Diagnosing Type 2 Diabetes Mellitus:

SYMPTOMATIC patients (e.g. polyuria, polydipsia, unexplained weight loss) ONE OF:

• A single fasting plasma glucose ≥7
• A single random plasma glucose ≥11.1
• A single HbA1c of ≥6.5% (48mmol/mol)

ASYMPTOMATIC patients ONE OF:

• A fasting glucose ≥7 on two separate occasions
• A random glucose ≥11.1 on two separate occasions
• An HbA1c ≥6.5% (48mmol/mol) on two separate occasions
• An HbA1c ≥6.5% AND a single elevated plasma glucose (fasting ≥7 or random ≥11.1)

Impaired Fasting Glucose

• Fasting plasma glucose 6.1–6.9 mmol/l (WHO Criteria)

Pre-Diabetes

• HbA1c 6–6.4% (42–47 mmol/mol) (NICE Guidelines)

Impaired Glucose Tolerance

• Fasting plasma glucose <7.0 mmol/l AND 2h plasma glucose (after 75g oral glucose load) 7.8–11mmol/l (WHO criteria)

Note that although impaired fasting glucose/pre-diabetes/impaired glucose tolerance are all distinct entities based on which diagnostic test you use, the clinical management is sufficiently similar that, in primary care, we can consider them to be one condition

Glucose tolerance tests are complex, expensive and less reproducible (NEJM 2012;367:542). They are still used in pregnancy (where HbA1c is inaccurate).

Glycosylated Haemoglobin

Glycosylated haemoglobin (HbA1c) is the most widely used measure of long-term glycaemic control in diabetes mellitus. HbA1c is produced by the glycosylation of haemoglobin at a rate proportional to the glucose concentration. The level of HbA1c therefore depends on:

• red blood cell lifespan
• average blood glucose concentration

A number of conditions can interfere with accurate HbA1c interpretation:

• Lower-than-expected levels of HbA1c (due to reduced red blood cell lifespan)
  • Sickle-cell anaemia
  • Hereditary spherocytosis
  • GP6D deficiency
• Higher-than-expected levels of HbA1c (due to increased red blood cell lifespan)
  • Iron-deficiency anaemia
  • Vitamin B12 / folic acid deficiency
  • Splenectomy

HbA1c is generally thought to reflect the blood glucose over the previous two to three months, although there is some evidence it is more likely to mainly reflect glucose levels of the past 2-4 weeks. The relationship between HbA1c and average blood glucose is complex but has been studied by the Diabetes Control and Complications Trial (DCCT). A new internationally standardised method for reporting HbA1c has been developed by the International Federation of Clinical Chemistry (IFCC). This will report HbA1c in mmol per mol of haemoglobin without glucose attached.