Chapter 3: Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome

Canadian Diabetes Association 2013 Clinical Practice Guidelines

Definition of Diabetes and Prediabetes

• Diabetes mellitus is a metabolic disorder characterized by the presence of hyperglycemia. This may be caused by defects in insulin secretion, insulin action, or both.
• Long-term hyperglycemia is associated with an increased risk for cardiovascular disease (CVD), as well as the development of microvascular complications involving the eyes, kidneys, and nerves.
• Prediabetes is a term referring to impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or a glycated hemoglobin (A1C) of 6.0% to 6.4%, each of which places individuals at high risk of developing diabetes and its complications.

Classification of Diabetes

TABLE 1

• Distinguishing between type 1 and type 2 diabetes is important because management strategies differ, but this may be difficult at the time of diagnosis in certain situations.
  • Physical signs of insulin resistance and autoimmune markers may be helpful, but have not been adequately studied as diagnostic tests in this setting. While very low C-peptide levels measured after months of clinical stabilization may favour type 1 diabetes, they are not helpful in acute hyperglycemia.
• Clinical judgement with safe management and ongoing follow-up is a prudent approach to diagnosis.

Diagnostic Criteria

Diabetes

TABLE 2

• A1C ≥ 6.5% was not previously defined as a diagnostic measure in the 2008 guidelines.
• A1C may be a misleading measure in individuals with blood-related deficiencies (e.g. anemias, hemoglobinopathies), severe hepatic or renal disease.
• A1C is not recommended for diagnostic purposes in children, adolescents, pregnant women or those with suspected type 1 diabetes.
• African Americans, American Indians, Hispanics and Asians may have A1C values that are up to 0.4% higher than those of Caucasian patients at similar levels of glycemia. The frequency of retinopathy begins to increase at lower A1C levels in American blacks than in American whites, which suggests a lower threshold for diagnosing diabetes in black persons.
• Research is required to determine if A1C levels differ in African Canadians or Canadian First Nations.
• A1C values are affected by age, rising by up to 0.1% per decade of life.
• More studies may help to determine if age- or ethnic-specific adjusted A1C thresholds are required for diabetes diagnosis.
•  Clinical judgment should be exercised when selecting a test for diagnosis. There are, however, several advantages to using A1C for diabetes diagnosis.

TABLE 3

Prediabetes

TABLE 4

• Prediabetes places individuals at high risk of developing diabetes and its complications but not all individuals with prediabetes will progress to diabetes.
• People with prediabetes do not have the increased risk for microvascular disease as seen in diabetes, but they are at risk for the development of diabetes and CVD and would benefit from CV risk factor modification.
• While there is no worldwide consensus on the definition of IFG, the CDA defines IFG as an FPG value of 6.1 to 6.9 mmol/L due to the higher risk of developing diabetes in these individuals compared to defining IFG as an FPG value of 5.6 to 6.9 mmol/L.
• The American Diabetes Association (ADA) defines prediabetes as an A1C between 5.7% and 6.4%, but the CDA has based the definition on a higher risk group and includes an A1C of 6.0% to 6.4%.
• A1C levels below 6.0% can still be associated with an increased risk for diabetes.
• The combination of an FPG of 6.1 to 6.9 mmol/L and an A1C of 6.0% to 6.4% is predictive of 100% progression to type 2 diabetes over a 5-year period.

Metabolic syndrome

TABLE 5

• Prediabetes and type 2 diabetes are often manifestations of a broader underlying disorder, including the metabolic syndrome.
• Metabolic syndrome is characterized by a group of abnormalities that include abdominal obesity, hypertension, dyslipidemia and elevated blood glucose.
• Individuals with the metabolic syndrome are at significant risk of developing CVD.
• Metabolic syndrome and type 2 diabetes often coexist and those with metabolic syndrome without diabetes are at significant risk of developing diabetes.
• Evidence exists to support an aggressive approach to identifying and treating people with hyperglycemia and associated CV risk factors that make up the metabolic syndrome in the hope of significantly reducing CV morbidity and mortality.

Table 1: Classification of diabetes

Type 1 diabetes*	Encompasses diabetes that is primarily a result of pancreatic beta cell destruction and is prone to ketoacidosis. This form includes cases due to an autoimmune process and those for which the etiology of beta cell destruction is unknown.
Type 2 diabetes	May range from predominant insulin resistance with relative insulin deficiency to a predominant secretory defect with insulin resistance.
Gestational diabetes mellitus	Refers to glucose intolerance with onset or first recognition during pregnancy.
Other	Specific types include a wide variety of relatively uncommon conditions, primarily specific genetically defined forms of diabetes or diabetes associated with other diseases or drug use (Appendix 1).
* Includes latent autoimmune diabetes in adults (LADA); the term used to describe the small number of people with apparent type 2 diabetes who appear to have immune-mediated loss of pancreatic beta cells.

