1. Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome Chapter 3 Ronald Goldenberg, Zubin Punthakee Canadian Diabetes Association 2013 Clinical Practice Guidelines

2. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Key Messages 1.Screen wisely. Diagnose precisely. 2.Diagnosis of diabetes can be made with: Fasting plasma glucose (FPG) level of 7.0 mmol/L 2-hr plasma glucose (2hPG) in 75 g OGTT 11.1 mmol/L A1C 6.5% 3.Prediabetes risk of developing diabetes Impaired fasting glucose (FPG 6.1-6.9 mmol/L) Impaired glucose tolerance (2hPG 75g OGTT 7.8-11.0) A1C 6.0- 6.4% 2013

3. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Classification of Diabetes TypeDefinition Type 1 DiabetesDiabetes due to pancreatic beta destruction and prone to ketosis Type 2 diabetesDiabetes that ranges from insulin resistance with relative insulin deficiency to a predominant secretory defect with insulin resistance Gestational Diabetes Mellitus Glucose intolerance with onset or first recognition in pregnancy Other typesVariety of uncommon diseases, genetic forms, or diabetes associated with drug use.

4. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association FPG 7.0 mmol/L Fasting = no caloric intake for at least 8 hours or A1C 6.5% (in adults) Using a standardized, validated assay, in the absence of factors that affect the accuracy of the A1C and not for suspected type 1 diabetes or 2hPG in a 75-g OGTT 11.1 mmol/L or Random PG 11.1 mmol/L Random= any time of the day, without regard to the interval since the last meal 2hPG = 2-hour plasma glucose; FPG = fasting plasma glucose; OGTT = oral glucose tolerance test; PG = plasma glucose Diagnosis of Diabetes 2013

5. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Single test in diabetes range Repeat confirmatory test on different day Use same test as confirmatory test Use FPG, A1C or 2hPG OGTT as confirmatory test Diagnosis made. Repeat not necessary Symptoms*No symptoms* If random PG used initially If FPG, A1C or 2hPG used initially If results of two different tests are available and both are above the diagnostic cutpoints, the diagnosis of diabetes is confirmed. 2013 Diagnosis of Diabetes

6. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Pima Indians Egyptians NHANES III Glycemia and Retinopathy Thresholds The International Expert Committee. Diabetes Care 2009; 32:1327-1334. Threshold levels for the development of retinopathy are similar in all 3 populations: FPG 7.0 mmol/L 2hPG 11.1 mmol/L A1C 6.5% FPG 2hPG HbA1c 70-89-93-97-100-105-116-109-136-226- 364-244-185-156-138-126-116-106-94-38- 3.4-4.8-5.0-5.2-5.3-5.5-5.7-6.0-6.7-HbA1c (%) 2hPG (mg/dl) FPG (mg/dl) Retinopathy (%) 9.5- 15 10 5 0 FPG 2hPG HbA1c 57-79-84-89-93-99-130-108-178-258- 386-304-218-155-125-110-99-90-80-39- 2.2-4.7-4.9-5.1-5.4-5.6-6.0-6.9-8.5-HbA1c (%) 2hPG (mg/dl) FPG (mg/dl) Retinopathy (%) 10.3 - 50 20 10 0 40 30 FPG 2hPG HbA1c 42-87-90-93-96-98-104-101-109-120- 195-154-133-120-112-102-94-86-75-34- 3.3-4.9-5.1-5.2-5.4-5.5-5.6-5.7-5.9-HbA1c (%) 2hPG (mg/dl) FPG (mg/dl) Retinopathy (%) 6.2- 15 10 5 0

7. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association DETECT-2: A1C 6.5% Threshold for Retinopathy Colagiuri S et al. Diabetes Care 2011; 34:145-150. Any retinopathy moderate NPDR 4.04.55.05.56.06.57.07.58.08.59.09.515.0+10.010.511.011.512.012.513.013.514.014.5 45 40 35 30 25 20 15 Prevalence (%) FPG by 0.5 mmol/L intervals 4.05.06.07.08.09.018.0+12.011.013.010.014.015.016.017.0 Prevalence (%) 2hPG by 0.5 mmol/L intervals 45 40 35 30 25 20 15 10 4.0 5.56.06.57.07.512.0+9.08.59.58.010.010.511.011.5 Prevalence (%) HbA1c by 0.5% intervals 5.04.5 5 0 45 40 35 30 25 20 15 10 5 0 5 0

8. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Considerations when using A1C for Diagnosis Need validated standardized assay Repeat confirmatory test on another day Recognize conditions leading to misleading A1C A1C is not used for diagnosis in children, adolescents, pregnancy or suspected type 1 diabetes Ethnicity and age can affect A1C results

9. Recognize pitfalls of A1C: conditions that can affect value Factors affecting A1C Increased A1CDecreased A1CVariable Change in A1C ErythropoiesisB12/Fe deficiency Decreased erythropoiesis Use of EPO, Fe, or B12 Reticulocytosis Chronic liver Dx Altered hemoglobin Fetal hemoglobin Hemoglobinopathies Methemoglobin Altered glycationChronic renal failure erythrocyte pH ASA, vitamin C/E Hemoglobinopathies erythrocyte pH Erythrocyte destruction SplenectomyHemoglobinopathies Chronic renal failure Splenomegaly Rheumatoid arthritis HAART meds, Ribavirin Dapsone AssaysHyperbilirubinemia Carbamylated Hb ETOH Chronic opiates Hypertriglyceridemia

10. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Pros and Cons of Diagnostic Tests TestAdvantagesDisadvantages FPGEstablished standard Fast and easy Single Sample Sample not stable Day-to-day variability Inconvenient to fast Glucose homeostasis in single time point 2hPG in 75 g OGTT Established standardSample not stable Day-to-day variability Inconvenient, Unpalatable Cost A1CConvenient Single sample Low day-to-day variability Reflects long term [glucose] $$$ Affected by medical conditions, aging, ethnicity Standardized, validated assay required Not used for age <18, pregnant women or suspected T1DM

11. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Diagnostic Testing With 3 Different Tests Dealing with Discordance Many people identified as having diabetes using A1C will not be identified as having diabetes by traditional glucose criteria, and vice versa. When results of more than one test are available (amongst FPG, A1C, 2hPG in a 75-g OGTT) and the results are discordant, the test whose result is above diagnostic cut-point should be repeated, and the diagnosis made on basis of the repeat test. FPG2hPG A1C

12. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Diagnosis of Prediabetes* TestResultPrediabetes Category Fasting Plasma Glucose (mmol/L) 6.1 - 6.9 Impaired fasting glucose (IFG) 2-hr Plasma Glucose in a 75-g Oral Glucose Tolerance Test (mmol/L) 7.8 – 11.0Impaired glucose tolerance (IGT) Glycated Hemoglobin (A1C) (%) 6.0 - 6.4Prediabetes * Prediabetes = IFG, IGT or A1C 6.0 - 6.4% high risk of developing T2DM 2013

13. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association A1C Level and Future Risk of Diabetes: Systematic Review A1C Category (%) 5-year incidence of diabetes 5.0-5.5<5 to 9% 5.5-6.09 to 25% 6.0-6.525 to 50% Zhang X et al. Diabetes Care. 2010;33:1665-1673.

14. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 2013 Screening for Type 2 Diabetes in Adults Algorithm presented on next slides

15. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Screening for Type 2 Diabetes in Adults (continued) *If both FPG and A1C are available, but discordant, use the test that appears furthest to the right side of the algorithm.

16. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

17. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

18. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association In the absence of symptomatic hyperglycemia, if a single laboratory test is in the diabetes range, a repeat confirmatory laboratory test (FPG, A1C, 2hPG in a 75-g OGTT) must be done on another day. It is preferable that the same test be repeated (in a timely fashion) for confirmation. If results of two different tests are available and both are above the diagnostic cutpoints, the diagnosis of diabetes is confirmed. Diabetes: In the absence of symptomatic hyperglycemia, if a single laboratory test is in the diabetes range, a repeat confirmatory laboratory test (FPG, A1C, 2hPG in a 75-g OGTT) must be done on another day. It is preferable that the same test be repeated (in a timely fashion) for confirmation. If results of two different tests are available and both are above the diagnostic cutpoints, the diagnosis of diabetes is confirmed.

19. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

20. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

21. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association **Prediabetes = IFG or IGT or A1C 6.0 to 6.4%

22. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association **Prediabetes = IFG or IGT or A1C 6.0 to 6.4%

23. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Definition of Metabolic Syndrome

24. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 1 1.Diabetes should be diagnosed by any of the following criteria: FPG 7.0 mmol/L [Grade B, Level 2] A1C 6.5% (for use in adults in the absence of conditions that affect the accuracy of A1C and not for use in suspected type 1 diabetes) [Grade B, Level 2] 2hPG in a 75-g OGTT 11.1 mmol/L [Grade B, Level 2] Random PG 11.1 mmol/L [Grade D, Consensus] 2013

25. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 2 2.In the absence of symptomatic hyperglycemia, if a single laboratory test is in the diabetes range, a repeat confirmatory laboratory test (FPG, A1C, 2hPG in a 75-g OGTT) must be done on another day. It is preferable that the same test be repeated (in a timely fashion) for confirmation, but a random PG in the diabetes range in an asymptomatic individual should be confirmed with an alternate test. Grade D, Consensus. 2013

26. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 2 (continued) 2.In the case of symptomatic hyperglycemia, the diagnosis has been made and confirmatory test is not required before treatment is initiated. In individuals in whom type 1 diabetes is likely (younger or lean or symptomatic hyperglycemia, especially with ketonuria or ketonemia), confirmatory testing should not delay initiation of treatment to avoid rapid deterioration. [Grade D, Consensus]. 2013

27. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 2.If results of two different tests are available and both are above the diagnostic cutpoints, the diagnosis of diabetes is confirmed. Grade D, Consensus. Recommendation 2 (continued) 2013

28. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 3 3.Prediabetes, defined as a state which places individuals at high risk of developing diabetes and its complications, is diagnosed by any of the following criteria: IFG (FPG 6.1 - 6.9 mmol/L) Grade A, Level 1. IGT (2hPG in a 75-g OGTT 7.8 to 11.0 mmol/L) Grade A, Level 1. A1C 6.0 - 6.4% (for use in adults in the absence of factors that affect the accuracy of A1C and not for use in suspected type 1 diabetes) Grade B, Level 2. 2013

29. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association CDA Clinical Practice Guidelines http://guidelines.diabetes.cahttp://guidelines.diabetes.ca – for professionals 1-800-BANTING (226-8464) http://diabetes.ca http://diabetes.ca – for patients