Type 1 Diabetes Mellitus Flashcards
How are type 1 and type 2 diabetes classified?
T1 - complete lack of insulin
T2 - relative lack of insulin & insensitivity
What ambiguity is there with diabetes?
Autoimmune T1DM can present later in life in Latent Autoimmune Diabetes in Adults
T2DM CAN present in childhood (more common in adult life).
Diabetic ketoacidosis (DKA) is only a feature of T1DM. - In T2DM, insulin production is sufficient to supress ketone production.
Monogenic diabetes can present as T1 or T2 (e.g. MODY).
Diabetes may present following pancreatic damage or other endocrine diseases
Which diabetes is more hereditary?
T2
*genetics play a rle in both types but T1 is usually autoimmune
Describe the pathogenesis of type 1 diabetes
There are multiple relapse-remitting processes including different antibodies destroying the beta-islet cells.
The honeymoon phase is the last instance where the beta cells produce a non-hyperglycaemic response with just enough insulin.
The effector T-cells are destructive and the T-reg cells are supposed to keep the effector T-cells in check. Eventually the T-effector cells overcome the T-reg cells and destruction occurs.
What is the importance of the immune basis of T1DM?
Patients with T1 diabetes have an immune background:
- This means increased prevalence of other autoimmune disorders
- a risk of autoimmunity in relatives
- more destruction of beta cells
- can measure auto-antibodies to confirm T1DM and can treat autoimmunity
What are some markers for T1DM?
HLA-DR3 and HLA-DR4 deletions pose a significant risk to chance of getting T1DM.
Environmental triggers – more T1DM patients present in the winter/autumn months (possible infectious cause).
Markers for T1DM: normally don’t need to measure.
- Islet cell antibodies.
- Insulin antibodies.
- Glutamic acid decarboxylase (GADA).
- Insulinoma-associated-2 autoantibodies receptor like family.
What are the signs and symptoms of T1DM?
Signs:
- Dehydration
- Cachexia - muscle wasting/weakness
- Hyperventilation - Kussmahl breathing
- Ketone smell
- Glycosuria and Ketonuria
Symptoms:
- Polyuria
- nocturia
- Polydipsia
- Blurring of vision
- “thrush”
- Weight loss
- Fatigue
What is the action of insulin? What happens in T1DM?
Insulin is released after eating and acts to absorb glucose into cells and create stores of energy.
insulin prevents glucose leaving liver and promotes glucose uptake into muscle - deficiency -> high blood glucose
insulin inhibits glycerol leaving adipocytes - deficiency of insulin enables glycerol to leave cells and TGs break down. Hence, T1DM are thin
the lack of insulin also allows FFAs to escape adipocytes and thus are turned into ketone bodies inside the liver.
The ketone bodies are then taken up by muscle and the brain but also cause Ketonuria
What are the aims of treatment?
reduce early mortality
avoid acute metabolic decompensation
prevent long term complications (i.e. retinopathy, neuropathy, nephropathy, vascular disease)
- Require exogenous insulin to preserve life -
Ketones define the insulin deficiency
What diet changes are recommended?
- Reduce calories as fat and refined carbohydrate
- Increase calories as complex carbohydrates and increase soluble fibre
- Distribute food evenly throughout the day with regular meals and snacks
How is insulin used as a treatment?
- there is always a basal level of insulin in a non-diabetic person so treatment must try to retain this
Insulin treatment must be given at:
- Meals – short-acting insulin and can be human or an analogue (Lispro, Aspart, Glulisine).
- Background – long-acting insulin and can be “non-c bound to zinc/protamine” or an analogue (Glargine, Determir, Degludec).
What are some alternative treatments?
Insulin pumps – give continuous delivery, have pre-programmed basal and bolus rates but do NOT measure glucose feedback.
Islet cell transplants – a donor can donate some pancreas islet cells that are inserted into the diabetic’s liver portal vessels to release insulin. The patient must be on continuous immunosuppressants though and the treatment is only reserved for those with erratic control of diabetes
How can we monitor the effectiveness of treatments?
Capillary monitoring – either via a continuous monitor attached to the belly or through finger pricks
- Allows adjustment of insulin dose
HbA1C red cell monitoring – glucose binds to RBCs irreversibly so can give a long-term view of glucose control
- Can allow you to monitor blood glucose over a 3-month long period (life of a RBC)
- Lowering HbA1C is associated with a lower risk of microvascular complications
- affected by sicke cell/ iron deficiency anaemia
What are some acute complications?
Metabolic acidosis (ketoacidosis) – due to circulating acetoacetate/hydroxybutyrate and osmotic dehydration and poor tissue perfusion - Diabetic ketoacidosis CAN occur in T2DM (afro-carribeans) and new onset diabetes BUT it is most common in T1DM
Hyperglycaemia – reduced tissue glucose utilisation and increased HGO.
- In treating hyperglycaemia, patients MAY become hypoglycaemic
What is hypoglycaemia?
Hypoglycaemia may occur due to TREATING diabetes and is defined as <3.6mmol/L glucose.
Most mental processes impaired at <3mmol/L.
Coma at <2mmol/L – severe hypoglycaemia may contribute to arrhythmia and sudden death.
Recurrent hypos result in a loss of warning to the body – ‘hypoglycaemia unawareness’
