15 - Type I diabetes mellitus Flashcards
Name a form of type I diabetes that presents late.
Latent Autoimmune Diabetes in Adults (LADA)
Can T2DM present in childhood?
yes, this is becoming more common with the increasing prevalence of childhood obesity
Diabetic ketoacidosis is more common in T _ DM, but can present in both type of diabetes
1
What is meant by monogenic diabetes? In what type of diabetes do they present?
State two monogenic causes of diabetes.
single gene mutation causes β-cell disfunction
present in both T1 and T2 DM
2 causes:
Mitochondrial Diabetes
Maturity Onset Diabetes of the Young (MODY)
What conditions and triggers are required for the onset of type 1 diabetes mellitus?
Environmental trigger in the presence of a genetic predisposition
-> leads to 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
Describe the presentation/onset of T1DM.
rapid onset and patients present very unwell (especially in children)
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) (Tc 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 diabetic markers used for?
can be measured but won’t change the course of treatment
can be used to help differentiate between type 1 and 2 diabetes
What are the two most significant markers of diabetes?
Islet Cell Antibodies (ICA)
Glutamic Acid Decarboxylase Antibodies (GADA)
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 (on breath) Glycosuria Ketonuria
What are the triglycerides in adipocytes broken down to?
Glycerol
Fatty Acids
What does insulin have a negative effect on? (4)
Hepatic glucose output (HGO)
Glycerol release from the fat cells
Protein breakdown in muscle
Ketone body generation by the liver
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 (4)
Neuropathy
Nephropathy
Retinopathy
Vascular Disease
Describe the dietary changes that are recommended in T1DM.
- reduce calories as fat
- reduce calories as refined carbs
- increased calories as complex carbs
- increase soluble fibre
- balance distribution of food over the course of the day with regular meals and snacks
What is the main treatment for T1DM?
Exogenous insulin
Describe the features of the insulin that is given with meals.
Short-acting
Human Insulin of insulin analogues
Name an insulin analogue that is given with meals
Lipsro
Aspart
Glulisine
Describe the features of background insulin.
Long-acting
Non-C bound to zinc or protamine
Name an insulin analogue that is given for background level maintenance
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
Who uses insulin pumps?
for patients who have used glucose pens, but still don’t have a good glucose profile and may suffer from hypoglycaemic attacks
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 (most accurate)
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?
Hyperglycaemia
Metabolic acidosis
diabetic ketoacidosis
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
Nocturnal
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
