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  • IGT = Impaired Glucose Tolerance
  • Review Data
  • In terms of publications, these colorful tip sheets provide basic information about type 2 diabetes and encourage young people to take steps to manage the disease for a long and healthy life. Written in simple language, the tip sheets are helpful for anyone who has type 2 diabetes and their loved ones. Topics include: What is Diabetes? Be Active. Stay at a Healthy Weight. Eat Healthy Foods. These tip sheets also are available online on the NDEP website. Additional tip sheets are in development covering dealing with diabetes and diabetes prevention.
  • The school guide is called Helping the Student with Diabetes Succeed. A Guide for School Personnel. NDEP took on this project because of reports from NDEP partner organizations and their constituents of the lack of awareness and knowledge on how to manage kids with diabetes during the school day and the discrimination against children with diabetes in the school setting. Numerous NDEP partners joined NDEP to create and pretest the school guide.

Transcript

  • 1. Francine Ratner Kaufman, M.D. Distinguished Professor of Pediatrics The Keck School of Medicine of USC Head, Center for Diabetes and Endocrinology Childrens Hospital Los Angeles Type 2 Diabetes in Youth
  • 2. Question What Do We Know About Type 2 Diabetes in Youth?
  • 3. Prevalence of Diabetes and IFG in US Adolescents – NHANES 1999-2002
    • Type 2 Diabetes
      • 0.5% of adolescents have diabetes
      • 71% type 1 and 29% type 2
        • Determined by insulin use vs no insulin use
      • 39,005 US teens with T2D
    • Impaired Fasting Glucose
      • 11% had IFG
      • 2,769,736 teens with IFG
    • Diabetes Increased 41% from 4.9 to 6.9/1000 from 1997 to 2003 - adults
    • Duncan, Arch Pediatr Adolesc Med 2006;160:523; Geiss, Am J Prevent Med 2006;30:371
  • 4. Is it an epidemic?
    • The incidence is increasing and probably underestimated
      • Population based estimates indicate an ~10-fold increase in incident cases over the past 10-15 years
      • 8% to 43% of all new cases of diabetes in the United States depending on ethnicity
      • The SEARCH Trial
      • What about prevalence??
      • Bloomgarden ZT. Diabetes Care . 2004;27:998-1010 Centers for Disease Control. Diabetes Fact Sheet. 2005
  • 5. Controversies as to the Nature of this Epidemic
    • Difficult to recruit for the TODAY trial
        • 13 centers across the country
        • Presence of antibodies
    • The SEARCH Trial
        • 19,000 new patients with T1D
        • 4,100 new patients with T2D
    FCP > 2.9 ng/ml + Ab Hybrid FCP > 2.9 ng/ml - Ab Type 2 FCP < 0.8 ng/ml + Ab Type 1a
  • 6. Diabetes Trends Among Adults in the US BRFSS 1990, 1995 and 2001
  • 7. Is Type 2 Diabetes An Epidemic? Little Rock, Cincinnati, San Antonio 0 5 10 15 20 25 30 35 % with type 2 87 88 89 90 91 92 93 94 95 96 J Pediatr 136:664-672, 2000
      • Ten-fold increase 0.7 vs 7.2/100000
      • 8% to 43% of all new cases of diabetes in youth in US depending on ethnicity
  • 8. Question Is the Presentation the Same as in Adults?
    • Does not appear to be preceded by long asymptomatic period
      • Do not find undiagnosed cases on screening
  • 9. Natural History of Type 2 Diabetes Genetic susceptibility Environmental factors Atherosclerosis Hyperglycemia Hypertension Retinopathy Nephropathy Neuropathy Blindness Renal failure CHD Amputation Onset of diabetes Complications Disability Death Ongoing hyperglycemia PRE Obesity Insulin resistance Risk for Disease Metabolic Syndrome
  • 10. Pre-diabetes (IGT) and T2D 0% 33% 15 subjects Weninger et al, 1980 4% 21% 112 multi-ethnic teens (>95 th %ile) Sinha et al, 2002 0% 28% 150 Hispanic +FH (8-13 years >85 th %ile) Goran et al, 2004 0% 25% 55 multi-ethnic youth (>95 th %ile) Sinha et al, 2002 6% 17% 66 multi-ethnic youth (4-16 years) Paulsen et al, 1968 T2D IGT Overweight Sample
  • 11.  
  • 12.  
