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The Epidemic of Type 2 Diabetes

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Hypertension. PCOS. Dyslipidemia. Tests To Diagnose Diabetes. FPG ... 45 years with FH, GDM, baby 9 lbs, dyslipidemia, hypertension, non-Caucasian ... – PowerPoint PPT presentation

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Title: The Epidemic of Type 2 Diabetes


1
  • The Epidemic of Type 2 Diabetes
  • During Childhood
  • Francine Ratner Kaufman, M.D.
  • Professor of Pediatrics
  • The Keck School of Medicine of USC
  • Head, Center for Diabetes and Endocrinology
  • Childrens Hospital Los Angeles

2
Natural History of Type 2 Diabetes
Onset ofdiabetes
Geneticsusceptibility Environmentalfactors Nutr
ition Obesity Physical inactivity
Complications
Disability
IGT
Ongoing hyperglycemia
Insulin resistance
Death
Hyperinsulinemia HDL-C TriglyceridesAtheroscl
erosisHypertension
BlindnessRenal failureCHDAmputation
RetinopathyNephropathyNeuropathy
AtherosclerosisHyperglycemiaHypertension
3
New-onset NIDDM diagnosed among youth ages 8-21
years at Arkansas Childrens Hospital
Scott et al. Pediatr. 1997
4
Characteristics - Case Series of 578 Patients at
Diagnosis with Type 2Fagot-Camgagna et al J
Pediatr 2000
  • Mean Age 12-14 years
  • Girls Boys 1.71
  • Obese BMI 85th
  • Minority Groups 94
  • Strong Family History 74-100
  • Acanthosis Nigricans 56-92

5
Characteristics Case Series of 578 Patients at
Diagnosis
  • Diagnosis made by Symptoms, not Screening
  • HbA1c 10-13
  • Weight loss 19-62
  • Glucose in urine 95
  • Ketosis 16-79
  • DKA 5-10
  • Absence of Islet Autoimmunity 85-95
  • Preservation of C-peptide 0.8-1nmol/l

Campagna et al J Pediatr 2000
6
Acanthosis Nigricans
7
  • TREATMENT OF
  • TYPE 2 DIABETES IN
  • CHILDREN AND TEENS

8
Treatment Protocols Multidisciplinary Team
  • Set Glycemic Targets
  • Diabetes Education
  • Patient and Family
  • Role of Intensive Lifestyle
  • Pharmacotherapy
  • Regimens Advocated
  • What are the outcome measures to assess efficacy,
    effectiveness

9
TREATMENT GOALS
  • Glucose control, HbA1c
  • Eliminate symptoms of hyperglycemia
  • Reduce microvascular complications
  • Maintenance of reasonable body weight
  • Improve cardiovascular risk factors
  • Improvement in physical and emotional well-being

10
Glycemic Targets
Glucose values are plasma (mg/mL).
Combined WHO recommendations and ADA guidelines.
DCCTDiabetes Control and Complications Trial.
11
ROLE OF FAMILY IN MANAGEMENT
  • African-American Family Study
  • Group 1, direct family supervision
  • Group 2, no direct supervision
  • Group 1 ending HbA1c 7.1 0.8
  • Group 2 ending HbA1c 12.3 0.6
  • P
  • Bradshaw, J Pediatr Endocrinol Meta 15, 2002

12
Intensive Lifestyle Rationale
  • Lifestyle and environment are risk factors
  • Consensus - modifying lifestyle primary goal
  • Might lead to remission
  • BUT
  • Mixed results in adult studies
  • More or less effective in kids?
  • Labor intensive and expensive
  • Do they work in the real world and school ?

