1. 2018 Clinical Practice Guidelines
Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Chapter 3
Zubin Punthakee MD MSc FRCPC,
Ronald Goldenberg MD FRCPC FACE,
Pamela Katz MD FRCPC

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3. Key Changes No change in the diagnostic criteria New information on
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Key Changes
2018
No change in the diagnostic criteria
New information on
methods to differentiate between type 1, type 2 and monogenic diabetes in clinical practice

4. Classification of Diabetes
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Classification of Diabetes
Type
Definition
Type 1 diabetes (including LADA form)
Pancreatic beta cell destruction, usually leading to absolute insulin deficiency
Immune mediated
Idiopathic
Type 2 diabetes
May range from predominantly insulin resistance insulin deficiency to a predominantly secretory defect with insulin resistance
Gestational
Diabetes
Glucose intolerance with onset or first recognition in pregnancy
Other types
Variety of uncommon diseases, genetic forms, or diabetes associated with drug use 4

5. 2018 Type 1 diabetes Type 2 diabetes Monogenic diabetes
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
2018
Clinical features
Type 1 diabetes
Type 2 diabetes
Monogenic diabetes
Age of onset (yrs)
Most <25 by can occur at any age (but not before the age of 6 months)
Usually >24 but incidence increasing in adolescents, paralleling increasing rate of obesity in children & adolescents
Usually <25
Neonatal diabetes <6 months*
Weight
Usually thin, but with obesity epidemic, can have overweight or obesity
>90% at least overweight
Similar to general population
Islet auto-antibodies
Usually present
Absent
C-peptide
Undetectable/low
Normal/high
Normal
Insulin production
Present
First line treatment
Insulin
Non-insulin antihyperglycemic agents, gradual dependence on insulin may occur
Depends on subtype of MODY
Family history of diabetes
Infrequent (5-10%)
Frequent (75-90%)
Multigenerational, autosomal pattern of inheritance
DKA
Common
Rare
Rare (except for neonatal diabetes*)
*Neonatal diabetes is a form of diabetes with onset <6 months of age, requires genetic testing, and may be amenable to therapy with oral sulfonylurea in place of insulin therapy

6. Fasting = no caloric intake for at least 8 hours
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Diagnosis of Diabetes
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
2hPG in a 75 g OGTT ≥11.1 mmol/L
Random PG ≥11.1 mmol/L
Random = any time of the day, without regard to the interval since the last meal
A1C, glycated hemoglobin; FPG, fasting plasma glucose; PG, plasma glucose

7. Glycemia and Retinopathy Thresholds
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Glycemia and Retinopathy Thresholds
FPG 15
2hPG
Pima Indians
HbA1c
Retinopathy (%) 10 5
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 (mg/dl)
70-
89-
93-
97-
100-
105-
109-
116-
136-
226-
2hPG (mg/dl)
38-
94-
106-
116-
126-
138-
156-
185-
244-
364-
HbA1c (%)
3.4-
4.8-
5.0-
5.2-
5.3-
5.5-
5.7-
6.0-
6.7-
9.5- 50
FPG
2hPG 40
HbA1c
Egyptians
Retinopathy (%) 30 20 10
FPG (mg/dl)
57-
79-
84-
89-
93-
99-
108-
130-
178-
258-
2hPG (mg/dl)
39-
80-
90-
99-
110-
125-
155-
218-
304-
386-
HbA1c (%)
2.2-
4.7-
4.9-
5.1-
5.4-
5.6-
6.0-
6.9-
8.5-
10.3-
As you can see through the graphs in different population such as the PIMA Indians, Egyptians and NHANES data, the threshold for retinopathy development is similar in all 3 population studies. (7.0 mmol/L = 126 mg/dL, 11.1 mmo/L = 200 mg/dL)
FPG 15
2hPG
HbA1c
NHANES III
Retinopathy (%) 10 5
FPG (mg/dl)
42-
87-
90-
93-
96-
98-
101-
104-
109-
120-
2hPG (mg/dl)
34-
75-
86-
94-
102-
112-
120-
133-
154-
195-
HbA1c (%)
3.3-
4.9-
5.1-
5.2-
5.4-
5.5-
5.6-
5.7-
5.9-
6.2-
The International Expert Committee. Diabetes Care 2009; 32:
A1C, glycated hemoglobin; FPG, fasting plasma glucose; PG, plasma glucose 7

