Type I diabetes mellitus Flashcards
What are the typical presentations of type I and type II DM?
There is ambiguity
Type I = thin, diabetic ketoacidosis, LADA (Latent autoimmune diabetes in adults - form of type I diabetes presenting in later life)
Type 2 = overweight. This can present in children due to obesity. Sometimes diabetic ketoacidosis
Monogenic diabetes can present phenotypically as T1 or T2 (MODY (AD) and mitochondrial diabetes)
Define T1DM
An autoimmune condition where there is destruction of insulin producing beta cells of the Islets of Langerhans
What are some secondary causes of DM? Which type of DM is more common?
Following pancreatic damage or other endocrine disease - Phaeochromocytoma, - Cushing’s syndrome, - Acromegaly These all cause hypoglycaemia
- Type II
- Only 10% of people have type T1 diabetes
- Males affected more than females
What is the relapsing and remitting disease theory?
Over time the beta cells reduce, then stabilise then reduce again
There is a theory that this is due to an imbalance between effector T cells and T-regulatory cells
NOTE: effector T cells cause the destruction of beta cells and T-regulatory cells control this destruction
Over time the effector T cells increase in number and the T-regulatory cells decrease
Describe the aetiology of DM?
See diagram
T1: environmental trigger on a background of a genetic component, leading to autoimmune destruction of beta cells.
The HLA gene is found on chromsome 6
- HLA-DR3 and HLA-DR4 increase your risk of having T1DM significantly.
- HLA-DR2 is protective.
T2: bigger genetic component, eventually also develop insulin deficiency as beta cells become exhausted and fail
Describe the pathogenesis of type I diabetes
1) Environmental triggers and regulators along with immune dysregulation leads to destruction of beta cells.
2) Eventually auto-antibodies are produced- further destruction
3) Patients lose first phase insulin (an indicator that a patient will go on to develop diabetes but can take years).
4) All beta cells are destroyed over time.
C-peptide:
- C peptide can be measured in the blood and is a marker of insulin function because it is linked to insulin production
- If C peptide levels reduce then the patient is insulin deficient
- Over time as insulin secretion decreases, the C peptide levels decrease as well
Why is the immune basis of type I diabetes so important?
Increased prevalence of other autoimmune diseases
- B12 deficiency
- Celiac disease
- Hashimoto syndrome (hypothyroidism)
Risk of autoimmunity diseases in relatives
More complete destruction of B-cells
Auto antibodies can be useful clinically - type I DM patient would typically have bloods taken
What markers define a patient with T1DM?
Use of markers: (mainly used in clinical practice) These are markers for disease progress and immune modulation treatment as well as diagnose.
1) ICA - Islet cell antibodies (essentially antibodies to the beta cells)
2) GADA - Glutamic acid decarboxylase antibodies (widespread neurotransmitter)
3) IAA - Insulin antibodies
4) IA-2A - Insulinoma-associated-2 autoantibodies (receptor like family)
What are the presentation of type I DM?
Polyuria, Nocturia, Polydipsia, blurring of vision (hyperglycemia), Thrush (increased risk of infection), Weight loss (insulin stores fatty acids in adipose tissues), fatigue
Signs - dehydration, cachexia, hyperventilation (patients have metabolic acidosis - so increased BR Kussmaul breathing), smell of ketones, glycosuria, ketonuria
What are the main functions of insulin?
- Insulin promotes glucose uptake into muscle
- Insulin decreases hepatic glucose output
- Insulin prevents the movement of glycerol out of adipocytes into the periphery (This is why you see the weight loss in type I DM patients - triglycerides –> glycerol –> glucose in the liver)
- Insulin decreases protein breakdown in muscle
Basically in type I DM where there is a deficiency in insulin - a lot of glucose goes out to the circulation but isn’t taken up by the tissues. HYPERGLYCAEMIA
What hormones promote increased blood glucose?
Growth hormone
Cortisol
Catecholamines
Glucagon
These hormones all act at the liver - increase hepatic glucose output
In terms of adipocytes what happens when you are insulin deficient?
Increased lipolysis: Triglycerides are broken down into glycerol and fatty acids.
1) glycerol leaves and converted to glucose in the liver
2) fatty acids leave and converted to ketone bodies in the liver. Normally inhibited by insulin
These ketones are used as an alternative energy source to glucose.
What do ketones cause?
Metabolic ketoacidosis (acute metabolic decompensation) - ketones make the pH acidic = bad for brain enzymes.
The low blood pH leads to Kausmals breathing
Hyperglycaemia - reduced tissue glucose utilisation + increased hepatic glucose production
Circulating acetoacetate and hydroxybutyrate (ketone bodies) cause osmotic dehydration and poor tissue perfusion
What are the aims of the treatment of T1DM?
- Reduce early mortality
- Avoid acute metabolic decompensation (diabetic ketoacidosis)
- Prevent long term complications (retinopathy, nephropathy, neuropathy, vascular disease).
Exogenous insulin required to preserve life measuring ketones can be used to define insulin deficiency
What diet should type I DM patients have?
1) Reduce calories as fat and refined carbohydrates
2) Have regular meals and snacks - balanced food distribution
3) Increase calories as complex carbohydrate
4) Increase soluble fibre