13
HbA1c Statistics for CHLA 2002Type 2
14
(No Transcript)
15
Mechanisms To Lower Glucose
16
TYPE 2 DIABETES . . . A PROGRESSIVE
DISEASE Progressive Decline of ?-Cell Function in
the UKPDS
100
80
60
?-Cell Function ( ?)
40
20
0
?10
?9
?8
?7
?6
?5
?4
?3
?2
?1
0
1
2
3
4
5
6
Years
Adapted from UK Prospective Diabetes Study
(UKPDS) Group. Diabetes. 1995 441249-1258.
6-4
17
Treatment of Type 2 DM in Children
diet/exercise
monthly review x 3 mo
HbA1c7, FPG120
HbA1c metformin
HbA1c7 FPG120
continue
add sulfonylurea? TZD?
add insulin
18
Diagnosis
Asymptomatic
BG 250 mg/dl
Diet and exercise
Start with insulin and diet, exercise
Monthly review, A1c q 3 m
Attempt to Wean insulin
7
Add metformin
7
Add sulfonylurea
Silverstein, Rosenbloom J Pediatr Endcrinol
Metab, 13,2000
7
Add Insulin
19
Studies to Treat Or Prevent Pediatric Type 2
Diabetes(STOPP-T2D)The TODAY Trial
TODAY
20
STOPP-T2 TREATMENTPRIMARY AIM
  • To compare the efficacy of 3 treatment regimens
  • Metformin
  • Metformin lifestyle
  • Metformin TZD
  • On Time to Treatment Failure and on Glycemic
    Control

TODAY
21
Outcome Measures
  • Glycemic Controls
  • Insulin Sensitivity and Secretion
  • Body Composition
  • Fitness and Physical Activity
  • Nutrition
  • Microvascular complications
  • CVD Risk
  • Quality of Life
  • Cost

22
  • How Do We Differentiate
  • Type 1 Diabetes from Type 2 Diabetes

23
Differentiation Between Type 1 and 2
  • 48 with type 2 vs 39 with type 1
  • Type 2
  • Ethnicity, 1st degree relative, BMI24,
    C-peptide, acanthosis

Hathout et al Pediatrics 107e102,June,2001
24
Barriers to Accurate Classification
  • 20-25 newly diagnosed TIDM obese
  • 15 of minority populations have ? FH T2DM
    baseline
  • 3X increase FH of T2DM in patients with T1DM
  • Overlap C-P measurements at onset first year or
    so
  • 30 T2DM with ketosis at onset

25
CO-MORBIDITIES
26
ComorbiditiesPercent of Patients 8 years with
BP 97th Percentile
27
Outcomes in First Nation Youth in CanadaDean, 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
28
100 PIMA CHILDREN ADOLESCENTS
  • AT DIAGNOSIS
  • 7 high cholesterol (200 mg/dL)
  • 18 hypertension (BP140/90)
  • 22 microalbuminuria (alb/Cr 30)
  • AFTER TEN YEARS mean HbA1c 12
  • 60 microalbuminuria
  • 17 macroalbuminuria (alb/Cr 300)

29
Screening Of Children and Youth forType 2
Diabetesand Prediabetes
30
Who Should be Tested for Type 2- Case
FindingADA/AAP RecommendationsDiabetes Care
232000
  • Age 10 years or onset of puberty
  • BMI 85th
  • First or Second Degree Relative
  • Race/Ethnic Group
  • Signs of Insulin Resistance
  • Acanthosis nigricans
  • Hypertension
  • PCOS
  • Dyslipidemia

31
Tests To Diagnose Diabetes
  • FPG Preferred
  • 2-h OGTT - Preferred
  • 2-h Postprandial or random post meal
  • HbA1c
  • In context of health visit
  • Every 2 years

32
ADA/NIDDK Screening Recommendations For
Prediabetes in AdultsDiabetes Care, 252002
  • Case Finding
  • Test
  • 45 years, BMI 25 kg/m2
  • 9 lbs,
    dyslipidemia, hypertension, non-Caucasian
  • At 3 yr intervals, if negative

33
ADA/NIDDK Recommendations In AdultsDiabetes
Care, 252002
  • How to Test
  • In context of health care visit
  • FPG, 2-h OGTT
  • Intervention
  • Prediabetes counsel for weight loss and PA,
    Follow-up counseling
  • Monitor for DM q 1-2 years, CVD risk factors
  • Avoid drug therapy

