Update in the management of childhood-onset T1DM

Transcription

1 KDA 2018 S2 Clinical diabetes & therapeutics 1 Update in the management of childhood-onset T1DM May 4, 2018 Jae Hyun Kim, MD Seoul National University Bundang Hospital Department of Pediatrics

2 본발표와관련된이해관계 없음

3 Contents Introduction T1DM in children and adolescents Management of T1DM in pediatric population Routine ambulatory care Insulin therapy Pumps/CGM Medications Future therapy Summary

4 Introduction Type 1 diabetes mellitus Chronic immune-mediated destruction of pancreatic ß-cells Partial, or in most cases, absolute insulin deficiency In most western countries, type 1 diabetes accounts for over 90% of childhood and adolescent diabetes, while across the lifespan, type 1 diabetes accounts for 5 10% of individuals with diabetes. Patients with type 1 diabetes mellitus (DM) require lifelong insulin therapy. Poor glycemic control was associated with micro- and macrovascular complications.

5 Global estimates for type 1 diabetes in children and adolescents (<20 years) for 2017 IDF Diabetes Atlas, 8 th ed. 2017

6 Incidence trends of T1DM diagnosed <15 years of age KOREA Western Countries Total 5.6%/yr Boys 6.4%/yr Girls 5.3%/yr 2 folds increase in 20 years 년 1.36 / 100,000 per yr x 년 3.19 / 100,000 per yr Lancet 2014;383:69 Pediatr Diabetes 2016;17:519

7 T1DM in children and adolescents 소아 는 성인의축소판 이아니다. 소아청소년당뇨인 은 성인당뇨인 과는다르다. The provider must consider the unique aspects of care and management of children and adolescents with type 1 diabetes, such as changes in insulin sensitivity related to physical growth and sexual maturation, ability to provide self-care, supervision in the child care and school environment, and neurological vulnerability to hypoglycemia and hyperglycemia in young children, as well as possible adverse neurocognitive effects of diabetic ketoacidosis (DKA) Attention to family dynamics, developmental stages, and physiological differences related to sexual maturity are all essential in developing and implementing an optimal diabetes treatment plan. Diabetes care 2014;37:2034

8 Developmental stages Puberty Infancy (0-12 mo) Toddler (13-26 mo) Preschooler and early elementary school (3-7 yr) Older elementary school (8-11 yr) Early adolescence (12-15 yr) Late adolescence (16-19 yr) Normal developmental tasks Type 1 diabetes management priorities Family issues in type 1 diabetes management Diabetes care 2014;37:2034

9 Major developmental issues and their effect on diabetes in children and adolescents Developmental Stages (ages) Normal developmental tasks T1D management priorities Family issues in T1D management Infancy (0 12 months) Developing a trusting relationship or bond with primary caregiver(s) Preventing and treating hypoglycemia Avoiding extreme fluctuations in blood glucose levels Coping with stress Sharing the burden of care to avoid parent burnout Toddler (13 26 months) Developing a sense of mastery and autonomy Preventing hypoglycemia Avoiding extreme fluctuations in blood glucose levels due to irregular food intake Establishing a schedule Managing the picky eater Limit-setting and coping with toddler s lack of cooperation with regimen Sharing the burden of care Preschooler and early elementary school (3 7 years) Developing initiative in activities and confidence in self Preventing hypoglycemia Coping with unpredictable appetite and activity Positively reinforcing cooperation with regimen Trusting other caregivers with diabetes management Reassuring child that diabetes is no one s fault Educating other caregivers about diabetes management Diabetes care 2014;37:2034

10 Developmental Stages (ages) Normal developmental tasks T1D management priorities Family issues in T1D management Older elementary school (8 11 years) Developing skills in athletic, cognitive, artistic, and social areas Consolidating selfesteem with respect to the peer group Making diabetes regimen flexible to allow for participation in school or peer activities Child learning short- and long-term benefits of optimal control Maintaining parental involvement in insulin and blood glucose management tasks while allowing for independent selfcare for special occasions Continuing to educate school and other caregivers Early adolescence (12 15 years) Managing body changes Developing a strong sense of self-identity Increasing insulin requirements during puberty Diabetes management and blood glucose control becoming more difficult Weight and body image concerns Renegotiating parent and teenager s roles in diabetes management to be acceptable to both Learning coping skills to enhance ability to self-manage Preventing and intervening in diabetes-related family conflict Monitoring for signs of depression, eating disorders, and risky behaviors Later adolescence (16 19 years) Establishing a sense of identity after high school (decisions about location, social issues, work, and education) Starting an ongoing discussion of transition to a new diabetes team (discussion may begin in earlier adolescent years) Integrating diabetes into new lifestyle Supporting the transition to Independence Learning coping skills to enhance ability to self-manage Preventing and intervening with diabetes-related family conflict Monitoring for signs of depression, eating disorders, and risky behaviors Diabetes care 2014;37:2034

