Diabetes – diagnosis and investigations

diagnosis

Assessing diabetes risk

Patients should be assessed for diabetes risk 

• every three years from 40 years of age using the Australian type 2 diabetes risk assessment tool (AUSDRISK)
• Aboriginal and Torres Strait Islander
  • AUSDRISK has limited use as a screening tool in this population.
  • instead proceed directly to blood testing for diabetes, in conjunction with other opportunistic screening (such as for cardiovascular risk assessment) from 18 years of age

Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK) 

• calculate your risk of developing type 2 diabetes in the next 5 years.

Based on 

1. age group (age 35-44 – 2p , age >65 – 8p)
2. gender (male: Male 3 points , female 0)
3. ethnicity/country of birth:
   1. australia (0p)
   2. ATSI (2p)
   3. Asia (including the Indian sub-continent), Middle East, North Africa, Southern Europe (2p)
4. Family Hx – parents, brothers/sisters with DM(1&2) – (3p)
5. high blood glucose (sugar) 
6. HTN and on Medication
7. current smoker
8. eating  vegetables/fruit = Every day vs Not every day 
9. Physical activity – least 2.5 hours of physical activity per week 
10. waist measurement taken below the ribs (usually at the level of the navel, and while standing)

AUSDRISK score	developing type 2 diabetes within five years
5 or less: Low risk
6–11: Intermediate risk
12 or more: High risk

The following people are also considered at high risk, regardless of AUDRISK score:

1. people aged ≥40 years who are overweight or obese
2. people of any age with IGT or IFG
3. people with a first-degree relative with diabetes
4. all patients with a history of a cardiovascular event (eg acute myocardial infarction, angina, peripheral vascular disease or stroke)
5. people of high-risk ethnicity/background (eg Pacific Islands, Indian subcontinent)
6. women with a history of GDM
7. women with polycystic ovary syndrome (PCOS)
8. people taking antipsychotic medication
9. Aboriginal and/or Torres Strait Islander people

High RISK PATIENTS

• tested every 3 years for diabetes with either FBG or HbA1c 
• People with IGT or IFG should be tested annually.

Impaired fasting glucose(IFG) and impaired glucose tolerance(IGT)

• The definition of diabetes is based on a collection of symptoms and agreed glycaemic

measures associated with escalating retinopathy risk. 

• Patients with elevated glucose not high enough to be diagnosed with type 2 diabetes might have either IFG or IGT, also known as ‘dysglycaemic states’ or ‘intermediate hyperglycaemia’. 
• IFG is identified by a FBG test, and IGT can be identified by a two-hour oral glucose tolerance test (OGTT) 
• These states are not considered benign, and they reflect a risk of developing diabetes in
• the future
• IFG and IGT have been shown to regress over three years in 18% of cases
  • if patients follow standard (ie non-intensive) lifestyle recommendations.
• Preventing progression to type 2 diabetes Recommendations:
  • lifestyle intervention programs to:
    • achieve and maintain a 7% reduction in weight
    • increase moderate-intensity physical activity to at least 150 minutes per week
    • diet low-energy diet rich in fruit, vegetables and fibre, and low in meat and fat.
  • may also benefit from a structured weight loss and exercise program to reduce their risk of developing type 2 diabetes

Tests to detect diabetes

Fasting blood glucose

• Measure plasma glucose levels on a fasting sample:
  • <5.5 mmol/l: Diabetes unlikely
  • 5.5–6.9 mmol/L: May need to perform an oral glucose tolerance test
  • ≥7.0 mmol/L (>11.1 non-fasting): Diabetes likely

repeat fasting blood sugar on a separate day to confirm

• 6.1-6.9 mmol/L Impaired fasting glucose

Glycated haemoglobin (HbA1c)

• Normal adult haemoglobin (HbA) comprises a haem moiety and two globin chains, the α and β chains (α2β2), making up approximately 97% of adult haemoglobin.
• Within HbA, approximately 6% is glycated (covalent attachment of glucose to the N-terminal valine of the haemoglobin β-chain in a nonenzymatic process known as glycation)
  • main component is HbA1c (5%) 
  • minor components : HbA1a & HbA1b (1%).

• HbA1c is dependent on the interaction between the concentration of blood glucose and the lifespan of the erythrocyte.
• As the mean erythrocyte lifespan is approximately 120 days, HbA1c acts as a surrogate marker of glucose concentration during the preceding 8–12 weeks
• As a result of the continuous turnover of erythrocytes, it is estimated that
  • only 50% of an HbA1c value represents glucose exposure in the preceding 30 days, while 
  • 40% represents exposure in the previous 31–90 days and 
  • 10% in the previous 91–120 days.

