what’s new in type 2? what’s new in type 2?

We are in a diabesity epidemic! Prevalence of type 2 diabetes and metabolic

syndrome is increasing in children and their parents

Risk of complications of type 2 are higher in type 2 with onset 18-45 than in older adults

Most children with diabetes are cared for by their primary doctors

We are in a diabesity epidemic! Prevalence of type 2 diabetes and metabolic

syndrome is increasing in children and their parents

Risk of complications of type 2 are higher in type 2 with onset 18-45 than in older adults

Most children with diabetes are cared for by their primary doctors

JCEM 88:1417,2003, GoranJCEM 88:1417,2003, Goran

Obesity

Visceral Adiposity

Adipocytokines Androgens

Puberty

Insulin ResistanceInflammation

Cardiovascular Disease

DyslipidemiaHypertension

Prevalence of obesity is increasing

Prevalence of obesity is increasing

Prevalence of overweight in US children doubled from 1980-1994

Overweight 50% higher in poor US teens 17%US children and teens overweight (BMI

>95%ile) 2004 NHANES 4% US children BMI>99%ile 1:17,741 pedi endos to obese kids in US Waist circumference increased 3.7 cm in

teens 1994-2004 NHANES

Prevalence of overweight in US children doubled from 1980-1994

Overweight 50% higher in poor US teens 17%US children and teens overweight (BMI

>95%ile) 2004 NHANES 4% US children BMI>99%ile 1:17,741 pedi endos to obese kids in US Waist circumference increased 3.7 cm in

teens 1994-2004 NHANES

Factors contributing to the obesity epidemic

Factors contributing to the obesity epidemic

Increase in intake of regular soda (high fructose corn syrup), fast foods, increase in portion size of fast foods, Increase in high carb snacks

Decrease in physical activity Increase in physical inactivity (TV, video,

computer time) each hour TV time=+167 kcal/day,

Wiecha,Arch Ped Adol Med 160:436,2006

Increase in intake of regular soda (high fructose corn syrup), fast foods, increase in portion size of fast foods, Increase in high carb snacks

Decrease in physical activity Increase in physical inactivity (TV, video,

computer time) each hour TV time=+167 kcal/day,

Wiecha,Arch Ped Adol Med 160:436,2006

The metabolic syndromeThe metabolic syndrome

Insulin resistanceHypertensionDyslipidemia

Insulin resistanceHypertensionDyslipidemia

Ford et al, Diabetes Care 31:587,2008

Ford et al, Diabetes Care 31:587,2008

Metabolic syndrome prevalence by IDF definition 4.5% US teens National health and nutrition examination survey 1999-2004 of 2014 teens age 12-17

Metabolic syndrome prevalence by IDF definition 4.5% US teens National health and nutrition examination survey 1999-2004 of 2014 teens age 12-17

Type 1 diabetesType 1 diabetes

beta cell destruction leading to absolute insulin deficiency

Autoimmuneidiopathic

beta cell destruction leading to absolute insulin deficiency

Autoimmuneidiopathic

Type 2 diabetes mellitus:Type 2 diabetes mellitus:

Both insulin resistance and relative insulin insufficiency:

Secretory defect with insulin resistanceInsulin resistance and insufficient

compensatory increase in insulin production

Both insulin resistance and relative insulin insufficiency:

Secretory defect with insulin resistanceInsulin resistance and insufficient

compensatory increase in insulin production

Other specific types of diabetes

Other specific types of diabetes

Genetic defects in beta cell function (MODY, mitochondrial DM)

Genetic defects in insulin action (type A) Diseases of exocrine pancreas (CF etc) Endocrinopathies (Cushing’s etc) Drug induced (steroids etc) Immune mediated ( insulin receptor

antibodies ) Genetic syndromes associated with DM Gestational diabetes

Genetic defects in beta cell function (MODY, mitochondrial DM)

Genetic defects in insulin action (type A) Diseases of exocrine pancreas (CF etc) Endocrinopathies (Cushing’s etc) Drug induced (steroids etc) Immune mediated ( insulin receptor

antibodies ) Genetic syndromes associated with DM Gestational diabetes

Definition of impaired fasting glucose/ glucose intoleranceDefinition of impaired fasting glucose/ glucose intolerance

Fasting plasma glucose 100-125 mg/dl (5.6-6.9 mmol/l)

2 h plasma glucose 140 mg/dl-199 mg/dl (7.8-11 mmol/l) on OGTT

Fasting plasma glucose 100-125 mg/dl (5.6-6.9 mmol/l)

