoimmune diseases Thyroid disease 10-20% Celiac disease 5% Addison s disease 1 in 200-500 Others: Vitiligo, SLE, Crohn s disease, vitamin B12 deficiency, hepatitis, premature ovarian failure.
Clinical Presentation How do children with new onset diabetes mellitus generally present? Answer : With the 3 P s... Weight Loss
Management Goals Physical and emotional well being Normal growth and development Avoid acute and chronic complications Normal HgbA1c levels or The lowest HgbA1c possible without: Unacceptable variations in blood sugar Significant hypoglycemia
Slims Disease
Insulin Therapy
Insulins Types: (short acting -> long acting) R NPH L UL Humulin Humalog R NPH L UL NPH L UL Levemir Brands: Novolin Aventis Analog Novolog R Degludec Apidra Lantus
Rapid Short Intermediate Long Insulin Onset Peak Duration Humalog 15-20 min 30-90 min 3-4 hrs Novolog 15-20 min 40-50 min 3-4 hrs Regular 30-60 min 80-120 min 4-6 hrs NPH 2-4 hrs 6-10 hrs 14-16 hrs Lente 3-4 hrs 6-12 hrs 16-18 hrs Ultralene 4-6 hrs 10-16 hrs 18-20 hrs Lantus 2-3 hrs no peak 18-26 hrs Degludec
Insulin Dosage Insulin requirements Prepubertal 0.5-1.0 units/kg/day Pubertal 1.0-1.5 units/kg/day Components of Insulin dosing Usual daily dosing Correction of sporadic high blood glucose
Diabetes Mellitus Insulin Resistance/Allergy The vast majority of insulin resistance is due to: noncompliance
HbA1c and Blood Glucose Risk of diabetes related complications Low High Very High Your Goal 4%.60 5% 90 Best 6%..120 7%.150 8% 180 Better 9%..210 10%.240 11% 270 12%..300 13%.330 HbA1c Average blood glucose
Children with T1DM should have a HgbA1c checked: a. b. c. d. Monthly Every 3 months Every 6 months Annually
Children with T1DM should have a HgbA1c checked: a. b. c. d. Monthly Every 3 months Every 6 months Annually
Glycosylated Hemoglobin Measures average blood glucose over approximately the previous 2 3 months Should months be measured ~ every 3
HbA1 = 7.5 HbA1 = 7.5 Blood Glucose (mg/dl) 300 200 100 0 1 2 3 4 5 6 7 8 9 10 11 12
Office visits every 3-4 mos Blood lipids yearly Thyroid profile/autoantibodies yearly Urinary microalbumin yearly* Eye examination yearly* * 5 years after diagnosis or following onset of puberty
Dietary Management Composition of diet CHO 50-55% FAT 30% Protein 15-20%
Principles and Goals of Good Nutrition Eat less fat Eat more carbohydrates (starches and breads) especially those high in fiber Eat less simple sugars Use less salt Use alcohol only in moderation
Insulin Resistance and Disease in Children
Definition of Obesity Weight > 95th % Weight for Height > 95th % > 120 % Ideal Body Weight > 95th % BMI for Age & Sex BMI > 30
True or False An elevated BMI is a surrogate marker of insulin resistance?
BMI is a surrogate maker for Insulin Resistance
The Evolution of Type 2 Diabetes Mellitus Insulin resistance Blood glucose Insulin production Normal IFG / IGT T2DM Hyperinsulinemia T2DM Insulinopenia
Opportunities for Intervention Life Style Modification Prudent diet / Regular exercise / Smoking avoidance or cessation BMI Hyperinsulinism? Oral agents Oral agents IFG/IGT T2DM Insulin Oral agents Oral agents + Insulin Treat hypertension and hyperlipidemia when present T2DM Insulin Insulin
Insulin Resistance Obesity - Exercise