<ul><li>The Epidemic of Type 2 Diabetes </li></ul><ul><li>During Childhood </li></ul><ul><li>Francine Ratner Kaufman, M.D....
Natural History of Type 2 Diabetes Genetic susceptibility Environmental factors Nutrition Obesity Physical inactivity Hype...
New-onset NIDDM diagnosed among youth ages 8-21 years at Arkansas Children’s Hospital Scott et al.  Pediatr.  1997
Characteristics - Case Series of 578 Patients at Diagnosis with Type 2 Fagot-Camgagna et al J Pediatr 2000 <ul><li>Mean Ag...
Characteristics Case Series of 578  Patients at Diagnosis <ul><li>Diagnosis made by Symptoms, not Screening </li></ul><ul>...
Acanthosis Nigricans
<ul><li>TREATMENT OF </li></ul><ul><li>TYPE 2 DIABETES IN  </li></ul><ul><li>CHILDREN AND TEENS </li></ul>
Treatment Protocols  Multidisciplinary Team <ul><li>Set Glycemic Targets </li></ul><ul><li>Diabetes Education  </li></ul><...
TREATMENT GOALS <ul><li>Glucose control, HbA1c <7% </li></ul><ul><ul><li>Eliminate symptoms of hyperglycemia  </li></ul></...
Glycemic Targets* Glucose values are plasma (mg/mL). * Combined WHO recommendations and ADA guidelines. DCCT=Diabetes Cont...
ROLE OF FAMILY IN MANAGEMENT <ul><li>African-American Family Study </li></ul><ul><li>Group 1, direct family supervision </...
Intensive Lifestyle  Rationale <ul><li>Lifestyle and environment are risk factors  </li></ul><ul><li>Consensus - modifying...
HbA1c Statistics for CHLA 2002 Type 2: 8.0 ± 2.2 71 Age 11-16 years 8.3 ± 2.5 26 Age >16 years 6.0 ± 0.9 3 Age 5-10 years ...
 
Mechanisms To Lower Glucose
TYPE 2 DIABETES . . . A PROGRESSIVE DISEASE Progressive Decline of   -Cell Function in the UKPDS 0 20 40 60 80 100  10 ...
Treatment of Type 2 DM in Children diet/exercise monthly review x 3 mo HbA1c <7% FPG <120 mg/dl continue HbA1c>7%, FPG>120...
Diagnosis Asymptomatic Start with insulin and diet, exercise Diet and exercise Monthly review, A1c q 3 m >7% Add metformin...
S tudies to  T reat  O r  P revent  P ediatric  T ype  2   D iabetes ( STOPP-T2D ) The TODAY Trial TODAY
STOPP-T2 TREATMENT PRIMARY AIM <ul><li>To compare the efficacy of 3 treatment regimens </li></ul><ul><ul><li>Metformin </l...
Outcome Measures <ul><li>Glycemic Controls </li></ul><ul><li>Insulin Sensitivity and Secretion </li></ul><ul><li>Body Comp...
<ul><li>How Do We Differentiate  </li></ul><ul><li>Type 1 Diabetes from Type 2 Diabetes </li></ul>
Differentiation Between Type 1 and 2 <ul><li>48 with type 2 vs 39 with type 1 </li></ul><ul><li>Type 2 </li></ul><ul><ul><...
Barriers to Accurate Classification <ul><li>20-25% newly diagnosed TIDM obese </li></ul><ul><li>>  15% of minority populat...
CO-MORBIDITIES
Comorbidities Percent of Patients >8 years with  BP >97 th  Percentile 6% 1% Diastolic 20.1% 3.4% Systolic Type 2 Type 1
Outcomes in First Nation Youth in Canada Dean, et al, Diabetes, 2002 Young adults, 18-33 years of age,  Diagnosed before a...
100 PIMA CHILDREN & ADOLESCENTS <ul><li>AT DIAGNOSIS </li></ul><ul><li>7% high cholesterol ( > 200 mg/dL) </li></ul><ul><l...
Screening  Of Children and Youth for Type 2 Diabetes and Prediabetes
Who Should be Tested for Type 2 - Case Finding ADA/AAP  Recommendations Diabetes Care 23:2000 <ul><li>Age  >  10 years or ...
