Insulin. Toronto: McLelland and Stewart, 1982.
Chapter 3 Diagnosis and classification of diabetes
Diabetes mellitus is diagnosed by identifying chronic hyperglycaemia. The World Health Organisation (WHO) and the American Diabetes Association (ADA) use a fasting plasma glucose (FPG) of 7 mmol/L or higher to define diabetes (Table 3.1). This originates from epidemiological studies in the 1990s which appeared to show that the risk of microvascular complications (e.g retinopathy) increases sharply at a FPG threshold of 7 mmol/L (Figure 3.1). Lately, the notion of a clear glycaemic threshold separating people at high and low risk of diabetic microvascular complications has been called into question. The relationship between plasma glucose and microangiopathy is likely to be continuous, thus a FPG of 7 mmol/L is an arbitrary cut‐off for defining diabetes which may be lowered in the future.
There are currently 34.2 million people in the USA with diabetes (10.5% of the population). Approximately 7 million of these are not yet aware that they have diabetes. The total number of people with diabetes worldwide is projected to increase from 171 million in 2000 to 366 million in 2030. A key demographic change to the rising prevalence of diabetes worldwide is an increasing proportion of people >65 years of age.
Table 3.1 Diagnostic criteria for Type 2 diabetes.
| Diabetes may be diagnosed based on plasma glucose criteria, either the fasting plasma glucose (FPG) or the 2‐h plasma glucose (2‐h PG) value after a 75‐g oral glucose tolerance test (OGTT) or A1C criteria. |
| Criteria for the diagnosis of diabetes. |
| FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.* |
| 2‐h PG ≥200 mg/dL (11.1 mmol/L) during an OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.* |
| A1C ≥6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.* |
| In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L). |
* In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing.
FPG, 2‐h PG after 75‐g OGTT, and A1C are equally appropriate for diagnostic testing. It should be noted that the tests do not necessarily detect diabetes in the same individuals. The concordance between the FPG and 2‐h PG tests is imperfect. The overlap depends on the ethnic and geographical population, and on other characteristics such as age and body mass index. Some individuals have asymptomatic, isolated post‐challenge hyperglycaemia, while others have fasting hyperglycaemia but normal post‐load glycaemic responses. The fasting criteria for diabetes tend to pick out younger and more obese subjects.
Table 3.2 Use of HbA1c >6.5% (48 mmol/mol) as a cut‐off for making the diagnosis of diabetes offers some advantages but there are several disadvantages.
| Advantages | Disadvantages |
|---|---|
| Avoids the need for a fasting blood sample, and the pre‐analytical instability of glucose measurements.HbA1c reflects glycaemia over several weeks.Lower biological variability of HbA1c compared with FPG or 2 h glucose.Virtual absence of significant retinopathy among people with HbA1c < 6.5%. | HbA1c measurements can give spurious results in:anaemia (Fe‐deficiency)haemoglobinopathiesrenal failuredifferent ethnic groups.Diagnosis by HbA1c will identify a different population to that diagnosed by FPG.Distribution of HbA1c values varies in different ethnic groups.HbA1c increases with ageSome patients and ethnic groups may be diagnosed with diabetes by some criteria but not others. |
Figure 3.1 Prevalence of diabetes‐specific retinopathy (moderate or more severe retinopathy) by vigintiles of the distribution of FPG, 2‐h PG, and A1C.
Adapted from Colaguiri et al. Diabetes Care 2011; 34: 145‐150.
Numerous studies have confirmed that, compared with FPG and A1C cut points, the 2‐h PG value diagnoses more people with diabetes. When using A1C to diagnose diabetes, it is important to recognize that A1C is an indirect measure of average blood glucose levels and to take other factors into consideration that may impact haemoglobin glycation independently of glycaemia including age, race/ethnicity, and anaemia/haemoglobinopathies.
Intermediate categories of hyperglycaemia: Pre‐diabetes
During the natural history of all forms of diabetes, the disease passes through a stage of impaired glucose tolerance (IGT), defined as a plasma glucose of 7.8–11.0 mmol/L (140–200 mg/dL) 2 hours after an OGTT (Figure 3.2). Impaired fasting glucose (IFG) is an analogous category based on fasting glucose levels, and is defined as a FPG of 6.1–6.9 mmol/L (110–126 mg/dL).
IGT and IFG are intermediate metabolic stages between normal glucose homeostasis and diabetes. They are both risk factors for future diabetes and cardiovascular disease, but the 2‐hour plasma glucose concentration is a particularly strong predictor of cardiovascular risk and mortality.
As with the glucose measures, several prospective studies that used A1C to predict the progression to diabetes as defined by A1C criteria demonstrated a strong, continuous association between A1C and subsequent diabetes. Based on numerous studies and meta‐analysis, it is now considered that A1C range of 5.7–6.4% (39–47 mmol/mol) as identifying individuals with prediabetes or with impaired glucose regulation IGR).
Figure 3.2 The relationship between 2‐hour plasma glucose and survival in patients with normal glucose tolerance, patients with IGT, those with newly‐diagnosed diabetes by OGTT, and those with known diabetes, as shown by the DECODE study (combining data from 13 European cohort studies). From Glucose tolerance and mortality: comparison of WHO and American Diabetic Association diagnostic criteria. The Lancet 354(9179), 617–621.
A proportion of patients with IFG, IGT and/or IGR (5‐10% per annum) will deteriorate metabolically into overt diabetes. Lifestyle modification (diet, exercise and weight loss) is the best approach to diabetes prevention for these patients.
For an OGTT, the subject is tested in the morning after an overnight fast, in the seated position. After taking a fasting blood sample, 75 g of glucose is given by mouth, often in the form of a glucose drink such as Lucozade (843 mL based on the new formulation of 8.9g/100ml of glucose). For children, the glucose dose is calculated as 1.75 g/kg. A further blood sample is taken at 2 hours, and the fasting and 2 hour glucose values are interpreted as in Figure