Download Diabetes Mellitus - Henry Ford Health System

Jacalyn Bishop, MD, FAAP
4/17/12
The Old

First century AD
 Aretaeus 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 century
 Dr. Thomas Willis “sampled” urine to determine if a
patient had diabetes. Sweet taste equaled diabetes
mellitus (mellitus - latin word for ‘honey sweet’)

17th – 20th century
 Low 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.

1923
 Frederick 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

1935
 Roger Hinsworth differentiates type 1 from type 2
diabetes

1950
 Sulfonylureas 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

1961
 Disposable syringe introduced
(no more glass syringes
or sharpening and boiling
needles to sterilize them!)

1969
 Ames Diagnostics releases the first portable
glucose meter

1979
 First 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 diabetes

 Incidence 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 diabetes
Presence of obesity and/or acanthosis nigricans
Presence, degree of dehydration
Ketone breath
Respiratory 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 glucose
 Urinalysis for glucose and ketones
○ If patient is unwell, needs evaluation and prompt treatment of
ketoacidosis:
 Above PLUS
 Serum electrolytes including bicarbonate
 Venous pH
 CBC
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. Welllooking 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
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*
12.1%
* >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
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 overweight
plus
Any 2 of the following:
Family history of type 2 DM in 1st or 2nd degree
relative
Ethnicity: American Indian, black, Hispanic/Latino,
Asian American, Pacific islander
Signs 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/dL
 Pre diabetes = 100-125mg/dL
 Diabetes = >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 12
 takes 4 weeks to become effective
 Start at low doses and increase gradually to
avoid GI upset
 Metformin 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. 2012
 FDA approved MySentry Remote
Glucose Monitor: glucose monitor that
can be used in another room to monitor
Medtronic sensor/pump data
More New Technology