T1DM Flashcards
Name a form of type I diabetes that presents late.
Latent Autoimmune Diabetes in Adults (LADA)
State two monogenic causes of diabetes.
Mitochondrial Diabetes
Maturity Onset Diabetes of the Young (MODY)
Diabetes can also present with endocrine diseases. Name three endocrine diseases that are associated with diabetes.
Phaeochromocytoma
Cushing’s Syndrome
Acromegaly
Why is there ambiguity in the diagnosis of T1DM?
Diseases like LADA and MODY present later than typical T1DM, and MODY can phenotypically resemble T2DM.
T2DM in youth and keto acidosis in T2DM are also rising.
Broadly what are the mechanism of T1 and T2 diabetes?
T1DM - AI Beta cell destruction (requires environmental trigger and genetic predisposition)
T2DM - Insulin resistance followed by Beta destruction (has larger genetic component than T1)
What can be measured in the blood to give an indication of insulin function?
C-peptide
How does the pathology of T1DM effect insulin and C-peptide levels?
Gradual AI destruction of beta cells leads to decline in insulin (and C-peptide) First phase insulin lost early.
There will be eventual destruction of all beta cells, however it is ‘relapsing-remitting’ as beta cell mass appears to reduce, then stabilise, then reduce again
There is a theory that this is due to the imbalance in effector T-cells and regulatory T-cells
What is the relevance of T1DM’s autoimmune basis?
Increases risk of other AI diseases
Increases risk in family members
Auto antibodies useful clinically
Immune modultion may offer novel treatment
What are the histological features of T1DM?
Lymphocyte infiltration of beta cells (which destroys the beta cells)
Which alleles convey a risk of diabetes? Which of these alleles is associated with the most significant risk?
DR alleles DR3 and DR4 = significant risk
Found on the HLA in chromosome 6
What are some ‘diabetes markers’ and their relevance?
Markers most not needed but can improve certainty in diagnosis
Common:
ICA (Islet cell antibodies)
GADA (Glutamic acid decarboxylase)
Rare:
IAA (Insulin antibodies)
IA-2A (Insulinoma-associated-2-auto antibodies)-receptor like family
What are some symptoms of T1DM?
polyuria polydipsia blurred vision from hyperglycaemia thrush or other vaginal infections weight loss fatigue
What are the signs of T1DM?
Dehydration Cachexia (wasting) Hyperventilation (kussmaul breathing) Smell of ketones Glycosuria Ketonuria
What does insulin have a negative effect on?
Hepatic glucose output (HGO)
Protein breakdown in muscle
Ketone body generation by the liver
Glycerol release from the fat cells (Product of triglycerade break down)
What does insulin have a positive effect on?
Glucose uptake by tissues
State 4 other hormones that increase hepatic glucose output.
Catecholamines
Cortisol
Growth Hormone
Glucagon
Describe how insulin deficiency leads to diabetic ketoacidosis (DKA).
Insulin has a suppressive effect on hepatic ketone body generation. In insulin deficiency, fatty acids from the breakdown of triglycerides, travel to the liver where they are used to produce ketone bodies.
State some complications of T1DM.
ACUTE:
Hypoglycaemia
Metabolic acidosis (Acetoacetone and Hydroxybutyrate circulate)
CHRONIC: Neuropathy Nephropathy Retinopathy Vascular Disease
What is the main treatment for T1DM?
Exogenous insulin
Describe the dietary changes that are recommended in T1DM.
Decreased fat
Decreased refined carbohydrates
Increased complex carbohydrates
Increased soluble fibre
Describe the features of the insulin that is given with meals.
Short-acting Human Insulin Insulin analogues are genetically engineered to mimic normal physiology
State three forms of insulin that are given with meals.
Lipsro
Aspart
Glulisine
Describe the features of background insulin.
Long-acting Non-C bound to zinc or protamine
State three forms of insulin that is given as background insulin.
Glargine
Detemir
Degludec
What do insulin pumps do?
Continuous insulin delivery There are pre-programmed basal rates and boluses for meals But these DO NOT measure blood glucose so the feedback loop isn’t complete
Describe the use of islet cell transplants.
Islet cells can be harvested from donors and injected into the liver of a patient with diabetes They must be on immunosuppressants for life.
How is capillary monitoring done and what does it give a measure of?
Prick the finger and test the blood drawn It is a measure of venous blood glucose NOTE: you can also get continuous monitors, which aren’t as accurate (need to be calibrated with capillary glucose)
What is HbA1c level used to gauge?
Glycaemic control over the past 3 months (red cell life span = 120 days)
What HbA1c level are T1DM patients aiming for?
< 7%
When might the HbA1c level not be accurate?
In any case of increased haemoglobin turnover e.g. haemolytic anaemia and haemoglobinopathies
Define hypoglycaemia.
Blood glucose < 3.6 mmol/L
Severe hypoglycaemia is any level where the patient needs someone else to treat it because they cannot themselves
What can recurrent hypos result in?
Loss of warning (hypoglycaemia unawareness) This can lead to poor glycaemic control
What can trigger a hypo?
Unaccustomed exercise
Missed meals
Inadequate snacks
Alcohol (may make you unaware of hypo symptoms) Inappropriate insulin regime
Due to these hypos are most common pre-lunch and during sleep.
State some signs and symptoms of hypoglycaemia.
Signs and symptoms are due to increased sympathetic activity and due to impaired CNS function
Palpitations Tremor Sweating Pallor/cold extremities Anxiety Drowsiness Confusion Altered behaviour Focal neurology Coma
How is hypoglycaemia treated?
Oral glucose
Complex carbohydrate (to maintain blood glucose after initial treatment)
Parenteral – if consciousness impaired
IV dextrose (e.g. 10% glucose infusion)
1 mg glucagon IM