Table 2: Diagnosis of diabetes

FPG ≥7.0 mmol/L Fasting = no caloric intake for at least 8 hours or	Grade B, Level 2
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 (see text) or	Grade B, Level 2
2hPG in a 75 g OGTT ≥11.1 mmol/L or	Grade B, Level 2
Random PG ≥11.1 mmol/L Random = any time of the day, without regard to the interval since the last meal	Grade D, Consensus
In the absence of symptomatic 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. 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. In the case of symptomatic hyperglycemia, the diagnosis has been made and a 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. If results of 2 different tests are available and both are above the diagnostic cutpoints, the diagnosis of diabetes is confirmed.	Grade D, Consensus
2hPG, 2-hour plasma glucose; A1C, glycated hemoglobin; FPG, fasting plasma glucose; OGTT, oral glucose tolerance test; PG, plasma glucose.

Table 3: Advantages and disadvantages of diagnostic tests for diabetes

Parameter	Advantages	Disadvantages
FPG	Established standard Fast and easy Single sample Predicts microvascular complications	Sample not stable High day-to-day variability >Inconvenient (fasting) Reflects glucose homeostatis at a single point in time
2hPG in a 75 g OGTT	>Established standard Predicts microvascular complications	Sample no stable High day-to-day variability Inconvenient Unpalatable Cost
A1C	Convenient (measure any time of day) Single sample Predicts microvascular complications Better predictor of macrovascular disease than FPG or 2hPG in a 75 g OGTT Low day-to-day variability Reflects long-term glucose concentration	Cost Misleading in various medical conditions (e.g., hemoglobinopathies, iron deficiency, hemolytic anaemia, severe hepatic or renal disease) Altered by ethnicity and aging Standardized, validated assay required Not for diagnostic use in children, adolescents, pregnant women or those with suspected type 1 diabetes
2hPG, 2-hour plasma glucose; A1C, glycated hemoglobin; FPG, fasting plasma glucose; OGTT, oral glucose tolerance test. ∗ Adapted from Sacks D. A1C versus glucose testing: a comparison. Diabetes Care. 2011;34:518–523.

Table 4: Diagnosis of prediabetes

Test	Result	Prediabetes Category
FPG (mmol/L)	6.1–6.9	IFG	Grade A, Level 1
2hPG in a 75 g OGTT (mmol/L)	7.8–11.0	IGT	Grade A, Level 1
A1C (%)	6.0–6.4	Prediabetes	Grade B, Level 2
2hPG, 2-hour plasma glucose; A1C, glycated hemoglobin; FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test.

Table 5: Harmonized definition of the metabolic syndrome: ≥3 measures to make the diagnosis of metabolic syndrome*

Measure	Categorical cutpoints
	Men	Women
Elevated waist circumference (population- and country-specific cutpoints):
Canada, United States	≥102 cm	≥88 cm
Europid, Middle Eastern, sub-Saharan African, Mediterranean	≥94 cm	≥80 cm
Asian, Japanese, South and Central American	≥90 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	<1.3 mmol/L
Elevated BP (antihypertensive drug treatment in a patient with a history of hypertension is an alternate indicator)	Systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg
Elevated FPG (drug treatment of elevated glucose is an alternate indicator)	≥5.6 mmol/L
BP, blood pressure; FPG, fasting plasma glucose; HDL-C, high-density lipoprotein cholesterol; TG, triglycerides. ∗ Adapted from Alberti KGMM, Eckel R, Grundy S, et al. Harmonizing the metabolic syndrome. Circulation. 2009;120:1640-1645. †; The most commonly used drugs for elevated TG and reduced HDL-C are fibrates and nicotinic acid. A patient taking 1 of these drugs can be presumed to have high TG and reduced HDL-C. High-dose omega-3 fatty acids presumes high TG.

For definitions of the levels of evidence cited in this chapter, please refer to the Guideline Recommendations: Levels of Evidence.

If you would like more details on this topic, including references, please visit the Canadian Diabetes Association Clinical Practice Guidelines: Chapter 3. For the etiologic classification of diabetes, see Appendix 1.