Tests To Diagnose Diabetes <ul><li>FPG – Preferred  </li></ul><ul><li>2-h OGTT - Preferred </li></ul><ul><li>2-h Postprand...
ADA/NIDDK Screening Recommendations For Prediabetes in Adults Diabetes Care, 25:2002 <ul><li>Case Finding </li></ul><ul><l...
ADA/NIDDK Recommendations In Adults Diabetes Care, 25:2002 <ul><li>How to Test:  </li></ul><ul><ul><li>In context of healt...
Prevention REDUCTION In  Obesity Pharmacotherapy vs Lifestyle
Agents that can be Used  for Obesity <ul><li>Agents that can be used for Obesity </li></ul><ul><li>Sibutramine </li></ul><...
Prevention with Metformin <ul><li>Six month study in 29 obese, hyperinsulinemic adolescents, positive family history </li>...
Prevention with Metformin Glucose Disposal HbA1c Lipids Insulin sensitivity No change No change <0.02 31.3 to 19.3 Fasting...
The Diabetes Prevention Program     A Randomized Clinical Trial  to Prevent Type 2 Diabetes  in Persons at High Risk   The...
0 1 2 3 4 0 10 20 30 40 Placebo (n=1082) Metformin (n=1073, p<0.001 vs. Plac) Lifestyle (n=1079, p<0.001 vs. Met , p<0.001...
Prevention of Type 2 with Lifestyle Intervention   Tuomilehto, et al ,  Turku ADA 2000 <ul><li>Intervention – 523  IGT, me...
PUBLIC HEALTH  RESPONSE
National Comprehensive Obesity-Diabesity Prevention Strategy  <ul><li>Educational </li></ul><ul><li>Behavioral </li></ul><...
Key Targets <ul><li>Communities </li></ul><ul><ul><li>Joint use schools, parks, libraries, organizations  </li></ul></ul><...
Breast Feeding   <ul><li>Decrease in obesity </li></ul><ul><li>In Pima population, dose related decrease in risk of type 2...
Breast Feeding <ul><li>Native Canadian Population </li></ul><ul><li>4-Fold decrease in type 2 diabetes in adolescents </li...
Promotion of:  RETURN TO ENERGY BALANCE <ul><li>Water intake </li></ul><ul><li>Fruits and Vegetables </li></ul><ul><li>Lim...
School Could Be A Setting For <ul><li>Public education </li></ul><ul><li>Epidemiological studies </li></ul><ul><li>Early i...
S tudies to  T reat  O r  P revent  P ediatric  T ype  2   D iabetes ( STOPP-T2D ) <ul><li>Population based trial </li></u...
CONCLUSIONS <ul><li>Why are Children Obese </li></ul><ul><ul><li>Too much food, no activity </li></ul></ul><ul><li>Insulin...
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The Epidemic of Type 2 Diabetes

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  • This chart contains the glycemic target values set by the American Diabetes Association (ADA). Note that the values in the column labeled “goal” are the levels that should be sought. There also is a column labeled “action suggested,” which essentially defines levels of unacceptable glycemic control.
  • There are several mechanisms by which glucose levels can be lowered. Various medications are available which act upon these different mechanisms.
