Pediatric Type 2 Diabetes: What is the big deal? Jay Shubrook DO FACOFP Professor, Diabetologist Touro University CA, COM

Transcription

1 Pediatric Type 2 Diabetes: What is the big deal? Jay Shubrook DO FACOFP Professor, Diabetologist Touro University CA, COM

2 Objectives Review epidemiology What is different about type 2 in kids Review current available treatments Discuss new and emerging options

3 Disclosures Advisory Board Lilly Diabetes NovoNordisk Intarcia Research Grant/Study Participation Lilly Astra Zeneca Takeda Theracos

4 Diabetes in California (1,2) 55% of adults in California have diabetes or prediabetes There are no classic symptoms for type 2 diabetes Screening is the best way to find diabetes Types of Diabetes in Children Type 1, type 2 Monogenic Diabetes of Youth (MODY) Neonatal diabetes cdc.gov/diabetes.

5 Type 2 Diabetes in Children 33% of all adolescents in US with DM have TYPE 2 (3) Over-representation from ethnic and racial minorities Hispanic/Latino African American First American Filipino Uncommon before puberty Increased 35% in US (4) Increased 109% (5) Rates much higher in female (4) Closely tied to Family History and Obesity

6 6

7 Rates of Type 1 and Type 2 DM in US Youth NEJM April 13, 2017

8 Risk Factors for T2DM in kids (7,8,9,10,11) Excessive body weight >85% of BMI for age and gender First American, Black, Hispanic, Pacific Islander, Asian FH of T2DM in first or second degree relatives Low Birth weight OR High Birth weight Maternal Gestational DM No breastfeeding Use of antipsychotics (increased risk x 3) Bobo WV JAMA Psych 2013) Age 12-16

9 Type 2 DM Progression (12,13,14) Lose 15% of beta cell function/year No change in insulin sensitivity- maximally resistant 31% loss of insulin medicated glucose disposal 78% loss of acute insulin response

10 Which kids should we screen for T2DM? (7,13) Start at age 10 or onset of puberty in: Any child who is overweight or obese Family history in 1 or 2 degree relative First American, Black, Hispanic. Asian, Pacific Islander Any sign of insulin resistance: Acanthosis Hypertension Dyslipidemia PCOS Repeat screening every 2 years Fasting glucose is preferred

11 Case: Adolescent with dirty neck A 14 year old AA female presents with concerns about a rash on her neck that will not wash away. Has been present for a couple years but seems to be worse. Child does not like it nor do parents. Does not seem to wash away Teacher said he was going to report to Children Services if nothing was done

12 Case: History and Physical History Always obese, late menarche, bilateral knee pain Rash was seen by mom at event- no quick changes, nothing seems to make it better or worse No meds, no allergies FH- hypertension in both parents, DM in mom, CRF in dad Social- doing fair in school, some friends, lives with mom and brother, Shared custody with dad Physical Obese adolescent (> 95% for gender, age and Ht) Truncal obesity Bp 148/92 (HIGH)

13 Case: labs A1c 9.2%. (high) Glucose 138 mg/dl (fasting) (high) AST 56 (high) ALT 62 (high) Lipid panel Total chol 258 mg/dl (high) HDL 30 mg/dl (low) LDL 172 mg/dl Trigs 380 mg/dl (high)

14 Where do we begin with this kid? Problem List Insulin resistance syndrome Metabolic syndrome Diabetes- probably T2 Possible fatty liver disease Dyslipidemia Suspect hypertension Obesity What are the top 3 things you would do now?

