Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease caused by the destruction of insulin-producing pancreatic beta cells. This results in absolute insulin deficiency and hyperglycaemia. It commonly presents in childhood and adolescence with the triad of polyuria, polydipsia and unexplained weight loss.
It is relatively common, with an incidence of 4 cases per 100,000 persons per year. It peaks between 20 and 30 years and affects men and women equally.
- Risk factors
- HLA-DR and HLA-DQ2 phenotypes
- Coeliac disease – this is also associated with HLA-DQ2 phenotypes
- Family history of T1DM
- Autoantibodies to islet cells, insulin, islet antigens (IA2 and IA2-beta), glutamic acid decarboxylase (GAD), and zinc transporter ZnT8
- Viral infections
- Cow’s milk ingestion
- Vitamin D deficiency
- Early introduction to cereals
- Pathophysiology
- Type IV hypersensitivty where CD4+ T cells and CD8+ T cells attack pancreatic beta cells → decreased insulin production → hyperglycaemia once 90% of islet cells are destroyed
- Pancreatic alpha cell dysfunction → overstimulation of glucagon → gluconeogenesis, glycogenolysis and ketogenesis → hyperglycaemia and diabetic ketoacidosis
- Long-term hyperglycaemia → chronic macrovascular and microvascular damage through oxidative stress, free radical damage, sorbitol production and glycosylation of tissues
- Signs and symptoms
- Polyuria
- Due to osmotic diuresis caused by hyperglycaemia
- Polydipsia
- Due to dehydration
- Unexplained weight loss
- Due to depletion of glycogen stores and adipose tissue to compensate for cellular glucose deficiency
- Fatigue
- Due to impaired glucose utilisation
- Blurred vision
- Due to changes in lens osmolality
- Glycosuria
- Due to glucose exceeding the renal threshold for reabsorption
- Ketosis
- Due to increased fat metabolism
- Nocturnal enuresis
- Genital pruritus or thrush
- Due to increased susceptibility to infections in a high-glucose environment
- Polyuria
- Differentials
- Type 2 diabetes mellitus (T2DM)
- Gestational diabetes
- Maturity-onset diabetes of the young (MODY)
- Latent autoimmune diabetes in adults (LADA)
- Drug-induced diabetes
- Antipsychtics
- Corticosteroids
- Tacrolimus
- L-asparaginase
- Exocrine pancreas insufficiency
- Cystic fibrosis
- Chronic pancreatitis
- Hereditary hemochromatosis
- Endocrinopathies
- Cushing’s syndrome
- Acromegaly
- Phaechromocytoma
- Glucagonoma
- Temporary hyperglycaemia
- Sepsis
- Drugs
- Neonatal hyperglycaemia
- Investigations
- Fasting plasma glucose ≥ 7.0 mmol/L
- Random plasma glucose ≥ 11..1 mml/L on more than one occasion in the presence of hyperglycaemia
- Plasma glucose ≥ 11 mmol/L 2 hours after a 75 g oral glucose load
- Glycated haemoglobin (HbA1C) ≥ 48 mmol/mol (6.5%) on two separate tests – this is unreliable if the patient has any condition that affects red cell survival
- Urine testing for glycosuria and ketonuria
- Autoantibody testing to confirm the diagnosis. These include:
- GAD antibodies
- Islet cell cytoplasmic autoantibodies (ICA)
- Insulinoma-associated-2 antibdies (IA-2A)
- Insulin autoantibodies (IAA)
- Low C-peptide measurement < 0.6 ng/mL along with hypoglycaemia suggests T1DM
- Treatment
- Acute complications
- Chronic complications
- Nephropathy
- Retinopathy
- Neurpathy
- Coronary artery disease
- Peripheral arterial disease
- Stroke