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
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New-onset NIDDM diagnosed among youth ages 8-21
years at Arkansas Childrens Hospital
Scott et al. Pediatr. 1997
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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

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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
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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

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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

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Glycemic Targets
Glucose values are plasma (mg/mL).
Combined WHO recommendations and ADA guidelines.
DCCTDiabetes Control and Complications Trial.
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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

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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 ?

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HbA1c Statistics for CHLA 2002Type 2
14
(No Transcript)
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Mechanisms To Lower Glucose
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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
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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
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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
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Studies to Treat Or Prevent Pediatric Type 2
Diabetes(STOPP-T2D)The TODAY Trial
TODAY
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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
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Outcome Measures

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

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

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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
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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

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CO-MORBIDITIES
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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
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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)

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Screening Of Children and Youth forType 2
Diabetesand Prediabetes
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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

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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

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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

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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

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PreventionREDUCTIONIn ObesityPharmacotherapy
vsLifestyle
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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

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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

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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
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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)
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Placebo
Metformin
Cumulative incidence ()
20
Lifestyle
10
0
0

1

2

3

4
Years from randomization
The DPP Research Group, NEJM 346393-403, 2002
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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)
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PUBLIC HEALTH RESPONSE
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National Comprehensive Obesity-Diabesity
Prevention Strategy

• Educational
• Behavioral
• Environmental
• Increase understanding and awareness
• Change behavior
• Ability to make the right choices

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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

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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

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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

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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

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School Could Be A Setting For

• Public education
• Epidemiological studies
• Early intervention with at-risk groups
• Screening and early detection

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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

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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