Diagnosing Diabetes In Adults– Type 1, LADA, or Type 2?

1. Diagnosing Diabetes In Adults– Type 1, LADA, or Type 2? Part 1 of 4 Stanley Schwartz MD, FACE, FACP Affiliate Main Line Health Emeritus, Clinical Assoc. Prof. of Medicine Perlman School of Medicine, University of Pennsylvania Struan F.A. Grant, Ph.DVanessa Guy Children’s Hospital of Philadelphia Children’s Hospital of Philadelphia Associate Professor, University of Pennsylvania Senior Clinical Research Coordinator Co-Investigators NIH RO-1, Genes in LADA

2. ORSince Confusion Abounds,Isn’t it Time for…A New Classification/Approach tothe Diagnosis of Diabetes

3. Disclosures • Vanessa Guy- none • Struan Grant- None • Stanley Schwartz • Ad boards- Janssen, Merck, Santarus, AZ-BMS, BI-Lilly • Speaker’s Bureaus- Takeda, Janssen, Merck, Novo, Salix, BI-LILLY

4. Purely Clinical AnswerEmpiric, Pragmatic Approach At this point in time, it doesn’t matter which label is applied  • Insulin Requiring • DKA: ketosis prone, die without insulin • Everyone else – Independent of Age, • “Label” Patient, ‘best guess’ • Treat ‘as needed’ to get glycemic control

5. But Need to be More Than Pragmatic!!’Diagnosis’: Has Many Functions Plan care − eg: imply ‘cause-specific’ studies and therapies Predict − who else might get disease • Prevent − disease development and progression • Proliferate Scientific Knowledge − about diabetes

6. Current Diabetes Classification • Note the OVERLAP • Diagnosis is Often IMPRECISE

7. Definitions: T1D, ‘LADA’, T2D Won’t belabor typical definitions- T1D and T2D! • ‘LADA’ use – ambiguous Includes: • Later age, therefore, SPIDDM- Slowly progressive T1D • ‘slower’ destruction of β-cells than T1D • Antibody positive T2D = ‘T1.5D’ • ‘faster’ destruction of β-cells than in T2D • T-cell abnormal SPIDDM • antibody negative

8. 1. 30 years of age 2. Positive for at least one of the four antibodies commonly found in T1D 3. Not treated with insulin within the first 6 months after diagnosis Implies: antibody positive adults, that may be on insulin, but may not be insulin dependent ‘Definitions of LADA’ The Immunology of Diabetes Society –LADA, and Action LADA ADA recognizes LADA as a variation of T1DM 1. Also called: • Type 1.5 • ‘Slowly’ progressive Type 1D • Latent-onset Type 1D • Implies: insulin-dependent antibody-positive adults

9. Visualization of the Overlap IMMUNITY AGE GENES BMI INSULIN THERAPY HLA++ HLA+ HLA ? child adult adult adult Strong +++ ++ + weak T1DM In children T1DM In adults LADA T2DM low normal normal high Immediate Intermediate Immediate Variable Infrequent Adapted from Leslie et al. Diabetes Metab Res Rev. 2008 Oct;24(7):511-9

10. Characteristics Frequently Overlap

11. Characteristics Frequently Overlap

12. Summary • Definitions are Imprecise, Ambiguous • Exceptions to ‘typical’ presentations • Overlapping Characteristics (eg: T1 with T2 parents) • They don’t take into account various causes of hyperglycemia that we know exist. CONCLUSION: We need to bring Nomenclature of Classification and Diagnosis in line with therapies: current and future, and vice versa