15. Type I diabetes mellitus

Question 1

What type of people are likely to get type I diabetes?

Answer 1

Lean, young individuals

Question 2

Why is there some ambiguity regarding the group of people most likely to suffer from type I diabetes?

Answer 2

• More and more older individuals diagnosed with insulin deficiency
- latent autoimmune diabetes in adults (LADA) - requires insulin as treatment
• Can present following pancreatic damage or other endocrine diseases

Question 3

Can type II diabetes present in childhood?

Answer 3

• Yes, prevalence of obesity is increasing

* Monogenic diabetes can present phenotypically as Type 1/2 diabetes e.g. MODY, mitochondrial diabetes

Question 4

Is type I or II diabetes more common?

Answer 4

Type II diabetes

Question 5

What factors can lead to autoimmune destruction of islet cells in T1D?

Answer 5

• Environmental (trigger)

* Genetic

Question 6

What factors can lead to insulin resistance in T2D?

Answer 6

• Genetic (stronger influence)

* Obesity (associated)

Question 7

Describe the pathogenesis of T1D

Answer 7

• Patient gets pre-diabetes => overt diabetes, as beta cells start to malfunction (steadily)
• Patients admit, sick from diabetic ketoacidosis (high risk effect of T1D)
• Beta cells continue to decline over time
• Relapsing remitting disease

Question 8

What affect does T1D have on other conditions (same group of conditions)?

Answer 8

• T1D is an autoimmune condition

* Therefore, increased prevalence of other autoimmune diseases

Question 9

What other cells can you see near beta cells in T1D?

Answer 9

• Lots of inflammatory cells (plasma cells)

* Lots of T-cells (role in destruction of beta cells)

Question 10

What is the HLA-DR allele and what does it show?

Answer 10

• Gene where a genetic abnormality can increase the risk of developing T1D
• Haplotypes from DR1 to DR9
• DR3 and DR4 are critical

Question 11

What evidence suggests there is an environmental influence on T1D?

Answer 11

• Higher prevalence in winter
• Could be a viral pathogen that targets beta cells during this period
• Also, certain places in the world with a higher prevalence

Question 12

What clinical measurements can you make to try and diagnose T1D?

Answer 12

• Islet cell antibodies (ICA) - grp O human pancreas
• Insulin antibodies (IAA)
• Glutamic acid decarboxylase antibodies (GADA) - widespread NT
• Insulinoma-associated-2-autoantibodies (IA-2A)-receptor like family

(there are some individuals with T1D that don’t have antibodies)

Question 13

What are the symptoms of diabetes?

Answer 13

• Polyuria
• Nocturia
• Polydipsia
• Blurred vision
• Thrush
• Weight loss
• Fatigue

Question 14

What are the signs of diabetes?

Answer 14

• Dehydration
• Cachexia (weakness and wasting of the body)
• Hyperventilation
• Smell of ketones
• Glycosuria
• Ketonuria

Question 15

What affect does insulin usually have on the liver, muscle and adipose?

Answer 15

• Reduced hepatic glucose output
• Increased glucose uptake by the muscle
- increased protein synthesis
• Stops fatty acids/glycerol from leaving adipose

Question 16

What affect does insulin deficiency have on the liver, muscle and adipose?

Answer 16

• Lot of glucose from the liver released into the circulation
• Glucose not taken up by the muscle
=> Hyperglycaemia
• Proteins released from muscle (increases glucose production in liver)
• Fatty acids in adipose tissue broken down
• Triglycerides release lots of fatty acids
• Fatty acids taken up by the liver, ketone bodies produced (which can go into the Kreb’s cycle to produce energy)

Question 17

What are the aims of treatment in T1D?

Answer 17

• Reduce early mortality
• Avoid acute metabolic decompensation
• Prevent long term complications e.g. vascular disease
• Need exogenous insulin to preserve life

Question 18

What diet do you need in T1D?

