Diabetes Screening and Haemochromatosis Lecture Notes

Screening for Type 2 

Diabetes in General and High-Risk Populations

• General Population Risk Assessment Frequency:

  • Risk assessment for Type 2 Diabetes should be conducted every $3$ years in individuals over the age of $40$.

• Specific Inclusion Criteria for Screening:

  • Presence of Intermediate Hyperglycemia.

  • History of Previous Gestational Diabetes.

  • Diagnosis of Polycystic Ovarian Syndrome (PCOS).

  • Presence of Clinical Cardiovascular Disease, including cases of acute Myocardial Infarction (MI), angina, or stroke.

  • Patients taking Antipsychotic Medication.

  • Patients taking long-term Steroids.

  • Individuals aged > 30 years who possess the following triple criteria:

    • Family history (first-degree relative with Type 2 Diabetes).

    • Obesity (defined as \text{BMI} > 30).

    • Hypertension.

• High Prevalence Ethnic Groups:

  • Groups such as Aboriginal and Torres Strait Islander Peoples (ATSIS) and Pacific Islanders should commence screening significantly earlier, beginning from $18$ years of age.

Diagnostic Procedures and Thresholds for Glucose Testing

• Venous Fasting Blood Glucose (VFBG):

  • Result < 5.5\,mmol/L: Diabetes is considered unlikely. Follow-up is recommended in $3$ years.

  • Result $5.5 - 6.9\,mmol/L$: Level is considered uncertain. An Oral Glucose Tolerance Test (OGTT) using $75\,g$ of glucose is required.

  • Result $\ge 7.0\,mmol/L$: Type 2 Diabetes is likely. If the patient is asymptomatic, the fasting glucose test should be repeated twice for confirmation.

• Oral Glucose Tolerance Test (OGTT) Interpretation (2-hour check):

  • If glucose is < 7.8\,mmol/L: Interpreted as impaired fasting glucose (IFG). Follow-up in $1$ year.

  • If glucose is $7.8 - 11.0\,mmol/L$: Interpreted as impaired OGTT (Impaired Glucose Tolerance - IGT). Follow-up in $1$ year.

  • If glucose is $\ge 11.1\,mmol/L$: Diagnostic for Type 2 Diabetes.

• Glycated Haemoglobin (HbA1c) Screening:

  • Result < 6.0\%\, (42\,mmol/mol): Diabetes unlikely. Retest in $3$ years if indicated.

  • Result $6.0 - 6.4\%\, (42 - 46\,mmol/mol)$: High risk or diabetes possible. Referral to "Preventing progression to type 2 diabetes" section is necessary. Retest in $1$ year

  • Result $\ge 6.5\%\, (48\,mmol/mol)$: Diabetes likely. This must be confirmed witha repeat HbA1c test.

• Screening Summary and Limitations:

  • Random Blood Glucose (RBG): $\ge 11.1\,mmol/L$ indicates diabetes is likely.

  • Important Caveat: Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG) cannot be diagnosed using HbA1c.

  • Negative Confirmatory Test: If a confirmatory test returns negative, repeat the assessment in one year (or earlier if the patient becomes symptomatic).

  • Diagnosis Threshold Note: HbA1c results < 6.5\% do not exclude diabetes if it is otherwise diagnosed via glucose-based tests.

  • Administrative/Technical Note: Medicare Benefits Schedule (MBS) item number $66841$ is for diagnostic use once every $12$ months. Requests should be annotated as HbA1c or for Service Incentive Payment (SIP)/Practice Incentives Program (PIP). Confirmatory HbA1c tests use MBS item number $68551$.

Secondary Causes of Hyperglycaemia

• I. Diseases of the Pancreas:

  • Pancreatitis.

  • Neoplasia.

  • Cystic fibrosis.

  • Haemochromatosis.

• II. Endocrinopathies:

  • Cushing's Syndrome.

  • Acromegaly.

  • Pheochromocytoma.

