Jacalyn Bishop, MD, FAAP

4/17/12

The Old

First century ADAretaeus coined the term “diabetes” – greek

word for “siphon”

“...For fluids do not remain in the body, but use the body only as a channel through which they may flow out.” “…For no essential part of the drink is absorbed by the body while great masses of the flesh are liquefied into urine.”

Eugene J. Leopold, Aretaeus the Cappodacian

17th centuryDr. Thomas Willis “sampled” urine to determine if a

patient had diabetes. Sweet taste equaled diabetes mellitus (mellitus - latin word for ‘honey sweet’)

17th – 20th centuryLow calorie diets used for treatment

“Despite physician’s valiant efforts to combat diabetes, their patients remained little more than human guinea pigs.”

Melissa Sattley, The History of Diabetes. DiabetesHealth, Dec 17, 2008

Insulin is Discovered! 1921 – Ontario Canada

Frederick Banting and his assistant Charles Best administer canine pancreas extract to a diabetic dog and keep it alive for 70 days.

1923Frederick Banting and J.J.

Macleod win the Nobel Prize for Medicine for their discovery of insulin.

J. L. Age 3 yrs. Weight 15 lbs, December 15, 1922. Courtesy of Eli Lilly and Company Archives." / "J. L. Weight 29 lbs, February 15, 1923. Courtesy of Eli Lilly

and Company Archives

1935Roger Hinsworth differentiates type 1 from type 2

diabetes

1950Sulfonylureas developed for type 2 diabetics

(Metformin not discovered until 1995).

1960s“Urine color wheels” to determine if glucose is in urine –

today’s glucose strips

1961Disposable syringe introduced

(no more glass syringes

or sharpening and boiling

needles to sterilize them!)

1969Ames Diagnostics releases the first portable

glucose meter

1979First insulin pump marketed

First Hba1c test devised

Diabetes According to the ADA

Normal fasting blood sugar: 60 – 100 mg/dL

Impaired Glucose Tolerance Fasting: 101 - 126 mg/dL OGTT: 2 hour 140 - 199 mg/dL Hba1c: 5.7-6.4%

Diabetes Fasting blood glucose >126 mg/dL on two occasions Random blood glucose >200 mg/dL + symptoms of diabetes Oral glucose tolerance test: 2hr post glutol blood sugar >200mg/dl Hba1c: >6.5%

Hba1c Interpretation

A1C levels between 5.5% and 6.0% have a 5 year cumulative incidence of diabetes ranging from 12-25%.

A1C levels between 6.0 and 6.5% are at very high risk of developing diabetesIncidence in this group is greater than 10 times

that of people with lower levels.

American Diabetes Association. Clinical Practice Recommendations 2012. Diabetes Care. January 2012; 35 (Supplement 1)

Diabetes Classification Type 1 (IDDM)

Primary defect is failure of beta cells resulting in insulin deficiency

Type 2 (NIDDM) Primary defect is resistance to insulin action and failure of beta cells

to compensate – ‘relative’ insulin deficiency

MODY (maturity onset diabetes of youth) Single gene defect (MODY 1- 6) Autosomal dominant Very rare – 70-110 per million

Idiopathic Diabetes Insulin deficiency without presence of antibodies Most commonly seen in patients of African or Asian ancestry Ketoacidosis and Insulin requirement may come and go

Other forms associated with syndromes Wolfram syndrome (DIDMOAD), Mitochondrial disease

Type 1 Diabetes Still the most common cause of diabetes in children Incidence increasing – Why? Current US incidence around 1-2 per 10,000 per year By 16 years of age, 1 in 330 will have diabetes Peak incidence is early adolescence (but can occur at

ANY age) More common in Caucasian, less in Asian and African

American

Type 1A = autoimmune Type 1B = non autoimmune – pancreatic disease e.g.

cystic fibrosis

Etiology of Autoimmune Diabetes

Genetic susceptibility Lifetime risk in general population: 0.4% Up to 50% concordance in monozygotic twins Sibling risk: 5%, Father to child risk: 6-12%, Mother to child risk: 4%

if <25 years at delivery and 1% if >25 years (Risk doubles if parent/sibling was younger than 11 at diagnosis.)

