Care for Children with Diabetes: Evaluation, Management, and Future Directions

Transcription

1 Care for Children with Diabetes: Evaluation, Management, and Future Directions Ayer s Children s Medical Center 2016 General Pediatric Conference September 17, 2016 William E. Russell, MD Jennifer Kelley, MD Ian M. Burr Division of Pediatric Endocrinology and Diabetes Vanderbilt University School of Medicine

2 Learning Objectives Understand the natural history and epidemiology of both type 1 and type 2 diabetes in children and articulate new concepts in the pathogenesis of type 1 diabetes. Identify the signs and symptoms of developing diabetes in children and adolescents and provide assessment and appropriate referral for at-risk patients. Be aware of options to identify family members at risk to develop type 1 diabetes. Demonstrate knowledge of the current standards of care, treatment options and long term monitoring needs of pediatric patients with diabetes.

3 Disclosures We have no conflicts of interest to disclose The type 1 diabetes prevention studies are investigational Do NOT try these treatments at home!

4 Why T1D Prevention Matters to Us 1. We follow almost 3,000 children with diabetes at Vanderbilt- they come from 8 states kids will come to us for new onset diabetes this year. 85% will have T1D 3. 15,000 children in the US will be diagnosed with T1D this year 4. We want to end this and make a difference

5 The Incidence of T1D is Rising 3-5% per Year: Why?? Incidence /100,000/ yr in children 0-14 yr Finland Sweden Colorado Poland Germany

6 The Nature of Type 1 Diabetes Starts as an immune system (autoimmune) disease Associated in families and in individuals with other autoimmune disorders: Hypo/hyperthyroidism Celiac Disease Addison Disease Pernicious anemia Inflammatory bowel disease Hypoparathyroidism (Juvenile) Rheumatoid Arthritis Lupus Scleroderma Alopecia Areata

7 The Nature of Type 1 Diabetes Evolves to become a metabolic disease Loss of immune tolerance of key b-cell antigens leads to their destruction and the development of an insulindeficient state Genetics and environment both play critical roles Although we have highly accurate tools to predict T1D risk, there is currently no safe and effective way to prevent it

8 Healthy Islet T1D Starts as a Genetic Disease Genes Load the Gun Over 50 genes associated with risk to develop T1D BETA CELL MASS T1D GENETIC SUSCEPTIBILITY NL GLUCOSE TOLERANCE: FPG < 110 MG/DL 2 HR <140 MG/DL TIME (months to years)

9 Healthy Islet T1D Becomes an Environmental Disease Environmental Triggers Viruses Casein Gluten Dietary fats Low Vitamin D Environment pulls the trigger BETA CELL MASS T1D GENETIC SUSCEPTIBILITY NL GLUCOSE TOLERANCE: FPG < 110 MG/DL 2 HR <140 MG/DL TIME (months to years)

10 Healthy Islet T1D Becomes an Immune System Disease Environmental Triggers Viruses Casein Gluten Dietary fats Low Vitamin D Antibodies in Serum Targets: Insulin GAD-65 ICA512 ZnT8 B cells Inflamed Islet T cells BETA CELL MASS T1D GENETIC SUSCEPTIBILITY INSULITIS BETA CELL INJURY NL GLUCOSE TOLERANCE: FPG < 110 MG/DL 2 HR <140 MG/DL TIME (months to years)

11 Healthy Islet Evolves to Become a Metabolic Disease Environmental Triggers Viruses Casein Gluten Dietary fats Low Vitamin D Antibodies in Serum Targets: Insulin GAD-65 ICA512 ZnT8 Inflamed Islet BETA CELL MASS T1D GENETIC SUSCEPTIBILITY INSULITIS BETA CELL INJURY Impaired First Phase Insulin Response DYSGLYCEMIA FPG MG/DL pmeal MG/DL Abnormal Glucose Tolerance TIME (months to years)

