S4C6

Question 1

What are factors for developing T2DM?

Answer 1

Underactivity
Over eating
Obesity
Excess triglycerides within cells
Older age
Family history
Ethnicity

Question 2

What surgery is linked to T2DM?

Answer 2

T2DM is the leading cause of non-traumatic amputation

Question 3

What is metabolic syndrome?

Answer 3

a cluster of conditions that occur together, increasing your risk of heart disease, stroke and type 2 diabetes. These conditions include increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels.

Question 4

What is the pathology of Type 2 diabetes?

Answer 4

Insulin is released normally, and will still bind to insulin receptors but it will not cause the normal physiological response inside the cell
Muscle cells show increase insulin resistance and decreased glucose uptake
The secretory failure of insulin occurs when there is increase Beta-islet cell apoptosis and the remaining cells fail to respond to insulin signalling

Question 5

How does the liver respond to insulin resistance?

Answer 5

Less glucose entering liver cells so the liver reacts as if the blood glucose were low and begins glycogenolysis and raises blood glucose even more

Question 6

What tests are done to diagnose HbA1c?

Answer 6

HbA1c >6.5%
Fasting blood glucose < 4- 6 mmol/L
Post-prandial bm <7.8 mmol/L
Random blood glucose >11mmol/L

Question 7

What is HbA1c?

Answer 7

A type of glycated haemoglobin
The higher the glucose levels, the greater amount of glycated haemoglobin (Rate of glycation is relatively consistent)
Indicator of glucose for 3 months (RBC lifespan)
Studies show complications of diabetes can be prevented when <7%

Question 8

What is the acute clinical presentation of T2DM?

Answer 8

Polyuria - due to osmotic diuresis that occurs when blood glucose levels exceed the renal threshold
Thirst - due to the resulting loss of fluid and electrolytes
Weight loss - due to fluid depletion and the accelerated breakdown of fat and protein reserves as a result of insulin deficiency

Question 9

What are the symptoms of T2DM?

Answer 9

Lethargy/ lack of energy
Polyuria
Polydipsia
Visual blurring - as a result of glucose affecting refraction
Frequent fungal/bacterial infections - often in the genitals
e.g. UTIs, Balanitis - inflammation of the glans penis, Pruritis vulvae in females - due to candida
(High glucose environment in the genital region encourages growth of pathogens)
Loss of sensation
Weight loss

Question 10

What are the clinical signs of insulin resistance?

Answer 10

Acanthosis nigricans - dark coloured skin with a velvet-like texture
Typically around the neck and axillae
Skin tags
Central obesity
Hirsutism - excess male pattern hair growth, most notable in women

Question 11

What treatments are available for T2DM patients?

Answer 11

Up to 30% of patients can be managed by diet alone
1/3 of patients will be managed by oral treatment
1/3 of patients will be managed by insulin

Question 12

What is the treatment plan for T2DM?

Answer 12

Step wise approach:

1. Lifestyle
2. Lifestyle +metformin
3. Lifestyle + metformin + secondary drug agent
4. Lifestyle + metformin + secondary drug agent + insulin

Question 13

What diet changes should a T2DM patient make?

Answer 13

Low sugar
High starch carbohydrate (esp. Foods with low glycaemic index)
Carbs should account for 40-60% of total energy intake
Three servings of whole grains daily is recommended
Confectionary should account for <10%

Question 14

Where is insulin produced and what is its function?

Answer 14

Beta cells

reduce blood glucose by promoting cellular glucose uptake

Question 15

Where is Glucagon produced and what is its function?

Answer 15

Alpha cells

increase blood glucose by stimulating glycogen breakdown

Question 16

How does insulin work?

Answer 16

Insulin binds to the α-receptor on cells which is linked to the transmembrane β-receptor. This activates Tyrosine kinase which phosphorylates enzymes.

Question 17

What are the actions of insulin?

Answer 17

Increase glucose disposal (e.g. Glycogen synthesis) in liver, muscle and adipose tissue
Stimulates biosynthesis in the presence of glucose and other metabolic fuel
Inhibits lipolysis and increase lipogenesis
Inhibits hepatic glucose synthesis (e.g gluconeogenesis)
Increases glycogen and fatty acid synthesis
Growth and gene expression
Glucose transport

Question 18

What are incretins?

Answer 18

a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood glucose-dependent mechanism.

Question 19

What are 2 examples of incretins?

Answer 19

GIP (Glucose dependent insulinotropic polypeptide)

GLP-1 (Glucagon like peptide-1)

Question 20

What are the functions of incretins?

Answer 20

Stimulates insulin release
Reduce alpha cell workload
Increase beta cell workload
Full feeling
Reduce glucose synthesis in the liver
Slow gastric emptying

Question 21

How are incretins linked to T2DM?

Answer 21

Secretion of GLP-1 is reduced
Sensitivity of beta cells is decreased
GIP response often markedly reduced or abolished completely

Question 22

What are the consequences of peripheral insulin resistance?