8. DETECT-2: A1C ≥6.5% Threshold for Retinopathy45 40
Any retinopathy 35
≥ moderate NPDR 30 25
Prevalence (%) 20 15 5 10
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
8.0
8.5
9.0
9.5
10.0
10.5
11.0
11.5
12.0
12.5
13.0
13.5
14.0
14.5
15.0+
FPG by 0.5 mmol/L intervals 45 40 35 30 25
Prevalence (%) 20 15 10 5
4.0
5.0
6.0
7.0
8.0
9.0
10.0
11.0
12.0
13.0
14.0
15.0
16.0
17.0
18.0+
2hPG by 0.5 mmol/L intervals
Diabetes Care Jan;34(1): doi: /dc Epub 2010 Oct 26.
Glycemic thresholds for diabetes-specific retinopathy: implications for diagnostic criteria for diabetes.
Colagiuri S, Lee CM, Wong TY, Balkau B, Shaw JE, Borch-Johnsen K; DETECT-2 Collaboration Writing Group.
Source
Boden Institute of Obesity, Nutrition, and Exercise, University of Sydney, Sydney, Australia.
Erratum in
Diabetes Care Aug;34(8):1888.
Abstract
OBJECTIVE:
To re-evaluate the relationship between glycemia and diabetic retinopathy.
RESEARCH DESIGN AND METHODS:
We conducted a data-pooling analysis of nine studies from five countries with 44,623 participants aged years with gradable retinal photographs. The relationship between diabetes-specific retinopathy (defined as moderate or more severe retinopathy) and three glycemic measures (fasting plasma glucose [FPG; n = 41,411], 2-h post oral glucose load plasma glucose [2-h PG; n = 21,334], and A1C [n = 28,010]) was examined.
RESULTS:
When diabetes-specific retinopathy was plotted against continuous glycemic measures, a curvilinear relationship was observed for FPG and A1C. Diabetes-specific retinopathy prevalence was low for FPG <6.0 mmol/l and A1C <6.0% but increased above these levels. Based on vigintile (20 groups with equal numbers) distributions, glycemic thresholds for diabetes-specific retinopathy were observed over the range of mmol/l for FPG, mmol/l for 2-h PG, and % for A1C. Thresholds for diabetes-specific retinopathy from receiver-operating characteristic curve analyses were 6.6 mmol/l for FPG, 13.0 mmol/l for 2-h PG, and 6.4% for A1C.
CONCLUSIONS:
This study broadens the evidence based on diabetes diagnostic criteria. A narrow threshold range for diabetes-specific retinopathy was identified for FPG and A1C but not for 2-h PG. The combined analyses suggest that the current diabetes diagnostic level for FPG could be lowered to 6.5 mmol/l and that an A1C of 6.5% is a suitable alternative diagnostic criterion. 45 40 35 30 25
Prevalence (%) 20 15 10 5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
8.0
8.5
9.0
9.5
10.0
10.5
11.0
11.5
12.0+
HbA1c by 0.5% intervals
Colagiuri S et al. Diabetes Care 2011; 34:
A1C, glycated hemoglobin; FPG, fasting plasma glucose; PG, plasma glucose 8

9. Confirmatory test required
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Confirmatory test required
In the absence of symptomatic hyperglycemia, if a single lab test result is in the diabetes range, a repeat confirmatory lab test (FPG, A1C, 2hPG in a 75 g OGTT) must be done on another day
Repeat the same test (in a timely fashion) to confirm
But a random PG in the diabetes range in an asymptomatic individual should be confirmed with an alternate test
If results of two different tests are available and both are above the diagnostic thresholds, the diagnosis of diabetes is confirmed
2hPG, 2-hour plasma glucose; AlC, glycated hemoglobin; FPG, fasting plasma glucose; OGTT, oral glucose tolerance test; PG, plasma glucose.

10. Confirmatory test NOT required
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Confirmatory test NOT required
In the case of symptomatic hyperglycemia, the diagnosis has been made and a confirmatory test is not required before treatment is initiated.
To avoid rapid metabolic deterioration in individuals in whom type 1 diabetes is likely (younger or lean or symptomatic hyperglycemia, especially with ketonuria or ketonemia), the initiation of treatment should not be delayed in order to complete confirmatory testing
2hPG, 2-hour plasma glucose; AlC, glycated hemoglobin; FPG, fasting plasma glucose; OGTT, oral glucose tolerance test; PG, plasma glucose.