12 And Eventually, the Clinical Disease we Know Healthy Islet Environmental Triggers Viruses Casein Gluten Dietary fats Antibodies in Serum Anti-insulin Anti-GAD-65 ICA512 Anti-ZnT8 Inflamed Islet BETA CELL MASS T1D GENETIC SUSCEPTIBILITY INSULITIS BETA CELL INJURY NL GLUCOSE TOLERANCE: FPG < 110 MG/DL 2 HR <140 MG/DL Impaired First Phase Insulin Response DYSGLYCEMIA Abnormal Glucose Tolerance FPG > 126 MG/DL 2HR > 200 MG/DL SYMPTOMATIC DIABETES TIME (months to years)

13 Type 2 Diabetes in Children and Adolescents Rise in prevalence in past three decades linked to rise in obesity 1990s: 3% of pediatrics diabetes 2003: 20% of pediatric diabetes Depending on locale, nearly half of cases among adolescents 15 to 19 years

14 Prevalence and Proportion of Diabetes in the SEARCH for Diabetes in Youth Study 2014 by American Diabetes Association David J. Pettitt et al. Dia Care 2014;37:

15 Additional Risk Factors for T2DM Positive family history Complex polygenic susceptibility Common polymorphisms confer small degrees of risk/protection Conditions associated with insulin resistance, eg, polycystic ovary syndrome Low birth weight Female sex Females 1.3 to 1.7 times more likely to develop T2DM Pregnancy complicated by gestational diabetes

16 Pathogenesis of T2DM Wanzhu Jin, and Mary-Elizabeth Patti Clin. Sci. 2009;116: by Portland Press Ltd

17 Clinical Presentation of T1DM Classic presentation: polydipsia, polyuria, weight loss, fatigue with hyperglycemia and/or ketonuria May have vague symptoms Diabetic ketoacidosis (DKA) (~30%) Risk associated with age and socioeconomic background May be misidentified as acute vomiting illness Asymptomatic incidental discovery (uncommon)

18 Clinical Presentation of T2DM Asymptomatic (~40%) Symptomatic (eg, polyuria, polydipsia, fatigue, lethargy, recurrent yeast infections; majority, 57-70%) DKA (~5%, more common in non-white children) Hyperosmolar hyperglycemic state (uncommon)

19 When You Suspect Diabetes: What s Next? Screening and diagnosis: Fasting plasma glucose (FPG) 126 mg/dl on >1 occasion Random plasma glucose 200 mg/dl with classic symptoms Plasma glucose 200 measured 2 hours post glucoseload of 1.75g/kg (maximum dose 75 g) in 2-hr oral glucose tolerance test (OGTT) Glycated hemaglobin (A1C) 6.5% using certified laboratory assay and confirmed with hyperglycemia

20 Screening for T2DM

21 Non-Diagnostic Testing, Pre-Diabetes and the OGTT A1C % and/or fasting plasma glucose normal OGTT is more sensitive Impaired fasting glucose 100 to 125 mg/dl Impaired glucose tolerance 140 to 199 mg/dl measured 2 hours after glucose load

22 Our Request of You Our philosophy strongly encourages an outpatient, wellness-affirming, and family-centered approach to new patient education. When you suspect or have a confirmed case of diabetes, call and discuss with the physician on call immediately DO NOT send the child to an emergency room (yours or ours) for evaluation or treatment unless there is a clear medical indication for emergency treatment. Talk with us first.

23 Our Promise to You We will see all children with new-onset diabetes in the Eskind Diabetes Clinic within 24 hours of referral We will uphold/respect the PCP role as the primary care physician for the patient We will communicate with the PCP regarding the patient s educational and diabetes management progress regularly

24 2015: Children s Diabetes Program at Vanderbilt, Franklin This image cannot currently be displayed. 1,330% Increase ( ) Eskind Diabetes Clinic Williamson County 2,700 children 275 new cases/yr From 9 states 85% T1D

25 2016: Also at Jackson, Cookeville, and Murfreesboro Cookeville Jackson Williamson Murfreesboro Murfreesboro Eskind Diabetes Clinic Williamson County Jackson Madison County Cookeville Regional Medical Center

