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Year 2 RE > Management of Type 2 Diabetes Mellitus > Flashcards

Management of Type 2 Diabetes Mellitus Flashcards

1
Q

Biguanides is more commonly known by what name in the treatment of T2DM?

A
  • metformin
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2
Q

Biguanides, commonly known as metformin are able to have what effects on the liver to treat T2DM?

A
  • activates AMPK which inhibits enzymes required for gluconeogenesis
  • reduced gluconeogenesis (non-carb substrates (such as lactate, amino acids, and glycerol) into glucose)
  • lower levels of gluconeogenesis mean lower glucose released into the blood
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3
Q

Biguanides, commonly known as metformin are able to have what effect on insulin receptors?

A
  • increase sensitivity (up-regulation of insulin receptors)

- GLUT-4 expression increased in muscle and fat allowing glucose to be absorbed

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4
Q

What are incretins?

A
  • group of hormones responsible for reducing blood glucose

- glucagon like peptide-1 (GLP-1) is an example

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5
Q

Incretins are a group of hormones responsible for reducing blood glucose, such as glucagon like peptide-1 (GLP-1). Enteroendocrine cells are specialised cells that are able to release incretins. What are the 2 locations where enteroendocrine cells can be located?

A

1 - pancreas

2 - small intestines

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6
Q

Incretins are a group of hormones responsible for reducing blood glucose, such as glucagon like peptide-1 (GLP-1). Enteroendocrine cells are specialised cells that are able to release incretins. What effects do biguanides, specifically metformin have on GLP-1?

A
  • increase the secretion of GLP-1 (GLP-1 binds to GLP GPCR on pancreas and releases insulin)
  • increased GLP-1 increases insulin absorption by tissues
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7
Q

What effect do biguanides, or metformin have on the synthesis of glucose, lipids and protein?

A
  • inhibit the synthesis of glucose, lipids and protein

- stimulate the uptake of glucose and fatty acid oxidation (using fat to produce energy)

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8
Q

5% of patients taking metformin experience what?

A
  • gastrointestinal symptoms
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9
Q

In addition to gastrointestinal symptoms what are the other 3 main side effects of metformin?

A

1 - headaches
2 - B12 deficiency (reduced absorption)
3 - hypoglycaemia (due to effect on insulin)

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10
Q

Where is metformin removed from the body?

A
  • metformin is not metabolised

- instead it is excreted unchanged in the urine

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11
Q

What are the 3 most common contradictions for metformin prescription?

A
  • acute metabolic acidosis (diabetic ketoacidosis and lactic acidosis)
  • eGFR <30ml/min/1.73m2 (as it is released from kidneys, with normal eGFR being >60))
  • liver dysfunction due to lactic acidosis
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12
Q

How can metformin cause lactic acidosis?

1 - increases lactate production in muscles
2 - alters pH of blood leading to lactic acidosis
3 - reduces gluconeogenesis which uses lactic acid
4 - increases enzymes responsible for lactate production

A

3 - reduces gluconeogenesis which uses lactic acid

  • lactate can be recycled in liver during gluconeogenesis to make energy
  • metformin inhibits gluconeogenesis meaning lactate remains in the blood
  • kidneys can remove lactate, but patient with diabetes have impaired eGFR meaning lactate cannot be effectively removed
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13
Q

What is the function of glucosidase?

A
  • enzyme that catalyze the hydrolysis of starch to simple sugars
  • important for carbohydrate digestion and absorption in the GIT
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14
Q

Alpha-glucosidase inhibitors are a medication used to treat diabetes. What is the mechanism of action of this drug?

A
  • inhibition of a-glucosidase
  • carbohydrate digestion and absorption is reduced
  • reduces postprandial hyperglycaemia
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15
Q

Alpha-glucosidase inhibitors are a medication used to treat diabetes, inhibiting a-glucosidase and therefore reducing carbohydrate digestion and absorption and reducing postprandial hyperglycaemia. What are the 2 most common side effects?

A
  • GI symptoms (food is undigested due to inhibition of enzyme)
  • liver injury (but rarer)
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16
Q

What are the 3 contraindications to prescribing a patient α-glucosidase?

A
  • digestion or absorption problems
  • inflammatory bowel disease
  • predisposition to intestinal obstruction
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17
Q

When glucose is present in the blood, which glucose transporter is present on beta cells to detect the blood glucose?

1 - GLUT-1
2 - GLUT-2
3 - GLUT-3
4 - GLUT-4

A

2 - GLUT-2

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18
Q

When glucose is present in the blood, GLUT-2 (glucose transporter) is present on beta cells to detect the blood glucose and allow glucose to enter the beta cell. The glucose undergoes glycolysis (glucose to ATP) and then when ATP levels reach a specific concentration what happens to the K+ channels on the beta cell?

A
  • the K+ channels close and depolarise the cell
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19
Q

When glucose is present in the blood, GLUT-2 (glucose transporter) is present on beta cells to detect the blood glucose and allow glucose to enter the beta cell. The glucose undergoes glycolysis (glucose to ATP) and then ATP levels rise causing K+ channels to close and depolarise the cell. What then must occur for insulin to be released by the beta cell?

