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Challenges and Opportunities in the Management of Type 1 Diabetes in Youth . Lori Laffel, MD, MPH Chief, Pediatric, Adolescent and Young Adult Section Investigator, Genetics and Epidemiology Section Joslin Diabetes Center, Harvard Medical School Type 1 Diabetes - Part 1.

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Challenges and Opportunities in the Management of Type 1 Diabetes in Youth


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    1. Challenges and Opportunitiesin the Management of Type 1 Diabetes in Youth Lori Laffel, MD, MPH Chief, Pediatric, Adolescent and Young Adult Section Investigator, Genetics and Epidemiology Section Joslin Diabetes Center, Harvard Medical School Type 1 Diabetes - Part 1

    2. JBW - January 2003 • 9 year old boy, otherwise healthy • Many classmates had flu • Onset of nausea, vomiting, lethargy • Call to local healthcare: • Asked about hydration status, time of last urination • Next morning, JBW found dead in bed

    3. Outline: Part 1 Changing epidemiology of diabetes in youth Type 1 vs type 2 Epidemic rates of type 1 diabetes Younger age of onset of type 1 diabetes Glycemic control Adolescents and the DCCT Factors related to glycemic control A1c guidelines and A1c outcomes in T1D Cases

    4. Outline: Part 2 Other challenges Hypoglycemia as a barrier to A1c goals Family impact of T1D Changing glycemic outcomes BG monitoring Insulin pump use and bolus dosing Other opportunities Continuous glucose monitoring Cases

    5. Epidemiology - 1 15,000 youth/yr in USA & 70,000 youth/yr worldwide are diagnosed with T1D 3,700 youth/yr in USA are diagnosed with T2D; ??? numbers/yr worldwide with T2D T1D occurs equally among males and females; T2D occurs 1.6x more often in females than males T1D is more common in whites than non-whites; T2D occurs more often in racial/ethnic minorities SEARCH Writing Group, JAMA 2007; 297:2716 WHO 2012 ADA. Diabetes Care. 2008; 31:S1-20 CDC 2012 ADA. Diabetes Care. 2010; 33:S11-61 IDF, World Diabetes Day 2012 CDC National diabetes fact sheet: 2011. Atlanta, GA: U.S. DHHS NIDDK. Available at:http://diabetes.niddk.nih.gov/dm/pubs/overview.index.htm. 2010

    6. Epidemiology - 2 ~75% of T1D is diagnosed in people <18 years old; majority of people with T1D are adults Majority of T2D is diagnosed in adults 215,000 total youth in USA and >500,000 youth worldwide <20 years old with diabetes in 2010 >371 million persons worldwide have diabetes; numbers will be >550 million by 2030 SEARCH Writing Group, JAMA 2007; 297:2716 WHO 2012 ADA. Diabetes Care. 2008; 31:S1-20 CDC 2012 ADA. Diabetes Care. 2010; 33:S11-61 IDF, World Diabetes Day 2012 CDC National diabetes fact sheet: 2011. Atlanta, GA: U.S. DHHS NIDDK. Available at:http://diabetes.niddk.nih.gov/dm/pubs/overview.index.htm. 2010

    7. Diabetes in Youth & Adults: Epidemiological Trends Epidemic of Childhood Obesity 1 out 3 children is overweight or obese Increasing occurrence of type 2 diabetes in youth 1 out of 3 children born in 2000 will develop diabetes Type 1 Diabetes in Youth Increasing incidence / prevalence during 20th and 21st C Shift towards younger age of onset Diabetes is increasing worldwide, with epidemic increases of type 2 diabetes in adults; rates of new onset type 1 diabetes in adults unclear

    8. Incidence of Diabetes in Youth in the United States 2435 youth with newly diagnosed diabetes in 2002–3 at 10 study locations: 78% T1D and 22% T2D Writing Group for the SEARCH for Diabetes in Youth Study Group. JAMA. 2007;297:2716-2724.

    9. Increasing Incidence of T1D in 0-17 year old Youth in Colorado IR of T1D increased 1.6-fold in Colorado 1978 to 2004: 14.8 to 23.9/100,000/year Vehik K et al. Diabetes Care. 2007;30:502-509.

    10. Numbers of youth with diabetes are expected to rise substantially by 2050 Estimates based up stable annual IR of T1D and T2D, there will be ~25% more youth with T1D and ~50% more youth with T2D by 2050 Estimates based upon the current annual IR increases of 2.3% in Colorado, USA (Vs 3.9% in Europe), there will be 300% more youth with T1D and 400% more youth with T2D by 2050 AND, IN TURN, THERE WILL BE MORE CASES OF DKA

    11. Nov 2, 2012 Annual death rates in USA from diabetes per 1,000,000 youths Death rates mainly from acute complications: hypoglycemia and DKA. Overall decline in death rates by 61% from 1968-2009. After initial decline, death rate increased from 1984-2009 in 10-19 y/o.