26 Current Standards of Care: T1DM Historical lessons from insulin therapy: [W]e invariably went through three stages of thought: first, the belief that we were succeeding...; then the uneasy feeling that we were losing ground; and finally, the realization that our efforts were fruitless. We protracted the illnesses, but nothing more, and this very partial success was so unsatisfactory from the children s point of view that had not there been always a hope that some new advance might appear, or some unexpected improvement arise, it seemed hardly worth while. Poynton FJ. Br Med J 1923;1: Major R. JAMA. 1923;80(22):

27 Intensive Glucose Control Multidisciplinary approach Primary provider, pediatric endocrinologist, advanced care registered nurse, dietitian, behavioral specialist, social worker, CDE/RN, patient and caregiver(s) Appropriate age-based care Frequent glucose monitoring Fingerstick testing ~4 times per day Continuous glucose monitor Improves glucose control and decreases hypoglycemic episodes Goal A1C <7.5% in children and adolescents

28 Insulin Therapy Intensive regimen: multiple daily injections (MDI) or continuous insulin infusion MDI: Typically once daily injection of long-acting insulin (ie, lantus/levemir) in combination with meal/snack boluses of rapid/short acting insulin Needle and syringe vs insulin pens Continuous insulin infusion: insulin pumps Subcutaneous delivery of small doses of rapid/short acting insulin every few minutes in combination with boluses given with meals/snacks

29 New Onset Care at Vanderbilt Children s Hospital ADA-Recognized Education Program Timeline: Visit 1: Diagnosis (MD, nurse educator) Visit 2: 5-10 days after diagnosis, APRN, RD Visit 3/4: 1-3 weeks following diagnosis; Group class (one-on-one teaching for age 4 years and under and as-needed) Visit 5: Last visit, MD/APRN, nurse educator, RD Ongoing Care: Every 3 month visit with MD/APRN

30 Current Standards of Care: T2DM Intensive lifestyle modification and nonpharmacologic therapy Dietary management: gradual and family-based change Physical activity and limited screen time Pharmacological options Metformin (biguanide): increases glucose uptake in peripheral tissue and decreases hepatic glucose production Insulin: typically with A1C 9%

31 TODAY Clinical Trial to Maintain Glycemic Control in Youth with T2DM TODAY Study Group. N Engl J Med 2012;366:

32 Autoimmune Conditions Management of Cardiovascular Health Microvascular Disease Thyroid Disease TSH soon after diagnosis, then every 1-2 years Hypertension Blood pressure measurements at each visit Albuminuria Annual spot urine albumin/cr once patient has had diabetes 5 years Celiac Disease Test at time of diagnosis, then 2-5 years later. Frequency thereafter not established (consider screening in children with symptoms or family history) Dyslipidemia Obtain fasting lipid profile in children 10 years, once glucose control established If normal, check every 3-5 years Smoking Discuss stopping smoking (and discourage starting) and assess for second hand smoke Retinopathy Dilated exam once 10 years (or after puberty starts), once patient has had diabetes 3-5 years and annual follow up thereafter Neuropathy Annual foot exam once 10 years (or at the start of puberty), once patient has had diabetes for 5 years

33 If you are going to prevent T1D, you first have to determine who is at risk:

34 Family Members of a T1D Proband are at Significant Risk Relative with Diabetes T1D Risk None 1 in 250 Mother 1 in 20 Niece/Nephew 1 in 20 Brother/Sister 1 in 20 Father 1 in 10 Identical Twin 2 in 3

35 Autoantibodies Precede the Development of T1D: Data of Identical Twins Redondo et al N Engl J Med 2008; 359:

36 Our Current Understanding An individual with multiple diabetes antibodies is in a pre-diabetic state and has a virtually 100% lifetime diabetes risk

