Causes of type 1 diabetes mellitus
Individuals with type 1 diabetes are metabolically normal before the disease is clinically manifest, but the process of β-cell destruction can be detected earlier by the presence of certain autoantibodies.
Type 1 diabetes usually is characterized by the presence of antiGAD, anti–islet cell, or anti-insulin antibodies, which reflects the autoimmune processes that have led to β-cell destruction.
Individuals who have one of more of these antibodies can be subclassified as having type 1A, immune-mediated type 1 diabetes.
Particularly in nonwhites, type 1 diabetes can occur in the absence of autoimmune antibodies and without evidence of any autoimmune disorder.
In this form of type 1 diabetes, the natural history also is one of progressive disease with marked hyperglycemia resulting in an insulin requirement for prevention of ketosis and survival.
The rate of β-cell destruction is quite variable, being rapid in some individuals, especially in infants and children, and slower in adults.
Some have modest fasting hyperglycemia that can rapidly change to severe hyperglycemia or ketoacidosis, and others, particularly adults, may retain some residual β-cell function for many years and have sometimes been termed as having “latent autoimmune diabetes.
Such individuals may become dependent on insulin for survival only many years after the detection of diabetes. Individuals with type 1 diabetes have low or undetectable levels of insulin and plasma C-peptide.
Patients with type 1A diabetes are also more likely to have other concomitant autoimmune disorders, such as Graves disease, Hashimoto thyroiditis, Addison disease, vitiligo, or pernicious anemia.
Type 1B, or idiopathic, diabetes is characterized by low insulin and C-peptide levels similar to those in type 1A. Such
patients are prone to ketoacidosis, although they have no clinical evidence of autoimmune antibodies.
Many of these patients are of African or Asian origin. They may suffer from episodic ketoacidosis, but the pathogenetic basis for their insulinopenia remains obscure.
Diagnosis of type 1 diabetes
Person presents with one or more symptoms suggestive of diabetes:
• Thirst, polydipsia
• Polyuria, new-onset bedwetting
• Weight loss
• Recurrent infections
• Patient, carer, or family member suspects diabetes
Assess the patient and perform finger-prick blood glucose
Patient ill* and finger prick glucose ≥ 11.1 mmol/l (*e.g. vomiting, dehydration, confusion, hypotension, collapse)
• Diabetes likely. Possible diabetic ketoacidosis Patient not ill but finger prick glucose ≥ 11.1 mmol/L Diabetes likely
• Seek diabetes specialist advice same day especially if ketones present in blood or urine Send venous sample to laboratory for glucose and HbA1c analysis but do not wait for result. Call paediatric or medical on call team if specialist unavailable.
Patient not ill and glucose 7.0–11.0 mmol/L
Send venous sample to laboratory for glucose and HbA1c analysis. (HbA1c confirms diabetes if ≥48 mmol/mol—but result < 48 mmol/mol does not exclude diabetes.) Tell patient or carer to contact GP straightaway if symptoms worsen:
Review within three days
Patient not ill and glucose below 7.0 mmol/L
Review if symptoms persist
People who are increased risk of developing type 1 diabetes
Autoimmune Family History e.g. type 1 diabetes, thyroid disease, coeliac disease, pernicious anaemia, Addison’s disease.