11. Considerations when using A1C for Diagnosis
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
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 (as the sole diagnostic test), pregnant women as part of routine screening for gestational diabetes, those with cystic fibrosis or those with suspected type 1 diabetes
Ethnicity and age can affect A1C results
African-Americans, American-Indians, Hispanics, and Asians have A1C values that are up to 0.4% higher at similar glycemic levels 11

12. Recognize pitfalls of A1C: conditions that can affect value
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Recognize pitfalls of A1C: conditions that can affect value
Factors affecting A1C
Increased A1C
Decreased A1C
Variable Change in A1C
Erythropoiesis
B12/Fe deficiency Decreased erythropoiesis
Use of EPO, Fe, or B12
Reticulocytosis
Chronic liver Dx
Altered hemoglobin
Fetal hemoglobin Hemoglobinopathies Methemoglobin
Altered glycation
Chronic renal failure
↓↓erythrocyte pH
ASA, vitamin C/E
Hemoglobinopathies
↑ erythrocyte pH
Erythrocyte destruction
Splenectomy
Splenomegaly
Rheumatoid arthritis
HAART meds, Ribavirin
Dapsone
Assays
Hyperbilirubinemia
Carbamylated Hb
ETOH
Chronic opiates
Hypertriglyceridemia
Script:
While HbA1c is an excellent measure for diagnosis, it is essential to know conditions where the value may not adequate reflect true glycemic control and other measures such as fasting blood sugar or OGTT may be more helpful.
Important conditions where the rate of red blood cell turnover is significantly shortened or extended, or the structure of hemoglobin is altered, A1C may not accurately reflect glycemic status
This includes common conditions such as B12 and Fe deficiency that can falsely increase hbA1c and also increased red cell turn over states and factors that increase erthropoeisis such as use of EPO, Fe, B12 deficiency – which can falsely lower hbA1c.
So While HbA1c is convenient for patients understanding the factors that affect the accuracy of it’s ability to diagnose diabetes.
TT: point of slide is to teach practioners to recognize common pitfalls and conditions where HbA1c might not be an accurate measure to use for diagnosis. 12

13. Pros and Cons of Diagnostic Tests
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Pros and Cons of Diagnostic Tests
Test
Advantages
Disadvantages
FPG
Established 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
Inconvenient, Unpalatable
Cost
A1C
Convenient
Single sample
Low day-to-day variability
Reflects long term glucose
$$$
Affected by medical conditions, aging, ethnicity
Standardized, validated assay required
Not applicable to every patient type
Script:
While all 3 approaches predict microvascular disease and can be used for diagnosis, A1c may be a better predictor of macrovascular disease. The decision of which test to use for diabetes diagnosis is left to clinical judgment. Each diagnostic test has advantages and disadvantages
TT: Slide compares the advantages and disadvantages of the different tests.
A1C, glycated hemoglobin; FPG, fasting plasma glucose; PG, plasma glucose 13

14. Dealing with discordance in results
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Dealing with discordance in results
FPG
2hPG
A1C
Many people identified as having diabetes using A1C will not be identified as having diabetes by traditional glucose criteria, and vice versa.
While there is overall in these three tests, there also may be discordant results whereby one test is diagnostic of diabetes while another does not agree. If this does occur, the tests whose result is above diagnostic cut-point should be repeated, and the diagnosis made on the basis of the repeat test.
When results of more than one test are available (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.
A1C, glycated hemoglobin; FPG, fasting plasma glucose; OGTT, oral glucose tolerance test; PG, plasma glucose 14

15. Diagnosis of prediabetes
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Diagnosis of prediabetes
Tests
Result
Prediabetes category
Fasting plasma glucose (mmol/L)
IFG
2h PG in a 75g OGTT (mmol/L)
IGT
A1C (%)
Prediabetes
2hPG, 2-hour plasma glucose; AlC, glycated  hemoglobin; FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test.

