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 function 2. Genetic defects in insulin action 3. Diseases of the exocrine pancreas 4. Endocrinopathies 5. Drug/ chemical - induced 6. Infections 7. Uncommon forms of immune-mediated diabetes 8. 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 Pancreas Increased Lipolysis Liver

Islet



Cell Degranulation; Reduced Insulin Content

↑ Glucose Production

Increased Glucose Output Reduced Plasma Insulin

Elevated Plasma FFA

↓

Muscle

Glucose Uptake

Adipose Tissue

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/m 2 – 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

Age of Onset Speed of Onset Response to lifestyle modification or oral agents Frequency of DKA Family History of DM Personal/Family History Autoimmune Disease Body Habitus

Type 1

<35 Rapid Poor High Uncommon Common Fit or lean

Type 2

>35 Slow Good Low Common Uncommon

LADA

>35 Slow Initial mixed then worsening Low Uncommon Common Acanthosisnigricans Metabolic syndrome C Peptide Level Anti-GAD/Anti-ICA/Anti-IA2 No No Undetectable Positive Overweight to Obese Normal to overweight Yes Yes No No Normal Negative Low/Normal 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