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.
• Risk factors and their associated points:
  • Age group:
    • 35–44 years: 2 points
    • 45–54 years: 4 points
    • 55–64 years: 6 points
    • 65+ years: 8 points
  • Gender:
    • Male: 3 points
    • Female: 0 points
  • Ethnicity/country of birth:
    • Born in Australia: 0 points
    • Aboriginal or Torres Strait Islander (ATSI): 2 points
    • Born in Asia (including the Indian subcontinent), the Middle East, North Africa, or Southern Europe: 2 points
  • Family history of diabetes (parent, brother, or sister with type 1 or type 2 diabetes):
    • Yes: 3 points
    • No: 0 points
  • History of high blood glucose (sugar):
    • Yes: 6 points
    • No: 0 points
  • Hypertension (high blood pressure) and being on medication for it:
    • Yes: 2 points
    • No: 0 points
  • Smoking status:
    • Current smoker: 2 points
    • Non-smoker or ex-smoker: 0 points
  • Fruit and vegetable intake:
    • Eats vegetables and fruit every day: 0 points
    • Does not eat vegetables or fruit every day: 1 point
  • Physical activity:
    • Engages in at least 2.5 hours of physical activity per week: 0 points
    • Does not engage in at least 2.5 hours per week: 2 points
  • Waist circumference measurement (measured at the level of the navel while standing):
    • For men:
      • 94 cm or less: 0 points
      • 95–102 cm: 4 points
      • More than 102 cm: 7 points
    • For women:
      • 80 cm or less: 0 points
      • 81–88 cm: 4 points
      • More than 88 cm: 7 points
• Scoring and interpretation:
  • A score of 12 or more suggests an increased risk of developing type 2 diabetes in the next 5 years.

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 AUSDRISK 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 Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT) should be tested annually.

IFG and IGT:

• Patients with elevated blood glucose that does not reach the diagnostic threshold for type 2 diabetes are said to have Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT). These conditions are also referred to as dysglycaemic states or intermediate hyperglycaemia.
  • IFG is diagnosed based on fasting blood glucose (FBG) levels between 6.1 and 6.9 mmol/L (110 to 125 mg/dL).
  • IGT is identified by a 2-hour plasma glucose level between 7.8 and 11.0 mmol/L (140 to 199 mg/dL) after a 75g oral glucose tolerance test (OGTT).

Risk of progression:

• IFG and IGT are not benign
• they both indicate an increased risk of developing type 2 diabetes in the future. Both states also increase the risk of cardiovascular disease.
• These dysglycaemic states often represent early stages of insulin resistance and pancreatic beta-cell dysfunction.

Natural history of IFG and IGT:

• Without intervention, patients with IFG or IGT are at a heightened risk of progressing to type 2 diabetes. However, regression to normoglycemia is possible.
• Studies have shown that approximately 18% of patients with IFG and IGT can revert to normal glucose regulation over three years, especially when following non-intensive lifestyle modifications such as increasing physical activity or improving diet.

Prevention of progression to type 2 diabetes:

• Intensive lifestyle intervention has been shown to reduce the risk of progression from IFG/IGT to type 2 diabetes significantly.
• Recommendations for lifestyle interventions include:
  • Achieving and maintaining a 7% reduction in body weight through a combination of diet and exercise.
  • Increasing moderate-intensity physical activity to at least 150 minutes per week, such as brisk walking, cycling, or swimming.
  • A low-energy, nutrient-dense diet that is rich in fruits, vegetables, and fibre, and low in fat (especially saturated fats) and red/processed meats.
• Structured weight loss programs and supervised exercise programs can provide additional benefit in reducing the risk of progression to type 2 diabetes.

Tests to detect diabetes

1. Fasting Blood Glucose (FBG) Test:

• This test measures plasma glucose levels after an individual has fasted for at least 8 hours.

Cutoffs:

• <5.5 mmol/L: Diabetes unlikely.
• 5.5–6.9 mmol/L: This range indicates the potential need for further testing, such as an oral glucose tolerance test (OGTT), to evaluate for impaired fasting glucose (IFG) or impaired glucose tolerance (IGT).
• ≥7.0 mmol/L (or ≥11.1 mmol/L non-fasting): Diabetes is likely. According to diagnostic criteria, two fasting plasma glucose values of ≥7.0 mmol/L on separate occasions or a random (non-fasting) glucose level of ≥11.1 mmol/L with symptoms of hyperglycemia would confirm a diagnosis of diabetes.
• 6.1–6.9 mmol/L: This range represents impaired fasting glucose (IFG), a state of intermediate hyperglycemia with an increased risk of developing type 2 diabetes.

Confirmation of Diagnosis:

• To confirm the diagnosis of diabetes, a second fasting blood sugar test should be repeated on a separate day if the initial result is elevated. Alternatively, a different test like the HbA1c or OGTT could confirm the diagnosis.

2. Glycated Hemoglobin (HbA1c) Test:

• HbA1c measures the percentage of hemoglobin that is glycated, providing an average blood glucose level over the preceding 8–12 weeks, based on the typical lifespan of erythrocytes (around 120 days).
• HbA1c is a reliable marker for longer-term glucose control.
• The HbA1c test can be expressed in two units:
  • Percentage (%): Known as the DCCT unit
    • DCCT stands for the Diabetes Control and Complications Trial, a landmark clinical trial that established the importance of HbA1c in monitoring long-term glucose control in people with diabetes.
    • used primarily in the US and some other countries.
    • HbA1c (%) = (HbA1c mmol/mol ÷ 10.929) + 2.15
  • mmol/mol: Known as the IFCC unit (mmol/mol)
    • is a newer, more standardized method, used internationally and is considered to provide a more accurate measurement of glycated hemoglobin

HbA1c Composition:

• The major form of hemoglobin in adults is HbA (α2β2), which comprises approximately 97% of adult hemoglobin.
• Around 6% of HbA is glycated to form different components: HbA1a, HbA1b, and primarily HbA1c (~5% of total HbA).
• HbA1c represents glucose that has attached to the N-terminal valine of the beta chain of hemoglobin in a non-enzymatic process known as glycation.