  • Transcript of "The Epidemic of Type 2 Diabetes"

    1. 1. <ul><li>The Epidemic of Type 2 Diabetes </li></ul><ul><li>During Childhood </li></ul><ul><li>Francine Ratner Kaufman, M.D. </li></ul><ul><li>Professor of Pediatrics </li></ul><ul><li>The Keck School of Medicine of USC </li></ul><ul><li>Head, Center for Diabetes and Endocrinology </li></ul><ul><li>Childrens Hospital Los Angeles </li></ul>
    2. 2. Natural History of Type 2 Diabetes Genetic susceptibility Environmental factors Nutrition Obesity Physical inactivity Hyperinsulinemia  HDL-C  Triglycerides Atherosclerosis Hypertension Atherosclerosis Hyperglycemia Hypertension Retinopathy Nephropathy Neuropathy Blindness Renal failure CHD Amputation Onset of diabetes Complications Disability Death Ongoing hyperglycemia IGT Insulin resistance
    3. 3. New-onset NIDDM diagnosed among youth ages 8-21 years at Arkansas Children’s Hospital Scott et al. Pediatr. 1997
    4. 4. Characteristics - Case Series of 578 Patients at Diagnosis with Type 2 Fagot-Camgagna et al J Pediatr 2000 <ul><li>Mean Age 12-14 years </li></ul><ul><li>Girls > Boys 1.7:1 </li></ul><ul><li>Obese BMI >85 th % </li></ul><ul><li>Minority Groups 94% </li></ul><ul><li>Strong Family History 74-100% </li></ul><ul><li>Acanthosis Nigricans 56-92% </li></ul>
    5. 5. Characteristics Case Series of 578 Patients at Diagnosis <ul><li>Diagnosis made by Symptoms, not Screening </li></ul><ul><li>HbA1c 10-13% </li></ul><ul><li>Weight loss 19-62% </li></ul><ul><li>Glucose in urine 95% </li></ul><ul><li>Ketosis 16-79% </li></ul><ul><li>DKA 5-10% </li></ul><ul><li>Absence of Islet Autoimmunity >85-95% </li></ul><ul><li>Preservation of C-peptide >0.8-1nmol/l </li></ul>Campagna et al J Pediatr 2000
    6. 6. Acanthosis Nigricans
    7. 7. <ul><li>TREATMENT OF </li></ul><ul><li>TYPE 2 DIABETES IN </li></ul><ul><li>CHILDREN AND TEENS </li></ul>
    8. 8. Treatment Protocols Multidisciplinary Team <ul><li>Set Glycemic Targets </li></ul><ul><li>Diabetes Education </li></ul><ul><ul><li>Patient and Family </li></ul></ul><ul><li>Role of Intensive Lifestyle </li></ul><ul><li>Pharmacotherapy </li></ul><ul><li>Regimens Advocated </li></ul><ul><ul><li>What are the outcome measures to assess efficacy, effectiveness </li></ul></ul>
    9. 9. TREATMENT GOALS <ul><li>Glucose control, HbA1c <7% </li></ul><ul><ul><li>Eliminate symptoms of hyperglycemia </li></ul></ul><ul><ul><li>Reduce microvascular complications </li></ul></ul><ul><li>Maintenance of reasonable body weight </li></ul><ul><li>Improve cardiovascular risk factors </li></ul><ul><li>Improvement in physical and emotional well-being </li></ul>
    10. 10. Glycemic Targets* Glucose values are plasma (mg/mL). * Combined WHO recommendations and ADA guidelines. DCCT=Diabetes Control and Complications Trial. Parameter Normal Goal Action Suggested Fasting (or Preprandial) Glucose <100 < 120 <80 or >140 Postprandial Glucose <140 <180 >180 Bedtime Glucose <120 90 to 150 <90 or >160 HbA 1c (DCCT Method) <6% <7% >8%
    11. 11. ROLE OF FAMILY IN MANAGEMENT <ul><li>African-American Family Study </li></ul><ul><li>Group 1, direct family supervision </li></ul><ul><li>Group 2, no direct supervision </li></ul><ul><li>Group 1 ending HbA1c = 7.1 + 0.8% </li></ul><ul><li>Group 2 ending HbA1c = 12.3 + 0.6% </li></ul><ul><li>P=<0.0005 </li></ul><ul><li>Bradshaw, J Pediatr Endocrinol Meta 15, 2002 </li></ul>
