Obesity and Type 2 Diabetes in children and

Obesity and Type 2 Diabetes in children and adolescents Eva Tsalikian M. D. Stead family Department of Pediatrics Pediatric Endocrinology and Diabetes April 16, 2014

Obesity and Type 2 Diabetes in 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

Rates of Overweight and Obese Children 2005 2007

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.

Identification Children (Ages 6 to 11) Prevalence (%) Adolescents (Ages 12 to 19) Prevalence (%) Race 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.

Why is this a problem? • Overweight children become overweight adults • Risk for diabetes, cardiovascular disease and many other chronic diseases Before becoming adults: • Psychological and self image problems • Medical problems: hypertension, dyslipidemia, diabetes

DIABETES : IN CHILDREN AND ADOLESCENTS HISTORICALLY • Type 1 Diabetes • Prevalence 1 in 500 • TYPE 1 DIABETES 95 -98% • OTHER TYPES OF DIABETES 2 -5%

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

DIAGNOSIS OF DIABETES World Health Organization and American Diabetes Association • • Fasting blood glucose 126 mg/d. L Post prandial glucose >200 mg/d. L Oral glucose Tolerance test not always necessary Elevated Hg. A 1 c

Type 2 Diabetes Risk Factors and Testing Criteria Who to screen? • Overweight (BMI >85 th percentile for age and gender; weight for height >85 th 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

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, A 1 C, 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.

Type 2 diabetes in children : World wide phenomenon

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 resistance In Adolescents • Pubertal insulin resistance compounded by obesity results in type 2 diabetes • Polycystic ovarian syndrome (PCOS) in adolescent females

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 A 1 c 6% (4. 2 -6%)

Physical characteristics in children and adolescents with diabetes

BMI in New onset Type 2 Diabetes

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 75 th - 95 th %ile – usually familial

Exogenous Obesity • Nature versus Nurture – Appetite – Efficient metabolism – Decreased exercise – Altered body image

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

Prevention • Lifestyle changes: Decreased caloric intake and increased physical activity extremely challenging • Pharmacologic intervention to reduce weight is not yet deemed appropriate for children

Case Presentation • Obese 11 y old w boy, no symptoms • Distant family history of type 2 Diabetes • Fasting and random blood glucose within normal limits • Hg. A 1 c 5. 9% (4. 2 -6%) • Serum insulin 687 u. IU/ml (5 -20 u. IU/ml)

Relationship between Insulin resistance, metabolic syndrome and Diabetes Insulin resistance Inadequate Insulin secretion Hyperinsulinemia Metabolic syndrome Type 2 Diabetes

When should we intervene? Prevention of weight gain Overweight and obesity Size of population Insulin resistance Metabolic syndrome IGT Diabetes Hypertension Hyperlipidemia

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

TYPICAL CASE PRESENTATION • 15 yr old w boy seen for routine sports physical: Asymptomatic UA: +glucose and ketones • HISTORY of nocturia x 1 for the last 2 -6 mo and 11 lbs wt loss • FAMILY HISTORY positive for Type 2 Diabetes in maternal grandfather • PE : HT 75 th % WT >>95 th % BP 130/68

TYPICAL CASE PRESENTATION (continued) • Fasting blood sugars locally on three different mornings : 208, 140, 153 mg/dl • Hg. A 1 c 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

Treatment of children and adolescents with type 2 diabetes • Goals of treatment are weight loss, normoglycemia and normal Hg. A 1 c. • 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

Therapeutic options in children and adolescents with Type 2 diabetes • Weight control through diet and exercise • Oral hypoglycemic agents • Insulin

TYPICAL CASE PRESENTATION (continued) • 3 month follow up: Wt loss, Hg. A 1 c • Further Follow up : Wt gain, Hg. A 1 c • Hypoglycemic agents

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)

TODAY Study

Effects of Metformin, Metformin Plus Rosiglitazone, and Metformin Plus Lifestyle on Insulin Sensitivity

Prevalence of Hypertension

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

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

In Summary: Treatment of Type 2 diabetes in children Nonpharmacologic Rx (weight control, activity) Monotherapy Metformin Combination therapy Metformin, Rosiglitazone • Severe hyperglycemia • very symptomatic • ketosis • autoimmune markers Insulin + Metformin

Thank you!!!