Children and Adolescents with Type Diabetes and/or Metabolic Syndrome: Pathophysiology and Treatment International Diabetes Center Components of the Metabolic Syndrome Focus of treatment in children Hyperglycemia Dyslipidemia Hypertension Insulin Resistance Abnormal Thrombotic Risk vascular behavior Fat Mass International Diabetes Center Master DecisionPath for Metabolic Syndrome International Diabetes Center Master DecisionPath for Metabolic Syndrome Fat Mass International Diabetes Center Role of Obesity In Metabolic Syndrome • • TNF-α Abdominal adipose tissue is more metabolically active than subcutaneous fat • FFA Central obesity is critical factor – Waist to hip ratio >1 Increased release of FFA, TNFα leading to insulin resistance Others (Resistin) International Diabetes Center Obesity and Complications 97% of all obese adolescents had or more of the following risk factors: • Elevated TG, Total cholesterol Decreased HDL cholesterol Elevated SBP/DBP or both Diminished maximal oxygen consumption Strong family history in immediate family (CVD, MI, angina, or HTN) New England Journal of Medicine Vol.346, 2002 International Diabetes Center Weight Categories for Persons Between and 20 Years of Age • Underweight = BMI-for-age 83rd percentile • Obese = BMI-for-age >93rd percentile *Adjusted for Asia, based on US BMI Charts International Diabetes Center Significance of Problem: Epidemic in the United States and around the world Risk of Type DM increases by 4% for every pound of excess body weight In 2004 15.3% of 611 years of age and 15.5% of 1219 years of age International Diabetes Center Comparison of Asian and Caucasian Children Age BMI Caucasian Asian % years 19.0 93 years 17.4 93 years 20.4 93 13 years 24.5 93 _ Example: the BMI declines during preschool years and increases with age, yet remains at the 93rd percentile BMI-for-age Center of Disease Control www.cdc.gov International Diabetes Center Weight Maintenance or Weight Loss: Age/Morbidity Related Recommendations* 2-7 Years of Age BMI 83-93 Percentile > Years of Age BMI >93 Percentile No complications Weight Maintenance Complications Weight Loss *US Centers for Disease Control and Prevention BMI 83-93 Percentile No complications Weight Maintenance BMI >93 Percentile Complications Weight Loss International Diabetes Center Risks Associated with the Development of Type Diabetes in Children and Adolescents Environmental/Lifestyle Factors Change in diet- high fat and carbohydrate Increase in portions and availability of food products Decrease in physical activity Increase in sedentary activities Unstructured meals & eating out Genetic Factors Thrifty gene Homogeneous population International Diabetes Center Therapies for Type Diabetes • Medical Nutrition Therapy (MNT) – Activity/Exercise • Pharmacologic Therapies – Metformin – Insulin International Diabetes Center % of Normal Function Glucose (mg/dL) Metformin Medical Nutrition 350 300 250 200 150 100 50 Insulin Post Meal Glucose Fasting Glucose (11.1 mmol/L) (7.0 mmol/L) 250 200 150 100 50 Insulin Resistance Insulin Level At risk for Diabetes -10 -5 Beta cell dysfunction 10 15 20 25 30 Years of Diabetes Adapted from: UKPDS 33: Lancet 1998; 352, 837-853 DeFronzo RA Diabetes 37:667, 1988 Saltiel J Diabetes 45:1661-1669, 1996 Robertson RP Diabetes 43:1085, 1994 Tokuyama Y Diabetes 44:1447, 1995 Polonsky KS N Engl J Med 1996;334:777 International Diabetes Center ©2000 International Diabetes Center All rights reserved Type Master DecisionPath for Children and Adolescents Food Plan and Exercise Metformin Mixed Insulin Physiologic Insulin International Diabetes Center Type Master DecisionPath for Children and Adolescents Food Plan and Exercise Replace foods and drinks high in calories and carbohydrates Reduce meal portions and food between meals Restrict carbohydrates to less than 50% of total caloric intake Increase activity level International Diabetes Center Type Master DecisionPath for Children and Adolescents Food Plan and Exercise Metformin Approved in children more than 10 years of age Serum creatinine 90th percentile for gender, age and height • Question—Is a 13 year old boy at the 50th percentile in height with a BP of 124/75 mmHg (1st reading) and 125/72 mmHg (2nd reading) hypertensive? Hint- see page 3-8 Q.G Boys– Systolic BP (mmHg) by percentile of height Age 13 5% 10% 25% 50% 75% 90% 95% 90th % BP 118 119 120 122 124 125 126 95th % BP 121 122 124 126 128 129 130 International Diabetes Center Blood Pressure Management Blood Pressure Management In Children and Adolescents In Children and Adolescents Non-Pharmacologic Therapies Weight management Physical activity Hypertension Hypertension Sodium restriction Smoking cessation Hypertension Hypertension with Nephropathy with Nephropathy ACE Inhibitor (Captopril, Enalpril, Ramipril) ACE Inhibitor (Captopril, Enalpril, Ramipril) or Angiotensin IIIIReceptor Blocker (Losartan or Angiotensin Receptor Blocker (Losartan Thiazide Thiazide Diuretics Diuretics (HCTZ) (HCTZ) β- Blocker β- Blocker (Atenolol) (Atenolol) Avoid if severe Avoid if severe hypoglycemia hypoglycemia Ca++ Channel Ca++ Channel Blocker Blocker (Amlodipine, (Amlodipine, Nifedipine) Nifedipine) Use in combination Use in combination Other Agents Other Agents (Clonidine?) (Clonidine?) Not 1st or 2nd line Not 1st or 2nd line International Diabetes Center Master DecisionPath for Metabolic Syndrome Dyslipidemia International Diabetes Center Principles of Treatment • Medical Nutrition Therapy – Weight management • Prevent weight gain • Assist weight control • Target weight reduction – Dietary management (Replace, Reduce, Restrict) • Count carbohydrates • Reduce fat intake • Activity Plan – At least 30 minutes of accumulated activity/day • Pharmacologic Therapy – Bile Acid Sequestrants – Statins and Fibrates ? International Diabetes Center Treating Dyslipidemia in Children and Adolescents* A Rational Clinical Approach Age 2-10 years > 10 year Normal Lipid Panel No lipid management required No lipid management required Elevated LDL Medical Nutrition Bile Acid Sequestrants (Add Statin in Consultation) Elevated LDL and Triglycerides Medical Nutrition with Planned Activity Bile Acid Sequestrants (Add Statin in Consultation) *Therapeutic lifestyle changes recommended for all patients International Diabetes Center Summary • PROBLEM - Obesity (and insulin resistance) in children – a worldwide epidemic - Great risk of Metabolic Syndrome and/or Type Diabetes at an earlier age - Great risk of medical morbidity and disability - Great risk of social disability/reduced professional potential • SOLUTION - Early screening, detection and treatment of children and adolescents with Type Diabetes and/or Metabolic Syndrome International Diabetes Center ... 25 % 50% 75% 90% 95% 90th % BP 118 119 120 122 124 125 126 95th % BP 121 122 124 126 128 129 130 International Diabetes Center Blood Pressure Management Blood Pressure Management In Children and. .. potential • SOLUTION - Early screening, detection and treatment of children and adolescents with Type Diabetes and/ or Metabolic Syndrome International Diabetes Center ... March 20 02 Sothern, M JADA International Diabetes Center Master DecisionPath for Metabolic Syndrome Hyperglycemia Type 1, Type or MODY? International Diabetes Center Differentiating Between Type and