    12. Discussion Point:Factors related to onset of T1D • In your practice, how do you explain new onset type 1 diabetes to families? What factors related to type 1 diabetes onset do you discuss with families? • Have a 3 minute discussion about this at each of your tables.

    13. DCCT and Adolescents

    14. DCCT – Adult & Adolescent Cohorts Adults Adolescents DCCT: N Engl J Med. 1993 J Peds, 1994

    15. DCCT: Adolescents Vs Adults • significantly higher A1c’s: intensive- 8.1 vs 7.1% conventional- 9.8 vs 9.0% • significantly more hypoglycemia: intensive- 86 vs 57/100-pt-yrs conventional- 28 vs 17/100-pt-yrs • had significantly more DKA than adults: intensive- 2.8 vs 1.8/100-pt-yrs conventional- 4.7 vs 1.3/100-pt-yrs

    16. Intensive insulin therapy: • Improved A1c compared with conventional therapy • Reduced risk of diabetic eye disease by 53-70% (P<.05) • Reduced risk of diabetic kidney disease by 55% (P<.05) • Intensive insulin therapy required: • Multi-disciplinary team management • Education and support for insulin dosing, diet, exercise • Frequent blood glucose monitoring • Regular follow-up care

    17. Risk of Hyperglycemia • Due to intensity of exposure Intensity = degreeof hyperglycemia X duration of hyperglycemia

    18. Risk of Retinopathy Progression According to A1c A1c of 10% x3 years Vs A1c of 8% x8 years JAMA 2002:287

    19. Glycemic Goals and Glycemic Outcomes in Youth with T1D

    20. Discussion Point:Treatment Targets • In your practice, what clinical guidelines do you consider when establishing treatment targets? What factors impact glycemic control in youth? • Have a 3 minute discussion about this at each of your tables.

    21. ADA Position Statement Care of Youth with T1DM 2005, updated Jan 2013 A lower goal is reasonable if it can be achieved without excessive hypoglycemia ISPAD Guidelines 90-145 80-180 <7.5% Adults <7% “…near normalization of blood glucose levels is seldom attainable in children and adolescents after the honeymoon…”

    22. Distribution of A1c in2,873 youths from 18 countries 30 Male Female 25 1995 Mean 8.61.7% 20 1998 Mean 8.71.8% Number of children (% total) 15 10 2005 Mean 8.651.5% 5 0 4 5 6 7 8 9 10 11 12 13 14 15 16 17 HbA1c (%) Mortensen et al: Diabetes Care 1997; Danne et al: Diabetes Care 2001; de Beaufort et al: Diabetes Care 2007.

    23. Glycemic Control in Youth with T1D: The SEARCH for Diabetes in Youth Study A1clevels reflecting poor glycemic control (≥9.5%) in 17% of youths with T1D Mean A1c 8.2% Swedish Childhood Diabetes Registry (n = 2180): mean A1c 8.3%, 30% A1c ≥9% Petitti DB, et al. J Pediatr 2009;155:668–72; Hanberger L, et al. Diabetes Care 2008;31:927–9. *Good: ADA age-specific target

    24. Diabetes Management is Suboptimal during Adolescence & Young Adulthood These groups have the greatest proportion of patients not achieving glycemic goals Exchange Registry data HbA1C (%) Age (years) Beck et al. J Clin Endocrinol Metab Dec 2012; 97(12) 4383-4389

    25. Wood J, et al. T1D Exchange Diabetes Care ePub Jan 2013 N=13,226

    26. Factors Related to Glycemic Control • Attained age • Gender / Puberty • Age of onset of diabetes • Adherence • Family involvement • Conflict • New technologies / intensive therapy

    27. IMPAIRED INSULIN ACTION IN PUBERTY A Contributing Factor To Poor Glycemic Control In Adolescents With Diabetes Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tamborlane WV. N Engl J Med. 1986 Jul 24;315(4):215-9.

    28. Effect of Puberty on Insulin-Stimulated Glucose Metabolism in Subjects with and without Diabetes Glucose Infusion Rate (mg/M2/min)

    29. A1c According to Attained Age A1c % Years Laffel LMB et al. Treatment of the child and adolescent with diabetes. Joslin’s Diabetes Mellitus, 2005. p. 711-36.