    12. 12. Intensive Lifestyle Rationale <ul><li>Lifestyle and environment are risk factors </li></ul><ul><li>Consensus - modifying lifestyle primary goal </li></ul><ul><li>Might lead to remission </li></ul><ul><li>BUT </li></ul><ul><li>Mixed results in adult studies </li></ul><ul><ul><li>More or less effective in kids? </li></ul></ul><ul><li>Labor intensive and expensive </li></ul><ul><ul><li>Do they work in the “real world” and school ? </li></ul></ul>
    13. 13. HbA1c Statistics for CHLA 2002 Type 2: 8.0 ± 2.2 71 Age 11-16 years 8.3 ± 2.5 26 Age >16 years 6.0 ± 0.9 3 Age 5-10 years 0 Age < 5 years 7.8 ± 2.3 56 Females 8.3 ± 2.2 44 Males 8.0 ± 2.3 100 All patients Average ± SD n
    14. 15. Mechanisms To Lower Glucose
    15. 16. TYPE 2 DIABETES . . . A PROGRESSIVE DISEASE Progressive Decline of  -Cell Function in the UKPDS 0 20 40 60 80 100  10  9  8  7  6  5  4  3  2  1 0 1 2 3 4 5 6 Years  -Cell Function (%  ) Adapted from UK Prospective Diabetes Study (UKPDS) Group. Diabetes . 1995; 44:1249-1258. 6-4
    16. 17. Treatment of Type 2 DM in Children diet/exercise monthly review x 3 mo HbA1c <7% FPG <120 mg/dl continue HbA1c>7%, FPG>120 metformin HbA1c>7% FPG>120 add sulfonylurea? TZD? add insulin
    17. 18. Diagnosis Asymptomatic Start with insulin and diet, exercise Diet and exercise Monthly review, A1c q 3 m >7% Add metformin Attempt to Wean insulin Add sulfonylurea Silverstein, Rosenbloom J Pediatr Endcrinol Metab, 13,2000 BG 250 mg/dl Add Insulin <7% >7% >7%
    18. 19. S tudies to T reat O r P revent P ediatric T ype 2 D iabetes ( STOPP-T2D ) The TODAY Trial TODAY
    19. 20. STOPP-T2 TREATMENT PRIMARY AIM <ul><li>To compare the efficacy of 3 treatment regimens </li></ul><ul><ul><li>Metformin </li></ul></ul><ul><ul><li>Metformin + lifestyle </li></ul></ul><ul><ul><li>Metformin + TZD </li></ul></ul><ul><ul><li>On Time to Treatment Failure and on Glycemic Control </li></ul></ul>TODAY
    20. 21. Outcome Measures <ul><li>Glycemic Controls </li></ul><ul><li>Insulin Sensitivity and Secretion </li></ul><ul><li>Body Composition </li></ul><ul><li>Fitness and Physical Activity </li></ul><ul><li>Nutrition </li></ul><ul><li>Microvascular complications </li></ul><ul><li>CVD Risk </li></ul><ul><li>Quality of Life </li></ul><ul><li>Cost </li></ul>
    21. 22. <ul><li>How Do We Differentiate </li></ul><ul><li>Type 1 Diabetes from Type 2 Diabetes </li></ul>
    22. 23. Differentiation Between Type 1 and 2 <ul><li>48 with type 2 vs 39 with type 1 </li></ul><ul><li>Type 2 </li></ul><ul><ul><li>Ethnicity, 1 st degree relative, BMI>24, +C-peptide, acanthosis </li></ul></ul><ul><ul><li>Hathout et al Pediatrics 107e102,June,2001 </li></ul></ul>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
    23. 24. Barriers to Accurate Classification <ul><li>20-25% newly diagnosed TIDM obese </li></ul><ul><li>> 15% of minority populations have  FH T2DM baseline </li></ul><ul><li>3X increase FH of T2DM in patients with T1DM </li></ul><ul><li>Overlap C-P measurements at onset & first year or so </li></ul><ul><li>> 30% T2DM with ketosis at onset </li></ul>
    24. 25. CO-MORBIDITIES
    25. 26. Comorbidities Percent of Patients >8 years with BP >97 th Percentile 6% 1% Diastolic 20.1% 3.4% Systolic Type 2 Type 1
    26. 27. Outcomes in First Nation Youth in Canada Dean, et al, Diabetes, 2002 Young adults, 18-33 years of age, Diagnosed before age 17 years Due to poor glycemic control 9% mortality rate 6.3% dialysis rate 38% pregnancy loss During 10-15 year observation period
