Clinical (Weeks 1 + 2 - Diabetes) Flashcards
1
Q
What antibodies might be present in T1DM?
A
Anti-GAD
Anti-islet cell
2
Q
When is a person though to have T2DM?
A
When they don’t have:
- T1DM - Monogenic DM - Other condition/Treatment causing secondary DM
3
Q
What are some risk factors for T2DM?
A
Central obesity
FHx
Gestational DM
Age
Ethnicity:
- Asian
- African
- Afro-Caribbean
PMHx of MI/CVA
Medications
IGT/IFG
4
Q
What are some symptoms of DM?
A
Thirst Polyuria Thrush Weakness Blurred vision Infections Weight loss
5
Q
What pancreatic diseases can cause secondary DM?
A
Chronic/Recurrent pancreatitis
Haemochromatosis
CF
6
Q
What endocrine diseases can cause secondary DM?
A
Cushing’s
Acromegaly
Phaeochromocytoma
Glucogonoma
7
Q
What drugs can induce DM?
A
Glucocorticoids
Diuretics
β-blockers
8
Q
What genetic disorders can result in DM?
A
CF
Monogenic dystrophy
Turner’s
9
Q
What are the principles of T2DM treatment?
A
Alleviate hyperglycaemia symptoms
Improve glycaemic control
Minimise:
- Hypoglycaemia
- Weight gain
Reduce complications
10
Q
What do biguanides do?
A
Increase insulin sensitivty
11
Q
What dose of biguanide do we usually start with?
A
500mg once/twice daily
12
Q
Give an example of a biguanide
A
Metformin
13
Q
Does metformin cause weight loss/no change/weight gain?
A
No change
14
Q
How much can metformin reduce a patient’s HbA1c?
A
15-20 mmol/L
15
Q
Does metformin cause hypoglycaemia?
A
Not if used as monotherapy
16
Q
What effect does metformin have on a patient’s lipid status?
A
Decreased triglycerides and LDL
17
Q
Is metformin safe in pregnancy?
A
Yes
18
Q
What are some side effects of metformin?
A
Anorexia
Nausea/Vomiting/Diarrhoea/Abdo. pain
Anaemia
Lactic acidosis:
- If in renal failure
- If in cardiac/liver failure
19
Q
In what patient’s should metformin be stopped?
A
Renal failure:
- If eGFR 150 micromol/L
Liver:
- Advanced cirrhosis
- Liver failure
20
Q
When might metformin be beneficial?
A
NAFLD
21
Q
In what patient’s should metformin be used with caution due to the increased risk of lactic acidosis?
A
Acute CHF Sepsis Acute MI Respiratory failure Hypotension
22
Q
How do sulphonylureas work?
A
Insulin secretagogues
23
Q
Give examples of SUs
A
Glicazide
Glipizide
Glimeparide
24
Q
What complications can metformin prevent?
A
Microvascular
Macrovascular
25
What complications can SUs prevent?
Microvascular
26
How do SUs manage hyperglycaemia?
Decrease HbA1c by 15-20 mmol/mol
Increased insulin secretion
More rapid action than metformin
27
When are SUs used?
1st line in underweight T2DM
| 2nd line as add-on to metformin/intolerant to metformin
28
What are some side effects of SUs?
Hypoglycaemia:
- Caution in elderly/alcoholics/liver disease
GI upset
Headache
29
What is the only available thiazolidinedione?
Pioglitazone
30
How do TZDs work?
They are PPARγ agonists - Increase insulin sensitivity
31
What effect do TZDs have on weight?
Increase is common:
| - Due to increased S/C fat and fluid retention
32
Why can TZDs increase the risk of CHF?
Fluid retention
33
What other effects do TZDs have?
Improve microalbuminaemia
Prevent macrovascular complications
Increase hip fracture risk
34
How dies Dapaglifozin work?
Act on the incretin pathway:
| - SGLT2 inhibitor
35
What are the incretins?
Stimulate intestinal secretion of insulin:
- GIP from K cells
- GLP-1 from L cells
36
What type of drug is exenatide?