  • 13. OGTT Feasibility Study Pre-diabetes and Diabetes by ADA Cut-offs 0.1% 0.0% 0.4% Diabetes (  126) 0.1% 2.0% 39.7% Pre-diabetes (100-125) 0.0% 0.2% 57.6% Normal (< 100) Diabetes (  200) Pre-diabetes (140-199) Normal (< 140) Fasting glucose 2-hour glucose
  • 14. Years from Clinical Diagnosis B-cell Function (%) UKPDS Data Type 2 Diabetes Progressive Pancreatic B-cell Failure ? Curve for Youth Prevention and Early Treatment
  • 15. Question Is the Pathophysiology the Same as in Adults?
    • Associated with significant ß-cell failure as well as insulin resistance
      • Occurs at the time of intense insulin resistance due to puberty
  • 16. Insulin Resistance Age Puberty Type 2 Diabetes Prediabetes Beta Cell Defect Obesity BP, Lipids Gender – Girls Polycystic ovary syndrome Genetics Ethnicity Sedentary Lifestyle Beta Cell Defect
  • 17. Insulin Resistance Autoimmunity Type 2 Diabetes Prediabetes Beta Cell Defect Genetic Defect Intrauterine IUGR, DM Glucose toxicity Beta Cell Defect Fat cell toxicity
  • 18. Question What distinguishes type 1 from type 2 diabetes in youth?
  • 19. Type 1 Versus type 2 Diabetes in youth? Kaufman, Endocrinol Meta Clinics N Am, 34;659-676: 2005 Antibody Ethnicity C-peptide Comorbid Relative with DM DKA Course Weight 15% (reported as high as 30%) NA, AA, HA, Asian, Pacific Islander 85% Whites predominate Normal or increased C-peptide can be preserved at DX Increase in polycystic ovary syndrome Acanthosis nigricans Thyroid, adrenal, vitiligo, celiac 74%-100% - 1 st –2 nd degree with T2DM 5% with T1DM Up to 30% may have with T2DM FH of T2 2-3Xs in person with T1 Ketonuria (33%) Mild DKA (5%-25%) 35%-40% Indolent Virtually none found on screening Rapid From DPT-1 can be indolent Virtually all BMI > 85%th percentile 20% may be overweight / obese T2DM T1DM
  • 20. Differentiation Between Type 1 and 2
    • 48 with type 2 vs 39 with type 1
    • Type 2
      • Ethnicity, 1 st degree relative, BMI>24, +C-peptide, acanthosis
      • Hathout et al Pediatrics 107e102,June,2001
    85% have islet autoimmunity 8.1% ICA 30% GAD 35%IAA Abs 1.8 + 3.5 ug/l 2.2 + 2.2 ug/l C-peptide 53% 33% DKA Type 1 Type 2
  • 21. Question How Does Type 2 Present in Youth? Is it asymptomatic or symptomatic in youth?
  • 22. Diagnosis with Type 2 Fagot-Campagna et al J Pediatr 2000
    • Mean Age 12-14 years
    • Girls > Boys 1.7:1
    • Obese BMI >85 th %
    • Minority Groups 94%
    • Strong Family History 74-100%
    • Acanthosis Nigricans 56-92%
    • Diagnosis made by Symptoms, not Screening
    • HbA1c 10-13%
    • Weight loss 19-62%
    • Glucose in urine 95%
    • Ketosis 16-79%
    • DKA 5-10%
  • 23. Question What Are Treatment Targets in Youth with Type 2 Diabetes? Are they the same as in adults?
  • 24. TREATMENT GOALS
    • Glucose control, HbA1c <7%
      • Eliminate symptoms of hyperglycemia
    • Maintenance of reasonable body weight
    • Improve cardiovascular risk factors
    • Reduce microvascular complications
    • Improvement in physical and emotional well-being
    A1c <7.0 Bed 100-160 FG 80-120 PP 100-160 Goals (Diabetes Care, 2000)
  • 25. Treatment Issues
    • Self-monitoring of blood glucose
      • Fasting and postprandial
      • Frequency depends on regimen
    • Medical Nutrition Therapy
    • Diabetes Education
      • Involves family
        • Direct family supervision produces better glycemic control outcomes 1
    • Lifestyle Coaching
    • Preconception counseling
    • Immunizations
    • Dental care
    • Smoking and alcohol counseling
        • 1. Bradshaw, J Pediatr Endocrinol Meta 15, 2002
    • 2. Pediatrics 112:2003 Prevention and treatment of type 2 diabetes in children with special emphasis on Native American Youth
  • 26. Question What are the Treatment Regimens for Youth?