Answer 22

Pancreas - impaired insulin secretion
Adipose tissue - Increased lipolysis, inhibition of lipgenesis, impaired glucose disposal
Skeletal muscle - impaired glucose disposal
Liver - Increased hepatic glucose production, increased VLDL and FFA, impaired glucose disposal

Question 23

How does ER stress occur?

Answer 23

Peripheral resistance increases the demand on beta cells to produce and secrete insulin

Question 24

What are the consequences of ER stress?

Answer 24

Contributes to protein misfolding and stress signalling

Causes apoptotic cell death and accumulation of amyloid fibrils

Question 25

What are the effects of hyperglycaemia?

Answer 25

Associate with ketoacidosis in T1 diabetics, is a medical emergency
Fatigue
Polydipsia
Polyuria
Headache and blurred vision

Question 26

What are the effects of hypoglycaemia?

Answer 26

<4mmol/L
At 3 mmol/L patients will experience mils neuroglycopenia and some mild cognitive impairment slightly below that level.
Activation of autonomic systems gives rise the sweating and tremor around 2-2.5 mmol/l (can be higher), elevated HR.
Convulsions as a result of severe neuroglycopenia at 1 mmol/L.
Coma and death result if prompt action is not taken

Question 27

What are the different subtypes of insulin secretagogues drugs?

Answer 27

DPP4 inhibitors
GLP-1 receptor agonist
Sulphonylureas
Meglitinides

Question 28

How do DPP4 inhibitors work?

Answer 28

DPP-4 inhibitors work by blocking the action of DPP-4, an enzyme which destroys the hormone incretin.

Question 29

How do GLP-1 receptor agonists work?

Answer 29

they mimic GLP-1 hormone by binding to GLP-1 receptors and stimulating insulin release, which reduces blood sugar. GLP-1 agonists also act on the stomach, brain, pancreas, and liver to increase feelings of fullness and reduce after meal blood sugars, which promotes weight loss and improves blood sugar control.

Question 30

How do Sulphonylureas/ Meglitinides work?

Answer 30

They bind to an ATP-dependent K+ (KATP) channel on the cell membrane of pancreatic beta cells and stimulate the production of insulin in the pancreas and increasing the effectiveness of insulin in the body.

Question 31

What are the subtypes of insulin sensitiser drugs?

Answer 31

Thiazolidinediones

Biguanides

Question 32

How do Thiazolidinediones work?

Answer 32

Bind to peroxisome proliferator-activated receptor gamma in adipocytes to promote adipogenesis and fatty acid uptake (in peripheral but not visceral fat).

Question 33

How do Biguanides work?

Answer 33

prevent the production of glucose in the liver, improving the body’s sensitivity towards insulin and reducing the amount of sugar absorbed by the intestines.

Question 34

How do SGLT2 inhibitors work?

Answer 34

Cause excess glucose to be eliminated in the urine reducing hyperglycaemia

Question 35

How do α-glucosidase inhibitors work?

Answer 35

slowing down the absorption of starchy foods from the intestine. This means that blood glucose levels rise more slowly after meals.

Question 36

What type of T2DM drug is metformin? What is its MOA?

Answer 36

Insulin sensitiser
decreases blood glucose levels by decreasing hepatic glucose production (gluconeogenesis), decreasing the intestinal absorption of glucose, and increasing insulin sensitivity by increasing peripheral glucose uptake and utilization

Question 37

Where are the hypothalamic centres for thirst and hunger?

Answer 37

The extreme lateral part of the ventromedial nucleus of the hypothalamus is responsible for the control of food intake
The hypothalamus contains specialized glucose-sensitive neurons (in the arcuate nucleus and ventromedial hypothalamus), which are important for appetite.

Question 38

What is the epidemiology of T1DM?

Answer 38

∼ 5% of all patients with diabetes
Childhood onset: typically < 20 years but can occur at any age; peaks at age 4–6 years and 10–14 years
Highest prevalence in non-Hispanic whites

Question 39

What is the aetiology of T1DM?

Answer 39

Autoimmune β cell destruction in genetically susceptible individuals
Can be autoimmune or idiopathic

Question 40

What is the pathophysiology of T1DM?

Answer 40

Genetic susceptibility
Environmental trigger (often associated with previous viral infection)
Autoimmune response with production of autoantibodies, that target insulin-producing cells
Causes progressive destruction of insulin-producing β cells in the pancreatic islets by autoreactive T cells (destruction of 80–90% of β cells)
Absolute insulin deficiency → elevated blood glucose levels

Question 41

What test can be done specifically for T1DM?

Answer 41

Specific autoantibodies:
Anti-GAD
Anti-tyrosine phosphatase-related islet antigen (IA-2)
Islet cell surface antibody (ICSA; against ganglioside)
C-peptide: ↓ C-peptide levels indicate an absolute insulin deficiency