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Obesity and Type 2 Diabetesin children and adolescents
Eva Tsalikian M.D.
Stead family Department of Pediatrics
Pediatric Endocrinology and Diabetes
April 16, 2014
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Obesity and Type 2 Diabetesin children and adolescents: outline
• Epidemiology and definitions• Pathophysiology of Type 2 diabetes• Obesity leading to metabolic syndrome and Type 2 diabetes• Treatment of Type 2 Diabetes in children and
adolescents• Case presentations
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Rates of Overweight and Obese Children
2005 2007
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The problem in children and adolescents
•Approximately 17% (or 12.5 million) of children and adolescents aged 2—19 years are obese.
• In 2011-2012, 8.4% of 2- to 5-year-olds were obese compared with 17.7% of 6- to 11-year-olds and 20.5% of 12- to 19-year-olds.
• The prevalence of obesity among children aged 2 to 5 years decreased significantly from 13.9% in 2003-2004 to 8.4% in 2011-2012.
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Identification
Children (Ages 6 to 11)
Prevalence (%)
Adolescents (Ages 12 to 19)Prevalence (%)
Race Overweight Obesity Overweight Obesity
Black (Non-Hispanic) 35.9 19.5 40.4 23.6
Mexican American 39.3 23.7 43.8 23.4
White (Non-Hispanic) 26.2 11.8 26.5 12.7
Source: CDC, National Center for Health Statistics, National Health and Nutrition Examination Survey. Ogden et. al. JAMA. 2002;288:1728-1732.
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Why is this a problem?• Overweight children become overweight adults• Risk for diabetes, cardiovascular disease and many
other chronic diseasesBefore becoming adults:• Psychological and self image problems• Medical problems: hypertension, dyslipidemia,
diabetes
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DIABETES :IN CHILDREN AND ADOLESCENTS
HISTORICALLY
• Type 1 Diabetes
• Prevalence 1 in 500
• TYPE 1 DIABETES 95-98%
• OTHER TYPES OF DIABETES 2-5%
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TYPE 2 DIABETES
DEFINITION• Syndrome associated with obesity, hypertension and
cardiovascular disease
• Characterized by both peripheral resistance to insulin action and insulin secretory defects
• Historically rare in children and adolescents, incidence has been increasing recently
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DIAGNOSIS OF DIABETES
World Health Organization and
American Diabetes Association
• Fasting blood glucose 126 mg/dL
• Post prandial glucose >200mg/dL
• Oral glucose Tolerance test not always necessary
• Elevated HgA1c
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Type 2 Diabetes Risk Factors and Testing Criteria
Who to screen?•Overweight (BMI >85th percentile for age and gender; weight for height >85th percentile; or weight >120 percent of ideal for height
•PLUS Any two of the following risk factors
--family history of type 2 diabetes in first- or second-degree relative
--race/ethnicity – American Indian, African American, Hispanic/Latino, Asian American, or Pacific Islander
--signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, polycystic ovarian syndrome, or small-for-gestational-age birth weight)
-- maternal history of diabetes or GDM during the child’s gestation
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When and how to screen
• Age to begin testing – 10 years old or at onset of puberty if puberty occurs earlier
• Frequency of testing – every 3 years• Tests to use – fasting plasma glucose, A1C, 2-h
oral glucose tolerance test• Clinical judgment should be used to perform
testing in children and adolescents who do not meet the above criteria.
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Type 2 diabetes in children :World wide phenomenon
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TYPE 2 DIABETES
PATHOPHYSIOLOGY
• Failure of insulin secretion to compensate for insulin resistance associated with obesity, in most cases
• Evidence of both genetically limited beta-cell reserve and heritable insulin resistanceIn Adolescents• Pubertal insulin resistance compounded by obesity
results in type 2 diabetes• Polycystic ovarian syndrome (PCOS) in adolescent
females
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Case presentation
• 11 year old boy was referred because father, who was recently diagnosed with Type 2 Diabetes, noted similar symptoms in son i.e. Polyuria, polydipsia, nocturia. Twelve lbs weight loss was noted.
• Child is overweight, no other abnormal findings.• Fasting blood sugar 124 mg/dl. OGTT did not meet
criteria for diagnosis of diabetes.
• Hg A1c 6% (4.2-6%)
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Physical characteristics in children and adolescents with diabetes
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BMI in New onset Type 2 Diabetes
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Why Are They Obese?
