CHILDHOOD DIABETES JACLYN GAYLIS OBJECTIVES What is Diabetes

CHILDHOOD DIABETES JACLYN GAYLIS

OBJECTIVES • What is Diabetes? • Pathophysiology • Risk Factors for Type 1 Diabetes • Genes • Environment • • • Clinical Presentation Problems that Occur with Type 1 Diabetes Tests and Diagnosis Treatment How to Manage and Live With Diabetes • Medical Therapy • Nutrition • Exercise

WHAT IS DIABETES? • Diabetes Mellitus (DM) is characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both • Diabetes Mellitus Type 1: • “Insulin-dependent diabetes mellitus” (IDDM) or “juvenile-onset diabetes” • Usually affects children and young adults, although disease onset can occur at any age • Autoimmune disorder—destruction of insulin-producing beta cells of the pancreas • Results in total insulin deficiency • Daily insulin replacement is necessary for treatment • Cannot be prevented and no way to predict who will get it

SCARY STATISTICS • Around 208, 000 children and adolescents are estimated to have diabetes, and this number is increasing • Every hour, a new case of Type 1 diabetes is diagnosed • Every year, about 13, 000 children are diagnosed with the disease… and more than 1 million people live with it every day • 1 in 20 people with diabetes have Type 1 diabetes • 7 th leading cause of death • Increases the risk of heart attack and stroke by 2 -4 fold

THE PANCREAS Autoimmunity results in a T cell immune targeting of the islet of Langerhans containing beta cells… • Beta Cells: secrete insulin • Alpha Cells: secrete glucagon • What is Insulin? • Peptide Hormone: regulates blood sugar • Causes body cells to take up glucose from the blood • Insulin receptors found on: • Liver cells • Skeletal muscles • Adipose tissue

PATHOPHYSIOLOGY: OVERVIEW • Triggers: • • Poorly understood, plenty of theories Molecular mimicry… Injury to islets… Random failure of self tolerance… • Cell mediated response: • Type 1 diabetes is caused by a T cell–mediated autoimmune destruction of the pancreatic beta cells • While younger children suffer a greater loss, by age 20 beta cell loss at onset could be as low as 40% Klinke, (2011)

PATHOPHYSIOLOGY: TRIGGERS • Molecular mimicry: similar epitopes between pathogen and host • HGAD 65: auto antigen • Coxsackie & h. CMV: Viral peptides • Viruses can produce proteins similar to those of the host • Immune cells present viral protein homologous to self protein Failure of tolerance and autoimmunity • Injury to Islet cells: macrophages provoke insulitis by release of interleukin • Insulitis: Severe loss of pancreatic beta cells and the infiltration of the pancreatic islets by lymphocytes • Can lead to presentation of cryptic antigens. . Roep et al. , (2002)

RISK FACTORS: GENES & ENVIRONMENT • The exact cause of Type 1 diabetes is unknown—multifactorial: • Genetics predisposition • Environmental factors • May promote chronic autoimmunity against pancreatic beta cells • Insulin key to sugar entering cells • Dangerous sugar level in bloodstream • Risk Factors: • A family history • Genetic susceptibility • Twin study • Viral exposure • Low vitamin D levels • Other dietary factors 3– 5% increase in Type 1 diabetes • Obesity consistently Liese AD, D’Agostino RB Jr, Hamman RF, et al. , (2006)

RISK FACTORS: GENES & ENVIRONMENT • Mostly Genetic: HLA (Human Leukocyte Antigen) complex= 50 -60% of the overall genetic risk from primarily through HLA class II haplotypes: • Alleles of HLA-DQB 1, a MHC-II: • DRB 1*03: 01 (DR 3), DQA 1*05: 01 -DQB 1*02: 01 (DQ 2) and HLA-DRB 1*04 (DR 4), DQA 1*03: 01 -DQB 1*03: 02 (DQ 8) greatest relative risk • Genetic evidence identifies autoimmunity as the predominant pathogenic mechanism • Environmental Factors: • Diagnosed rates between subjects with high-risk HLA genotypes and low-risk or even protective HLA genotypes • Viruses • Cold Temperatures • Diet, stress, etc. Morran et al. , (2008) Vetere et al. , (2014)