34
PreventionREDUCTIONIn ObesityPharmacotherapy
vsLifestyle
35
Agents that can be Used for Obesity
  • Agents that can be used for Obesity
  • Sibutramine
  • Blocks central reuptake of norepinephrine,
    serotonin
  • Suppresses appetite
  • Increases energy expenditure
  • Orlistat
  • Inhibits pancreatic lipase
  • Increases fecal fat loss

36
Prevention with Metformin
  • Six month study in 29 obese, hyperinsulinemic
    adolescents, positive family history
  • Randomized, double-blinded, placebo-controlled
  • Freemark, Bursey, SPR, Boston, 2000. Freemark,
    Bursey Pediatrics 1072001

37
Prevention with Metformin
38
The Diabetes Prevention Program A Randomized
Clinical Trial to Prevent Type 2 Diabetes in
Persons at High Risk The DPP Research Group
39
Type 2 Diabetes Prevention
Percent developing diabetes

Risk reduction 31 by metformin 58 by lifestyle
All participants
All participants
Lifestyle (n1079, pPlac )
Metformin (n1073, p40
Placebo (n1082)
30
Placebo
Metformin
Cumulative incidence ()
20
Lifestyle
10
0
0

1

2

3

4
Years from randomization
The DPP Research Group, NEJM 346393-403, 2002
40
Prevention of Type 2 with Lifestyle Intervention
Tuomilehto, et al , Turku ADA 2000
  • Intervention 523 IGT, mean age 55, BMI 31
  • Diet, exercise, frequent visits vs advice yearly

Incidence of diabetes reduced 58 (p.0003)
41
PUBLIC HEALTH RESPONSE
42
National Comprehensive Obesity-Diabesity
Prevention Strategy
  • Educational
  • Behavioral
  • Environmental
  • Increase understanding and awareness
  • Change behavior
  • Ability to make the right choices

43
Key Targets
  • Communities
  • Joint use schools, parks, libraries,
    organizations
  • Workplace
  • Wellness programs, insurance,
  • Government
  • Funding, policies
  • Individual/Family
  • Behavior change
  • Health Sector
  • Schools
  • PE, nutrition services, health education

44
Breast Feeding
  • Decrease in obesity
  • In Pima population, dose related decrease in risk
    of type 2 with breast feeding
  • Most significant with exclusive breast feeding
  • Breast feeding regimen
  • exclusive for 6 months
  • total for 12 months
  • Simmons D, Lancet 97, 157

45
Breast Feeding
  • Native Canadian Population
  • 4-Fold decrease in type 2 diabetes in adolescents
  • Exclusive Breast Feeding
  • Young et al, Arch Pediatr Adolesc Med, 2002

46
Promotion of RETURN TO ENERGY BALANCE
  • Water intake
  • Fruits and Vegetables
  • Limiting Juice
  • Avoiding Sugar Containing Sodas
  • Decreasing Saturated Fat
  • Near Eliminating High Density/Low Nutrient Foods

47
School Could Be A Setting For
  • Public education
  • Epidemiological studies
  • Early intervention with at-risk groups
  • Screening and early detection

48
Studies to Treat Or Prevent Pediatric Type 2
Diabetes(STOPP-T2D)
  • Population based trial
  • Increase physical activity
  • Nutrition promotion
  • Social Marketing, Behavioral Component
  • Biologic outcome measures primary
  • Reduction in risk factors

49
CONCLUSIONS
  • Why are Children Obese
  • Too much food, no activity
  • Insulin Resistance and Relative Beta Cell Failure
  • Intrauterine environment, postnatal feeding
  • Type 2 Diabetes
  • Symptomatic presentation, treatment algorithms,
    screening
  • Public Health/Advocacy
  • School policies, legislative agenda
  • Concentrate on pre and perinatal periods
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