Diabetes Mellitus in the Pediatric Patient

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1 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

2 Disclosures None

3 Definitions to Know So you don t get stuck

4 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*

5 Impaired fasting glucose is defined by a plasma glucose: a. > 90 mg / dl b mg / dl c mg / dl d. > 125 mg / dl

6 Impaired fasting glucose is defined by a plasma glucose: a. > 90 mg / dl b mg / dl c mg / dl d. > 125 mg / dl

7 Diagnosis Impaired fasting glucose (IFG ) Fasting glucose mg/dl Impaired glucose tolerance (IGT) 2 hr post prandial glucose mg/dl

8 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.

9 Insulin Insufficiency & Diabetes Maximum insulin production capacity Insulin need less than insulin capacity Onset of symptoms 0 Type I Diabetes

10 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

11 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

12 Diabetes Mellitus Basic Pathophysiology Type I - IDDM Insulin deficient Type II - NIDDM Insulin resistant +/- Insulin deficiency

13 Diabetes Mellitus Type 1 aka T1DM or IDDM

14 Epidemiology of IDDM Prevalence /1000 population IDDM affects males and females equally

15 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.

16 Classification Type 1 1A Immune mediated 1B Nonimmune mediated Type 2 MODY Congenital Specific Genetic Syndromes

17 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

18 ... 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

19 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/ DRB1*04/04;DQB1*0302/ DRB1*03/04;DQb1*0201/ DRB1*X/X;DQB1*0602/X DR 3 / DR 4 Increased Risk

20 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

21 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

22 Type 1 Diabetes Mellitus Etiology Toxins Autoimmunity Pancreatic Destruction (Cystic Fibrosis)

23 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

24 Associated autoimmune diseases Thyroid disease 10-20% Celiac disease 5% Addison s disease 1 in Others: Vitiligo, SLE, Crohn s disease, vitamin B12 deficiency, hepatitis, premature ovarian failure.

25 Clinical Presentation How do children with new onset diabetes mellitus generally present? Answer : With the 3 P s... Weight Loss

26 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

27 Slims Disease

28 Insulin Therapy

29 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

30 Rapid Short Intermediate Long Insulin Onset Peak Duration Humalog min min 3-4 hrs Novolog min min 3-4 hrs Regular min min 4-6 hrs NPH 2-4 hrs 6-10 hrs hrs Lente 3-4 hrs 6-12 hrs hrs Ultralene 4-6 hrs hrs hrs Lantus 2-3 hrs no peak hrs Degludec

31 Insulin Dosage Insulin requirements Prepubertal units/kg/day Pubertal units/kg/day Components of Insulin dosing Usual daily dosing Correction of sporadic high blood glucose

32 Diabetes Mellitus Insulin Resistance/Allergy The vast majority of insulin resistance is due to: noncompliance

33 HbA1c and Blood Glucose Risk of diabetes related complications Low High Very High Your Goal 4%.60 5% 90 Best 6% %.150 8% 180 Better 9% % % % %.330 HbA1c Average blood glucose

34 Children with T1DM should have a HgbA1c checked: a. b. c. d. Monthly Every 3 months Every 6 months Annually

35 Children with T1DM should have a HgbA1c checked: a. b. c. d. Monthly Every 3 months Every 6 months Annually

36 Glycosylated Hemoglobin Measures average blood glucose over approximately the previous 2 3 months Should months be measured ~ every 3

37 HbA1 = 7.5 HbA1 = 7.5 Blood Glucose (mg/dl)

38 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

39 Dietary Management Composition of diet CHO 50-55% FAT 30% Protein 15-20%

40 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

41 Insulin Resistance and Disease in Children

42 Definition of Obesity Weight > 95th % Weight for Height > 95th % > 120 % Ideal Body Weight > 95th % BMI for Age & Sex BMI > 30

43 True or False An elevated BMI is a surrogate marker of insulin resistance?

44 BMI is a surrogate maker for Insulin Resistance

45 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?

46 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

47 Insulin Resistance Obesity - Exercise

associated with serious complications, but reduce occurrences with preventive measures

Wk 9. Management of Clients with Diabetes Mellitus 1. Diabetes Mellitus body s inability to metabolize carbohydrates, fats, proteins hyperglycemia associated with serious complications, but reduce occurrences