16. A1C Level and Future Risk of Diabetes: Systematic Review
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
A1C Level and Future Risk of Diabetes: Systematic Review
A1C Category (%)
5-year incidence of diabetes
<5 to 9%
9 to 25%
25 to 50%
Script: Zhang et al did a systematic review on A1c level and future risk of diabetes and you as the A1C increased from 6.0 to 6.5%, this covereted to a 5-year incidence of diabetes across 25% -50%.
Zhang X et al. Diabetes Care. 2010;33:
A1C, glycated hemoglobin 16

17. Definition of Metabolic Syndrome
Measure
Categorical thresholds
Elevated waist circumference (population/country specific)
Canada, United States of America
Middle Eastern, Sub-Saharan African, Mediterranean, Europids
Asians, Japanese, South and Central Americans
Men
Women
≥102 cm
≥94 cm
≥90 cm
≥88 cm
≥80 cm
Elevated TG (drug treatment for elevated TG is an alternate indicator†)
≥1.7 mmol/L
Reduced HDL-C (drug treatment for reduced HDL-C is an alternate indicator†)
<1.0 mmol/L in males; <1.3 mmol/L in females
Elevated BP (antihypertensive drug treatment in a person with a history of hypertension is an alternate indicator)
systolic ≥130 mmHg or diastolic ≥85 mmHg
Elevated FPG (drug treatment of elevated glucose is an alternate indicator)
≥5.6 mmol/L
Adapted from: Alberti KG, et al. Circulation 2009;120:1640
† Commonly used drugs for elevated TG and reduced HDL-C are fibrates and nicotinic acid. A person taking one of these drugs can be presumed to have high TG and reduced HDL-C. High-dose omega-3 fatty acids presumes high TG 17

18. 2018 Diabetes Canada CPG – Chapter 3
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Recommendation 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 factors that affect the accuracy of A1C and not for use in those with 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]

19. Recommendation 1 cont’d
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Recommendation 1 cont’d
In the presence of symptoms of hyperglycemia, a single test result in the diabetes range is sufficient to make the diagnosis of diabetes.
In the absence of symptoms of hyperglycemia, if a single laboratory test result is in the diabetes range, a repeat confirmatory laboratory test (FPG, A1C, 2hPG in a 75 g OGTT) must be done on another day

20. Recommendation 1 cont’d
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Recommendation 1 cont’d
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.
If results of two different tests are available and both are above the diagnostic cut-points, the diagnosis of diabetes is confirmed [Grade D, Consensus]

21. Recommendation 1 cont’d
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Recommendation 1 cont’d
To avoid rapid metabolic deterioration in individuals in whom type 1 diabetes is likely (younger or lean or symptomatic hyperglycemia, especially with ketonuria or ketonemia), the initiation of treatment should not be delayed in order to complete confirmatory testing [Grade D, Consensus]

22. Recommendation 2 IFG (FPG 6.1-6.9 mmol/L) [Grade A, Level 1]
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Recommendation 2
2. 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 mmol/L) [Grade A, Level 1]
IGT (2hPG in a 75 g OGTT 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]

23. 2018 Diabetes Canada CPG – Chapter 3
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Key Messages
The chronic hyperglycemia of diabetes is associated with significant long-term microvascular and CV complications
A FPG of ≥7.0 mmol/L, a 2hPG value in a 75 g OGTT of ≥11.1 mmol/L or an A1C of  ≥6.5% can predict the development of retinopathy. This permits the diagnosis of diabetes to be made on the basis of each of these parameters

24. 2018 Diabetes Canada CPG – Chapter 3
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Key Messages
The term "prediabetes" refers to impaired fasting glucose, impaired glucose tolerance or an A1C of 6.0% to 6.4%, each of which places individuals at increased risk of developing diabetes and its complications

25. Key Messages for People with Diabetes
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Key Messages for People with Diabetes
There are two main types of diabetes. Type 1 diabetes occurs when the pancreas is unable to produce insulin. Type 2 diabetes occurs when the pancreas does not produce enough insulin or when the body does not effectively use the insulin that is produced
Gestational diabetes is a type of diabetes that is first recognized or begins during pregnancy
Monogenic diabetes is a rare disorder caused by genetic defects of beta cell function

26. Key Messages for People with Diabetes
2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome
Key Messages for People with Diabetes
Prediabetes refers to blood glucose levels that are higher than normal, but not yet high enough to be diagnosed as type 2 diabetes. Although not everyone with prediabetes will develop type 2 diabetes, many people will
You should discuss the type of diabetes you have with your diabetes health-care team
There are several types of blood tests that can be done to determine if a person has diabetes and, in most cases, a confirmatory blood test is required to be sure

27. Visit guidelines.diabetes.ca

28. Or download the App

29. Diabetes Canada Clinical Practice Guidelines
– for health-care providers
1-800-BANTING ( )
– for people with diabetes