  • 27. GLP
  • 28. TZD = thiazolidinedione Silverstein JH, Rosenbloom AL. J Pediatr Endcrinol Metab . 2000;13 Suppl 6:1406-1409. Diagnosis Asymptomatic Start with insulin and diet, exercise Diet and exercise Monthly review, A1C q3mo > 7% Add metformin Add metformin Attempt to wean insulin Add insulin, TZD, sulfonylurea BG 250 mg/dL or 12 mmol/L Add 3rd agent < 7% > 7% > 7% < 7%
  • 29. LWPES Survey 130 Clinical Practices
    • 48% treated with insulin alone
      • 2 injections
    • 44% with oral agents
      • 71% metformin
      • 46% sulfonylurea
      • 9% TZD
      • 4% meglitinide
    • 8% lifestyle
  • 30. A1c at CHLA 2005 3.31 + 1.8 3.20 + 1.3 Visit Number 5.84 + 4.10 Duration years 13.57 + 4.70 Age years 7.85 + 2.21 8.07 + 1.48 A1c % Type 2 n=276 Type 1 n=1534 Diabetes Type
  • 31. Intensive Therapy for Diabetes: Reduction in Incidence of Complications *Not statistically significant due to small number of events. † Showed statistical significance in subsequent epidemiologic analysis. DCCT Research Group. N Engl J Med . 1993;329:977-986; Ohkubo Y, et al. Diabetes Res Clin Pract . 1995;28:103-117; UKPDS 33: Lancet. 1998;352: 837-853; Stratton IM, et al. Brit Med J . 2000;321:405-412. T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus . 16%*  52* 41%* Cardiovascular disease – 58% 60% Neuropathy 24% – 33% 70% 54% Nephropathy 17% – 21% 69% 63% Retinopathy 8%  7% 9%  7% 9%  7% A1C T2DM UKPDS T2DM Kumamoto T1DM DCCT
  • 32. Long term outcome Arslanian S. Hormone Res 2002; 57 Suppl 1: 19-28 Dean., Diabetes 2002;51(Suppl 2):A24.
    • Pima Indians - diagnosed < 20 years of age
      • 22% had microalbuminuria at diagnosis
      • Increased to 60% at 20-29 years of age
    • Indigenous Canadians - mean age 23 yrs, 9 yrs duration of diabetes
      • HbA1c 10.9%
        • 67% poor glycemic control
      • 45% hypertension requiring treatment
      • 35% microalbuminuria (6% required dialysis)
      • 38% pregnancy loss
      • 9% mortality
  • 33. Uncontrolled diabetes can lead to… Kidney failure Amputations Loss of Sensations Heart disease and strokes Blindness Death
  • 34. An Answer The Today Trial?
  • 35. Studies to Treat Or Prevent Pediatric Type 2 Diabetes STOPP-T2D Funded by National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health
  • 36. STOPP-T2 TREATMENT PRIMARY AIM
    • To compare the efficacy of 3 treatment regimens
      • Metformin
      • Metformin + lifestyle
      • Metformin + TZD
      • On Time to Treatment Failure and on Glycemic Control
    TODAY
  • 37. Primary Outcomes
    • Treatment goal
      • HbA1c < 6% (glycemic control)
    • Treatment failure
      • HbA1c  8.0% over 6 consecutive months
      • OR
      • Inability to wean from temporary insulin therapy due to metabolic decompensation
  • 38. Outcome Measures
    • Glycemia
      • HbA1c, fasting and postprandial glucose by home monitoring
    • Insulin sensitivity and secretion
      • OGTT, HOMA, QUICKI, proinsulin, C-peptide
    • Body composition
      • BMI, DEXA, waist circumference, abdominal height
    • Fitness and physical activity
      • PDPAR, PWC 170, accelerometer
  • 39. Outcome Measures (continued)
    • Nutrition
      • food frequency questionnaire
    • Cardiovascular disease risk
      • BP, lipids, inflammatory markers, coagulation factors
    • Microvascular complications
      • microalbuminuria, neuropathy
    • Quality of life
    • Cost
  • 40. Inclusion Criteria
    • Age 10 to 17 years
    • Duration of diabetes < 2 years
    • BMI  85 th percentile
    • Adult involved in the daily activities of the child agrees to participate in the intervention
    • Absence of pancreatic autoimmunity
    • Fasting C-peptide > 0.6 mmol/L
    • Fluency in English or Spanish
  • 41. National Diabetes Education Program’s Tip Sheets for Kids with Type 2
    • What is Diabetes?
    • Be Active
    • Stay at a Healthy Weight
    • Eat Healthy Foods
                             
  • 42. Helping the Student with Diabetes Succeed
  • 43. Conclusion
    • Increased incidence
    • Difficult to distinguish from type 1
    • Occurs at the time of intense insulin resistance due to puberty
    • Does not appear to be preceded by long asymptomatic period
    • More insulin deficiency and requirement for exogenous insulin early
    • Safety and efficacy of therapeutic agents
    • Rapid progression of co-morbidities and complications
  • 44. Thank you [email_address]