  • Hyperthyroidism.

• III. Drug-induced Hyperglycaemia:

  • Antipsychotics (e.g., Olanzapine).

  • Thiazide diuretics.

  • Oestrogen.

  • Glucocorticosteroids.

• IV. Genetic Syndromes:

  • Turner Syndrome.

  • Down Syndrome.

  • Klinefelter's Syndrome.

Haemochromatosis (Bronze Diabetes)

• Overview:

  • Hereditary haemochromatosis is a disorder characterized by iron overload.

  • Mechanism: Iron deposits within the pancreas, resulting in organ damage and subsequent diabetes (referred to as "Bronze Diabetes").

  • Diagnostic Indicator: Serum transferrin saturation greater than $70\%$.

• Systemic Consequences of Organ Damage:

  • Liver: Liver problems.

  • Pancreas: Diabetes.

  • Heart: Heart problems.

  • Pituitary Gland: Functional impairment leading to a reduction in FSH and LH. This causes loss of sex drive, erection problems, infertility, and amenorrhea.

  • Thyroid: Thyroid dysfunction.

• Clinical Symptoms:

  • Tiredness and weakness.

  • Increased susceptibility to infections.

  • Abdominal pain and joint pain.

  • Tanning/pigmentation of skin ("bronze").

  • Hair loss.

  • Shortness of Breath (SOB).

• Diagnostic Investigations and Markers:

  • Blood markers: High ferritin levels and a high ratio of iron to transferrin.

  • Serum Ferritin Thresholds (Positive for iron overload):

    • Men and older women: > 300\,\mu g/L.

    • Young women: > 200\,\mu g/L.

  • Transferrin Saturation (Positive):

    • Men: > 50\%.

    • Women: > 45\%.

  • Genetic Testing (HFE Gene Link):

    • C282Y homozygote.

    • H63D homozygote.

    • C282Y/H63D compound heterozygote.

  • Differential Diagnosis: If positive for iron overload but negative for HFE mutations, consider other genetic links (Ferroportin, haemojuvelin, African iron overload, transferrin receptor 2, hepcidin) or secondary iron overload.

  • Conclusive Procedure: Liver biopsy.

• Treatment and Management:

  • First-line Treatment: Phlebotomy (or Erythrocytapheresis if phlebotomy is contraindicated).

    • Induction Phase: Weekly or biweekly treatments. Hemoglobin levels checked before each session (Reduce rate if < 12\,g/dl, pause if < 11\,g/dl). Ferritin checked every $4$ phlebotomies until $200\,\mu g/L$ is reached; then every $1 - 2$ sessions. Induction target ferritin is $50\,\mu g/L$.

    • Maintenance Phase: Generally $2 - 6$ phlebotomies per year. Ferritin and transferrin saturation checked every $6$ months. Maintenance target ferritin is $50 - 100\,\mu g/L$.

  • Erythrocytapheresis: Therapeutic option with fewer hemodynamic changes and shorter treatment duration in induction. Mild citrate reactions are common.

  • Second-line Treatment: Iron-chelating drugs (Deferoxamine, Exjade, Feriprox). Used in selected cases like severe juvenile haemochromatosis or when first-line options are unsuitable. Target ferritin is higher than in phlebotomy.

  • Patient Counseling and Diet:

    • Avoid iron and Vitamin C supplements.

    • Avoid daily red meat consumption and heavy alcohol intake.

    • Proton-pump inhibitors (PPIs) may reduce phlebotomy requirements.

    • Abstain from alcohol if liver disease is advanced.

    • Avoid raw/undercooked seafood and contact with seawater due to the risk of Vibrio vulnificus infection.

Specific Physical Findings

• Acanthosis Nigricans:

  • Description: A dark patch or band of velvety skin.

  • Locations: Commonly found on the back of the neck, armpit, or groin.

  • Significance: Indicates hyperinsulinemia (too much insulin in the blood).