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YR2: Endocrinology > The Aetiology and Treatment of Type 2 Diabetes Mellitus > Flashcards

The Aetiology and Treatment of Type 2 Diabetes Mellitus Flashcards

1
Q

What tests are performed to diagnose diabetes and what are the defining values?

A 
Fasting Blood Glucose: 
Normal < 6
Impaired Fasting Glucose = 6-7
Diabetes > 7
Glucose Tolerance Test (2 hr measurement) 
Normal < 7.8
Impaired Glucose Tolerance = 7.8-11.1
Diabetes > 11.1
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2
Q

State 3 factors that influence the pathophysiology of T2DM.

A

Genetics
Intrauterine environment
Adult environment

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3
Q

How is the intrauterine environment important in the pathogenesis of T2DM?

A

Epigenetic changes take place in utero which affect blood glucose control in the future

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4
Q

What is MODY?

A

Mature onset diabetes of the young (8 types)
Autosomal dominant
Ineffective pancreatic B cell insulin production
Caused by mutations of transcription factor genes (glucokinase gene)
Positive family history with NO obesity

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5
Q

What can modulate insulin resistance through adult life before someone develops diabetes?

A

Adipocytokines

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6
Q

What type of babies are more likely to develop T2DM in later life?

A 
Small babies (low birth weight)  
Due to intrauterine growth restriction
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7
Q

How does insulin resistance lead to hypertension?

A

Insulin resistance leads to a compensatory hyperinsulinaemia
Though the insulin doesn’t affect the glycaemic control pathway, it stimulates the mitogenic pathway causing smooth muscle hypertrophy causing high BP

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8
Q

What eventually happens to the beta cells in T2DM?

A

Insulin resistance damages the B cells, eventually results in B cell failure

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9
Q

Describe how beta cell potential for insulin secretion and insulin resistance change with age.

A

Potential for insulin secretion decreases with age

Insulin resistance increases with age

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10
Q

Describe the metabolism + presentation of a typical patient with T2DM.

A 
Heterogeneous
Obese (80%) 
Insulin resistance + insulin secretion deficit  
Hyperglycaemia + dyslipidaemia 
Acute + chronic complications
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11
Q

What dietary changes can someone with T2DM make to reduce the effect of the missing first phase insulin release?

A

Complex carbohydrates: release glucose more slowly

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12
Q

Describe glucose clearance and hepatic glucose output in T2DM.

A

Glucose clearance is decreased (less able to enter muscle + less stored as glycogen)
HGO is increased

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13
Q

What normally happens to insulin secretion as insulin resistance increases?

A

Insulin secretion increases to compensate for the increased insulin resistance

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14
Q

Which adipocytes are particularly marked for breakdown of triglycerides?

A

Omental adipocytes (thus, omental fat correlates with risk of heart disease)

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15
Q

What happens to fatty acids when they go into the liver?

A

Can’t be used to make glucose so are converted to VLDL’s which are highly atherogenic

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16
Q

Describe how gut microbiota is implicated in T2DM.

A

May alter host signalling: they ferment lipopolysaccharides to short chain fatty acids, which enter the circulation + modulate bile acids (so affect host metabolism)
Associated with inflammation + adipocytokine pathways

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17
Q

What is a very common side effect of diabetes treatment?

A

Weight gain

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18
Q

Which diabetes treatment does not cause weight gain?

A

Metformin

19
Q

What are the management strategies for T2DM?

A

Education
Diet
Pharmacological treatment
Complication screening

20
Q

What dietary measures are recommended for someone with T2DM?

A

Decreased fat (particularly sat. fats) + refined carbs
Increased complex carbs + soluble fibre
Control total calories + increase exercise
Reduce salt

21
Q

What is orlistat and why is it sometimes used in T2DM?

A

Pancreatic Lipase Inhibitor
Reduces break down of fats in the intestines thus reducing absorption of fats
More is excreted

22
Q

State 7 classes of drugs that are used to treat T2DM and state how they work.

A

Insulin: reduces HGO
Metformin: insulin sensitiser
Sulphonylureas: makes existing pancreas produce more insulin
Alpha-glucosidase inhibitors: prolongs absorption of glucose from the intestine
Thiazolidinediones: act on insulin resistance (central + peripheral)
GLP-1 agonists + DPP4 inhibitors: increase insulin secretion + have anti-glucagon effect
SGLT2 inhibitors: act on PCT to increase glycosuria

23
Q

When should you NOT use metformin?

A

Severe liver failure
Severe cardiac failure
Mild renal failure

24
Q

Name one sulphonylurea.

A

Glibenclamide

Given to lean patients with T2DM (as causes weight gain)

25
Q

Explain how sulphonylureas work.

A

Bind to receptors + block the ATP-sensitive K+ channel

Leads to Ca2+ influx, which causes insulin release

26
Q

Name one alpha-glucosidase inhibitor. Explain how it works and state 1 side effect.

A

Acarbose
Prolongs absorption of oligosaccharides + allows the body to cope with the loss of 1st phase insulin
Side effect: flatus

27
Q

Name a thiazolidinedione. What are its effects?

A

Pioglitazone
=PPAR agonist
Insulin sensitises mainly in peripheral tissues (leads to peripheral weight gain)

28
Q

What does GLP-1 do?

A

Responsible for the incretin effect (where oral glucose stimulates more insulin than IV glucose)
Stimulates insulin + suppresses glucagon

29
Q

What breaks down GLP-1?

A

Dipeptidyl peptidase-4 (DPP4)

30
Q

How do gliptins work?

A 
Inhibit DPP4 (increase half life of GLP1)
Increases [GLP1]
Decreases [glucagon]
Decreases [glucose]
Neutral on weight
31
Q

Name a GLP1 agonist. Describe the action of GLP1 agonists

A 
Exenatide.
Injectable, long acting
Decrease [glucagon]
Decrease [glucose]
Cause weight loss
32
Q

Name an SGLT2 inhibitor and describe its mechanism of action

A

Empaglifozin
Inhibits Na-Glu transporter
Increases glycosuria

33
Q

What can occur during pregnancy to identify women who are at high risk of getting diabetes in the future?

A

Gestational diabetes

34
Q

Define Diabetes Mellitus

A

State of chronic hyperglycaemia sufficient to cause long-term damage to specific tissues e.g. retina, kidney, nerves + arteries

35
Q

Is T2DM ketosis prone?

A

No

36
Q

What 3 clinical signs and symptoms indicate T2DM?

A

Osmotic symptoms
Infections
Presentation of complication e.g. hyperosmolar coma, ischaemic heart disease, retinopathy

37
Q

List 3 microvascular complications of T2DM

A

Retinopathy
Nephropathy
Neuropathy

38
Q

List 2 metabolic complications of T2DM

A

Lactic acidosis

Hyperosmolar coma

39
Q

List 4 macrovascular complications of T2DM

A

Ischameic heart disease
Cerebrovascular disease
Renal artery stenosis
Peripheral vascular disease

40
Q

What treatment complications may arise in T2DM?

A

Hypoglycaemia

Weight gain

41
Q

What 4 elements must be targeted in treatment of T2DM?

A

Weight
Glycaemia
Blood pressure
Dyslipideamia

42
Q

What weight loss treatment may cause T2DM to go into remission?

A

Gastric bypass surgery

43
Q

By what mechanisms does metformin reduce insulin resistance?

A

Reduced HGO

Increases peripheral glucose disposal

44
Q

What intervention is most effective at reducing incidence of T2DM?

A

Lifestyle changes

YR2: Endocrinology (19 decks)

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