Diabetes mellitus

Question 1

Define diabetts

Answer 1

Chronic, non-communicable disease characterised by hyperglycaemia

Question 2

What is type 1 diabetes

Answer 2

Chronic autoimmune disease characterised by immune mediated disruption of pancreatic beta cells within islets of Langerhans

Question 3

What must always be injected in type 1 diabetes

Answer 3

Insulin deficiency

Question 4

Name 3 pieces of evidence that suggest T1D is an immune-mediated disease

Answer 4

• Infiltration of pancreas islets by mononuclear cells
• Almost 90% of patients possess autoantibodies against islets
• Immunosupression after diagnosis delays beta cell disruption

Question 5

What % of people with diabetes have T2D

Answer 5

85-90%

Question 6

What characterises type 2 diabetes

Answer 6

Abnormal insulin action adn secretion

Question 7

What genes are suspected to be responsible for T2D

Answer 7

GKRP, PPARG

Question 8

Name some risk factors for T2D

Answer 8

Obesity
Family history
Age
Ethnicity
Environemental factors (urbanisation)

Question 9

Briefly describe how obesity is suspected to cause T2D

Answer 9

• Accumulation of lipids and their metabolites/ increased concentration of circulating free fatty acids
• Adipose tissue releases factors called adipokines which affect insulin resistance
• Chronic inflammation

Question 10

Why does hyperinsulinaemia occur in T2D? What is the effect of this

Answer 10

Pancreas produces more insulin in response to the body not responding to insulin anymore
Increases lipid synthesis which worsens situation

Question 11

How do levels of circulating adipokines contribute to insulin resistance

Answer 11

• Act as level or IRS so phosphorylate IRS in another residue
• Because its phosphorulated can’t be phosphorylated on tyrosine anymore
• Pathway is blocked at this stage

Question 12

Which 2 physiological conditions is insulin resistance associated with in healthy people

Answer 12

Pregnancy

Body weight gain

Question 13

How is physiological insulin resistance different to pathological insulin resistance

Answer 13

In physiological insulin resistance new beta cells can be generated so beta cells can compensate

Question 14

How do islets change during insulin resistance

Answer 14

Increase in size (beta cells increase in size and number)

Increased beta function

Question 15

How do islets change during T2D

Answer 15

Number of islets decrease

Signification decrease in number of beta cells per islet

Question 16

What types of genes are the susceptability genes associated with T2D

Answer 16

Regulators of cell turover or regeneration

Question 17

What happens to glucagon in diabetics

Answer 17

Excessive circulating levels of glucagon because theres no regulation
HYPERGLUCAGONAEMIA

Question 18

Why does hyperglucagonaemia occur in T1D

Answer 18

No insulin in the body to regulate glucagon

Question 19

Why does hyperglycagonaemia occur in T2D

Answer 19

Reduction of beta cells, alpha cells could also be resistant to insulin and hyperglycaemia

Question 20

What is MODY

Answer 20

Maturity onset diabetes of the young- autosomal dominantly inherited form
Pancreatic beta cell dysfunction

Question 21

What is LADA

Answer 21

Latent autoimmune diabetes of the adult

Question 22

2 situations in which diabetes can be diagnosed

Answer 22

• One abnormal plasma glucose in presence of symptoms

- Two fasting venous plasma in abnormal range

Question 23

What should plasma glucose be in oral glucose tolerance test in healthy person

Answer 23

Fasting= <6.1
2h= <7.8

Question 24

What should plasma glucose be in oral glucose tolerance test in person with diabetes

Answer 24

Fasting>7

2h> 11.1

Question 25

What are the advantages of measuring HbA1c

Answer 25

Reliable Stable Patient convenience

Question 26

What is the recommended cut off point of HbA1c for diagnosing patients

Answer 26

48mmol/mol (6.5%)

Question 27

Aims of diabetes treatment

Answer 27

Reduce insulin resistance or reduce hyperglycaemia

Question 28

What drug is the first line treatment for treating diabetes

Answer 28

Metformin

Question 29

Functions of metformin

Answer 29

Improve function of insulin receptor | Improve transport of glucose from blood into muscle

Question 30

What does tzd do

Answer 30

Tackles insulin resistance | Resistant muscles pushed to uptake glucose as well as preventing the liver from producing glucose

Question 31

Why does the liver produce glucose in diabetes

Answer 31

Essentially in starvation condition

Question 32

Where can drug targets be to prevent excessive insulin secretion

Answer 32

Potassium channels | Calcium channels

Question 33

Name 2 drugs that work at the level of potassium channels

Answer 33

Sylfonylureas and meglifinides

Question 34

What is the role of GLP-1

Answer 34

Inhibits secretion of glucagon

Question 35

Effect of metformin on GLP-1

Answer 35

Increases GLP-1 secretion

Question 36

What drug inhibits DDP-4

Answer 36

Sitagliptin

Question 37

What is the threshold for hypoglycaemia

Answer 37

<70mg/dL | <3.9mmol/L

Question 38

Name 5 causes of hypoglycaemia

Answer 38

``` Alcohol excess Insulinoma Excessive exercise Reactive hypoglycaemia Type 1 diabetes ```

Question 39

How does alcohol excess lead to hypoglycaemia

Answer 39

Gluconeogenesis inhibited at the level of lactate dehydrogenase

Question 40

Symptoms of hypoglycaemia

Answer 40

- Trembling - Palpitation - Sweating - Anxiety - Hunger - Tingling

Question 41

What hormones are secreted in hypoglycaemia

Answer 41

Growth hormone | Cortisol

Question 42

What are the consequences of prolonged hypoglycaemia

Answer 42

- Neuroglycopaenia - Permenant brain damage - Loss of cognitive function

Question 43

Name 3 microvascular complications of diabetes

Answer 43

- Nephopathy - Neuropathy - Retinopathy

Question 44

What pathway does glucose activate that isn't normally activated

Answer 44

protein kinase C pathways

Question 45

How does hypoeractivation of PKCs can damage blood vessels

Answer 45

- Increased permeability - Increased occlusion - Increased reactive oxygen species - Increased inflammation - Mitochondrial dysfunction

Question 46

How do glycation end products mediate cellular damage

Answer 46

Lipids modified when they attach molecule of glucose | Products from glucose attach to the proteins leading to changes in activity

Question 47

What is non proliferative diabetic retinopathy

Answer 47

Dilation of retina veins and microaneurysms can cause internal haemorrhaging and oedema in the retina. Oedema in central retina is main cause of vision loss

Question 48

What is proliferative diabetic retinopathy

Answer 48

Fragile, new blood vessels form near the optic disc and grow on vitreous chamber Bleed, reducing vision and leads to separation and detachment of areas of retina

Question 49

What characterises diabetic nephopathy

Answer 49

Proteinuria Glomerular hypertrophy Decreased GFR Renal fibrosis

Question 50

What is peripheral diabetic neuropathy

Answer 50

Pain or loss in feelings in hands/ arms/ feet/ legs

Question 51

What is autonomic diabetic neuropathy

Answer 51

Changes in digestion, bowel and bladder control problems, erectile dysfunction

Question 52

What is proximal diabetic neuropathy

Answer 52

Pain in thighs and hips | Weakness in legs

Question 53

What can promote macrovascular disease

Answer 53

Advanced glycation end production formation

Question 54

How does AGE formation promote macrovascular disease

Answer 54

AGE modification of oxidised LDLR leads to enhanced LDL uptake Induces pro-inflammatory cytokine production