Pathophysiology and Treatment of Type I Diabetes Mellitus 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
Diabetes can also present with endocrine diseases. Name three endocrine diseases that are associated with diabetes.
Phaeochromocytoma
Cushing’s Syndrome
Acromegaly
What conditions and triggers are required for the onset of type 1 diabetes mellitus?
Environmental trigger in the presence of a genetic predisposition –> autoimmune attack of islet cells
Which type of diabetes has a bigger genetic component?
Type 2 Diabetes Mellitus
What can be measured in the blood to give an indication of insulin function?
C-peptide
Describe the pathogenesis of T1DM.
You get gradual autoimmune destruction of beta cells resulting in gradually reducing levels of insulin (and C-peptide)
One of the first signs will be the loss of first phase insulin
There will be eventual destruction of all beta cells
Why is T1DM described as a ‘relapsing-remitting’ disease?
Over time the 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 importance of the autoimmune basis of T1DM?
Increased prevalence of other autoimmune diseases (e.g. rheumatoid arthritis, thyroid disease)
What are the histological features of T1DM?
Lymphocyte infiltration of beta cells (which destroys the beta cells)
On which chromosome is the HLA found?
Chromosome 6
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
What are the two most significant markers of diabetes?
Islet Cell Antibodies (ICA)
Glutamic Acid Decarboxylase Antibodies (GADA)
State two other antibody markers of diabetes that are not used in clinical practice?
Insulin Autoantibodies (IAA) Insulinoma-associated-2 autoantibodies (IA-2A)- receptor like family
State some symptoms of T1DM.
Polyuria Nocturia Polydipsia Blurring of vision Thrush (due to increased risk of infection) Weight loss Fatigue
What are the signs of T1DM?
Dehydration Cachexia Hyperventilation (kussmaul breathing) Smell of ketones Glycosuria Ketonuria
What are the triglycerides in adipocytes broken down to?
Glycerol
Fatty Acids
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
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.
What is a defining feature of insulin deficiency?
Ketone Bodies
NOTE: some cases of T2DM can also get DKA but this is mainly a complication of T1DM
State some long-term complications of T1DM.
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 gage?
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
What are the main acute complications of T1DM?
Hypoglycaemia
Metabolic acidosis
What are the two main ketones that circulate in metabolic acidosiscaused by T1DM?
Acetoacetone
Hydroxybutyrate
DKA tends to be in patients with T1DM, however, some subsets of T2DM also get ketoacidosis. What are these subsets?
Black and Asian patients with T2DM
May be due to pancreatic insufficiency at a time of stress
Define hypoglycaemia.
Blood glucose < 3.6 mmol/L
Define severe hypoglycaemia.
Any level of hypoglycaemia that requires another person to treat it
What can recurrent hypos result in?
Loss of warning (hypoglycaemia unawareness)
This can lead to poor glycaemic control
At what times during the day do hypos tend to happen?
Pre-lunch
Nocturna
What can trigger a hypo?
Unaccustomed exercise Missed meals Inadequate snacks Alcohol (may make you unaware of hypo symptoms) Inappropriate insulin regime
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
