1. Background notes Audience: diabetes professional (entry level), patients with diabetes First slide: ADD your name/institution ‘Sponge bob’ slide: hemoglobin is like a sponge the ‘soaks’ up the glucose Case example get audience involved Stress YOU (audience member) may need to know HbA1c method if results do not make sense Some slides have ‘Notes’ to help you

2. Diabetes and the laboratory ADD YOUR NAME AND FACILITY HERE

3. Example case Annual ‘Executive Physical’ 54-year-old Caucasian male with a history of well controlled mild hypertension During yearly routine physical complains of malaise for 2 months Routine chemistry tests were normal except for glucose of 280 mg/dL (65-110)

4. Case continued Therapy is instituted and the patient’s glucose normalized Urinary microalbumin is normal Hemoglobin A1c 17.5 (< 7)

5. Case continued Patient is followed for three months All glucose (in office and from patient’s glucose meter) are < 160 mg/dL Energy level is ‘back to normal’ Repeat hemoglobin A1c 9.5 (< 7)

6. Case continued What do you think his medical problem is? What do you do now?

7. Major Methods for Diabetes Monitoring Pre-Meal glucose Normal < 110 Goal 80 – 120 Possible intervention: 140 Bedtime glucose Normal < 120 Goal 100 – 140 Possible intervention 160

8. Fasting triglycerides Normal < 150 Goal < 150 Possible intervention > 250 to 300 LDL cholesterol Normal < 130 Goal < 100 Possible intervention > 130

9. HDL cholesterol Normal > 35 Goal > 35 Possible intervention < 35 Hemoglobin A 1c Normal < 6 Goal < 7 Possible intervention > 8

10. What is Hemoglobin A 1c ? A marker for the amount of glucose consumed in the last 3 months. Measured bi-annually. Key to diagnosis and monitoring of diabetes. Normal: Less than 5.7% Pre-diabetes: 5.7% to 6.4% Diabetes: 6.5% or higher

11. Hemoglobin A 1c Normal: Less than 5.7% Pre-diabetes: 5.7% to 6.4% Diabetes: 6.5% or higher Many (>30) different Glyco-hemoglobin assay methods in current use. Most common is HPLC.

12. HPLC Hemoglobin A1C Results (TOSOH)

13. Goal to standardize measurements ‘To standardize Hemoglobin A 1c test results so that clinical laboratory results are comparable to those reported in the DCCT (%) where relationship for diabetic complication risk have been established.’

14. Vitamins C and E are reported to falsely lower test results False positive with some assays (e.g. elevated fats, bilirubin, chronic alcoholism) Shortened erythrocyte survival or decreases mean erythrocyte age falsely lowers results Iron-deficiency anemia reported to increase test results May not be interpretable with specific hemoglobinopathies (e.g., Hb S, C, Graz, Sherwood Forest, D, and Padova) Can be affected by hemoglobin variants Limitations of Hemoglobin A 1c

15. HPLC Hemoglobin A1C Results (TOSOH)

16. Distribution of Hemoglobin variants

17. Hemoglobin variants by region RegionNumber of individual with Diabetes (million) Prevalence (%) South-East Asia71.49.2 European52.86.7 North America and Caribbean 37.710.7 Middle East and North America 32.611.0 Africa14.74.5

18. Prevalence of diabetes where there are hemoglobin variants

19. Average blood glucose and Hb A 1c

20. How good is good enough In general, 0.5% Hemoglobin A 1c is considered a significant change 2011 Guidelines Within laboratory < 2% Between laboratory <3.5%

21. Hemoglobin A 1c No consensus on optimal frequency of testing Expert opinion recommends testing at least two times a year in patients meeting treatment goals, have stable glycemic control More frequently (quarterly assessment) in patients whose therapy has changed or who are not meeting glycemic goals ADA Provider Recognition Program and HEDIS 2000

22. Patient Outcome? We know that our patient has a Hemoglobin A1C value of 9.5. What can we say about our patient now given our knowledge of Hemoglobin A1C?

23. ADA criteria for diagnosis of Diabetes A1c ≥ 6.5% OR Fasting plasma glucose ≥ 126 OR 2 hour plasma glucose ≥ 200 during an Oral Glucose Tolerance Test OR Classic symptoms of hyperglycemia or hyperglycemic state, random glucose ≥ 200

24. Age adjusted percentage of U.S. adults obese or diabetes

25. Long term effects of Diabetes Eye Problems Sexual dysfunction Miscarriage and stillbirth Kidney disease, also known as diabetic nephropathy Nerve damage, also known as peripheral neuropathy

27. Thank you and Questions