A
  • Ca2+ channels open due to depolarisation
  • Ca2+ entry into the cell signals exocytosis of vesicles containing insulin
  • insulin is released into the blood
20
Q

What is the mechanism of action of the drug group sulphonylureas, with the drug we need to know Gliclazide?

A
  • K+ ATP sensitive channel not as sensitive in T2DM
  • binds and blocks K+ channels from opening
  • K+ cannot leave the beta cell and the cell depolarises, Ca2+ channels open and insulin is released
21
Q

What are the 3 main side effects of sulphonylureas, with the drug we need to know Gliclazide?

A

1 - hypoglycaemia
2 - weight gain
3 - secondary failure of beta cells due to excessive stress

22
Q

What are the 3 main contraindications of sulphonylureas, with the drug we need to know Gliclazide?

A
  • ketoacidosis
  • acute porphyuria (build up of chemical in the body, likely due to kidneys)
  • cautions: age, obesity (as drug can cause weight gain) and G6PD deficiency
23
Q

What are sodium-dependent glucose co-transporters (SGLT-2)?

A
  • mediates activity of apical sodium and glucose transport across cell membranes
24
Q

Sodium-dependent glucose co-transporters (SGLT-2) mediates activity of apical sodium and glucose transport across cell membranes. Because Na+ is required to transport glucose, which membrane bound channel is crucial to ensure SGLT-2 functions effectively?

A
  • driven by active sodium extrusion by the basolateral sodium/potassium-ATPase
  • glucose can then move against its concentration gradient
25
Q

Where are sodium-dependent glucose co-transporters (SGLT-2) located in the body?

A
  • in the nephron of the kidneys

- specifically the convoluted proximal tubule

26
Q

In a normal healthy person does glucose pass through the glomerulus into the filtrate and then through the collecting tubules?

A
  • yes
27
Q

In a normal healthy person glucose passes through the glomerulus, into the filtrate and then through the collecting tubules. What then happens to the glucose?

A
  • normally 100% of glucose is reabsorbed along with Na+, mainly in the convoluted proximal tubule
  • no glucose in the urine, which if present is called glycosuria or glucosuria
28
Q

If there is hyperglycaemia, like when it occurs in T2DM there is too much glucose in the blood. What level must the blood glucose reach in order for the convoluted proximal tubule not to be able to absorb 100% of the glucose?

A
  • > 10mmol/L
29
Q

Once glucose and Na+ is re-absorbed by the sodium-dependent glucose co-transporters (SGLT-2), what happens to it?

A
  • it diffuses back into the blood
30
Q

What is the mechanism of action of sodium-dependent glucose co-transporters (SGLT-2) inhibitors?

A
  • inhibit SGLT-2
  • Na+ and glucose are not reabsorbed and instead passed through urine
  • this reduces blood glucose
31
Q

What are the 3 drugs that come under the class of sodium-dependent glucose co-transporters (SGLT-2) inhibitors that we need to know about?

A

1 - Dapagliflozin
2 - Canagliflozin
3 - Empagliflozin

ALL END IN GLIFOZIN

32
Q

DO sodium-dependent glucose co-transporters (SGLT-2) inhibitors affect insulin secretion?

A
  • no
33
Q

What are the main side effects of sodium-dependent glucose co-transporters (SGLT-2) inhibitors?

A
  • glucosuria
  • genital and urinary tract infection (lots of sugar increases risk of infection)
  • euglyaemic (normal blood glucose) DKA, can often be missed as blood glucose appears normal
  • polyuria
  • hypotension (due to water loss)
  • reduce bone density
34
Q

What are the 4 main contraindications for sodium-dependent glucose co-transporters (SGLT-2) inhibitors?

A

1 - risk of diabetic ketoacidosis
2 - chronic kidney disease
3 - age (fluid volume loss)
4 - heart failure (loss of volume)

35
Q

What are the 4 key drugs we need to know that are part of the glucagon like peptide-1 (GLP-1) class?

A

1 - Dulaglutide
2 - Exanatide
3 - Liraglutide
4 - Semaglutide

36
Q

Incretins are a group of hormones responsible for reducing blood glucose, such as glucagon like peptide-1 (GLP-1). in addition to inducing insulin secretion from the beta cells of the pancreas what are 3 other mechanisms of GLP-1 agonists that occur outside of the pancreas?

A

1 - reduces hepatic gluconeogenesis
2 - increases peripheral insulin sensitivity
3 - delayed gastric emptying meaning a slower spike in blood glucose

37
Q

Incretins are a group of hormones responsible for reducing blood glucose, such as glucagon like peptide-1 (GLP-1). in addition to inducing insulin secretion from the beta cells of the pancreas, what are 3 other mechanisms of GLP-1 agonists that occur inside pancreas?

