Lecture 8.1: Type 1 and 2 Diabetes Mellitus

Question 1

What is Diabetes Mellitus?

Answer 1

A disease in which the body’s ability to produce or. respond to the hormone
insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood

Question 2

Type 1 Diabetes

Answer 2

Occurs when body is unable to produce enough insulin
Tends to develop at young age
Cannot be prevented
Require insulin therapy

Question 3

Type 2 Diabetes

Answer 3

Occurs due to insulin resistance
Tends to develop at an older age
Can be prevented with lifestyle changes
Can be managed with lifestyle modifications alone is diagnosed early

Question 4

Diabetes Symptoms: Type 1 and 2

Answer 4

Frequent urination
Increased thirst and hunger
Unintentional weight loss
Fatigue
Blurry vision
Sores/wounds heal slowly
Numbness/tingling in arms and feet

Question 5

Prediabetes

Answer 5

Means you have a “higher than normal” blood sugar level

It’s not high enough to be considered type 2 diabetes, but without lifestyle changes, adults and children with prediabetes are more likely to develop type 2 diabetes

Question 6

Characteristics of Blood Glucose Regulation Disorders

Answer 6

• Chronic hyperglycaemia
• Long-term clinical complications
• Elevated glucose levels in urine
• Patients are thirsty

Question 7

Diagnosis of Diabetes Mellitus

Question 8

How is glucose used?

Answer 8

• Taken up by cells to be used as energy for all organs
• Liver and muscle metabolise glucose to glycogen
• When glycogen stores full
• Liver metabolises glucose to triacylglycerols
• Carried to adipose tissue as VLDLs for storage

Question 9

Why would blood glucose rise to abnormal levels?

Answer 9

• Glucose remains in the blood. Not taken up by tissues. Hyperglycaemia.

This is because of:
• Lack of insulin (relative or absolute)
• Or ineffective insulin
• The body is essentially starved of glucose

Question 10

How would Hyperglycaemia present?: Osmotic Effects

Answer 10

Polyuria
Dehydration
Thirst (polydipsia)
Glycosuria
Opportunistic Infections (thrush, UTIs)

Question 11

How would Hyperglycaemia present?: Metabolic Impact

Answer 11

Inadequate Energy Utilisation (wasting)
Lethargy

Question 12

Catabolic Crisis

Answer 12

Diabetic KetoAcidosis (DKA)

“Melting of flesh into urine”

Question 13

When does ketogenesis start?

Answer 13

Mitochondrial oxaloacetate depleted

Acetyl CoA reacts with itself to form acetoacetate and 3-hydroxybutyrate (ketone bodies)

Body is in desperate need for fuel source

Question 14

Hyperosmolar Hyperglycaemic State

Answer 14

• HHS, used to be called HONK (HyperOsmolar Non-Ketotic State)
• Very high levels of solute in the blood affecting the osmotic balance
• Resulting in severe dehydration
• Water lost in urine
• Water from cells of body tissues (including brain) drawn out into blood
• High risk of blood clots

Question 15

Long-term effects of hyperglycaemia (2)

Answer 15

Glycation of proteins (Glucose reacts non-enzymatically with free amino groups in cellular and extracellular proteins)

Formation of Reactive Oxygen Species (ROS) (free radicals: damaging lipids, proteins and DNA)

Question 16

Effects of Glycation of Proteins

Answer 16

“Sticky” Blood

Causing microvascular damage/stiffened vessels:
• Neuropathy
• Retinopathy
• Nephropathy
• Hypertension

Question 17

Formation of Reactive Oxygen Species (ROS)

Answer 17

Contribute to vascular damage

Beta cells thought to be particularly prone to enhanced oxidative phosphorylation, causing oxidative stress and loss of β cell function.

A vicious circle…

Question 18

Diabetic Peripheral Neuropathy

Answer 18

Peripheral neuropathy is nerve damage caused by chronically high blood sugar and diabetes

It leads to numbness, loss of sensation, and sometimes pain in your feet, legs, or hands

Question 19

Diabetic Retinopathy

Answer 19

Issue at the back of the eye (retina)

At first, diabetic retinopathy might cause no symptoms or only mild vision problems but may eventually lead to partial or complete blindness

Question 20

Diabetic Nephropathy

Answer 20

Kidney damage caused by diabetes

Damage blood vessels in the kidneys as well as nephrons so they don’t work as well as they should

Many people with diabetes also develop high blood pressure, which can damage kidneys too

Question 21

Macrovascular complications of Diabetes

Answer 21

Cerebrovascular, cardiovascular, peripheral vascular disease
– Stroke
– Heart Attack
– Intermittent Claudication
– Gangrene

Question 22

Cost of Diabetes

Answer 22

Diabetes accounts for about 10% of the NHS budget and 80% of these costs are due to complications

Diabetes will increase the cost of social care; an amputation significantly impacts a person’s ability to look after themselves independently

Question 23

Why the rapid increase in prevalence of Diabetes?

Answer 23

• Obesity
• Longevity
• Unsatisfactory Diets
• Sedentary Lifestyle
• Urbanisation & Economic Development

Question 24

Diagnosis: Haemoglobin A1C

Answer 24

Glycated plasma proteins causing ‘sticky’ blood

HbA1C is a commonly measured glycated protein, minor component of haemoglobin

Level of HbA1C tells us cumulative exposure to plasma glucose concentration, over last 120 days

Most reliably demonstrate 8 week average glucose control

Question 25

Diagnosis

Question 26

Diagnosis

Question 27

Treatments for Type 1 Diabetes

Answer 27

Insulin Injection

Question 28

Treatments for Type 2 Diabetes: Excluding Non-Insulin Therapies

Answer 28

• Lifestyle
• Insulin

Question 29

Treatments for Type 2 Diabetes: Non-Insulin Therapies

Answer 29

Insulin sensitizers

Insulin secretagogues:
• Biguanides (metformin)
• Sulphonylureas
• Thiazolidinediones (rosiglitazone)
• GLP1 analogues
• DPP4 inhibitors
• α-glucosidase inhibitors
• SGLT2s

Question 30

Latrogenic Risks: Hypoglycaemia

Answer 30

• Emergency, so treat immediately
• Brain damage
• Cardiac arrest
• Coma
• Death

Question 31

How do we monitor patients with diabetes? (6)

Answer 31

• Wellbeing
• Educate and empower to monitor own diabetes
• Glucose control - capillary blood glucose testing vs urine glucose testing
• HbA1c – glycated haemoglobin
• Other vascular risk factors – BP, lipids, smoking, exercise, diet
• Surveillance for complications