2 h plasma glucose 140 mg/dl-199 mg/dl (7.8-11 mmol/l) on OGTT

Prevalence of diabetes in children under 18 years

Prevalence of diabetes in children under 18 years

Overall 1/300 (all types) (incidence 15/100,000)

Type 2 diabetes 4-30% depending on ethnic mix of population

Prevalence of Type 2 diabetes is rapidly increasing with increase of obesity and inactive lifestyle

Overall 1/300 (all types) (incidence 15/100,000)

Type 2 diabetes 4-30% depending on ethnic mix of population

Prevalence of Type 2 diabetes is rapidly increasing with increase of obesity and inactive lifestyle

Risk factors for type 2 diabetes

Risk factors for type 2 diabetes

Obesity with signs of insulin resistance (acanthosis nigricans, polycystic ovary syndrome) usually post pubertal

Ethnic heritage (African American, Native American, Asian, Latino, pacific islander)

Family history of type 2 history of SGA or LGA

Obesity with signs of insulin resistance (acanthosis nigricans, polycystic ovary syndrome) usually post pubertal

Ethnic heritage (African American, Native American, Asian, Latino, pacific islander)

Family history of type 2 history of SGA or LGA

Screening for type 2 diabetesScreening for type 2 diabetes

BMI of 85%ile or weight > 120% above ideal body weight, age 10 or above or pubertal and: Family history of type 2 diabetes At risk ethnic group Signs or conditions associated with insulin

resistance (acanthosis nigricans, hypertension, hyperlipidemia, PCOS)

BMI of 85%ile or weight > 120% above ideal body weight, age 10 or above or pubertal and: Family history of type 2 diabetes At risk ethnic group Signs or conditions associated with insulin

resistance (acanthosis nigricans, hypertension, hyperlipidemia, PCOS)

Screening obese children for diabetes

Screening obese children for diabetes

Fasting blood sugar consider fasting lipidsconsider insulin level : fasting

glucose/insulin > 4.5 normal (insulin not always accurate in commercial labs)

Glucose 2 hour post 75 gm (1.75 gm/kg) glucose load (not yet the official recommendation of the AAP, ADA)

Fasting blood sugar consider fasting lipidsconsider insulin level : fasting

glucose/insulin > 4.5 normal (insulin not always accurate in commercial labs)

Glucose 2 hour post 75 gm (1.75 gm/kg) glucose load (not yet the official recommendation of the AAP, ADA)

Impaired glucose tolerance in children with marked obesity Impaired glucose tolerance in children with marked obesity

Impaired glucose tolerance in 25% of very obese children ages 4-10 years

Impaired glucose tolerance in 21% very obese adolescents, 4% silent diabetes

Fasting blood glucose screening would miss many individuals with impaired glucose tolerance (N Eng J Med 2002;346:802)

Impaired glucose tolerance in 25% of very obese children ages 4-10 years

Impaired glucose tolerance in 21% very obese adolescents, 4% silent diabetes

Fasting blood glucose screening would miss many individuals with impaired glucose tolerance (N Eng J Med 2002;346:802)

Teen diabetes and the pediatrician

Teen diabetes and the pediatrician

Coordinate care with an endocrinologistAddress adolescent health issues

Acute infections (including STDs) Contraceptive needs Smoking cessation Depression Family support issues

Coordinate care with an endocrinologistAddress adolescent health issues

Acute infections (including STDs) Contraceptive needs Smoking cessation Depression Family support issues

Diabetes Specialty visitsDiabetes Specialty visits

At least every 3 months for education, review of blood sugars, med adjustment

Monitor growth, blood pressure (<130/80) Glucose control goals (individualize):

Hemoglobin A1c<7% (ideal) (lower in type 2): Preprandial plasma glucose 90-130 mg/dl Post prandial <180 mg/dl Yearly microalbumin, lipids, retinopathy screen

At least every 3 months for education, review of blood sugars, med adjustment

Monitor growth, blood pressure (<130/80) Glucose control goals (individualize):

Hemoglobin A1c<7% (ideal) (lower in type 2): Preprandial plasma glucose 90-130 mg/dl Post prandial <180 mg/dl Yearly microalbumin, lipids, retinopathy screen

