Pathophysiology and Treatment of Type I Diabetes Mellitus

Question 1

Name a form of type I diabetes that presents late.

Answer 1

Latent Autoimmune Diabetes in Adults (LADA)

Question 2

State two monogenic causes of diabetes.

Answer 2

Mitochondrial Diabetes

Maturity Onset Diabetes of the Young

Question 3

Diabetes can also present with endocrine diseases. Name three endocrine diseases that are associated with diabetes.

Answer 3

Phaeochromocytoma
Cushing’s Syndrome
Acromegaly

Question 4

What conditions and triggers are required for the onset of type 1 diabetes mellitus?

Answer 4

Environmental trigger in the presence of a genetic predisposition –> autoimmune attack of islet cells

Question 5

Which type of diabetes has a bigger genetic component?

Answer 5

Type 2 Diabetes Mellitus

Question 6

What can be measured in the blood to give an indication of insulin function?

Answer 6

C-peptide

Question 7

Describe the pathogenesis of T1DM.

Answer 7

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

Question 8

Why is T1DM described as a ‘relapsing-remitting’ disease?

Answer 8

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

Question 9

What is the importance of the autoimmune basis of T1DM?

Answer 9

Increased prevalence of other autoimmune diseases (e.g. rheumatoid arthritis, thyroid disease)

Question 10

What are the histological features of T1DM?

Answer 10

Lymphocyte infiltration of beta cells (which destroys the beta cells)

Question 11

On which chromosome is the HLA found?

Answer 11

Chromosome 6

Question 12

Which alleles convey a risk of diabetes? Which of these alleles is associated with the most significant risk?

Answer 12

DR alleles

DR3 and DR4 = significant risk

Question 13

What are the two most significant markers of diabetes?

Answer 13

Islet Cell Antibodies (ICA)

Glutamic Acid Decarboxylase Antibodies (GADA)

Question 14

State two other antibody markers of diabetes that are not used in clinical practice?

Answer 14

Insulin Autoantibodies (IAA) Insulinoma-associated-2 autoantibodies (IA-2A)- receptor like family

Question 15

State some symptoms of T1DM.

Answer 15

Polyuria 
Nocturia 
Polydipsia 
Blurring of vision  
Thrush (due to increased risk of infection) 
Weight loss 
Fatigue

Question 16

What are the signs of T1DM?

Answer 16

Dehydration 
Cachexia 
Hyperventilation (kussmaul breathing) 
Smell of ketones  
Glycosuria 
Ketonuria

Question 17

What are the triglycerides in adipocytes broken down to?

Answer 17

Glycerol

Fatty Acids

Question 18

What does insulin have a negative effect on?

Answer 18

Hepatic glucose output (HGO)
Protein breakdown in muscle
Ketone body generation by the liver
Glycerol release from the fat cells

Question 19

What does insulin have a positive effect on?

Answer 19

Glucose uptake by tissues

Question 20

State 4 other hormones that increase hepatic glucose output.

Answer 20

Catecholamines
Cortisol
Growth Hormone
Glucagon

Question 21

Describe how insulin deficiency leads to diabetic ketoacidosis (DKA).

Answer 21

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.

Question 22

What is a defining feature of insulin deficiency?

Answer 22

Ketone Bodies

NOTE: some cases of T2DM can also get DKA but this is mainly a complication of T1DM

Question 23

State some long-term complications of T1DM.

Answer 23

Neuropathy
Nephropathy
Retinopathy
Vascular Disease

Question 24

What is the main treatment for T1DM?

Answer 24

Exogenous insulin

Question 25

Describe the dietary changes that are recommended in T1DM.

Answer 25

Decreased fat Decreased refined carbohydrates Increased complex carbohydrates Increased soluble fibre

Question 26

Describe the features of the insulin that is given with meals.

Answer 26

Short-acting Human Insulin Insulin analogues are genetically engineered to mimic normal physiology

Question 27

State three forms of insulin that are given with meals.

Answer 27

Lipsro Aspart Glulisine

Question 28

Describe the features of background insulin.

Answer 28

Long-acting | Non-C bound to zinc or protamine

Question 29

State three forms of insulin that is given as background insulin.

Answer 29

Glargine Detemir Degludec

Question 30

What do insulin pumps do?

Answer 30

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

Question 31

Describe the use of islet cell transplants.

Answer 31

Islet cells can be harvested from donors and injected into the liver of a patient with diabetes They must be on immunosuppressants for life

Question 32

How is capillary monitoring done and what does it give a measure of?

Answer 32

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)

Question 33

What is HbA1c level used to gage?

Answer 33

Glycaemic control over the past 3 months (red cell life span = 120 days)

Question 34

What HbA1c level are T1DM patients aiming for?

Answer 34

< 7%

Question 35

When might the HbA1c level not be accurate?

Answer 35

In any case of increased haemoglobin turnover e.g. haemolytic anaemia and haemoglobinopathies

Question 36

What are the main acute complications of T1DM?

Answer 36

Hypoglycaemia | Metabolic acidosis

Question 37

What are the two main ketones that circulate in metabolic acidosiscaused by T1DM?

Answer 37

Acetoacetone | Hydroxybutyrate

Question 38

DKA tends to be in patients with T1DM, however, some subsets of T2DM also get ketoacidosis. What are these subsets?

Answer 38

Black and Asian patients with T2DM | May be due to pancreatic insufficiency at a time of stress

Question 39

Define hypoglycaemia.

Answer 39

Blood glucose < 3.6 mmol/L

Question 40

Define severe hypoglycaemia.

Answer 40

Any level of hypoglycaemia that requires another person to treat it

Question 41

What can recurrent hypos result in?

Answer 41

Loss of warning (hypoglycaemia unawareness) | This can lead to poor glycaemic control

Question 42

At what times during the day do hypos tend to happen?

Answer 42

Pre-lunch | Nocturna

Question 43

What can trigger a hypo?

Answer 43

``` Unaccustomed exercise Missed meals Inadequate snacks Alcohol (may make you unaware of hypo symptoms) Inappropriate insulin regime ```

Question 44

State some signs and symptoms of hypoglycaemia.

Answer 44

``` 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 ```

Question 45

How is hypoglycaemia treated?

Answer 45

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