1. 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

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; 297:2716WHO 2012 ADA. Diabetes Care. 2008; 31:S1-20CDC 2012 ADA. Diabetes Care. 2010; 33:S11-61IDF, 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; 297:2716WHO 2012 ADA. Diabetes Care. 2008; 31:S1-20CDC 2012 ADA. Diabetes Care. 2010; 33:S11-61IDF, 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 20 th and 21 st 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. 2435 youth with newly diagnosed diabetes in 2002–3 at 10 study locations: 78% T1D and 22% T2D Incidence of Diabetes in Youth in the United States Writing Group for the SEARCH for Diabetes in Youth Study Group. JAMA. 2007;297:2716-2724.

12. Vehik K et al. Diabetes Care. 2007;30:502-509. 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

13. 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

14. 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.

15. 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.

16. DCCT and Adolescents

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

18. 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

19.  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

20. Risk of Hyperglycemia Due to intensity of exposure Intensity = degree of hyperglycemia X duration of hyperglycemia

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

22. Glycemic Goals and Glycemic Outcomes in Youth with T1D

23. 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.

24. “…near normalization of blood glucose levels is seldom attainable in children and adolescents after the honeymoon…” Adults <7% ISPAD Guidelines 90-145 80-180 <7.5% 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

25. Distribution of A 1c in 2,873 youths from 18 countries Mortensen et al: Diabetes Care 1997; Danne et al: Diabetes Care 2001; de Beaufort et al: Diabetes Care 2007. 1995 Mean 8.6  1.7% 2005 Mean 8.65  1.5% 1998 Mean 8.7  1.8% 4567891011121314151617 0 5 10 15 20 25 30 Number of children (% total) HbA 1c (%) Male Female

26. A1c levels reflecting poor glycemic control (≥9.5%) in 17% of youths with T1D Glycemic Control in Youth with T1D: The SEARCH for Diabetes in Youth Study A1c in youth with T1D %* nGoodIntermediatePoorp All394744.438.816.8 Age at exam, years<.001 0-5 40266.925.18.0 6-12174854.134.711.3 13-18149932.444.423.3 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 Mean A1c 8.2% Swedish Childhood Diabetes Registry (n = 2180): mean A1c 8.3%, 30% A1c ≥9%

27. Diabetes Management is Suboptimal during Adolescence & Young Adulthood These groups have the greatest proportion of patients not achieving glycemic goals HbA 1C (%) Age (years) Exchange Registry data Beck et al. J Clin Endocrinol Metab Dec 2012; 97(12) 4383-4389

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

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

30. 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.

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

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

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

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

35. Komulainen, Diab Care 22:1950 (1999) Rapid Loss of Endogenous Insulin in Toddlers 0 0.1 0.2 0.3 diagnosis 3 weeks 3 months 6 months 12 months 18 months24 months c-peptide (nmol/L) < 2 years 2.0 - 4.9 years 5 - 14.9 years

36. 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

37. DCCT Intensive Rx Conventional Rx

38. Case

39. 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%

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

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

42. 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?

43. 12345 65 70 75 80 85 90 95 100 Quality of Life Score Diabetes-specific family conflict level quintiles (1 = low, 5 = high) QoL: quality of life Model R 2 = 0.21, p < 0.02. Conflict only significant predictor (p < 0.01) of QoL Adjusted for age, T1D duration, A1c, parental involvement Child report of diabetes-specific family conflict predicts QoL in T1D Laffel LM, et al. Diabetes Care 2003;26:3067-73.

44. 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 2

45. 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

46. Hypoglycemia Risk

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

48. Changing IR of hypoglycemia & HbA 1c in population-based cohort Bulsara MK, et al. Diabetes Care 2004;27:2293–8. 1992 11.0 10.0 8.5 8.0 2 4 6 8 10 Rate /100 patient years Calendar year 10.5 9.5 9.0 12 14 16 18 20 22 1994 1996 19982000 2002 Mean HbA 1c 1992 1994 1996 19982000 2002 Calendar year Severe hypoglycemia-LOC

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

50. 29.6 48.4 41.8 37.0 33.4 Severe Hypoglycemia CSII vs injectionp=0.009 CSII vs NPHp<0.0001 CSII vs B-Bp=NS B-B vs NPHp=0.015 Seizure/Coma CSII vs injectionp<0.0001 CSII vs NPHp<0.0001 CSII vs B-Bp=0.02 B-B vs NPHp=NS Katz M, et al. Diabetes 2010. Diab Med 2012. Incidence rate of hypoglycemia by regimen Seizure/coma With help Injections