Associated with HLA DR3/DR4 genes

Environmental trigger Incidence more common in fall and winter - viral infection trigger? Possibly multiple potential triggers in early infancy: viruses, cows

milk, toxins

Auto-antibodies: 1 or more present in 85-90% at diagnosis:○ GAD 65, islet cell, insulin and tyrosine phosphatases (IA-2 & IA-2B)

antibodies○ GAD 65 (glutamic acid decarboxylase) most common: protein found in

the beta cell which shares sequence homology with some viruses

Case Study 12 year old girl, brought to her PCPs office. Complaining of heart

racing and generally feeling unwell. Mother is concerned that she has started wetting the bed, having been dry at night since 4 years of age.

What pertinent questions do you want to ask the family?

○ Weight loss (amount, duration)○ Energy level○ Behavior changes○ Appetite changes (early stages increased, then decreased)○ Vomiting○ Presence of fever or intercurrent viral illness○ Vaginal yeast infection○ Medications ○ Family history of diabetes and/or autoimmune disease

Case Study 12 year old girl, brought to her PCPs office. Complaining of heart

racing and generally feeling unwell. Mother is concerned that she has started wetting the bed, having been dry at night since 4 years of age.

What should you look for on your physical exam?

Physical exam often NORMAL in early type 1 diabetesPresence of obesity and/or acanthosis nigricansPresence, degree of dehydrationKetone breathRespiratory rate and effort (Kussmaul respirations?)Infection (girls: candidal vulvovaginitis common)Thyromegaly (coexisting autoimmune thyroiditis common)

Case Study 12 year old girl, brought to her PCPs office. Complaining of heart

racing and generally feeling unwell. Mother is concerned that she has started wetting the bed, having been dry at night since 4 years of age.

What laboratory tests do you want to order?

○ If patient is well with no signs/symptoms suggestive of ketoacidosis:Capillary blood glucose, confirmed by serum glucoseUrinalysis for glucose and ketones

○ If patient is unwell, needs evaluation and prompt treatment of ketoacidosis:Above PLUSSerum electrolytes including bicarbonateVenous pHCBC

Case Study - Findings 12 year old girl, brought to her PCPs office. Complaining of heart

racing and generally feeling unwell. Mother is concerned that she has started wetting the bed, having been dry at night since 4 years of age.

History positive for 12 lbs. weight loss over past 4 months, despite a good appetite. Drinking a lot during the day and waking at night to drink. Also having trouble concentrating at school. A maternal grandmother developed diabetes at 73 years and does not require insulin.

Physical exam: height 25th percentile, weight 10th percentile. Well- looking girl with no acanthosis or thyromegaly, vital signs and respirations normal, no signs of dehydration

CBG 310, confirmed by serum blood glucose Urinalysis: heavy glucosuria, ketones moderate

Diagnosis?

Case Study - Diagnosis

TYPE 1 DIABETES,

without ketoacidosis

Further investigations?

Case Study - Investigations 12 year old girl, brought to her PCPs office. Complaining of heart

racing and generally feeling unwell. Mother is concerned that she has started wetting the bed, having been dry at night since 4 years of age.

Diagnosis?TYPE 1 DIABETES, without ketoacidosis

Further investigations?

○ HbA1c○ Free T4 and TSH○ Celiac screen (?)○ (Insulin, C-peptide, autoantibodies only necessary when diagnostic

uncertainty about type 1 vs. type 2 diabetes)

Management of Newly Diagnosed Diabetes

Admit child to hospital for education / insulin or, if patient stable, establish immediate follow-up care with pediatric endocrinologist as outpatient

Treat DKA if necessary Establish insulin regimen – typically MDI Education – diabetes educator and dietician Typical education lasts 4-5 hours over 2 days

if not in DKA

Goals of Management

Devise a schedule which allows minimum disruption to daily life of the child and family

Educate parents and caregivers

Balance the risk of long term complications 2° to chronic high blood sugars vs. the risk of severe hypoglycemia

Home Glucose Monitoring Check blood sugars 4 times/day: before

breakfast, lunch, dinner, and bedtime with occasional checks in the middle of the night

Goal = 80%-90% of the readings within the “ target range”

Parents or older teens review the values every 3-7 days and adjust insulin as necessary

Lipohypertrophy at shot sites may cause erratic blood sugars

HbA1c, How is it helpful in following patients with diabetes

Can’t be altered by the patient

Compliments home glucose monitoring, equivalent blood sugar equals HbA1C X 30 – 60.