RISK FACTORS: GENES & ANTIBODIES • • 4 antibodies: glutamic acid decarboxylase (GADA), islet tyrosine phosphatase (IA 2), zinc transporter 8 A (Zn. T 8 A), insulin autoantibodies (IAA) • > 90% newly diagnosed +Abs; 3. 5– 4% of unaffected first-degree relatives 40– 50% of genetic predisposition on chromosome 6: Class II HLA region of the Major Histocompatibility Complex (MHC) • Whites= HLA-DR 3 or HLA-DR 4, Blacks= HLA-DR 7, Japanese= HLA-DR 9 • ~11 other loci, insulin gene chromosome 11 (INS-VNTR), T-cell activation and regulation genes (CTLA-4), protein tyrosine phosphatase N 22 (PTPN 22), genes in interleukin pathway (IL-2 R) • HLA, CTLA-4, and PTPN 22 are associated with other autoimmune diseases Ziegleret al. , (2013).

RISK FACTORS: ENVIRONMENT Enteroviruses: infects thymus and impair thymic selection maternal or early life enterovirus infections may disrupt central tolerance and synergize with the genetic mechanisms Study in U. K. • Showed infections could repeatedly or chronically trigger autoimmune responses over time • Collection of pancreata from newly diagnosed patients showed viral protein in a high proportion of Type 1 diabetes pancreata • Enteroviruses may induce functional changes in beta cells and influence beta cell replication in human pancreata Lin et al. , (2014), Laitinen et al. , (2014), Richardson et al. , (2009) Study in Taiwan • Young people who have had an enterovirus infection are 50% more likely to develop Type 1 diabetes • Scientists propose that when immune system attacks enteroviruses, it may infect and destroy pancreatic beta cells • No one has yet shown that a viral infection occurs before the immune system begins to turn on the pancreas • Which comes first, the virus or the immune attack, is still unknown…

CLINICAL PRESENTATION • The signs and symptoms of Type 1 diabetes in children usually develop quickly, over a period of weeks: • • • Polyuria: Excessive Urine Polydipsia: Excessive Thirst Polyphagia: Excessive Hunger Weight loss Loss of energy Diabetic ketoacidosis (DKA) • Emergency condition of nausea, vomiting, dehydration and can lead to coma • Hyperglycemia: high blood glucose • Glycosuria: Sugar in the urine • Lipidemia: Lack of insulin starves body of glucose, body begins metabolizing fatty acids as energy source • Ketoacidoses: Ketones build up in blood, dropping p. H • Ketouria: Ketones in urine

PROBLEMS THAT OCCUR WITH DIABETES HYPOGLYCEMIA • Low blood glucose • Caused by too much insulin, skipping or delaying meals or snacks, or excessive physical activity • Most immediate danger to children with diabetes • Usually mild and can be easily treated by giving the child a food containing fast-acting carbohydrate food or beverage • • • glucose tablets or gel fruit juice regular soda (not diet) sugar cubes hard candy HYPERGLYCEMIA • High blood glucose • Occurs when body gets too little insulin, too much food, or decreased exercise • Also when body is under stress from a cold, sore throat, or other illness • Hyperglycemia may develop into diabetic ketoacidosis (DKA)

LONGER TERM COMPLICATIONS • Type 1 diabetes can affect nearly every major organ in a child's body, including the heart, blood vessels, nerves, eyes and kidneys: • Heart and blood vessel disease • Nerve damage (neuropathy) • Kidney damage (nephropathy) • Eye damage • Foot damage (nerve damage) • Skin conditions • Osteoporosis • Proper treatment can stop or control these adverse effects of Type 1 diabetes and reduce the risk of long-term problems