Time Representation:

• The HbA1c result reflects average blood glucose over the past 8–12 weeks, but the breakdown is not entirely even:
  • 50% of the value reflects glucose exposure in the last 30 days.
  • 40% reflects glucose exposure in the previous 31–90 days.
  • 10% reflects glucose exposure from 91–120 days ago.

Diagnostic Cutoffs:

• ≥6.5% (48 mmol/mol): Diagnostic of diabetes.
• 5.7%–6.4% (42–47 mmol/mol): Indicates pre-diabetes.
• <5.7% (42 mmol/mol): Considered normal.

Confirmation of Diagnosis:

• As with FBG, abnormal HbA1c values should generally be confirmed by repeating the test on a different day, especially in asymptomatic patients. However, if two abnormal tests (e.g., elevated FBG and HbA1c) are obtained on the same day, confirmation may not be necessary.

3. Limitations of HbA1c:

HbA1c may be unreliable in certain conditions that affect red blood cell turnover or hemoglobin structure, including:

• Hemoglobinopathies (e.g., sickle cell disease, thalassemia)
• Anemia (especially hemolytic anemia or conditions with reduced erythrocyte lifespan)
• Chronic kidney disease
• Recent blood transfusions or erythropoietin therapy

In these cases, alternative tests such as FBG or OGTT are more reliable for diagnosing diabetes.

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 glycemic control, and are there alternatives?

HbA1c is widely used to assess long-term glycemic control, as it reflects average blood glucose levels over the preceding 8–12 weeks. However, studies have shown that HbA1c alone does not fully capture the complexity of glucose control. Complications of diabetes, such as retinopathy or nephropathy, can sometimes develop in patients with lower-than-average HbA1c, while others may avoid complications despite elevated HbA1c.

The most likely explanation is that HbA1c does not account for day-to-day glycemic variability. Patients with similar HbA1c levels can have widely different glucose profiles (such as frequent episodes of hyperglycemia or hypoglycemia). HbA1c provides an average but does not reflect intra-day glycemic excursions, which are fluctuations in blood glucose throughout the day. Such variability can contribute to the risk of complications and affect quality of life. Therefore, relying solely on HbA1c without corroborative glucose measurements (such as self-monitoring of blood glucose or continuous glucose monitoring) may lead to incomplete management of diabetes.

Reducing glycemic variability, for example, by avoiding hypoglycemia, can significantly improve patient outcomes and quality of life, even if HbA1c remains unchanged.

Alternatives and Complementary Tests to HbA1c:

1. Oral Glucose Tolerance Test (OGTT):
   • The OGTT is the only method capable of diagnosing impaired glucose tolerance (IGT), which reflects how well the body handles glucose after a meal.
   • It may also detect impaired fasting glucose (IFG) concurrently.
   • Procedure:
     • The patient must fast for at least 8 hours.
     • A baseline fasting venous blood sample is taken.
     • The patient then consumes a 75 g oral glucose solution.
     • A second venous blood sample is taken 2 hours later.
   • Interpretation:
     • Diabetes: Fasting plasma glucose ≥7.0 mmol/L or 2-hour plasma glucose ≥11.1 mmol/L.
     • Impaired Glucose Tolerance (IGT): 2-hour plasma glucose between 7.8 and 11.0 mmol/L.
     • Normal: 2-hour plasma glucose <7.8 mmol/L.
2. Fasting Blood Glucose (FBG):
   • FBG is commonly used for diagnosing diabetes, especially in asymptomatic patients.
   • A fasting glucose level ≥7.0 mmol/L on two separate occasions confirms the diagnosis of diabetes.
3. Continuous Glucose Monitoring (CGM):
   • CGM provides detailed, real-time data on glucose levels throughout the day, capturing glucose excursions and variability that HbA1c cannot.
   • CGM can detect periods of hyperglycemia and hypoglycemia, which can help adjust treatment plans to achieve better overall glycemic control and reduce fluctuations.

Diagnosing Diabetes in Asymptomatic Patients:

Patients who do not exhibit symptoms of hyperglycemia but fall into high-risk categories (e.g., those with obesity, a family history of diabetes, or previous gestational diabetes) or where there is clinical suspicion of diabetes should be tested using one of the following:

• Fasting Blood Glucose (FBG)
• HbA1c
• Oral Glucose Tolerance Test (OGTT)

For a confirmed diagnosis of diabetes in asymptomatic patients, it is important to obtain a second concordant laboratory result (either repeating the same test or using another method). It is recommended that the same test be repeated using a new blood sample for a greater likelihood of consistent results.

SCREENING

Diagnosing Diabetes in Symptomatic Patients

The presence of symptoms suggestive of hyperglycemia (see below for ‘Clinical symptoms suggestive of diabetes’) along with one of the following criteria is confirmatory of a diagnosis of diabetes:

• The patient presents with a hyperglycemic crisis (e.g., diabetic ketoacidosis or hyperosmolar hyperglycemic state).
• A single elevated fasting blood glucose (FBG) of ≥7.0 mmol/L.
• A single HbA1c result of ≥6.5% (48 mmol/mol).
• A random blood glucose measurement of ≥11.1 mmol/L.

A second confirmatory laboratory test is not required if the patient has typical symptoms of hyperglycemia or is in hyperglycemic crisis. However, if there is diagnostic uncertainty (e.g., the patient is asymptomatic or the result is borderline), a second test may be performed for confirmation.