15 TODAY Trial (Treatment Options for T2DM in Adolescents and Youth) (16) A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes Compared Treatment of Youth with : A) Metformin B) Metformin + Lifestyle changes C) Metformin + Rosiglitazone Failure rate declined 13.1% with addition of rosiglitazone

16 TODAY study results (16,17)

17 Medications for T2DM in children FDA APPROVED Metformin Aspart Lispro Glulisine NPH, R insulin Have been studies/used/reported Glargine Detemir Degludec Glimepiride age > 8 years old Rosiglitazone age 10+ Pioglitazone age 15+ Exenatide bid age 15+

18 What about the newer medications? ALL OFF LABEL Very few studies to support (left to opinion) Meds shown to prevent type 2 DM (in adults) Metformin TZDs Acarbose Liraglutide What meds look attractive? Incretin based therapies DPP-4 inhibitors (all once a day tablets)- few side effects GLP-1 RA (all currently injections)- weight loss Insulin pulses

19 Pediatric Guidelines for T2DM in children/adolescents (15) Clinical Practice Guideline: Management of Newly diagnosed Type 2 Diabetes Mellitus (T2DM) in Children and Adolescents. Pediatrics 2013:

20 Pediatric Endocrine Society Recommendations (15) Committee: AAP, ADA, PES, AAFP, and AND Criteria: Age:10-<18 ( months) Diagnoses of T2DM (excluded T1DM, GDM, pre-dm, PCOS, and insulin resistance) 6 Key action statements in guidelines for newly diagnosed adolescents

21 Statement #1 :Use insulin when unsure (15) Start Insulin Immediately in T2DM if DKA/ketosis (inpatient) Random glucose >250 mg/dl HbA1C >9% Unclear T1DM vs T2DM Start with a basal insulin units/kg/day Quicker glycemic control B cells can rest and recover Improve adherence and monitoring (seriousness of disease) In patients with unclear DM type- gives time for testing Once controlled and differentiated-often can wean and manage with oral med and lifestyle modifications Some evidence of a legacy effect

22 Statement #2- Initial Treatment Recommendations (15) For those newly DX but do not meet criteria #1 First line therapy for T2DM- Metformin + Lifestyle Modification Metformin dose 2000 mg (titration and meal reduce AE) Lifestyle: physical activity and nutrition-structured and family based Previously- lifestyle only Problems: adherence, progression of disease <10% reach goal with LM only

23 Statement #3: Lab Monitoring (15) Monitor HbA1C q3 months, q6 months if stable Intensify monitoring and treatment if goals not met Target HbA1C <7% Can aim for lower- but avoid hypoglycemia Glycemic control is related to decreasing risk of microvascular complications Clinical Practice Guideline: Management of Newly diagnosed Type 2 Diabetes Mellitus (T2DM) in Children and Adolescents. Pediatrics 2013:

24 Statement #4- BG Monitoring (15) New dx: BG Fasting, Pre-meal, and bedtime until stable and regimen set up Oral/basal Oral only: frequency based on control Bedtime long acting: fasting BG Oral + long acting: 2x/day- FBG + 1 postprandial Basal-Bolus (Multiple Injections) Pre-meal and bedtime testing (4x/day) Using carb ratio and sensitivity for mealtime Increase frequency with illness, hypo/hyperglycemia BG target Using pre-meal and postprandial to improve control when HbA1C and FBG incongruent Clinical Practice Guideline: Management of Newly diagnosed Type 2 Diabetes Mellitus (T2DM) in Children and Adolescents. Pediatrics 2013:

25 Statement #5- Weight management (15) Incorporation of AND s Pediatric Weight Management Evidence- Based Nutrition Practice Guidelines (Note: studies done in overweight) Reduced energy intake 450kcal/day 58% reduction in progression to DM at 2.8 yr f/u Refer to dietician Increase activity Dietary intake Age kcal/day >1200 kcal/day Protein sparing, modified fast >120% ideal weight with Medical condition Clinical Practice Guideline: Management of Newly diagnosed Type 2 Diabetes Mellitus (T2DM) in Children and Adolescents. Pediatrics 2013:

26 Statement #6: Physical Activity (15) Encourage patients to: Engage in moderate to vigorous exercise >60 min/day Moderate: can talk but not sing Vigorous: can t talk without losing breath Makes person breathe hard, raises heart rate, and makes them perspire 60 min can be broken up into min sessions Writing Rx and being sensitive to finances Involving the families Adjust insulin/meds Limit non-academic screen-time to <2 hr/day No screens in bedroom Clinical Practice Guideline: Management of Newly diagnosed Type 2 Diabetes Mellitus (T2DM) in Children and Adolescents. Pediatrics 2013:

27 Importance of Family-Centered Care Addressing cultural issues within family Peer-enhanced activities Engaging the family helps in younger ages: Adherence to meds Lifestyle changes Provides support system

28 Team Approach Consult subspecialist at diagnosis then at least annual visits PCP needs to follow closely and work with specialist for advice on intensifying therapy when needed Communication with healthcare providers

29 Depression (18) 3 x higher in youth with DM Search study- depression males T2DM>T1DM Screen for at diagnosis and periodically thereafter (APA criteria) Associated with poor glycemic control and ED visits Treatment: mental health referral, counseling, meds Springer SC, Copeland KC, Silverstein J, et al. Technical report: Management of Type 2 Diabetes Mellitus in Children and Adolescents. Pediatrics 2013: e648-e664.

30 Unique Challenges in the Emerging Adult (24) Leaving home for the first time Responsible for own care and reports Responsible to get medications Freedom Sex Drugs Dramatic changes in schedules Eating disorders Relationships Diabetes Care for Emerging Adults: Recommendations for Transition From Pediatric to Adult Diabetes Care Systems. Diabetes Care Diabetes Care (11):

31 Discuss handoffs of care (24) Need a transition team Helps to provide goals for independence Introduce child to new provider Helps to support in gaps of care College Job Lack of insurance/underinsurance Rebel years The Primary Care Pediatrician can be a VERY valuable resource for these kids- Diabetes Care for Emerging Adults: Recommendations for Transition From Pediatric to Adult Diabetes Care Systems. Diabetes Care Diabetes Care (11):

32 Recent T2DM Recommendations Youth-onset type 2 diabetes consensus report: Current Status, Challenges and Priorities. Diabetes Care (9): American Diabetes Association 2018 Standards of Care for People with Diabetes. Chapter 12. Children and Adolescents. Diabetes Care (Supplement 1):S126-S136.

33 Summary Type 2 DM in children is on the rise Type 2 diabetes is MORE progressive and harder to treat in children Use treatments as early as possible Consider a comprehensive team based approach

34 What are we doing at Touro CA? Project HAPPY (Tami Hendriksz DO with Katherine Yu and Sonia Shenoi and a team of TUCA students) Teaching kids to be family leaders in health MOBEC DREAM team Free community based screening And Education

35 What are we doing at Touro CA?

36 Questions? Thanks! FACEBOOK: DREAMTEAM

37 Diabetes Co-morbidities Updates and Recommendations as Addressed in Technical Report (18)

38 Hypertension (18-20) Present in 36% of T2DM youths within 1.3 yrs of diagnosis (65% of participants in Search Study) BP measurements at each clinic visit Appropriate sized cuff Plot against norms for age, height, gender Treatment- if BP is >95% on 3 occasions Weight loss Increased activity Reduce salt intake After 6 months if BP is >95%: ACE or ARB

39 Dyslipidemia (18-20) Search Study % hypertriglyceridemia 73% with low HDL Screening: baseline fasting lipids after initial glycemic control If normal- f/u q2 years Treatment: Dietician c/s BMI>95% LDL <130 goal, <100 ideal; >130- diet x 6 mos, recheck, if start statin (diet: no trans, chol <200/day, <30% cal fat, <7% sat fat) Triglycerides <150 goal, wt loss, decrease fat and simple carbs, > start niacin or fibrate if age >10

40 Microvascular: Retinopathy (18, 21) Presents earlier than in adults (controversial) Japanese study found adolescents with retinopathy prior to DM diagnosis (may relate to demographics) Initial dilated eye exam following dx (not 3-5 yrs as in T1DM) Subsequent exams annually (more frequent if progressing, less frequent if normal) Referral for laser photocoagulation therapy for patients with proliferative diabetic retinopathy, macular edema, and severe non-proliferative DR