51. Case

52. Case 2 – Young School Age Child 6-year-old with T1DM presently on insulin before meals and long-acting insulin At visit, physician notes BG at bedtime is almost always above 200 mg/dL (12 mmol/L) Q: Why? A: Fear of hypoglycemia After lunch, BG is over 200 mg/dL (12 mmol/L) Q: Why? A: Insulin given after lunch Q: How do we help correct these events?

53. Question #2 What would you do? A: Prescribe less insulin B: Start pump therapy with CGM C: Provide additional education and support

54. Children with T1DM (n = 583) Children with special healthcare needs (n = 39,944) Children without special healthcare needs (n = 4,945) p*p*p†p† Any family impact75%45%17%<.0001 Work restriction35%24%4%.0002<.0001 Financial impact38%23%6%<.0001 Financial probs 32%18%4%<.0001 Med exp >$1K41%20%8%<.0001 Time impact24%9%3%<.0001 School absence20%14%2%.06<.0001 * p value for T1DM vs Children with Special Healthcare Needs † p value for T1DM vs Children without Special Healthcare Needs Katz M, Laffel L, et al. J Pediatr 2012 Family impact measures in children with T1DM: With or without special healthcare needs

55. Children with T1DM (n = 583) Children with special healthcare needs (n = 39,944) Children without special healthcare needs (n = 4,945) p*p*p†p† Any family impact75%45%17%<.0001 Work restriction35%24%4%.0002<.0001 Financial impact38%23%6%<.0001 Financial probs 32%18%4%<.0001 Med exp >$1K41%20%8%<.0001 Time impact24%9%3%<.0001 School absence20%14%2%.06<.0001 * p value for T1DM vs Children with Special Healthcare Needs † p value for T1DM vs Children without Special Healthcare Needs Katz M, Laffel L, et al. J Pediatr 2012 Family impact measures in children with T1DM: With or without special healthcare needs

56. Discussion Point: Obstacles to Achieving Management and Metabolic Goals: At your tables, identify 3 obstacles that you think are responsible for making it difficult for patients and their families to achieve optimal metabolic goals. –Have a 3 minute discussion about this at each of your tables.

57. Adherence and Family Behavior in Children with Type 1 DM 1) Advances in DM treatment (“intensive therapy”) a) improves metabolic control, prevents complications b) increases the importance of adherence c) places increased demands on youth and their families 2)  family conflict (DM and general) correlate with  treatment adherence 3)  developmentally appropriate parental involvement leads to  adherence and  metabolic control

58. Factors influencing treatment adherence in adolescents with T1D Borus JS, Laffel L. Curr Opin Pediatr 2010;22:405–11. Adherence Gender Family Peers/school Technologies Disordered eating Affective disorders Diabetes-specific conflict Age Diabetes duration

59. Factors influencing treatment adherence in adolescents with T1D Borus JS, Laffel L. Curr Opin Pediatr 2010;22:405–11. Adherence BGM Insulin Delivery Gender Family Peers/school Technologies Disordered eating Affective disorders Diabetes-specific conflict Age Diabetes duration

60. Blood Glucose Monitoring is Key

61. BG Monitoring Improves HbA1c Anderson: J Peds, 1997 Levine: J Peds, 2001 Laffel: J Peds, 2003 P<0.02

62. A1c was 0.2% lower per each additional BG check per day across the range of BG checks. A1c was 0.5% lower per each additional BG check per day from 0-5 checks per day. N=26,179

63. 63 A1c by Frequency of BG Monitoring Miller et al. Diab Care 2013 Feb 1. [Epub ahead of print]

64. Family involvement is necessary for successful adherence to treatment programs – new technologies, pumps, etc.

65. Motivation for Pump Use

66. Total (N= 2743) Pump MDI: Basal Analog/ Rapid MDI: Basal Analog/ Rapid + Other MDI: No Basal Analog One-Two Injections/ No Basal Analog Age (yr)13.214.0 12.313.012.1 Age at Dx (yr)7.87.68.76.67.97.3 Duration (yr)5.06.04.95.34.74.4 A1C8.5±1.58.0±1.18.5±1.68.9±1.68.6±1.68.6±1.7 Total100.0%22.0%24.8%10.5%15.7%27.0% Mean A1c by Insulin Regimen in The SEARCH for Diabetes in Youth Study Paris CA, et al. J Pediatr 2009;155:183–9.