• HbA1c can be expressed as a
  • percentage (DCCT unit) or as a 
  • value in mmol/mol (IFCC unit)

• Diagnostic Cutoffs:
  • >6.5% (48 mmol/mol) diabetes
  • 5.7% – 6.4% (42-47 mmol/mol) pre-diabetes
  • <5.7% (42 mmol/mol) normal

• Abnormal HbA1c values generally should be repeated in asymptomatic patients and confirmed on a different day, unless two abnormal tests (eg FBG and HbA1c) are already available from the same day
• Note that HbA1c may lack accuracy (specificity and/or sensitivity) in the following cases, in which FBG or OGTT may assist diagnosis:

Causes of falsely low or high glycated haemoglobin (HbA1c)
Mechanism	Falsely low HbA1c	Falsely high HbA1c
Change in red blood cell lifespan or turnover	Acute and chronic blood loss Renal failure Haemolytic anaemia Spherocytosis Hypersplenism PregnancyIron/erythropoietin-stimulating agent administration Blood transfusion Cystic fibrosis–related diabetes	Iron deficiency Vitamin B12 deficiency Folate deficiency Asplenia
Change in glycation	Vitamin E	Blood transfusion
Altered haemoglobin	Haemoglobin variants Haemoglobinopathies
Assay-related artifacts		Hypertriglyceridaemia Hyperbilirubinaemia Uraemia Aspirin-induced acetylated haemoglobin Cigarette-associated carboxyhaemoglobin

Is HbA1c the best method of assessing glycaemic control and are there alternatives?

• Studies have indicated that progression of diabetic complications cannot be solely explained by HbA1c, as complications may occur despite lower-than-average HbA1c, and vice versa
• The most likely explanation is that HbA1c does not account for day-to-day glycaemic variabilities. 
• Patients with widely differing glucose profiles may have the same HbA1c (Figure 1), and the use of HbA1c alone without any corroborative glucose measurements will not allow appreciation of intra-day glycaemic excursions. 
• A reduction in glycaemic variability alone – for example, by hypoglycaemic avoidance – can lead to improved quality of life.

Oral glucose tolerance test

• Only method able to detect IGT
• May concurrently detect IFG
• Fasting (eight hours)
• 75 g glucose administered orally
• Blood is collected from a fasting venous sample and two-hour post-glucose challenge venous sample 
• Diabetes is diagnosed if fasting plasma glucose is ≥7.0 mmol/L or two-hour plasma glucose is ≥11.1 mmol/L. 
• If the two-hour plasma glucose is between 7.8 and 11.0 mmol/L, there is impaired glucose tolerance. A two-hour result <7.8 mmol/L is considered normal

Diagnosing diabetes in asymptomatic patients

• People who do not have symptoms of hyperglycaemia but who fall in the high-risk categories cited above, or people for whom there is clinical suspicion of diabetes, should be tested using FBG, HbA1c or OGTT
• A second concordant laboratory result is required to confirm a diagnosis of diabetes in asymptomatic patients 
• It is recommended that the same laboratory test be repeated, using a new blood sample, for a greater likelihood of concurrence.

FBG, fasting blood glucose;HbA1c, glycated haemoglobin; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test; RBG, random blood glucose

Note: IGT and IFG cannot be diagnosed using HbA1c.

*Using AUSDRISK (score ≥12) or in specific high-risk categories

† Medicare Benefits Schedule (MBS) item number 66841 allows for diagnostic use only, once every 12 months. The request slip should be annotated as HbA1c or for Service Incentive Payment (SIP) and Practice Incentives Program (PIP) purposes. However, a confirmatory HbA1c test (MBS item number 66551) should be ordered before treatment initiation

‡ HbA1c results <6.5% do not exclude diabetes diagnosed by glucose tests

§ If confirmatory test is negative, repeat assessment one year or earlier if symptomatic

Diagnosing diabetes in symptomatic patients

• The presence of symptoms suggestive of hyperglycaemia (refer below to ‘Clinical symptoms suggestive of diabetes’) with one of the following is confirmatory of a diagnosis of diabetes:
  • a patient presenting with hyperglycaemic crisis
  • a single elevated FBG ≥7.0 mmol/L
  • single HbA1c ≥6.5%
  • a random blood glucose ≥11.1 mmol/L.

A second laboratory test is not required to confirm the diagnosis, unless diagnostic uncertainty remains.