41 Microvascular: Nephropathy/Albuminuria (18, 22,23) Albumin to creatinine ratio mg/g in spot urine Screen at diagnosis and annually Higher rates in T2DM than T1DM Treatment: ACE inhibitor- titrate to normalized levels Monitor q3-6 months HTN treatment Tobacco Cessation Referral to Nephrologist if treatment fails

42 Diabetes Resources for Peds AAP American Academy of Nutrition and Dietetics

43 Peds DM/Obesity Resources CDC

44 References for Lecture 1. CDC.gov/diabetes fact sheet California Diabetes Report Alberti G, et al. IDF Workshop Type 2 Diabetes in the young. An evolving Epidemic. Diabetes Care (7): Diabelea D et al. Incidence of diabetes in youth in the US. JAMA (24): Obesity and T2DM as Documented in Private Claims Data. A FAIR Health White Paper. FAIR Health Inc. January Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, Imperatore G, Linder B, Marcovina S, Pettitt DJ, Pihoker C, Saydah S, Wagenknecht L, SEARCH for Diabetes in Youth Study. Incidence Trends of Type 1 and Type 2 Diabetes Among Youths, The New England Journal of Medicine 2017;376: PMID: ADA Standards of Care Diabetes Care Meyer-Davis EJ et al. Breast Feeding and T2DM in youth of three ethnic groups. The SEARCH for diabetes in youth case control study. Diabetes Care (3): Wei JN et al. Low birth weight and high birth weight infants are both at increased risk to have T2DM among school children in Taiwan. Diabetes Care (2):

45 References for Lecture 9. Wei JN et al. Low birth weight and high birth weight infants are both at increased risk to have T2DM among school children in Taiwan. Diabetes Care (2): Meyer-Davis EJ et al. Breast Feeding and T2DM in youth of three ethnic groups. The SEARCH for diabetes in youth case control study. Diabetes Care (3): Bobo WV et al. Antipsychotics and the Risk of T2DM in Children and Youth. JAMA Psychiatry : Gungor N, Arslanian S. Progressive beta cell failure in T2DM of youth. J Pediatrics (5): Weyer C et al. The natural history of insulin secretory function and insulin resistance in the pathogenesis of T2DM. J Clin Invest (6):

46 References for Lecture 14. Kendall D et Bergenstal R. International diabetes Center Copeland KC et al. Clinical Practice Guidelines. Management of Newly Diagnosed T2DM in children and adolescents. Pediatrics (2): Zeitler P et al. Treatment options for T2DM in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle in adolescents with T2DM. Pediatric Diabetes (2): Zeitler P, Hirst K, Pyle L, et al; TODAY Study Group. A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes. N Engl J Med. 2012; 366(24):

47 References for Lecture 18. Springer SC, Copeland KC, Silverstein J, et al. Technical report: Management of Type 2 Diabetes Mellitus in Children and Adolescents. Pediatrics 2013: e648-e Hillier TA, PedulaKl. Complications in young adults with early onset T2DM:losing the relative protection of youth. Diabetes Care (11): Tryggestad JB et al. Complications and comorbidities of T2DM in adolescents:findings from the TODAY study. Journal of Diabetes and Its Complications :(2): Krakoff J et al. Incidence of retinopathy and nephropathy in youth onset compared to adult onset T2DM. Diabetes Care (1): Dart AB et al. High burden of Kidney Disease in Young onset T2DM. Diabetes Care (1): Solis-Herrera C, Triplitt CL. Nephropathy in Youth and Young Adults with T2DM. Curr Diabetes Reports :456-y. 24. Diabetes Care for Emerging Adults: Recommendations for Transition From Pediatric to Adult Diabetes Care Systems. Diabetes Care Diabetes Care (11):

48 References for lecture 25. Youth-onset type 2 diabetes consensus report: Current Status, Challenges and Priorities. Diabetes Care (9): American Diabetes Association 2018 Standards of Care for People with Diabetes. Chapter 12. Children and Adolescents. Diabetes Care (Supplement 1):S126- S136.