    27. 28. 100 PIMA CHILDREN & ADOLESCENTS <ul><li>AT DIAGNOSIS </li></ul><ul><li>7% high cholesterol ( > 200 mg/dL) </li></ul><ul><li>18% hypertension (BP > 140/90) </li></ul><ul><li>22% microalbuminuria (alb/Cr > 30) </li></ul><ul><li>AFTER TEN YEARS [mean HbA1c 12%] </li></ul><ul><li>60% microalbuminuria </li></ul><ul><li>17% macroalbuminuria (alb/Cr > 300) </li></ul>
    28. 29. Screening Of Children and Youth for Type 2 Diabetes and Prediabetes
    29. 30. Who Should be Tested for Type 2 - Case Finding ADA/AAP Recommendations Diabetes Care 23:2000 <ul><li>Age > 10 years or onset of puberty </li></ul><ul><li>BMI > 85th% </li></ul><ul><li>First or Second Degree Relative </li></ul><ul><li>Race/Ethnic Group </li></ul><ul><li>Signs of Insulin Resistance – </li></ul><ul><ul><li>Acanthosis nigricans </li></ul></ul><ul><ul><li>Hypertension </li></ul></ul><ul><ul><li>PCOS </li></ul></ul><ul><ul><li>Dyslipidemia </li></ul></ul>
    30. 31. Tests To Diagnose Diabetes <ul><li>FPG – Preferred </li></ul><ul><li>2-h OGTT - Preferred </li></ul><ul><li>2-h Postprandial or random post meal </li></ul><ul><li>HbA1c </li></ul><ul><li>In context of health visit </li></ul><ul><li>Every 2 years </li></ul>
    31. 32. ADA/NIDDK Screening Recommendations For Prediabetes in Adults Diabetes Care, 25:2002 <ul><li>Case Finding </li></ul><ul><li>Test: </li></ul><ul><ul><li>> 45 years, BMI > 25 kg/m2 </li></ul></ul><ul><ul><li><45 years with + FH, GDM, baby > 9 lbs, dyslipidemia, hypertension, non-Caucasian </li></ul></ul><ul><ul><li>At 3 yr intervals, if negative </li></ul></ul>
    32. 33. ADA/NIDDK Recommendations In Adults Diabetes Care, 25:2002 <ul><li>How to Test: </li></ul><ul><ul><li>In context of health care visit </li></ul></ul><ul><ul><li>FPG, 2-h OGTT </li></ul></ul><ul><li>Intervention: </li></ul><ul><ul><li>Prediabetes counsel for weight loss and PA, Follow-up counseling </li></ul></ul><ul><ul><li>Monitor for DM q 1-2 years, CVD risk factors </li></ul></ul><ul><ul><li>Avoid drug therapy </li></ul></ul>
    33. 34. Prevention REDUCTION In Obesity Pharmacotherapy vs Lifestyle
    34. 35. Agents that can be Used for Obesity <ul><li>Agents that can be used for Obesity </li></ul><ul><li>Sibutramine </li></ul><ul><ul><li>Blocks central reuptake of norepinephrine, serotonin </li></ul></ul><ul><ul><li>Suppresses appetite </li></ul></ul><ul><ul><li>Increases energy expenditure </li></ul></ul><ul><li>Orlistat </li></ul><ul><ul><li>Inhibits pancreatic lipase </li></ul></ul><ul><ul><li>Increases fecal fat loss </li></ul></ul>
    35. 36. Prevention with Metformin <ul><li>Six month study in 29 obese, hyperinsulinemic adolescents, positive family history </li></ul><ul><li>Randomized, double-blinded, placebo-controlled </li></ul><ul><li>Freemark, Bursey, SPR, Boston, 2000. Freemark, Bursey Pediatrics 107:2001 </li></ul>
    36. 37. Prevention with Metformin Glucose Disposal HbA1c Lipids Insulin sensitivity No change No change <0.02 31.3 to 19.3 Fasting Insulin 77.2 to 82.6 84.8 to 74.8 FPG 2.3% <0.05 1.3% BMI P value Placebo Metformin
    37. 38. The Diabetes Prevention Program A Randomized Clinical Trial to Prevent Type 2 Diabetes in Persons at High Risk The DPP Research Group
    38. 39. 0 1 2 3 4 0 10 20 30 40 Placebo (n=1082) Metformin (n=1073, p<0.001 vs. Plac) Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac ) Percent developing diabetes All participants All participants Years from randomization Cumulative incidence (%) Placebo Metformin Lifestyle Type 2 Diabetes Prevention Risk reduction 31% by metformin 58% by lifestyle The DPP Research Group, NEJM 346 :393-403, 2002
