Biochemistry of Type 2 Diabetes Flashcards Preview

MD1 Metabolism > Biochemistry of Type 2 Diabetes > Flashcards

Flashcards in Biochemistry of Type 2 Diabetes Deck (35):
1

What is the single highest risk factor for type 2 diabetes?

BMI >25

2

Can diet make a difference to the risk of developing type 2 diabetes?

Yes, independent of BMI

3

Below what blood glucose concentration is it critical hypoglycaemia?

2.2 mM

4

Why does type 2 diabetes develop?

Can't compensate for loss of insulin sensitivity

5

What is the initial hyperinsulinaemic phase of type 2 diabetes?

Increased insulin production by pancreas compensates for insulin resistance of peripheral tissues
- Beta cell mass can expand

6

What leads to hyperglycaemia in type 2 diabetes?

Loss in beta cell function/mass

7

What is the onset of type 2 diabetes?

Gradual

8

What are the three phases of type 2 diabetes progression?

1) Hyperinsulinaemia
2) Impaired glucose tolerance
3) Hyperglycaemia in fasting state

9

What happens during the hyperinsulinaemia phase in type 2 diabetes?

Peripheral tissues have insulin resistance
To compensate pancreatic insulin secretion increases
Normal glucose
Elevated insulin

10

What happens during the impaired glucose tolerance phase in type 2 diabetes?

Hyperglycaemia despite elevated insulin > pre-diabetic
Elevated glucose
Elevated insulin

11

What happens during the hyperglycaemia in the fasting state phase in type 2 diabetes?

Insulin secretion declines > overt diabetes
Elevated glucose
Decreased insulin

12

What is the earliest detected abnormality in people who are likely to develop type 2 diabetes?

Insulin resistance

13

What is insulin resistance?

When biological effects of insulin subnormal for glucose disposal in skeletal muscle and suppression of endogenous glucose production by liver

14

When is the action of insulin impaired?

After it binds to insulin receptor - signalling affected

15

How can insulin resistance be observed?

Hyperinsulinaemia in response to glucose load

16

What are the key precipitating factors of insulin resistance?

High circulating levels of free fatty acids
- Activation of TLRs
- Intracellular signalling
Enhanced pro-inflammatory cytokines in obesity
- TNF-alpha
- IL-6
Extra altered intracellular activities
- Mitochondrial ROS
- ER stress

17

What is the end signalling result of the key precipitating factors of insulin resistance?

Phosphorylation of serine residues on IRS1 > inhibition of signalling cascade activated by insulin binding
Increased SOCS levels > degrade IRS1 > prevent signalling

18

Why might bariatric surgery decrease the severity of type 2 diabetes?

Weight control
Altered timing and amount of secretion of gut hormones > influence insulin production
Increased production of certain bile acids > make more cells sensitive to insulin
Surgery-induced changes to gut microbiome

19

What is the response of beta pancreatic cells in type 2 diabetes?

Responses blunted

20

What do higher blood glucose levels in type 2 diabetes trigger in beta pancreatic cells?

Lower insulin secretion rates

21

What is the pattern of beta pancreatic cell loss in type 2 diabetes?

Delayed but progressive

22

What does a smaller beta cell population in type 2 diabetes mean for the remaining cells?

Remaining cells must individually produce higher insulin levels to maintain total insulin production > extra strain on remaining cells

23

How might obesity impact beta cell dysfunction?

Exposure to free fatty acids > loss of co-localisation of voltage-gated Ca channels and insulin secretory granules > Ca channels open but influx occurs in "wrong" place > no secretion

24

What are the factors contributing to beta cell decline?

Direct glucotoxicity
Dietary fatty acid
Obesity
Inflammation-induced cytokines
ER stress

25

What is ER stress?

Imbalance between protein folding capacity of ER and protein load
Accumulation of misfolded proteins > trigger downstream signalling events = unfolded protein response

26

What are the long term complications of diabetes closely related to?

Severity and duration of hyperglycaemia

27

What is the most common cause of diabetic ketoacidosis in Australia?

Poor adherence to treatment

28

What factors, other than poor adherence, can cause diabetic ketoacidosis?

Infection/other illness
- Higher levels of hormones countering effect of insulin
Drugs affecting carbohydrate metabolism
- Corticosteroids
- Sympathomimetics
- Atypical antipsychotics
- SGLT1 inhibitors

29

What is SGLT1?

Glucose transporter in kidney's proximal tubule

30

What are the clinical features of diabetic ketoacidosis?

Hyperglycaemia
Hyperketonaemia
Metabolic acidosis

31

What is the key diagnostic criterion for diabetic ketoacidosis?

Direct measurement of beta-hydroxybutyrate

32

What are the clinical features of hyperglycaemic hyperosmolar state?

Slower onset than diabetic ketoacidosis - several days
More severe manifestations of
- Hyperglycaemia
- Dehydration
- Plasma hyperosmolality

33

What are common causes of hyperglycaemic hyperosmolar state?

Infection
Poor adherence to therapy

34

What is the key diagnostic criterion for hyperglycaemic hyperosmolar state?

Plasma glucose >33.3 mM
Absence of acidosis and ketonaemia

35

What is the most frequent and serious adverse effect of antidiabetic therapy?

Hypoglycaemia