Type 1? Type 2? LADA?
A Diagnostic Challenge
David Winmill, DNP, CDE, BC-ADM
Diabetes Update 2010
Case Study: C. F.
• 52 year old woman presenting with new onset
diabetes, presumably type 1.
• HPI: 6 week history of fatigue, thirst, blurred
vision, polyuria
• PMH: hypothyroidism, hyperlipidemia,
depression.
• Medications: simvastatin, duloxetine, metformin
850 mg bid, insulin glargine 8 units
• Family Hx: Father – Type 2 DM, Son Type 1 DM
• SH: Married with 5 children (none > 9 lbs),
secretary
Case Study CF
• Physical exam
– Wt. - 156.4 Ht. – 63” BP 132/82, HR 72,
– Normal HEENT, Neck, Chest, Cardiovascular, Abdominal,
Neurologic
• Laboratories
– HgA1C – 10.0%, glucose 268, normal renal and liver
function, normal urine microalbumin
What do you think of her diagnosis?
Type 1, Type 2 or LADA?
Objectives:
• Compare and contrast diagnostic and clinical criteria
of type 1, type 2 diabetes and latent autoimmune
diabetes (LADA) in the adult?
• Discuss role of autoimmunity in the pathogenesis of
type 1 diabetes and LADA.
• Identify clinical characteristics & manifestations of
autoimmunity vs. insulin resistance in differentiating
diabetes typology.
Definition
• Diabetes mellitus is a group of metabolic diseases
characterized by hyperglycemia resulting from defects in
insulin secretion, insulin action, or both.*
• The name 'diabetes mellitus' derives from:
Greek: 'diabetes' – “siphon” or “to pass through”
Latin: 'mellitus' – “honeyed” or “sweet”**
* Diagnosis and Classification of Diabetes Mellitus. ADA 2009.
**
http://science.jrank.org/pages/2044/Diabetes-Mellitus.html
Classification
•
•
•
Type 1 diabetes
Type 2 diabetes
Other
1.
2.
3.
4.
5.
6.
7.
8.
•
Genetic defects of beta cell function
Genetic defects in insulin action
Diseases of the exocrine pancreas
Endocrinopathies
Drug/ chemical - induced
Infections
Uncommon forms of immune-mediated diabetes
Genetic syndromes sometimes associated with diabetes
Gestational diabetes mellitus
Epidemiology
•
•
•
•
•
•
20.8 million Americans (7% of US population)
About 10% have Type 1 DM
14.6 million diagnosed
6.2 million remain undiagnosed
41 million have pre-diabetes
Lifetime risk for developing DM (Type 1 or 2) is 33 % in
males and 39% in females for individuals born in 2000
• Up to 45% of newly diagnosed cases of DM in US
children and adolescents are type 2
AACE Diabetes Mellitus Guidelines, EndocrPract. 2007;13(Suppl 1) 2007
Type 1 diabetes mellitus
• Absolute insulin deficiency
• Autoimmune destruction of the pancreaticβ cells
– Islet-cell antibodies (ICA)
– Glutamicacid decarboxylase [anti-GAD]
– IA-2 and anti-insulin)
• Rapid onset
• Ketosis Prone
Atkinson MA and Eisenbarth GS. Lancet 2001;358:221-229.
Diabetes Mellitus Type 1 & Autoimmune Diseases
•
•
•
•
•
•
Hypothyroidism
Celiac disease
Addison’s Disease
Rheumatoid arthritis
Pernicious anemia
Vitiligo
Type 2 diabetes
• Central feature: Insulin resistance
• Relative impairment in insulin secretion
(hyperinsulinemia may exist)
• Associated metabolic features (hyperlipidemia)
• Ketosis occurs rarely
Type 2 Diabetes: Insulin Resistance &
β Cell Dysfunction
Cell Dysfunction
Insulin Resistance
Increased
Lipolysis
Pancreas
Liver
Elevated
Plasma FFA
Islet Cell Degranulation;
Reduced Insulin Content
↑Glucose
Production
Increased Glucose Output
↓Glucose
Uptake
Muscle
Adipose Tissue
Reduced
Plasma Insulin
Hyperglycemia
Decreased Glucose
Transport & Activity
(expression)
of GLUT4
Type 2 Diabetes and Associated Factors
•
•
•
•
Obesity
Sedentary lifestyle
Gradual onset
History
– Gestational diabetes
– Family history
– PCOS
• Hyperpigmented skin
(acanthosisnigricans)
Latent Autoimmune Diabetes in Adults (LADA)
• Adult-onset diabetes with circulating islet antibodies
but not requiring insulin therapy initially.
• Alternate references
– Type 1.5 diabetes
– Skinny Type 2 diabetes
• Typical characteristics
– Age of onset > 50 years of age
– Gradual onset with initial improvement to oral
agents/lifestyle changes.
– BMI <25 kg/m2
– Personal or family history of autoimmune disease
*A clinical screening tool identifies autoimmune diabetes in adults. Fourlanos S; Perry C; Stein MS; Stankovich J;
Harrison LC; Colman PG. Diabetes Care. 2006 May;29(5):970-5
Characteristics of Type 1, Type 2 and LADA
Characteristic
Type 1
Type 2
LADA
Age of Onset
<35
>35
>35
Speed of Onset
Rapid
Slow
Slow
Response to lifestyle
modification or oral agents
Poor
Good
Initial mixed then
worsening
Frequency of DKA
High
Low
Low
Family History of DM
Uncommon
Common
Uncommon
Personal/Family History
Autoimmune Disease
Common
Uncommon
Common
Body Habitus
Fit or lean
Overweight to Normal to
Obese
overweight
Acanthosisnigricans
No
Yes
No
Metabolic syndrome
No
Yes
No
C Peptide Level
Undetectable
Normal
Low/Normal
Anti-GAD/Anti-ICA/Anti-IA2
Positive
Negative
Positive
Adapted from: Appel et al. (2009). J Am Acad Nurse Pract, 21(3), 156-159.
Followup Case Study – C. F.
• FollowupLaboratories
– Glutamic Acid Carboxylase (GAD-65) – 94.9 (Reference 01.5)
– Islet cell antibody IgG 1:16 (Reference <1:4)
– C Peptide – 0.9 (1.1-5.0)
Your thoughts on this woman’s diagnosis????
Type1 . . . Type 2 . . . LADA
Summary
Clinical indicators that can aid in
the diagnosis of diabetes type:
– History of onset
– Family history
– Presence of autoimmune
indicators
– Evidence of insulin resistance