• Endocrine disorders– Hypothyroidism– Glucocorticoid excess (iatrogenic or endogenous)– Growth hormone deficiency– All cause linear growth failure associated with short stature
• Genetic syndromes– Prader-Willi– Bardet-Biedl (mental retardation, hypogonadism, polydactyly,
retinitis pigmentosa)– Albright’s hereditary osteodystrophy (short stature, short fourth
metacarpal, mental retardation, hypocalcemia)• Exogenous
– usually tall above the 75th - 95th %ile– usually familial
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Exogenous Obesity
• Nature versus Nurture
– Appetite
– Efficient metabolism
– Decreased exercise
– Altered body image
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What Can We Do About Childhood Obesity?
• Identify medical risk factors
– Blood pressure
– Cholesterol levels
– Sleep apnea
– Diabetes
• Identify and treat medical causes.
– Hypothyroidism, Cushing’s syndrome
– Prader-Willi Syndrome
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Prevention
• Lifestyle changes: Decreased caloric intake and increased physical activity extremely challenging
• Pharmacologic intervention to reduce weight is not yet deemed appropriate for children
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Case Presentation
• Obese 11y old w boy, no symptoms • Distant family history of type 2 Diabetes• Fasting and random blood glucose within
normal limits• HgA1c 5.9% (4.2-6%)• Serum insulin 687uIU/ml (5-20uIU/ml)
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Relationship between Insulin resistance, metabolic syndrome and Diabetes
Insulin resistance
HyperinsulinemiaInadequateInsulin secretion
Metabolic syndrome
Type 2 Diabetes
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When should we intervene?
Size of populationSize of population
Preventionof weight gain
Overweightand obesity
Insulin resistanceMetabolicsyndrome
IGTDiabetes HypertensionHyperlipidemia
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Effects of metformin on fasting glucose and insulin levels in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes mellitus. Freemark, M et al JCEM, 88(1):3
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TYPICAL CASE PRESENTATION
• 15 yr old w boy seen for routine sports physical: Asymptomatic
UA: +glucose and ketones
• HISTORY of nocturia x1 for the last 2-6mo and 11 lbs wt loss
• FAMILY HISTORY positive for Type 2 Diabetes in maternal grandfather
• PE : HT 75th % WT >>95th % BP130/68
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TYPICAL CASE PRESENTATION (continued)
• Fasting blood sugars locally on three different mornings : 208, 140, 153 mg/dl
• HgA1c 6.6% (4.5-6%)• Fasting glucose, Insulin, c-peptide • No autoimmune markers
• Diagnosis : Type 2 Diabetes• Therapeutic Plan: Diet and Exercise Blood glucose monitoring
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Treatment of children and adolescents with type 2 diabetes
• Goals of treatment are weight loss, normoglycemia and normal HgA1c.
• Young age at onset of type 2 diabetes means longer duration and thus more microvascular and macrovascular complications: Grave public health implications.
• 33% will have ketosis and 10% ketoacidosis: require insulin
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Therapeutic options in children and adolescents with Type 2 diabetes
• Weight control through diet and exercise
• Oral hypoglycemic agents
• Insulin
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TYPICAL CASE PRESENTATION (continued)
• 3 month follow up: Wt loss, HgA1c
• Further Follow up : Wt gain, HgA1c
• Hypoglycemic agents
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TODAY Study
• 15 clinical centers funded by NIDDK• 699 adolescents with Type 2 diabetes
Participants randomized 1:1:1 to(i) metformin alone(ii) metformin plus rosiglitazone(iii) metformin plus an intensive lifestyle
intervention called the TODAY Lifestyle Program (TLP)
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TODAY Study
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Effects of Metformin, Metformin Plus Rosiglitazone, and Metformin Plus Lifestyle on Insulin Sensitivity
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Prevalence of Hypertension
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In Summary: Testing children and adolescents
for type 2 diabetes• Criteria Overweight (BMI >85% for age and sex)• Risk factors (any two) Family history of type 2 diabetes, Race/ ethnicity, Signs of insulin resistance: Acanthosis
Nigricans, Hypertension, dyslipidemia, PCOS• Age of initiation: 10 years of age • Frequency: every 2-3 years• Test: FPG preferred
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In Summary: Approach to Treatment
• Prevention of type 2 diabetes needs to start at young ages
• Diet and exercise interventions should be started early in high risk individuals
• Delaying the onset of type 2 diabetes may also be a significant benefit
• Therapy might need to be individualized (e.g. boys better with Lifestyle +metformin, girls metformin +TZD, NHB vs Hispanics)
• Polypharmacy may be required
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In Summary: Treatment of Type 2 diabetes in children
Nonpharmacologic Rx(weight control, activity)
MonotherapyMetformin
Combination therapyMetformin, Rosiglitazone
•Severe hyperglycemia•very symptomatic •ketosis •autoimmune markers
Insulin + Metformin
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Thank you!!!