67. Glargine-Based MDI Compared to CSII

68. Insulin Delivery Method according to Age Beck et al. JCEM 2012

69. Discussion Point: Obstacles to Achieving Management and Metabolic Goals: At your tables, identify 3 challenges related to insulin pump therapy. –Have a 3 minute discussion about this at each of your tables.

70. Challenges of Pump Use Vs Injection R x p<0.0001

71. Q: When kids forget one bolus of insulin every other day, 1:___it has no impact on glycemic control or the A1c. 2:___the A1c increases by 0.5%. 3:___the A1c increases by 1.0%. 4:___the A1c increases by 2.0%.

72. Consistent bolus dosing is important

73. Burdick J, et al. Pediatrics 2004;113:e221–4. Missed insulin meal boluses and A1c A1c correlated with number of missed insulin meal boluses per day (r = 0.4; n = 48) A1c increases 1% / 4 missed boluses / week Missed boluses per week 10 6 6.5 7 7.5 8 8.5 9 9.5 0 2 468 HbA 1c (%)

74. *p < 0.001 for AUC glucose and glucose Missed insulin boluses for snacks in youth with T1D 9 youth with T1DM, sensor-augmented pump Rx 15 y/o, diabetes for 8 yrs, mean A1c 7.6% Over 3 months: 101 snacks with insulin, 94 snacks without insulin Vanderwel BW, et al. Diabetes Care 2010;33:507–8. Comparison of glucose excursions for snacks with and without insulin bolus Glucose level (mg/dL) * 50 100 150 200 250 300 350 0 50 100 150 200 Time (minutes) Snacks with insulin Snacks without insulin

75. 90 youths with T1D for 8 ± 4 yrs, 12-18 y/o (15±2 yr) CSII for 3 years, A1c 8.3 ± 1.2% 24 hour diet recall compared with bolus Hx from pump download –Insulin omission was common, associated with less BGM, higher basal rates, and higher A1c *p ≤ 0.001 Olinder AL, et al. Pediatr Diabetes 2009;10:142–8. Missed bolus doses: devastating for metabolic control in csii-treated adolescents with T1D Missed ≤15% (n = 56) (62%) Missed >15% (n = 34) (38%) Age (yr)14.8 ± 2.214.9 ± 2.0 Diabetes duration (yr)7.6 ± 3.88.3 ± 3.7 Pump therapy duration (yr)3.1 ± 1.83.9 ± 1.9 HbA 1c (%)8.0 ± 1.08.8 ± 1.2 Mean doses / day for 4 wks (n)5.3 ± 1.73.8 ± 1.7 SMBG per day (n)3.6 ± 1.82.4 ± 1.8 Insulin dose (U/kg)0.83 ± 0.180.82 ± 0.17 Basal dose/total dose (%)55 ± 1265 ± 14 * * * *

76. % Of participants reporting missing an insulin dose at least once weekly Type 1 diabetes exchange, AADE Indianapolis 2012

77. Why is remeal bolusing is important?

78. 0.2 U/kg bolus of rapid-acting insulin analog at time = 0 Peak insulin levels at ~60 min Swan KL, et al. Diabetes Care 2009;32:240–4. 21 youths with T1DM 8–17 years old HbA 1c 6.5–8.9% PD and PK properties of rapid-acting insulin analog in pump therapy in youth with T1DM 03060120210240270 0 10 20 30 40 50 Insulin levels (  U/mL) Time (min) 90150180300 60 70 80 90 100 110 Pre-pubertal Pubertal

79. Pharmacodynamics of Aspart Pharmacodynamics of rapid-acting insulin analog GIR 37% greater in pre-pubertal vs pubertal patients, p < 0.01 03060120210240270 0 1.0 2.0 3.0 4.0 GIR (mg/kg/min) Time (min) 90150180300 5.0 6.0 7.0 8.0 9.0 Swan KL et al. Diabetes Care 2009;32:240–4. Time to peak insulin action at ~100 min Pre-pubertal Pubertal Time to peak similar in pre- and pubertal pts