Answer 18

• Reduce calories as fat
• Reduce calories as refined carbohydrate
• Increase calories as complex carbohydrate
• Increase soluble fibre
• Balance distribution of food over course of day with regular meals and snacks

Question 19

What kind of insulin is used as treatment with meals and in the background?

Answer 19

• With meals: short acting, human insulin, insulin analogues (lispro, aspart, glulisine)
• Background: long actin, non-c bound to zinc/protamine, insulin analogues (glargine, determir, degludec)

Question 20

What does a diabetic patient inject themselves with when they eat?

Answer 20

• Short and long acting insulin
• Long acting insulin lasts until their next meal
• Insulin analogues (long acting) give a good, 24-hour long profile
• This is called a basal-bolus regime

Question 21

What percentage of diabetic patients have a basal-bolus regime?

Answer 21

90%

Question 22

How do insulin pumps work?

Answer 22

• Administers continuous insulin
• Pre-programmed basal rates and bolus for meals
• Does not measure glucose

Question 23

How can T1D be invasively treated?

Answer 23

• Islet cell transplant
• Beta cells taken from donor pancreas
• Cells are isolated and injected into patient’s liver
• Move through hepatic veins and migrate around the body
- can then produce insulin
• Immunosuppresive agents needed

Question 24

How can you measure how successful treatment for T1D is?

Answer 24

• Measure capillary glucose levels (vary dependent on tissue perfusion)
• Glucose monitor - real time
• Look at HbA1c

Question 25

What is the HbA1c test?

Answer 25

• Blood sample that relies on red cells attaching to the glucose monitor • HbA1c red cells react with glucose - irreversible and non-covalent • Lifespan of red cells in around 120 days, so test gives an idea of glucose levels over 3 months • Ideal for long-term glycaemic control • May not be accurate: - rate of glycation is faster in some individuals - haemaglobinopathy (SCA, thalassaemia) can change red cell half life - renal failure, blood loss

Question 26

What does a high HbA1c mean?

Answer 26

Higher blood glucose

Question 27

At what blood glucose level is someone considered to be hypoglycaemic?

Answer 27

< 3.6 mmol/l

Question 28

Explain the significance of hypoglycaemia in diabetic patients?

Answer 28

* Occasional hypoglycaemic episodes are inevitable as a result of treating diabetes * Major cause of anxiety in patients + families * Source of major misconceptions in media * Blood glucose < 3 mmol/l: most mental processes impaired * Blood glucose < 2 mmol/l: consciousness impaired

Question 29

When is hypoglycaemia defined as sever?

Answer 29

* Any hypoglycaemic episode that requires the help of another person to treat it * May contribute to arrhythmia and sudden death

Question 30

What is the main risk factor of hypoglycaemia in diabetic patients?

Answer 30

Quality of glycaemic control

Question 31

When do hypoglycaemic episodes happen?

Answer 31

* Can occur at any time | * Often a clear pattern e.g. pre-lunch, nocturnal

Question 32

Why does hypoglycaemia occur?

Answer 32

* Patients may start going to the gym while not changing their insulin dose * May miss meals/inadequate snack * Alcohol * Inappropriate insulin regime

Question 33

What are the symptoms and signs of hypoglycaemia?

Answer 33

``` Due to increased autonomic activation • palpitations (tachycardia) • tremor • sweating • pallor/cold extremities • anxiety ``` ``` Due to impaired CNS function • drowsiness • confusion • altered behaviour • focal neurology •coma ```

Question 34

How can hypoglycaemia be treated?

Answer 34

Oral (feed if patient is unconscious) • quick acting glucogels • complex CHO (to maintain blood glucose after initial treatment) Parenteral (if unconscious) • IV dextrose (10%) glucose infusion • 1mg glucagon (IM) • Avoid conc. solutions e.g. 50% glucose - can cause severe skin reactions

Question 35

A patient can be sent home with a glucagon emergency pack, but when might this not be useful?

Answer 35

* Relies on the liver having enough glucose * If you have been fasting for days, glycogen stores in liver will be depleted * Glucagon may not work