Type 1 Diabetes Flashcards
What is T1DM?
A metabolic disorder characterised by beta-cell destruction, usually leading to absolute insulin deficiency, mostly by immune-mediated mechanisms.
This could also be idiopathic.
Aetiology of T1DM
Certain HLA, particularly HLA-DR and HLA-DQ alleles, increase susceptibility to or provide protection from the disease.
Autoantibodies detected against pancreatic islet appear in the circulation within the first few years.
Among viruses, the strongest associations have been found with human enteroviruses.
Among dietary factors, supplementation with vitamin D may be protective.
Which autoimmune diseases is T1DM associated with?
Autoimmune thyroid disease
Coeliac disease
Addison’s disease
Pernicious anaemia
Pathophysiology of T1DM
Beta-cell destruction proceeds sub-clinically for months to years as insulitis (inflammation of the beta cells)
When 80-90% of beta cells have been destroyed, hyperglycaemia develops
Insulin resistance is not associated with T1DM
There’s increased secretion of catabolic hormones such as glucagon, adrenaline, cortisol and GH.
These hormones promote gluconeogenesis, glycogenolysis and ketogenesis in the liver.
As a result, patients present with hyperglycaemia and anion gap metabolic acidosis.
Complications of T1DM
Hyperglycaemia leads to vascular complications due to glycosylation of proteins in tissue, serum production of sorbitol and free radical damage. Microvascular complications include: Retinopathy Neuropathy Nephropathy Macrovascular complications include: Cardiovascular Cerebrovascular Peripheral vascular disease
Classification of T1DM
Autoimmune or classical T1DM
Idiopathic T1DM
Signs & Symptoms of T1DM
Polyuria Polydipsia Weight loss Generalised weakness Blurred vision Some patients present with DKA: Symptoms of this include nausea, vomiting, abdominal pain, tachypnoea, tachycardia and lethargy.
Diagnosis of diabetes mellitus
Random blood glucose measurement of > 11 mmol/L (non-fasting).
Fasting plasma glucose > 6.9 mmol/L (after a minimum of 8 hour fast)
Oral glucose tolerance: 2 hour post-load glucose after 75g oral glucose >11.1 mmol/L
HbA1c of 48 mmol/mol or greater
- Any of 3 measures of glucose metabolism but repeated diagnostic test.
Routine investigations include:
Fasting lipid profile
Urine ketones
ECG
Urinary albumin excretion
Random C-peptide
Serum creatinine
Dilated retinal examination
Ankle-brachial index (ABI)
-Any of 3 measures of
Which tests indicate T1DM rather than T2DM?
Random C-peptide: Low C-peptide levels indicates T1DM and it shows low insulin production.
Elevated plasma or urine ketones in the presence of hyperglycaemia suggests T1DM.
Differentials of T1DM
Monogenic diabetes
Neonatal diabetes
LADA
T2DM
Management of T1DM
The long-term goal is the prevention of chronic complications by maintaining blood glucose levels as close to normal as possible.
Current guidelines recommend a target HbA1c of <59 mmol/mol for kids and <53 mmol/mol for adults.
Good glycaemic control in T1DM requires attention to diet, exercise and insulin therapy.
Insulin is usually administered by a pen injection device and site should be changed regularly.
Differences between T1DM and T2DM
Age- Younger patients (<30) usually have T1DM
Weight- T1DM patients are usually lean
Symptom duration- Weeks (T1DM), months/years (T2DM)
Higher risk ethnicity- Northern European (T1DM), Asian/African/Polynesian (T2DM)
Seasonal onset- Yes (T1DM) No (T2DM)
Herediatary- HLA-DR3 or DR4 (T1DM) No HLA links (T2DM)
Pathogenesis- Autoimmune (T1DM) No immune disturbances (T2DM)
Ketouria- Yes (T1DM) No (T2DM)
Clinical- Insulin deficiency + ketoacidosis (T1DM), Partial insulin deficiency (T2DM)
Biochemical- C-peptide disappears (T1DM) C-peptide persists (T2DM)
What is monogenic DM?
Genetic defect of B-cell function
11 genes mostly B-cell transcription factors
Autosomal dominant
Previously called maturity-onset diabetes of the young- MODY
Should be considered in people presenting with early-onset diabetes.