    39. 40. Prevention of Type 2 with Lifestyle Intervention Tuomilehto, et al , Turku ADA 2000 <ul><li>Intervention – 523 IGT, mean age 55, BMI 31 </li></ul><ul><li>Diet, exercise, frequent visits vs advice yearly </li></ul>Incidence of diabetes reduced – 58% (p=.0003) 57 Cases 22% -0.8 -0.8 Control 26 cases 10% -3.5 -4.2 Intervention 4 th Year 2 nd Year 1 st Year Weight Loss
    40. 41. PUBLIC HEALTH RESPONSE
    41. 42. National Comprehensive Obesity-Diabesity Prevention Strategy <ul><li>Educational </li></ul><ul><li>Behavioral </li></ul><ul><li>Environmental </li></ul><ul><ul><li>Increase understanding and awareness </li></ul></ul><ul><ul><li>Change behavior </li></ul></ul><ul><ul><li>Ability to make the right choices </li></ul></ul>
    42. 43. Key Targets <ul><li>Communities </li></ul><ul><ul><li>Joint use schools, parks, libraries, organizations </li></ul></ul><ul><li>Workplace </li></ul><ul><ul><li>Wellness programs, insurance, </li></ul></ul><ul><li>Government </li></ul><ul><ul><li>Funding, policies </li></ul></ul><ul><li>Individual/Family </li></ul><ul><ul><li>Behavior change </li></ul></ul><ul><li>Health Sector </li></ul><ul><li>Schools </li></ul><ul><ul><li>PE, nutrition services, health education </li></ul></ul>
    43. 44. Breast Feeding <ul><li>Decrease in obesity </li></ul><ul><li>In Pima population, dose related decrease in risk of type 2 with breast feeding </li></ul><ul><li>Most significant with exclusive breast feeding </li></ul><ul><li>Breast feeding regimen </li></ul><ul><ul><li>exclusive for 6 months </li></ul></ul><ul><ul><li>total for 12 months </li></ul></ul><ul><li>Simmons D, Lancet 97, 157 </li></ul>
    44. 45. Breast Feeding <ul><li>Native Canadian Population </li></ul><ul><li>4-Fold decrease in type 2 diabetes in adolescents </li></ul><ul><li>Exclusive Breast Feeding </li></ul><ul><li>Young et al, Arch Pediatr Adolesc Med, 2002 </li></ul>
    45. 46. Promotion of: RETURN TO ENERGY BALANCE <ul><li>Water intake </li></ul><ul><li>Fruits and Vegetables </li></ul><ul><li>Limiting Juice </li></ul><ul><li>Avoiding Sugar Containing Sodas </li></ul><ul><li>Decreasing Saturated Fat </li></ul><ul><li>Near Eliminating High Density/Low Nutrient Foods </li></ul>
    46. 47. School Could Be A Setting For <ul><li>Public education </li></ul><ul><li>Epidemiological studies </li></ul><ul><li>Early intervention with at-risk groups </li></ul><ul><li>Screening and early detection </li></ul>
    47. 48. S tudies to T reat O r P revent P ediatric T ype 2 D iabetes ( STOPP-T2D ) <ul><li>Population based trial </li></ul><ul><li>Increase physical activity </li></ul><ul><li>Nutrition promotion </li></ul><ul><li>Social Marketing, Behavioral Component </li></ul><ul><li>Biologic outcome measures – primary </li></ul><ul><ul><li>Reduction in risk factors </li></ul></ul>
    48. 49. CONCLUSIONS <ul><li>Why are Children Obese </li></ul><ul><ul><li>Too much food, no activity </li></ul></ul><ul><li>Insulin Resistance and Relative Beta Cell Failure </li></ul><ul><ul><li>Intrauterine environment, postnatal feeding </li></ul></ul><ul><li>Type 2 Diabetes </li></ul><ul><ul><li>Symptomatic presentation, treatment algorithms, screening </li></ul></ul><ul><li>Public Health/Advocacy </li></ul><ul><ul><li>School policies, legislative agenda </li></ul></ul><ul><ul><li>Concentrate on pre and perinatal periods </li></ul></ul>
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