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Francine Ratner Kaufman, M.D. Distinguished Professor of Pediatrics The Keck School of Medicine of USC Head, Center for Diabetes and Endocrinology

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Prevalence of Diabetes and IFG in US Adolescents - PowerPoint PPT Presentation


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Type 2 Diabetes in Youth. 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. Question . What Do We Know About Type 2 Diabetes in Youth?.

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slide1

Type 2 Diabetes in Youth

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

slide2

Question

What Do We Know About Type 2 Diabetes in Youth?

prevalence of diabetes and ifg in us adolescents nhanes 1999 2002
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

is it an epidemic
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

controversies as to the nature of this epidemic
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
slide7

Is Type 2 Diabetes An Epidemic?

Little Rock, Cincinnati, San Antonio

35

30

25

20

% with type 2

15

10

5

0

87

88

89

90

91

92

93

94

95

96

  • 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

J Pediatr 136:664-672, 2000

slide8

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
natural history of type 2 diabetes
Natural History of Type 2 Diabetes

Complications

Geneticsusceptibility

Environmentalfactors

Onset ofdiabetes

Disability

PRE

Ongoing hyperglycemia

Obesity Insulin resistance

Death

Risk for

Disease

Metabolic

Syndrome

BlindnessRenal failureCHDAmputation

RetinopathyNephropathyNeuropathy

AtherosclerosisHyperglycemiaHypertension

slide14

Prevention and Early Treatment

Type 2 Diabetes

Progressive Pancreatic B-cell Failure

UKPDS Data

B-cell Function (%)

? Curve for Youth

Years from Clinical Diagnosis

slide15

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
slide16

Type 2 Diabetes

Prediabetes

Beta Cell Defect

Beta Cell Defect

Age

Puberty

Obesity

BP,

Lipids

InsulinResistance

Genetics

Ethnicity

Sedentary Lifestyle

Gender – Girls

Polycystic ovary syndrome

slide17

Type 2 Diabetes

Prediabetes

Beta Cell Defect

Autoimmunity

Genetic Defect

Beta Cell Defect

Fat cell

toxicity

Intrauterine

IUGR, DM

Glucose

toxicity

InsulinResistance

slide18

Question

What distinguishes type 1 from type 2 diabetes in youth?

slide19

Type 1 Versus type 2 Diabetes in youth?

Kaufman,Endocrinol Meta Clinics N Am, 34;659-676: 2005

differentiation between type 1 and 2
Differentiation Between Type 1 and 2
  • 48 with type 2 vs 39 with type 1
  • Type 2
    • Ethnicity, 1st degree relative, BMI>24, +C-peptide, acanthosis
  • Hathout et al Pediatrics 107e102,June,2001
slide21

Question

How Does Type 2 Present in Youth?

Is it asymptomatic or symptomatic in youth?

diagnosis with type 2 fagot campagna et al j pediatr 2000
Diagnosis with Type 2Fagot-Campagna et al J Pediatr 2000
  • Mean Age 12-14 years
  • Girls > Boys 1.7:1
  • Obese BMI >85th %
  • 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%
slide23

Question

What Are Treatment Targets in Youth with Type 2 Diabetes?

Are they the same as in adults?

treatment goals
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
slide25

Question

What are the Treatment Regimens for Youth?

slide27

Diagnosis

BG 250 mg/dL or 12 mmol/L

Asymptomatic

Start with insulin and diet, exercise

Diet and exercise

<7%

<7%

Monthly review, A1C q3mo

Add metformin

Attempt to

wean insulin

>7%

Add metformin

>7%

Add insulin, TZD, sulfonylurea

>7%

Add 3rd agent

TZD = thiazolidinedione

Silverstein JH, Rosenbloom AL.

J Pediatr Endcrinol Metab. 2000;13 Suppl 6:1406-1409.

lwpes survey 130 clinical practices
LWPES Survey130 Clinical Practices
  • 48% treated with insulin alone
    • 2 injections
  • 44% with oral agents
    • 71% metformin
    • 46% sulfonylurea
    • 9% TZD
    • 4% meglitinide
  • 8% lifestyle
intensive therapy for diabetes reduction in incidence of complications
Intensive Therapy for Diabetes:Reduction in Incidence of Complications

T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.

*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.

long term outcome
Long term outcome
  • 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

Arslanian S. Hormone Res 2002; 57 Suppl 1: 19-28Dean., Diabetes 2002;51(Suppl 2):A24.

slide32

Blindness

Amputations

Loss of Sensations

Heart disease

and strokes

Uncontrolled diabetes

can lead to…

Death

Kidney failure

slide33

An Answer

The Today Trial?

studies to treat or prevent pediatric type 2 diabetes stopp t2d

Studies to Treat Or Prevent Pediatric Type 2 DiabetesSTOPP-T2D

Funded by

National Institute of Diabetes and Digestive

and Kidney Diseases

National Institutes of Health

stopp t2 treatment primary aim
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

primary outcomes
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
outcome measures
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
outcome measures continued
Outcome Measures (continued)
  • Nutrition
    • food frequency questionnaire
  • Cardiovascular disease risk
    • BP, lipids, inflammatory markers, coagulation factors
  • Microvascular complications
    • microalbuminuria, neuropathy
  • Quality of life
  • Cost
inclusion criteria
Inclusion Criteria
  • Age 10 to 17 years
  • Duration of diabetes < 2 years
  • BMI  85th 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
national diabetes education program s tip sheets for kids with type 2
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
conclusion
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
ad