Treatment goals for diabetesTreatment goals for diabetes

Hemoglobin A1c <7%Preprandial blood glucose 90-130 mg/dlPostprandial blood glucose < 180 mg/dlBlood pressure < 130/80LDL cholesterol < 100 mg/dlTriglycerides < 150 mg/dlHDL cholesterol > 40 mg/dl

Hemoglobin A1c <7%Preprandial blood glucose 90-130 mg/dlPostprandial blood glucose < 180 mg/dlBlood pressure < 130/80LDL cholesterol < 100 mg/dlTriglycerides < 150 mg/dlHDL cholesterol > 40 mg/dl

Management of hyperlipidemia

Management of hyperlipidemia

Dietary counseling, repeat lipids in 3 months LDL 130-159 mg/dl consider medication

(family history, blood pressure, smoking) LDL> 160 mg/dl : begin statin at low dose,

monitor LFTs, watch for persistent muscle pains, use with extreme caution in sexually active females (Diabetes Care 26:2194,2003)

Dietary counseling, repeat lipids in 3 months LDL 130-159 mg/dl consider medication

(family history, blood pressure, smoking) LDL> 160 mg/dl : begin statin at low dose,

monitor LFTs, watch for persistent muscle pains, use with extreme caution in sexually active females (Diabetes Care 26:2194,2003)

Barriers to good diabetes control

Barriers to good diabetes control

Expense of blood glucose monitoring, medications

Cultural bias against insulin or medical intervention: fatalistic attitude toward illness

Insufficient parental supervision of medications and monitoring

Normal adolescent development (denial) Depression Increasing obesity

Expense of blood glucose monitoring, medications

Cultural bias against insulin or medical intervention: fatalistic attitude toward illness

Insufficient parental supervision of medications and monitoring

Normal adolescent development (denial) Depression Increasing obesity

Encouraging optimum diabetes control

Encouraging optimum diabetes control

Give credit for honesty and effortDiabetes visit should build self esteemSupport parental involvementSet realistic goals with teen and familyKeep it interesting (new technologies)Encourage regular visits and contactGroup programs for teens (camps)

Give credit for honesty and effortDiabetes visit should build self esteemSupport parental involvementSet realistic goals with teen and familyKeep it interesting (new technologies)Encourage regular visits and contactGroup programs for teens (camps)

Presentation of type 2 diabetes

Presentation of type 2 diabetes

most teens with type 2 diabetes are identified by screening

Polyuria/ polydipsia/ nocturia common symptoms but not always complaints

Girls may present with recurrent yeast infections

5-25% present in DKA or hyperosmolar dehydration

up to 33% have ketones at presentation

most teens with type 2 diabetes are identified by screening

Polyuria/ polydipsia/ nocturia common symptoms but not always complaints

Girls may present with recurrent yeast infections

5-25% present in DKA or hyperosmolar dehydration

up to 33% have ketones at presentation

Is it type 1 or type 2? More likely type 2 if overweight and:

Is it type 1 or type 2? More likely type 2 if overweight and:PubertalMilder symptomsAcanthosis nigricansFamily history of type 2High risk ethnic group

PubertalMilder symptomsAcanthosis nigricansFamily history of type 2High risk ethnic group

Features of type 2 diabetesFeatures of type 2 diabetes

Insulin /C peptide over upper limit of normal for assay

Negative pancreatic antibody panelInitial insulin requirements 1.3-1.5

units/kg/day falling to little or no insulin requirement over 1-2 months

Ketosis seldom occurs spontaneously

Insulin /C peptide over upper limit of normal for assay

Negative pancreatic antibody panelInitial insulin requirements 1.3-1.5

units/kg/day falling to little or no insulin requirement over 1-2 months

Ketosis seldom occurs spontaneously

14 year old male with ? diabetes

14 year old male with ? diabetes

2 weeks ago, vomiting, diarrhea,fatigueGlucosuria, random blood sugar in 180sRepeat BG=286 mg/dl occasional

nocturia, no thirst, 6 lb weight lossBW 7 lb, MGM, MGGM type 2 diabetesMaternal aunt low thyroidBMI 35, 99%ile, 101kg ht 170 cmSMR 3, acanthosis, psoriasis

2 weeks ago, vomiting, diarrhea,fatigueGlucosuria, random blood sugar in 180sRepeat BG=286 mg/dl occasional

nocturia, no thirst, 6 lb weight lossBW 7 lb, MGM, MGGM type 2 diabetesMaternal aunt low thyroidBMI 35, 99%ile, 101kg ht 170 cmSMR 3, acanthosis, psoriasis