    30. A1c Trajectories Pre to Post Adolescence Mean A1c Adolescence to Young Adulthood Mean A1c Beck et al. JCEM 2012

    31. According to Age at Onset HbA1c % Years Laffel LMB et al. Treatment of the child and adolescent with diabetes. Joslin’s Diabetes Mellitus, 2005. p. 711-36.

    32. Rapid Loss of Endogenous Insulin in Toddlers < 2 years 0.3 2.0 - 4.9 years 5 - 14.9 years 0.2 c-peptide (nmol/L) 0.1 0 3 weeks 6 months 3 months diagnosis 18 months 24 months 12 months Komulainen, Diab Care 22:1950 (1999)

    33. Young Boy using CSII HbA1c: 8.1%, 3/15/07 12 8/12 y/o boy with T1D of 11+ years duration DOB 7/15/94 T1D diagnosed 1/96 at age 18 months

    34. Intensive Rx Conventional Rx DCCT

    35. Case

    36. Case #1: Overview • A 14 year old boy with high A1c treated with a continuous subcutaneous insulin infusion (insulin pump) • He has had diabetes for 5 years and been on the pump for 3 years • A1c was relatively stable at 7.5% until the past 1 ½ years, when it started rising to 9%

    37. Question #1 • What would you do? A: Prescribe more insulin B: Take him off the pump C: Talk to him about complications

    38. Impaired Insulin Action in Puberty: A Contributing Factor to Poor Glycemic Control in Adolescents with Diabetes Effect of Puberty on Insulin-Stimulated Glucose Metabolism Glucose Infusion Rate Amiel SA et al. N Engl J Med. 1986;315:215-219.

    39. Case #1: Issues to Consider • Division of diabetes-related responsibility • What is going on in other areas of patient’s life? • Family conflict (general and diabetes-specific) • How does he feel about his A1c? • Is this a safety issue? Does he need to be taken off pump?

    40. Child report of diabetes-specific family conflict predicts QoL in T1D 100 95 90 85 Quality of Life Score 80 75 70 65 1 2 3 4 5 Diabetes-specific family conflict levelquintiles (1 = low, 5 = high) QoL: quality of lifeModel R2 = 0.21, p < 0.02. Conflict only significant predictor (p < 0.01) of QoLAdjusted for age, T1D duration, A1c, parental involvement Laffel LM, et al. Diabetes Care 2003;26:3067-73.

    41. Challenges and Opportunitiesin the Management of Type 1 Diabetes in Youth Lori Laffel, MD, MPH Chief, Pediatric, Adolescent and Young Adult Section Investigator, Genetics and Epidemiology Section Joslin Diabetes Center, Harvard Medical School Type 1 Diabetes - Part 2

    42. Outline: Part 2 Other challenges Hypoglycemia as a barrier to A1c goals Family impact of T1D Changing glycemic outcomes BG monitoring Insulin pump use and bolus dosing Other opportunities Continuous glucose monitoring Cases

    43. Hypoglycemia Risk

    44. Risk of hypoglycemia as A1c in the DCCT NEJM 1993

    45. Changing IR of hypoglycemia & HbA1c in population-based cohort 22 11.0 20 10.5 18 16 10.0 14 Mean HbA1c Rate /100 patient years 12 9.5 10 9.0 8 6 8.5 4 2 8.0 1998 2000 1992 1996 1994 2002 1998 2000 1992 1996 1994 2002 Calendar year Calendar year Severe hypoglycemia-LOC Bulsara MK, et al. Diabetes Care 2004;27:2293–8.

    46. Severe hypoglycemic events and A1C 85.7 Severe hypoglycemic events(per 100 pt-yrs) 55.5 p<0.001 29.4 27.8 A1c (%) p<0.001 Adol. DCCTConvent.(N = 103) Cohort 1 (1997)(N = 299) Cohort 2 (2002)(N = 152) Adol. DCCTIntensive (N = 103) Svoren BM, et al. Pediatrics 2003;112:914–22.

    47. Incidence rate ofhypoglycemia by regimen With help 48.4 Seizure/coma 41.8 37.0 33.4 29.6 Injections Severe Hypoglycemia CSII vs injection p=0.009 CSII vs NPH p<0.0001 CSII vs B-B p=NS B-B vs NPH p=0.015 Seizure/Coma CSII vs injection p<0.0001 CSII vs NPH p<0.0001 CSII vs B-B p=0.02 B-B vs NPH p=NS Katz M, et al. Diabetes 2010. Diab Med 2012.