Type 1 Diabetes

Autoimmune destruction of the pancreatic beta-cells resulting in beta-cell deficiency and therefore absolute insulin deficiency

Aetiology

Types of diabetes

• Type 1 diabetes is subdivided into 1A (immune mediated) and 1B (non-immune mediated)

• Type 1A accounds for the vast majority of T1DM patients and involves an environmental trigger in a genetically susceptible individual mediated by an auto-immune process within the pancreatic β-cell
• A 'slow-burning' variant of type 1A with slower progression to insulin deficiency occurs in later life and is termed latent autoimmune disease in adults (LADA)

• Type 1B (idiopathic) involves patients with permanent insulinopenia and who are prone to DKA but have no evidence of β-cell dysfunction or autoantibodies
• Accounts for a minority of patients with T1DM (~5%)
• Most patients are of African or Asian ancestry
• Strongly inherited and not HLA associated

Risk factors

• 85% of DM in under 20s, peak 10-14 years

• 25% diagnosed as adults - small peak in late 30s (LADA)

• Clinical presentation at all ages up to 9th decade

• HLA genes represent ~50% of familial risk of T1DM - high risk HLA genotypes include DR3-DQ2 and DR4-DQ8

• If both patients have HLA alleles risk of offspring developing diabetes is 30%

• Only 5% of those with susceptible HLA genes develop DM - indicates strong environmental contribution

• At least 47 non-HLA genes or gene regions that influence risk to a minor extent

• Maternal factors e.g. gestational infection and older age

• Viral infections e.g. enteroviruses such as Coxsackie B4

• Exposure to dietary constituents such as early introduction to cow's milk and relative deficiency of vitamin D

• Environmental toxins e.g. alloxan

• Childhood obesity

• Psychological stress

Pathophysiology

1. Genetic susceptibility

2. Environmental trigger (often associated with previous viral infection)

3. T-cell mediated autoimmune response with production of autoantibodies that target and destroy β-cells 
1. Insulitis visable on β-cell biopsy with lymphocytic infiltrate

4. Absolute insulin deficiency → elevated blood glucose levels

Clinical presentation

• Usually acute onset

• Polydipsia

• Polyuria

• Thrush

• Weakness, fatigue

• Blurred vision

• Infections

• Severe weight loss

Investigations

Diagnostic criteria

• Fasting glucose ≳7.0 mmol/l with symptoms, if asymptomatic repeat test OR

• Random glucose ≳11.1 mmol/l with symptoms, if asymptomatic repeat test

• Often T1DM is diagnosed on positive findings as above, history and presentation (e.g. DKA) but if in doubt GAD/IA2 antibodies and C peptide may help

• HbA1c not used in diagnosis of T1DM but is used to monitor disease after diagnosis

Autoantibodies

Management

Insulin

• Usually basal (long-acting once daily) bolus (short-acting with meals) regimen which aims to mimic normal endogenous insulin production

• Most people should be treated with MDI (3-4x injections per day) or CSII

• Most people with T1DM should use insulin analogues to reduce hypoglycaemia risk

• Rotate injection site to avoid lipohypertrophy

Education and self-monitoring

• Patients should have a method of self-monitoring their blood glucose and also have access to a ketone monitor

• Most people should be educated how to match prandial insulin dose to carbohydrate intake, pre-meal glucose and anticipated activity, as well as sick day rules
• There are structured education courses avaliable for patients e.g. DAFNE, BERTE

• Regular DSN and dietician contact

Annual review assessment

• Weight

• Blood pressure

• Bloods: HbA1c, renal function and lipids

• Retinal screening

• Foot risk assessment

• Record severe hypoglycaemic episodes or admission with DKA

Pancreas transplant

• Pancreatic islets harvested from cadavers and then are injected into the portal vein where they seed themselves in the liver

• Typically reserved for those with:
• Episodes of severe hypoglycaemia
• Severe and progressive long-term complications despite maximal therapy
• Uncontrolled diabetes despite maximal treatment

• The goal of treatment is to prevent severe hypoglycaemia but about 50-70% of people receiving islet cell transplants also achieve insulin independence after 5 years

• Most often undertaken in people with T1DM and end-stage kidney disease at the same time as a kidney transplant

• Pancreas transplant may be performed after a kidney transplant or alone

• Indications: severe hypoglycaemia/metabolic complications, incapacitating clinical or emotional problems