TESTS AND DIAGNOSIS • Random blood sugar test: • Casual glucose ≥ 200 mg/d. L • 2 -hour post load glucose ≥ 200 mg/d. L during oral glucose tolerance test (OGTT) • Glycosylated hemoglobin (A 1 C) test: • An A 1 C level ≥ 6. 5 % on two separate tests • Used in adults but not established in children • Fasting blood sugar test: • Detection of antibodies against islet antigens (insulin/beta cells) in the serum before clinical • Fasting plasma glucose ≥ 126 mg/d. L Hardest to diagnosis in infants/toddlers

TREATMENT • All people with Type 1 diabetes must take insulin through insulin shots or an insulin pump • Insulin and medications are not a cure—they only help control the disease • Early and Persistent Glucose Control= Most Important • Types of Insulin: • fast acting • slow acting • Delivery: • subcutaneous injection • insulin pump

MANAGING AND LIVING WITH T 1 D Main goal= control blood glucose levels • Blood glucose monitoring • Check few times a day • Medications: Insulin • Injections or insulin pump/pen • Medical Nutritional Therapy • Balancing food: Timing of meals and managing amount of sugar and CHOs • Physical activity • Help control blood sugar levels • Education • Work closely with doctor and diabetes health care team New tools include: • Intensive insulin therapy • New medications • Blood glucose self-monitoring devise • Continuous blood glucose monitoring • Psychological intervention • Inclusion and education for family and support persons • Insulin/food adjustment for exercise • State of the art medical nutritional therapy

MEDICAL NUTRITIONAL THERAPY (MNT) • Main goal: provide adequate energy to ensure normal growth and development, integrate insulin regimens into usual eating and PA habits • Individualized MNT is best provided by a registered dietitian • Insulin therapy should be integrated into an individual’s dietary and PA pattern • Adjust the meal and snack insulin doses based on the CHO content of the meals and snacks ABCs (A 1 C, Blood pressure and Cholesterol): • Diet and PA are critically important • CHO counting= 60 -70% energy intake • Whole grains, fruits, vegetables and low-fat milk • Glycemic effects of CHO • Total amount of CHO in meals/snacks is more important than the source/type • Sucrose should be substituted for other CHO sources or, if added, covered with insulin • Premeal insulin should be adjusted for the CHO content of meal • High fiber (40 -50 g/day) • Positive effects on glycemia

WHAT SHOULD CHILDREN EAT? • Consistently eating at the same time every day is important for those taking long-acting insulin • If a meal is skipped or delayed, one is at risk for developing low blood glucose • CHO: 50 -60% of total caloric content of the diet • CHO= complex and high in fiber • Protein: 10 -15% total energy (0. 8 -1 g/kg of desirable body weight) • Requirements increase for • Both animal and vegetable sources • Fat: 25 -35% of calories per day • < 7% of calories per day should be from saturated fat • Cholesterol: restricted and limited to 300 mg or less daily • For planned exercise, insulin doses can be adjusted • For unplanned exercise, extra CHO may be needed

DIABETES MEDICAL MANAGEMENT PLAN • A Diabetes Medical Management Plan (DMMP) should be implemented for every student with diabetes—developed by the American Diabetes Association • DMMP is: • Developed by the student’s personal health care team and family and signed by a member of student’s personal health care team • Implemented collaboratively by the school diabetes team, including: • • School nurse Student Parents/guardians Other school personnel

A FUTURE CURE? • Type 1 diabetes is currently non-preventable but can be well managed with appropriate… • Drugs? • Diet? … Mostly in experimental stages…Further research is required • Pancreas transplantation? Some success in mice • Islet cell transplantation? • Steps to Lower the Risk of Diabetes Complications: • Blood glucose monitoring Hgb A 1 C < 6. 5 % • Blood pressure < 140/80 mm HG • Cholesterol (LDL) < 100 mg/d. L statin therapy for high risk • Make healthy food choices and be active • Get recommended screenings and early treatment for complications

QUESTIONS? ? ? THANK YOU!

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