Idiopathic diabetesIdiopathic diabetes

African American / Asian teens with negative antibodies

Insulinopenia: ketosis prone (episodic ketosis)

Family history positive for early onset of diabetes in multiple generations

Absolute requirement for insulin replacement may come and go between episodes of ketosis

Control is usually poor without insulin

African American / Asian teens with negative antibodies

Insulinopenia: ketosis prone (episodic ketosis)

Family history positive for early onset of diabetes in multiple generations

Absolute requirement for insulin replacement may come and go between episodes of ketosis

Control is usually poor without insulin

Healthy eating and activityHealthy eating and activity

Avoid regular soda/ large amounts of fruit juice

Encourage whole fruits, vegetables, low fat milk, (? low glycemic index choices, increased fiber)

Have healthy foods for all at home Limit inactivity (TV off), encourage activity (30

minutes per day, 5+ days /week) ?discuss cigarette smoking

Avoid regular soda/ large amounts of fruit juice

Encourage whole fruits, vegetables, low fat milk, (? low glycemic index choices, increased fiber)

Have healthy foods for all at home Limit inactivity (TV off), encourage activity (30

minutes per day, 5+ days /week) ?discuss cigarette smoking

Management of type 2 diabetes in teens

Management of type 2 diabetes in teens

If presenting in DKA or severe hyper osmolar state, start with insulin (be aware of cultural biases against insulin)

Teach blood sugar monitoring from the beginning (pre and some post meal)

Teach healthy eating and exercise Begin metformin at low dose increasing over

several weeks if no contraindications Address lipid issues

If presenting in DKA or severe hyper osmolar state, start with insulin (be aware of cultural biases against insulin)

Teach blood sugar monitoring from the beginning (pre and some post meal)

Teach healthy eating and exercise Begin metformin at low dose increasing over

several weeks if no contraindications Address lipid issues

Use of metformin in type 2 diabetes

Use of metformin in type 2 diabetes

Start low (500 mg with meal, go slow) Increase slowly to max 1000 mg bid, 850 mg

tid with meals (or Glucophage XR) GI side effects common (nausea, diarrhea,

abdominal discomfort) in first two weeks Avoid dehydration (stop if vomiting) Home BG monitoring premeal and some 2 h

post meal Yearly CBC, BUN, creat, ALT,AST ? multivitamin

Start low (500 mg with meal, go slow) Increase slowly to max 1000 mg bid, 850 mg

tid with meals (or Glucophage XR) GI side effects common (nausea, diarrhea,

abdominal discomfort) in first two weeks Avoid dehydration (stop if vomiting) Home BG monitoring premeal and some 2 h

post meal Yearly CBC, BUN, creat, ALT,AST ? multivitamin

Advantages of metforminAdvantages of metformin

Mild weight loss (teens love this)Decreased insulin requirement/

decreased insulin resistanceNot associated with hypoglycemiaBeneficial effects on cardiovascular

disease shown in adults

Mild weight loss (teens love this)Decreased insulin requirement/

decreased insulin resistanceNot associated with hypoglycemiaBeneficial effects on cardiovascular

disease shown in adults

When to begin insulin rather than oral agent in type 2:

When to begin insulin rather than oral agent in type 2:

Ketones presentMarked hyperglycemia with dehydrationContraindications to metformin

(significantly abnormal LFTs, elevated BUN/ creatinine, pregnancy)

Ketones presentMarked hyperglycemia with dehydrationContraindications to metformin

(significantly abnormal LFTs, elevated BUN/ creatinine, pregnancy)

When metformin is not enough:

When metformin is not enough:

Add insulin (NPH, glargine,detemir, or short acting insulin with meals or combinations)

Add a second oral agentTake a look at lifestyle again (food and

beverage choices, activity) Enlist more adult support

Add insulin (NPH, glargine,detemir, or short acting insulin with meals or combinations)

Add a second oral agentTake a look at lifestyle again (food and

beverage choices, activity) Enlist more adult support

Prevention of type 2 diabetesPrevention of type 2 diabetes

Lifestyle modification (exercise, healthy eating)

Treatment of prediabetic conditions with metformin or other insulin sensitizing agents? Glucose intolerance Extreme obesity with insulin resistance Polycystic ovary syndrome

Lifestyle modification (exercise, healthy eating)

Treatment of prediabetic conditions with metformin or other insulin sensitizing agents? Glucose intolerance Extreme obesity with insulin resistance Polycystic ovary syndrome