11 Clinical evaluation Components Initial Annual Quarterly F/U Height, Weight, BMI percentile O O O Blood pressure O O O General physical exam O O O Thyroid exam O O O Injection/infusion sites O O O Comprehensive foot exam If needed, based on age Beginning with older teens with diabetes since childhood Visual foot exam O If needed, based on high-risk characteristics Retinal exam by eye care specialist O In some cases, may be done every 2 years Depression screen O O O Hypoglycemia assessment O O O Diabetes self-management skills O O O Physical activity assessment O O O Assess clinically relevant issues (alcohol, drug, tobacco, use of contraception, driving) O As needed for teens As needed for teens Nutritional knowledge O O As needed Query for evidence of other autoimmune disease O As needed As needed Immunization as recommended by KCDC O O As needed Diabetes care 2014;37:2034 O

12 2017 성장도표

13 2017 성장도표

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15 Laboratory assessments Components Initial Annual Quarterly F/U A1c O O Every 3 months Creatinine clearance / estimated GFR O Lipid panel Once glycemia is stable O As need based on treatment TSH O O Frequency of testing varies treatment based on clinical symptoms, presence of antibodies, and/or if on treatment Antithyroid antibodies Celiac antibody panel Urine albumin-tocreatinine ratio Islet cell antibodies C-peptide levels O Frequency of testing is unknown; test if symptoms are present or for periodic screening O Frequency of testing is unknown; test if symptoms are present or for periodic screening O Repeat as clinically indicated Repeat as clinically indicated As need based on treatment Starting 5 years after diagnosis O As need based on treatment O May be needed in new-onset patients to establish diagnosis O Occasionally needed to establish T1D in a patient on insulin or to verify T1D for insurance purposes - always measure a simultaneous blood glucose level Diabetes care 2014;37:2034

16 2014 년까지 2015 년이후

17 Diabetes-Self Management Education (DSME) Infancy (birth 18 months) Period of trust versus mistrust Providing warmth and comfort measures after invasive procedures is important Feeding and sleeping or nap routines Vigilance for hypoglycemia Play age (3 5 years) Reassurance that body is intact, use of Band-Aids and kisses after procedures Identification of hypoglycemic signs and symptoms (temper tantrums and nightmares are common) Include child in choosing injection and finger-prick sites Positive reinforcement for cooperation Begin process for teaching child awareness of hypoglycemia School age (6 12 years) Integrate child into educational experience Determine skill level Identify self-care skills Determine roles and responsibilities Communication with peers and school staff who and when to tell about diabetes

18 Diabetes-Self Management Education (DSME) Adolescence (12 18 years) Begin transition care planning Personal meaning of diabetes Determine roles and responsibilities in care Social situations and dating Who or when to tell about diabetes Driving Sex and preconception counseling Alcohol and drugs College and career planning Young adults Personal meaning of diabetes Roles and responsibilities in care Social situations and dating Who or when to tell about diabetes Genetic risks, conception, and preconception Travel Choosing or pursuing a career Workplace rights Health or life insurance Involving friends and significant others in diabetes care Safety Creating a support network Establishing or maintaining independence

19 Transition in care of T1DM patients Children Adolescents Adults Children Adolescents Emerging adulthood Adults Pediatric clinic Adult clinic Early phase yr Later phase yr Transition

20 Insulin therapy Conventional therapy Intensive diabetes management A mode of treatment for the person with diabetes that has the goal of achieving euglycemia or near-normal glycemia, using all available resources to accomplish this goal MDI: Multiple Daily Injection A management strategy for insulin delivery that includes the use of three or more injections of insulin daily to provide both basal and bolus insulin requirements Insulin (infusion) pump A continuous subcutaneous insulin injection (CSII) system that delivers rapid-acting insulin in an open-loop fashion into a subcutaneous site from a computer driven, externally mounted reservoir Conventional Tx MDI Insulin Pump

21 DCCT / EDIC Median HbA1c concentrations during DCCT, the training period between DCCT and EDIC, and EDIC DCCT intensive treatment did not achieve target HbA 1c <6.05% 44% of patients reached target 1 times during trial Median HbA1c was 7.2% (intensive) vs. 9.1% (conventional) David M. Nathan, and for the DCCT/EDIC Research Group Dia Care 2014;37:9-16

22 DCCT / EDIC Adverse effects: Severe hypoglycemia Severe hypoglycemia: 62/100 patient-years Coma or seizure: 16/100 patient-years x3 higher than in CONV Severe hypoglycemia Symptoms consistent with hypoglycemia The patient required the assistance of another person Associated with a blood glucose level < 50 mg/dl (2.8 mmol/l) prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration Weight gain: +4.6 kg in the intensive group Largely dissipated during the EDIC NEJM 1993;329:997;Diabetes care 2014;37:9

