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. Genetic defects of beta cell function2. Genetic defects in insulin action3. Diseases of the exocrine pancreas4. Endocrinopathies5. Drug/ chemical - induced 6. Infections7. Uncommon forms of immune-mediated diabetes8. 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

Pancreas

Insulin Resistance

Liver

Hyperglycemia

Islet Cell Degranulation;Reduced Insulin Content

Muscle Adipose Tissue

Decreased Glucose Transport & Activity

(expression) of GLUT4

Increased Lipolysis

↑GlucoseProduction

↓GlucoseUptake

ReducedPlasma Insulin

Increased Glucose Output

Cell Dysfunction

Elevated Plasma FFA

Type 2 Diabetes and Associated Factors

• Obesity• Sedentary lifestyle• Gradual onset• History

– Gestational diabetes– Family history– PCOS

• Hyperpigmented skin (acanthosisnigricans)

*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

• 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

Latent Autoimmune Diabetes in Adults (LADA)

Characteristics of Type 1, Type 2 and LADACharacteristic 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 Obese

Normal to 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 0-

1.5)– 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