A

1 - reduce stress on beta cells, therefore enhancing beta cells replication
2 - prevents beta-cells apoptosis
3 - inhibition of glucagon secretion

38
Q

Incretins are a group of hormones responsible for reducing blood glucose, such as glucagon like peptide-1 (GLP-1). Enteroendocrine cells are specialised cells that are able to release incretins. What are the 3 main side effects of GLP-1 agonists?

A
  • gastrointestinal side effects (nausea and loose stools)
  • hypersensitivity (has been linked with auto immunity)
  • local skin reactions to injection sites
39
Q

Incretins are a group of hormones responsible for reducing blood glucose, such as glucagon like peptide-1 (GLP-1). Enteroendocrine cells are specialised cells that are able to release incretins. What are the 6 main contraindications of GLP-1 agonists?

A 
1 - diabetic gastroparesis and other GI disorders
2 - > 75 years or over 
3 - diabetic ketoacidosis
4 - diabetic retinopathy (Semaglutide)
5 - history of pancreatitis
6 - severe congestive heart failure
40
Q

What are the 5 main side effects associated with insulin?

A 
1- hypoglycaemia (6% of deaths in T1DM)
2 - weight gain 
3- reaction at injection site 
4 - cancer risk – non consistent results
5 - cardiovascular risk related to hypoglycaemia
41
Q

If a patient has been diagnosed with T2DM, or is at risk of developing T2DM as per a rise in HbA1c >48mmol/mol (6.5%), what are the first 2 things that must be discussed prior to medications?

1 - diet only
2 - exercise only
3 - metformin
4 - diet and exercise

A

4 - diet and exercise

42
Q

If a patient has been diagnosed with T2DM, or is at risk of developing T2DM as per a rise in HbA1c >48mmol/mol (6.5%), the first 2 things that must be discussed prior to medications are exercise/physical activity and diet. If diet and exercise fail, what is the first line medication treatment for this group of patients that could be prescribed with diet and exercise?

1 - sulphonylureas
2 - insulin
3 - metformin
4 - SGLT-2 inhibitors

A

3 - standard metformin

- if poorly tolerated (GI symptoms) modified metformin should be prescribed (reduces GI effects)

43
Q

If a patient has been diagnosed with T2DM, or is at risk of developing T2DM as per a rise in HbA1c >48mmol/mol (6.5%), the first 2 things that must be discussed prior to medications are exercise/physical activity and diet. If diet, exercise and metformin fail at trying to reduce HbA1c below 48mmol/mol, what is the next treatment option for patients?

1 - diet, exercise and stronger does of metformin
2 - diet, exercise, metformin and bariatric surgery
3 - diet, exercise, metformin and a sulphonylureas (gliclazide) or SGLT-2
4 - diet, exercise, metformin and a sulphonylureas (gliclazide) and SGLT-2

A

3 - diet, exercise, metformin and a sulphonylureas (gliclazide) or SGLT-2

44
Q

If a patient has been diagnosed with T2DM, or is at risk of developing T2DM as per a rise in HbA1c >48mmol/mol (6.5%), the first 2 things that must be discussed prior to medications are exercise/physical activity and diet. If diet, exercise, metformin and a sulphonylureas (gliclazide) or SGLT-2 fail at trying to reduce HbA1c below 48mmol/mol, what is the next treatment option for patients?

1 - diet, exercise and stronger does of metformin
2 - diet, exercise, metformin and bariatric surgery
3 - diet, exercise, metformin and a sulphonylureas (gliclazide) or SGLT-2
4 - diet, exercise, metformin and a sulphonylureas (gliclazide) and SGLT-2

A

4 - diet, exercise, metformin and a sulphonylureas (gliclazide) and SGLT-2

45
Q

If a patient has been diagnosed with T2DM, or is at risk of developing T2DM as per a rise in HbA1c >48mmol/mol (6.5%), the first 2 things that must be discussed prior to medications are exercise/physical activity and diet. If diet, exercise, metformin, sulphonylureas (gliclazide) and SGLT-2 fail at trying to reduce HbA1c below 48mmol/mol, what is the next treatment option for patients?

1 - diet, exercise, metformin and a sulphonylureas (gliclazide), SGLT-2 and insulin
2 - diet, exercise, metformin and bariatric surgery
3 - diet, exercise, metformin and a sulphonylureas (gliclazide) or SGLT-2
4 - diet, exercise, metformin and a sulphonylureas (gliclazide) and SGLT-2

A

1 - diet, exercise, metformin and a sulphonylureas (gliclazide), SGLT-2 and insulin

46
Q

If a patient has a HbA1c >48mmol/ml (6.5%), they have failed to respond to lifestyle changes, and they are unable to be prescribed metformin, what would be the first line treatment?

1 - sulphonylureas or SGLT-2 inhibitors
2 - insulin or SGLT-2 inhibitors
3 -SGLT-2 inhibitors and bariatric surgery
4 - SGLT-2 inhibitors alone

A

1 - sulphonylureas or SGLT-2 inhibitors

Year 2 RE (53 decks)

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