1. Type 1? Type 2? LADA? A Diagnostic Challenge David Winmill, DNP, CDE, BC-ADM Diabetes Update 2010

2. 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

3. 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?

4. 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.

5. 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

6. 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

7. 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

8. 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

9. Atkinson MA and Eisenbarth GS. Lancet 2001;358:221-229.

10. Diabetes Mellitus Type 1 & Autoimmune Diseases Hypothyroidism Celiac disease Addison’s Disease Rheumatoid arthritis Pernicious anemia Vitiligo

11. Type 2 diabetes Central feature: Insulin resistance Relative impairment in insulin secretion (hyperinsulinemia may exist) Associated metabolic features (hyperlipidemia) Ketosis occurs rarely

12. 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 ↑ Glucose Production ↓ Glucose Uptake Reduced Plasma Insulin Increased Glucose Output  ­Cell Dysfunction Elevated Plasma FFA

15. Type 2 Diabetes and Associated Factors Obesity Sedentary lifestyle Gradual onset History –Gestational diabetes –Family history –PCOS Hyperpigmented skin (acanthosisnigricans)

16. * 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/m 2 –Personal or family history of autoimmune disease Latent Autoimmune Diabetes in Adults (LADA)

17. Characteristics of Type 1, Type 2 and LADA Adapted from: Appel et al. (2009). J Am Acad Nurse Pract, 21(3), 156-159.

18. 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

19. 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