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 some symptoms of T1DM.

Answer 14

Polyuria

Nocturia

Polydipsia

Blurring of vision

Thrush (due to increased risk of infection)

Weight loss

Fatigue

Question 15

What are the signs of T1DM?

Answer 15

Dehydration

Cachexia

Hyperventilation (kussmaul breathing)

Smell of ketones

Glycosuria

Ketonuria

Question 16

What are the triglycerides in adipocytes broken down to?

Answer 16

Glycerol

Fatty Acids

Question 17

What does insulin have a negative effect on?

Answer 17

Hepatic glucose output (HGO)

Protein breakdown in muscle

Ketone body generation by the liver

Glycerol release from the fat cells

Question 18

What does insulin have a positive effect on?

Answer 18

Glucose uptake by tissues

Question 19

State 4 other hormones that increase hepatic glucose output.

Answer 19

Catecholamines

Cortisol

Growth Hormone

Glucagon

Question 20

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

Answer 20

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 21

What is a defining feature of insulin deficiency?

Answer 21

Ketone Bodies

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

Question 22

State some long-term complications of T1DM.

Answer 22

Neuropathy

Nephropathy

Retinopathy

Vascular Disease

Question 23

What is the main treatment for T1DM?

Answer 23

Exogenous insulin

Question 24

Describe the dietary changes that are recommended in T1DM.

Answer 24

Decreased fat

Decreased refined carbohydrates

Increased complex carbohydrates

Increased soluble fibre

Question 25

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

Answer 25

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

Question 26

State three forms of insulin that are given with meals.

Answer 26

Lipsro Aspart Glulisine

Question 27

Describe the features of background insulin.

Answer 27

Long-acting Non-C bound to zinc or protamine

Question 28

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

Answer 28

Glargine Detemir Degludec

Question 29

What do insulin pumps do?

Answer 29

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 30

Describe the use of islet cell transplants.

Answer 30

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 31

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

Answer 31

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 32

What is HbA1c level used to gage?

Answer 32

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

Question 33

What HbA1c level are T1DM patients aiming for?

Answer 33

< 7%

Question 34

When might the HbA1c level not be accurate?

Answer 34

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

Question 35

What are the main acute complications of T1DM?

Answer 35

Hypoglycaemia Metabolic acidosis

Question 36

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

Answer 36

Acetoacetone Hydroxybutyrate

Question 37

Define hypoglycaemia.

Answer 37

Blood glucose < 3.6 mmol/L

Question 38

Define severe hypoglycaemia.

Answer 38

Any level of hypoglycaemia that requires another person to treat it

Question 39

What can recurrent hypos result in?

Answer 39

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

Question 40

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

Answer 40

Pre-lunch Nocturna

Question 41

What can trigger a hypo?

Answer 41

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

Question 42

State some signs and symptoms of hypoglycaemia.

Answer 42

``` 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 43

How is hypoglycaemia treated?

Answer 43

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