Type 2 Diabetes Flashcards
(51 cards)
1
Q
What is type 2 diabetes?
A
Metabolic syndrome, characterized by hyperglycemia resulting in insulin resistance. Relative insulin insufficiency.
2
Q
What other effects can chronic diabetes have?
A
Damage nerves, eyes, blood vessels, heart, and kidneys.
3
Q
How does type 2 diabetes occur? (6)
A
- Increase glucose and not enough insulin, so glucose increases more. (Also, inulin may not respond well due to genetics)
- Body produces more insulin to make up for this.
- Beta cells over stimulated to produce inclusion reducing activity and therefore reducing insulin production.
- When insulin accumulates, it also increases amylin.
- This amylin, causes amyloid deposition, this damages the beta cells. therefore, reducing insulin production.
- So increased blood glucose
4
Q
Beta cell hyperplasia
A
Increase in beta cells
5
Q
Beta cell hypertrophy
A
Increase beta cell size
6
Q
Why does DKA not happen in type 2?
A
As there is still some insulin in the blood.
7
Q
HHS
A
Hyperosmolar hyperglycemic state
8
Q
Treatment for type 2 diabetes
A
- Lifestyle
- Oral antidiabetic meds
- Sometimes insulin
9
Q
Drugs that can cause diabetes
A
Steroids and thiazides
10
Q
Diabetes risk factors
A
- Obesity
- Age
- Family History
- Gestational diabetes
- PCOS
- Ethnicity
- Metabolic Syndrome
- Dyslipidaemia (high TC and low HDL)
- Hypertension
- Dietary factors
- Sedentary lifestyledssd
11
Q
Presenting feature of type 2 diabetes
A
- Not usually weight loss
- No ketonuria
- Onset over months
- Usually insidious
- After age 20 (more children now though)
12
Q
Diagnosis for Type 2?
A
- HbA1c
- Fasting plasma glucose
- OGTT (oral glucose tolerance test)
13
Q
Fasting plasma glucose: < 5.6mmol/L
A
No diabetes
14
Q
Fasting plasma glucose: 6.1-6.9 mmol/L
A
Pre-diabetes
15
Q
Fasting plasma glucose: >7 mmol/L
A
Diabetes
16
Q
HbA1c: < 42mmol/mol (6%)
A
No diabetes
17
Q
HbA1c: 42-47 mmol/mol (6-6.4%)
A
Pre-diabetes
18
Q
HbA1c: > 48 mmol/mol (6.5%)
A
Diabetes
19
Q
2 hour post prandial: < 7.8 mmol/L
A
No diabetes
20
Q
2 hour post prandial: 7.8-11 mmol/L
A
Pre-diabetes
21
Q
2 hour post prandial: >11 mmol/L
A
Diabetes
22
Q
Diet advice for type diabetes
A
- Wide range of foods – fruit, veg and some starchy foods. Balanced
- Keep sugars and fats to a minimum
- Do not skip meals
23
Q
DSMOND/XPERT course
A
- Prepare individuals with diabetes to cope with complex chronic disease
- Help patients make informed decisions about their care
- Help patients make behavioral changes that will support self-management
- Type 1 = Week, Type 2 = Couple days
24
Q
Macrovascular vs microvascular complications
A
Macro = before type 2
Micro = At diagnosis as it is dependent on blood sugar levels
25
First line treatment for Type 2
Diet and exercise plan
| Metformin (and SGLT2 CVD and high BMI)
26
UTI and type 2
Hyperglycemia mean glucose in urine so more likely to suffer from UTI.
27
Three treatment targets
0.9% reduction in HbA1c
1mmol/L reduction in cholesterol (lipids)
10/5 mmHg reduction in BP (most important)
28
Microvascular complications
Cognitive impairment
Diabetic retinopathy
Diabetic neuropathy
Diabetic nephropathy (kidney)
29
Macrovascular complications
Cerebrovascular disease
Coronary heart disease
Peripheral vascular disease
30
Why does obesity lead to insulin resistance?
Free fatty acids
Adipokines
Inflammation
PPARγ
31
Free fatty acids leading to insulin resistance
1. FFA. When in excess they are transformed in second messenger DAG.
2. DAG activates ser/thr kinases, which phosphorylate insulin receptor
3. The weakens insulin receptor signal.
32
Adipokines leading to insulin resistance
1. Released by adipocytes
3. Adiponectin is anti-hyperglycemic, because improves insulin sensitivity by activating AMPK, enzyme promoting lipolysis in liver and muscle
4. Adiponectin expression is reduced in obesity, (more pro-hyperglycemic). So less insulin sensitivity.
33
Twp types of adipokines
Pro-hyperglycemic or anti-hyperglycemic adipokines
34
Inflammation leading to insulin resistance
1. Adipocytes produce IL-6 and IL-1 which attract macrophages to fat deposits
2. Experimental reduction of cytokine levels improve insulin sensitivity
35
Adipokines leading to insulin resistance
1. Nuclear receptor involved in adipocyte differentiation
2. Promotes secretion of anti-hyperglycemic adipokines
3. Mutations can cause diabetes
4. Agonists used in therapy
36
AMPK activator used in type 2
Metformin
37
Thiazolidinediones e.g.
Pioglitazone
38
Thiazolidinediones mechanism
Agonist of nuclear receptor PPARγ
- Promotes expression and secretion of anti-hyperglycaemic adipokines (so increase lipolysis)
- Increase hypoglycaemic action of insulin by sensitizing cells to its action
- Collectively reduce insulin-resistance in liver and other peripheral tissues
39
Metformin mechanism
Suppress glucose release from liver
- Activate AMPK
- increase lipolysis in liver and muscles and therefore improving insulin receptor signaling
- Suppress glucose release from liver
40
Sulphonylureas e.g.
Glicazide
41
Sulphonylureas mechanism
Bind to sulphonylurea receptors expressed on
membranes of β cells
- Block ATP-sensitive K + channels in β cells
- K + accumulates inside cells
- β cells depolarize
- Ca++ channels open and allow insulin
secretion by exocitosis
42
α glucosidase inhibitors
Acarbose
43
α glucosidase inhibitors
- Delay carbohydrates absorption, reducing the postprandial increase in blood glucose
- Useful in obese type 2 patients
44
α2 adrenoreceptor antagonists
Increase insulin secretion
45
Selective β3 agonists
- β3 adrenoreceptors control lipolysis in fat cells
- Under development
- Potentially important for treating obese patients with type 2 diabetes
46
Types of long-term consequences of diabetes
Microvascular and macrovascular
47
Microvascular
Damage to small blood vessels
Retinopathy
Neuropathy (foot)
Nephropathy (kidney)
48
Macrovascular
Damage to medium and large blood vessels
Coronary artery disease
Cerebrovascular Disease
Peripheral vascular disease
49
Mechanism of long term consequences
1. Increased FFA and glucose are oxidized so release ROS.
2. The ROS are responsible for the microvascular complications first
3. Eeventually to macrovascular. (These are also worsened by aging, smoking, obesity, high cholesterol).
50
AGEs receptor binding mechanism mechanisms
1. AGE receptor biding -> AGE-R1 leads to clearance and less ROS
2. AGE receptor biding -> RAGE leads to ROS, inflammation and metabolic structural defect.
51
AGEs crosslinking to protein mechanism
1. AGE’s crosslink with collagen
2. The basal membrane of the endothelium thickens
3. The thickened endothelium traps LDL and IgGs
4. Oxidation, complement activation and inflammation
5. Blood vessel damage