80. Diabetes Care 2006; 29:2355-60 To examine longitudinal outcomes of pump use To identify predictors of insulin pump success To assess rates of and reasons for pump discontinuation Of 161 youth, 29 (18%) discontinued pump use over 3.8 years 28% DKA, insulin omission 28% diabetes burnout 21% infusion site issues 14% body image concerns 10% weight gain

81. Glycemic Control According to Pump Use BGM frequency3.6 Vs4.0 Vs X/day4.1*4.7* (n=29) (n=132)

82. Factors Associated with Unsuccessful Pump Rx Comparison of youth resuming MDI with youth continuing CSII: Slight female excess: 90% Vs 67% (p<0.02) Slight post-pubertal excess: 97% Vs 74% (p<0.03) Single parent families: 29% Vs 4% (p<0.01) Increase in hypoglycemia with CSII: 23.2 Vs 7.4 events/100 pt-yrs (p<0.01) Wood, Laffel et al. Diabetes Care 2006

83. Case

84. Case #3: Overview A 17 year old girl with 2 hospitalizations for DKA in the past year –T1D since age 10 –Relatively good control of diabetes until age 15, then A1c up to 11% –She does all diabetes management on own – does not want parents involved

85. Question #3 What would you do? A: Tell the parents to get more involved in her care B: Tell the parents they should absolutely NOT have involvement in her care – she is almost an adult C: Try to find out more about why this is happening

86. Factors influencing treatment adherence in adolescents with T1D Borus JS, Laffel L. Curr Opin Pediatr 2010;22:405–11. Adherence Gender Family Peers/school Technologies Disordered eating Affective disorders Diabetes-specific conflict Age Diabetes duration

87. Case #3: Issues to Consider What is going on in other areas of her life? Anything new in past year? Possible eating disorder? How does she feel about her diabetes? Why is she omitting insulin? How does the family interact around diabetes?

88. ~30% of females teens with T1D had DEBs or EDs ~30% used insulin restriction or omission for weight loss Those with DEB/EDs had higher A1c by ~2% During 4 years of F/U, those with DEB/EDs had 3x the risk of retinopathy and 2x the risk of microalbuminuria

89. Opportunities with CGM Use  Continuous data, revealing rate and direction of change  Improve diabetes management and self-efficacy  Immediate feedback regarding insulin, diet, exercise, stress  Alarms and trend data can help prevent hypo- and hyper-glycemia  Retrospective data allows refinement of Rx  Reduce anxiety about hypoglycemia  Reduce family conflict due to better control, or greater awareness that BG numbers do not always reflect behavior in a predictable way

90. Challenges of CGM Use  Increase anxiety and/or depressive symptoms  Too much information/overwhelming?  CGM leads to excessive focus on numbers?  Increase awareness of out-of-range values  Disagreement between CGM and traditional BGM values  Burden associated with insertion, calibration, tape, alarms  Increase family conflict (e.g., parental blame if awareness of out-of-range values increases) With negative impact of CGM less CGM usage

92. Relationship Between Change in HbA1c and Frequency of CGM Use Change in HbA1c

93. Glucose Monitoring: SMBG & CGM SMBGCGM Beck et al. JCEM 2012

94. Challenges of CGM Use for Families and Youth with T1D Parents seek improved approaches to care; parents provide consent, youth “go along for the ride” Youth expect devices to make management easier; unrealistic expectations for “cure” with artificial pancreas Parents of younger children remain involved, parents of adolescents disengage with increased adolescent autonomy and need for privacy (sensors worn on body = personal invasion) Parents of younger children often fear low BGs more than high BGs Children do not look at receiver; adolescents often ignore “nuisance” alarms

95. Opportunities & Ongoing Challenges In the post-DCCT era, more pediatric patients with T1DM receive intensive diabetes management leading to improved glycemic control There remains a significant gap between current glycemic outcomes and glycemic targets in pediatric patients today Present: education, technologies, and multi-disciplinary support to reduce the gap Future: CGM and closing the loop

96. Diabetes management from childhood to adolescence to young adulthood CHILDHOODADOLESCENCEYOUNG ADULTHOOD Diabetes is NOT a do-it-yourself condition at any age! Garvey, Markowitz, Laffel Curr Diab Reports 2012

97. THANK YOU!