Goals: Type 1

<6 years 7.5-8.5%6-12 years <8%13-19 years <7.5%Adults < 7%

Type 2 : <7%

Factors Affecting Weight in Diabetes

Abnormal weight loss

Poor control

Celiac Disease

Graves’ Disease

Addison’s Disease Eating Disorders

Weight gain

Too many lows

Developing insulin resistance

Organ Specific Autoimmune Disorders Associated with Diabetes Hypothyroidism

free T4 and TSH at diagnosis and every 1-2 years and if poor growth or other symptoms

Celiac disease Tissue transglutaminase Ab (TTg Ab) with serum IgA if

symptoms like diarrhea, FTT, slow growth, abdominal pain/bloating, unusually low insulin dose, distended abdomen, erratic blood sugars (many lows)

Addison’s disease ACTH stimulation test if unusually low insulin dose, lots of

hypoglycemia, poor growth, excessive tan, low energy

Type 2 Diabetes

Who’s at risk???

Percentage of U.S. Children and Adolescents Who Were Overweight*

* >95th percentile for BMI by age and sex based on 2000 CDC BMI-for-age growth charts**Data are from 1963-65 for children 6-11 years of age and from 1966-70 for adolescents 12-17 years of age

Source: National Center for Health Statistics

12.1%

Boys vs. Girls

The Facts

Obesity in adolescents has increased by 18% over the last 30 years

There has been a 33% increase in prevalence of type 2 diabetes in childhood over the last 15 years

Type 2 diabetes now accounts for 20% of diabetes in children aged 10-19 years

Type 2 Diabetes

More common in non-whites (African American, Native American)

Remains unusual in preadolescent children (consider MODY, particularly if not obese)

Stronger (poly)genetic basis than type 1 Almost 100% concordance in monozygotic twins Often a positive family history of type 2 diabetes

Etiology & Diagnosis of Type 2 DM

Etiology: Long standing hyperinsulinemia with normal glucose levels, “insulin resistance” with eventual beta cell failure and decline in insulin levels leading to hyperglycemia.

Most typical presentation is mild hyperglycemia, with negative urine ketones. May be asymptomatic.

May need oral glucose tolerance test to diagnose

Ketoacidosis can occur (glucose toxicity to beta cell) - a more common presentation of type 2 diabetes in adolescence than in adulthood

Screening Guidelines Criteria to begin screening

Patient overweight or at risk for overweightplus

Any 2 of the following:Family history of type 2 DM in 1st or 2nd degree relativeEthnicity: American Indian, black, Hispanic/Latino, Asian American, Pacific islanderSigns of, or conditions associated with, insulin resistance

American Diabetes Association. Type 2 diabetes in children and adolescents. Diabetes Care 2000;23:386

When and How to Screen Screen every 2 years, starting at age 10 or at

onset of puberty if this occurs 1st

Perform a fasting plasma glucose

Normal = less than 100mg/dLPre diabetes = 100-125mg/dLDiabetes = >126mg/dL (repeat on subsequent

day to confirm)

American Diabetes Association. Type 2 diabetes in children and adolescents. Diabetes Care 2000;23:386

Initial Type 2 Diabetes Management

• At diagnosis:

Hba1c

lipid profile (if normal, repeat every 3-5yrs)

opthalmologic exam

diabetes education

psychosocial assessment

nutrition therapy

review goals of care and treatment plan

Treatment - After acute management

Insulin? Diet and exercise (of course!) but only

effective in 10% of youths Next up – Metformin (Glucophage)

approved down to the age of 12takes 4 weeks to become effectiveStart at low doses and increase gradually to

avoid GI upsetMetformin XR in same doses causes less GI

upset

Blood sugar checks 1-2x/day

Ongoing Diabetes Management (for all types!)

Quarterly:

• Assess injection site – if applicable• Assess psychosocial adjustment, self-management skills, dietary

needs and physical activity level• Discuss tobacco, drug and alcohol use• Measure a1c• Review blood glucose records

Annually:

• Flu vaccine• Physical to address comorbidities including PCOS, fatty liver,

foot lesions, etc…• Measure urine microalbumin/creatinine ratio (normal <30)• Ophthalmologic exam (if over 10 years and diabetes for more

than 3 years

Now for the New… 2009

Medtronic released Paradigm Veo pump with low-glucose suspend feature. Awaiting US FDA approval…

Jan 2012 FDA issued guidance for work toward

approved artificial pancreas

Feb. 2012FDA approved MySentry Remote

Glucose Monitor: glucose monitor that can be used in another room to monitor Medtronic sensor/pump data

More New Technology