37 Individuals with Multiple Diabetes Autoantibodies will Develop of T1D 13,377 Genetically At-Risk Individuals Followed >15 years Study Populations: Colorado Finland Germany ,377 High-risk children followed from birth Antibodies: GAD65 Insulin IA2/ICA512 5 year: 43% 10 year: 67% 15 year: 85% Ziegler et al JAMA 2013; 309: 2473

38 Redefining T1D in 3 Stages Stage 1: Autoimmunity with normal glucose tolerance Stage 2: Autoimmunity with abnormal glucose tolerance Stage 3: Symptomatic T1D that requires insulin therapy Stage 1 Beta Cell Mass Genetic Risk Immune Islet Injury DYSGLYCEMIA Stage 2 Clinical Diabetes Stage 3 Time ADA, Endocrine Society, JDRF Diabetes Care 2015, 38:

39 Gene Therapy How Do You Go About Preventing Type 1 Diabetes? Modify Environmental Triggers Induce Immune Tolerance Inhibit Autoimmunity Inhibit Inflammation T1D GENETIC SUSCEPTIBILITY IINSULITIS BETA CELL INJURY Preserve/Regenerate b Cells PRE DIABETES DIABETES

40 Early Attempts at Immune-based Intervention: Azathioprene + Steroids Improve Endogenous Insulin Production in Recently-Diagnosed T1D Silverstein et al, NEJM, :

41 Type 1 Diabetes TrialNet An international network of major diabetes research centers Established in 2001 Mission: to develop new approaches to prevent or delay T1D Locations: 14 North American sites funded by NIH 4 International sites funded by JDRF

42 TrialNet Organization: N. American Clinical Centers and >200 Affiliates Vanderbilt Affiliates * ** * * * * * * * * * * * * * Vanderbilt Affiliate * 1. TC Thompson CH, Chattanooga, TN 2. Univ Diab/Endo Consultants, Chattanooga, TN 3. UT Methodist /LeBonheur, Memphis, TN 4. KY Diab/ Endo Ctr, Lexington 5. Univ. Ped Endo. Louisville, KY 6. UNC, Chapel Hill 7. DuPage Medical Grp, Chicago, IL 8. Midwest Endocrinology, Chicago, IL 9. Holston Medical Group, Kingsport, TN 10. Atlanta Diabetes Assoc. 11. Mass General Hosp, Boston 12. Mountain Diabetes and Endo. Asheville, NC 13. U MS Jackson, MS 14. Physicians East, NC 15. BMG-The Endocrine Clinic Memphis, TN 16. AM Diabetic Center, Memphis,TN

43 Who is Eligible to Screen? Proband has T1D if diagnosed before age 40 & started on insulin in first year

44 What s Involved in T1D Risk Screening? Confirm Eligibility/ Obtain Informed consent Single blood draw for T1D autoantibodies Without cost Protected health information Benefits of participation Learn individual risk for T1D Close follow up for high-risk individuals Opportunity to participate in prevention research Early diagnosis can avoid illness at presentation

45 How can YOU get involved? Many of your patients are TrialNet Families Most want to know their risk, some want be in trials Identify and engage them in T1D screening/prevention Keep asking and updating for T1D probands in family Endorse screening- without being coercive Display TrialNet materials in patient areas Remote Screening Brochures Posters Contact the TrialNet team: We take it from there Call: Kim Flowers:

46 Screening Options 1. At Vanderbilt Eskind Diabetes Clinic 1. Remote Screening Program (Anywhere in the U.S.) Subject contacts the TrialNet office to discuss eligibility Consent forms mailed to subject or downloaded from website Telephone consent obtained, forms signed and returned by fax, mail or TrialNet team sends a lab kit that subject takes to PCP, LabCorp, or Quest Blood drawn and sample returned in mailer to Vanderbilt

47 How Can T1D Screening Benefit Families? AB + individuals may be eligible to participate in clinical trials to delay or prevent the disease Those not eligible/interested in a trial remain in Monitoring Close follow up to diagnose T1D early- before significant illness Screening does not obligate participation in a clinical trial Pathway to Prevention Prevention Trials Oral Insulin Study Screening Oral Insulin Mechanistic Study Abatacept Study Monitoring Anti-CD3 Study

