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Phase 2 3. Endocrinology > Type 2 diabetes > Flashcards

Type 2 diabetes Flashcards

1
Q

What significant morbidity is linked to T2DM?

A 
Cancer
Cirrhosis
Retinopathy
Stroke
Heart disease
Nephropathy
Foot problems
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2
Q

What is T2DM?

A

Combination of insulin resistance allied to a failure of adequate insulin secretion
Imbalance results in T2DM
Insulin output is unable to match resistance levels

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3
Q

Describe the key features of T2DM disease progression

A

Hyperinsulinaemia
Insulin resistance
Hyperglycaemia

Macrovascular complications occur earlier on
Microvascular complications are observed later

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4
Q

Why does insulin resistance occur?

A 
> Genetic susceptibility
> Environmental triggers
> Two major predictors:
   - Poverty
   - Ethnicity
> Visceral fat producing adipokines
> Genetic conditions 
  - small no. with insulin receptor mutations: severe hyperinsulinaemia, associated with acanthosis nigricans and features of hyperandrogenism -> Very strong genetic predisposition - normally all family members are affected
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5
Q

What are adipokines?

A

Cytokines secreted by the adipose tissue

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6
Q

List the adipokines

A

Leptin
Adiponectin
TNFalpha
Resistin

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7
Q

Where are adipokines found?

A

In the visceral fat around organs

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8
Q

What is leptin?

A

An adipokine

- Tells hypothalamus about amount of stores fat

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9
Q

What is adiponectin?

A

An adipokine

- Reduced levels of free fatty acids

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10
Q

What is TNFalpha

A

An adipokine

- Associated with low-grade inflammation

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11
Q

What is resistin?

A

An adipokine

- Enhances hypothalmic stimulation of glucose production

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12
Q

What factors can affect insulin secretion?

A

> Glucotoxicity can lead to impaired beta cell function
Glucokinase defects impair insulin secretion
Pancreatic beta cell transcription factor mutations lead to reduced insulin production in response to glucose - still senses glucose levels but inadequate insulin production

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13
Q

What is microvascular disease?

A

Complications related to smaller blood vessels (e.g. in kidney, eyes and nerves)

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14
Q

How can microvascular disease be prevented?

A

Reduction of glucose levels

Reducing HbA1c by 10mmol/mol results in a 20% overall risk reduction

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15
Q

Which drug acts on the gut?

A

Acarbose

  • inhibits alpha glucosidase, (a small intestine brush border enzyme) and pancreatic alpha-amylase
  • reduces digestion of complex carbohydrates, minimising glucose absorption
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16
Q

Which drugs acts at the muscle bed?

A

Metformin & Pioglitazone modify glucose uptake at the muscle bed

Insulin also has an impact on glucose uptake at the muscle bed

17
Q

Which drug acts on the kidney?

A

SGLT2 inhibitors

18
Q

Which drugs increase insulin secretion?

A

> Insulin
sulfonylurea -> constant insulin release
DDP-4 inhibitors -> augment insulin secretion in a glucose-dependent manner
GLP-1 receptor agonists -> augment insulin secretion in a glucose-dependent manner

19
Q

Which drugs act on the liver?

A

Reduce glucose production

> Metformin
GLP-1 receptor agonists
DPP-4 inhibitors
Insulin

20
Q

What are GLP-1 effects in humans?

A

Secreted upon the ingestion of food

> beta cell - enhances glucose-dependent insulin secretion in the pancreas
alpha cell - suppresses post-prandial glucagon secretion
liver - reduces hepatic glucose output
stomach - slows the rate of gastro emptying
brain - promotes satiety and reduces appetite

21
Q

How can GLP-1 levels be influenced?

A

Preventing breakdown by DPP-4 to increase physiological levels

Exogenous GLP-1 agonist

22
Q

What are the effects of using exogenous GLP-1 agonists?

A

Significant glucose-lowering benefit

Weight loss

23
Q

Name DPP-4 inhibitors

A 
Sitagliptin
Vildagliptin
Saxagliptin
Linagliptin
Alogliptin
24
Q

Name GLP-1 receptor agonists

A 
Exanatide
Liraglutide
Exenatide
Lixisenatide
Dulaglutide
25
Q

What is the mechanism of action of SGLT2 inhibitors

A

Inhibits SGLT2, which reabsorbs 90% glucose in the proximal tubule of the kidney

  • More glucose is excreted
  • Plasma glucose levels drop
  • Weight decreases due to calorie loss

NB: causes osmotic diuresis -> lowers blood pressure
Can predispose to significant acidosis in patients with insufficient insulin
Should NOT be used in T1DM

26
Q

Name SGLT2 inhibitors

A

Dapaglifloxin
Canagliflozin
Empagliflozin

27
Q

What is the first line treatment for T2DM

A

Lifestyle measures

Metformin or sulphonylurea (if intolerent to metformin or osmotic symptoms present)

28
Q

What is the second line treatment for T2DM?

A 
If not reaching target after 3-6 months:
Check adherence
Add one of:
- sulphonylurea
- pioglitazone
- DPP-4 inhibitor
- SGLT2 inhibitor
29
Q

What is the third line treatment for T2DM?

A 
If not reaching target after 3-6 months:
Check adherence
Add either an oral agent of a different class:
- sulphonylurea
- pioglitazone
- DPP-4 inhibitor
- SGLT2 inhibitor
OR an injectable agent:
- if BMI >30 = GLP-1 agonist
- if BMI <30 = basal insulin

Phase 2 3. Endocrinology (25 decks)

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