23 Insulin regimen Japan (JSGIT cohort) Germany/Austria (DPV registry) France (Camp attendees) Pediatr Diabetes 2014;15: Pediatr Diabetes 2017;18: PLoS ONE 2016;11(8):e

24 Glycemic control Japan (JSGIT) Pediatr Diabetes 2017;18: Diabetes Care 2012;35:80-86 Germany/Austria (DPV registry)

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26 A meta-analysis of CSII vs MDI Glycemic control: Mean difference in HbA1c on CSII vs MDI This meta-analysis of 25 randomised controlled trials looked at the glycaemic control and rate of hypoglycaemia in 1414 patients, including adults and children Mean difference = HbA1c on MDI HbA1c on CSII Mean difference = 0; CSII = MDI Mean difference positive: favours CSII Mean difference negative: favours MDI Significantly better control of HbA1c on CSII compared with MDI Pickup J et al., Severe hypoglycaemia and glycemic control in type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabetic Medicine 2008;25:

27 A meta-analysis of CSII vs MDI Rate ratio of severe hypoglycemia (SH): CSII vs MDI Rate Ratio = SH on MDI SH on CSIII Rate ratio = 1: rate of SH on CSII = MDI Rate ratio > 1: rate of SH favours CSII Rate ratio <1: rate of SH favours MDI SH significantly and markedly reduced during CSII compared with MDI Pickup J et al., Severe hypoglycaemia and glycemic control in type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabetic Medicine 2008;25:

28 당뇨소모성재료지원품목확대 ( 현행 ) 4 품목 : 혈당측정검사지, 채혈침, 인슐린주시기, 인슐린주사바늘 ( 확대 ) 7 품목 : 인슐린펌프용주사기, 인슐린펌프용주입세트, 연속혈당측정용전극 ( 센서 ) 추가 하지만, 1 일상한금액은 2,500 원으로동일 예정?

29 New Insulin formulations Fiasp (Fast-acting insulin aspart injection) The safety and efficacy of Fiasp in children and adolescents below 18 years of age have not been established.

30 New Insulin formulations Ryzodeg (Insulin Aspart / Insulin Degludeg) Korea: 만 2 세이상의소아와청소년및성인에서의당뇨병치료 Europe: Treatment of diabetes mellitus in adults, adolescents and children from the age of 2 years. USA: RYZODEG 70/30 is indicated to improve glycemic control in patients 1 year of age and older with diabetes mellitus.

31 Bionic pancreas Conventional Tx MDI Insulin Pump Bionic pancreas? Insulin only Insulin + Glucagon Reduced mean CGM-measured and plasma glucose concentrations Reduced hypoglycaemia, Reduced frequency of carbohydrates given to treat hypoglycaemia relative to the control period Lancet Diabetes Endocrinol 2016;4:233

32 Metformin HbA1c (-) BMI (+) BMI z-score (-) TIDD (+) Pediatric Diabetes. 2017;18:

33 Metformin Pediatric Diabetes. 2017;18:

34 SGLT2 inhibitors Double-blind Phase 2 trial of young adults (age years) with poorly controlled T1D (A1C 9.0%), 87 patients were randomized 1:1 to placebo or SOTA 400 mg once daily for 12 weeks. Well tolerated with evidence of improvements in glycemic control and weight reduction. ISPAD annual meeting 2017

35 T1DM and BCG vaccination Safe Elimanation of disease causing T-cell Restore insulin production PLoS ONE 7(8): e41756

36 T1DM and BCG vaccination Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes (Phase 2 trial) ClinicalTrials.gov Identifier: NCT

37 Stem cell derived therapy Hematopoietic stem cell transplant Islet cell transplant Islet cell replacement therapy (VIACYTE)

38 Hypoglycemia Glucagon 글루카겐하이포키트 (GlucaGen Hypokit, Novo Nordisk) 한국희귀의약품센터 / 각병원 29,000 원 /kit 2~8 냉장보관

39 Intranasal glucagon Eli Lily; Locemia Solution Pediatr Diabetes 2018;1-7

40 Intranasal glucagon Pediatr Diabetes 2018;1-7

41 T1D Registry USA (T1D exchange) Germany/Austria (DPV registry) Korea (-) UK (NPDA) Japan (JSGIT) Hvidoere group SWEET project Australia/NZ (ADDN)

42 Summary Children are not little adults A multidisciplinary team of specialists trained in pediatric diabetes management and sensitive to the challenges of children and adolescents with T1D and their families should provide care for this population. Application of new knowledge and advanced technology is important to the care for patients with type 1 diabetes.

43 Upcoming publications ISPAD (International Society for Pediatric and Adolescent Diabetes) Clinical Practice Consensus Guidelines 2018 Chiang J, Garvey KC, Hood K, et al. Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes Care. In press

44 Thank you for your attention.