48 The End of T1D may be In Sight We want to see that end Contact Us: WEB: PHONE: / diabetesresearch@vanderbilt.edu bill.russell@vanderbilt.edu

49 Specialized Clinics/Programs at Vanderbilt Children s Hospital Pediatric Endocrinology Program Adolescent Gynecology (C) Najjar/Duffy Turner Syndrome (C) Duffy Hereditary Bone Diseases (C) Simmons Pediatric Lipid Disorders (C) Kelley Disorders of Sex Development (P) Russell/Brady Gender Dysphoria (P) Najjar only Children s Diabetes Program Type 1 Diabetes (C) Lybarger (ADA Recog) Type 2 Diabetes (C) Shoemaker Cystic Fibrosis-Related Diabetes (C) Potter Pre-Type 2 Diabetes (C) Shoemaker Behavioral Medicine (C) Jaser

50 Pre-Type 2 Diabetes Clinic Ashley Shoemaker, MD Mission: Evaluate children at high risk for prediabetes or type 2 diabetes. Full work-up including oral glucose tolerance testing. Emphasis is on lifestyle changes/group class with dietitian. Pilot program with Weight Management Clinic to provide additional counseling and motivational interviewing on diet/exercise changes. Patients identified with T2D impaired glucose tolerance are prescribed metformin and followed in the Pediatric Diabetes Clinic. Patients with insulin resistance but normal glucose tolerance are not followed. Referral criteria: Hemoglobin A1C 5.7%, fasting BG 100 mg/dl or random BG 180 Location: Eskind Pediatric Diabetes Clinic; 2 nd and 4 th Friday of the month Contact:

51 Pediatric Lipid Clinic Jennifer Kelley, MD Mission: To provide diagnostic and treatment services to children with cholesterol and triglyceride disorders Focus on prevention of cardiovascular disease later in life. Management of genetic disorders of lipid metabolism as well as secondary (acquired) causes of lipid abnormalities. Multidisciplinary approach includes evaluation by pediatric endocrinologist and nutritional assessment and education with registered dietitian. Family-centered Referral Criteria: Fasting LDL cholesterol > 150 mg/dl or <60 mg/dl Fasting triglyceride levels > 300 mg/dl Fasting HDL cholesterol <35 mg/dl Location: 100 Oaks, Every Wednesday Morning Contact:

52 Behavioral Medicine Clinic in the Children s Diabetes Program Sarah Jaser, PhD Mission: Provide behavioral health services to families who have a child with diabetes Referral Criteria: Current patient of Children s Diabetes Program To help patients and their families improve adherence, adjust to the new diagnosis or treatment, cope with diabetes-related stress/burnout, and manage anxiety Children > 5 years old through young adulthood seen by Dr. Jaser Children <5 years old, the focus of the work is with the parent/caregiver Supplements our Social Work and Child Life services Location: Eskind Diabetes Clinic and 2105 Edward Curd Lane Every other Friday (Eskind), every other Monday (ECL) Contact:

53 Hereditary Bone Disease Clinic Jill Simmons, MD Mission: Comprehensive, multi-disciplinary clinic for individuals and families with hereditary bone diseases: Osteogenesis Imperfecta; Hypophosphatasia; Hypophosphatemic Rickets Patients see pediatric (Simmons) and/or adult endocrinologist (Kathryn Dahir), physical therapy, orthopedics, pediatric pain specialist, and dietitian, as needed. Appropriate laboratory and radiographic testing, generally on the same day: audiology, echocardiograms, PFT, X-rays, renal ultrasound, DXA. Clinical care, clinical trials, and other research opportunities for patients. Referral Criteria: Patients with confirmed/ presumed diagnoses of metabolic bone disease Patients with frequent fractures/other concerns for bone disease should be referred to Dr. Simmons in her regular clinic Location: Doctors Office Tower; 2nd Tuesday of the month Contact: Becca

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