GLP-1 receptor agonist
37
How does exenatide work?
```
Increased insulin secretion (no hypos)
Suppress glucagon
Decrease gastric emptying -> Early satiety
Reduce appetite
Weight loss
```
38
What are some side effects of exenatide?
Nausea
| Pancreatitis
39
Give some examples of DPP-IV inhibitors
Vildagliptin
Sitagliptin
Saxagliptin
Linagliptin
40
What drugs are less potent; GLP-1 receptor agonist, DPP-IV inhibitors?
DPP-IV inhibitors:
- Only work on what's present
- DLP-1 decreased in T2DM
41
What are some benefits of DPP-IV inhibitors?
Increase insulin secretion (no hypos)
Decrease glucagon
Weight neutral
42
How do SGLT2 inhibitors work?
Decrease sugar uptake by ~25%:
- Glycosuria (~80g/day)
- ~1lb decrease in weight/week
43
What side effects are common with SGLT2 use?
Sugar in urine:
- Thrush
- UTIs
44
What type of insulin is used in T2DM?
Basal insulin
45
When is bariatric surgery considered?
When 30
46
What is acanthosis nigricans?
```
Skin becomes:
- Hyperpigmented
- Velvety
Found at:
- Axilla
- Neck
```
47
What is acanthosis nigricans a sign of?
Insulin resistance ie T2DM
48
What are some microvascular complications of T2DM?
```
Retinopathy
Nephropathy
Neuropathy:
- Impotence
- Digestion/Urination problems
Amputation
```
49
What are some macrovascular complications of T2DM?
CVS disease:
- MI
- CHD
- CVA
- PAD
- Angina
50
How can alcohol result in hypoglycaemia?
Increases insulin activity
51
How long do rapid-acting insulin analogues last and give examples?
```
~5 hours
Examples:
- Humalog
- Novorapid
- Apidra
```
52
How long do short-acting insulin analogues last and give examples?
```
~8 hours
Examples:
- Humulin S (human insulin)
- Actrapid
- Insuman rapid
```
53
How long do intermediate-acting insulin analogues last and give examples?
```
~20 hours
Examples:
- Insulatard
- Humulin I
- Insuman basal
```
54
How long do long-acting insulin analogues last and give examples?
~24 hours:
- Lantus (Levels remain high at end of day)
- Levemir (Levels reduced at end of day)
55
How can we evaluate glucose control?
```
Home blood glucose monitoring
Urine testing:
- Glucose
- Ketones
HbA1c
```
56
What does glycated Hb give us an idea of?
Measure of blood glucose over 6-8 weeks
57
What is the ideal HbA1c target?
48 mmol/mol
58
What are the downsides to injectable insulin?
It's into the S/C tissue (instead of portal blood)
Peaks too slow -> Can't prevent post-meal hyperglycaemia
Slow clearance
59
What factors affect the absorption of injectable insulin?
```
Pen accuracy
Leakage
Temperature
Injection site
Exercise
```
60
When is IV insulin prescribed?
DKA
HSS
Acute illness
Fasting patients who cannot tolerate PO intake
61
What monitoring is important during the delivery of IV insulin?
```
Hourly BG (5-12 mmol/L)
Free of hypos
Ketones if BG > 12 mmol/L
U+Es daily
Transition from IV to S/C
```
62
What are some indications for a pancreas transplant?
Imminent/ERSD with kidney transplant
Severe hypos
Incapacitating problems
63
What are the four mains steps in islet transplantation?
1. Donation and retrieval
2. Islet isolation
- Sterility
- Pancreas digestion
- Islet purification
3. Islet culture (24 hours)
4. Transplantation
64
What are some signs and symptoms of hypoglycaemia?
```
Shaking
Sweating
Anxious
Dizzy
Hungry
Tachycardia
Decreased vision
Weakness + fatigue
```
65
What can severe hypoglycaemia lead to?
Seizures
| Unconsciousness
66
What is the immediate treatment of hypoglycaemia?
1. 15-20g of glucose/simple carbohydrates
2. Recheck BG after 15 minutes
3. If still hypo -> Repeat
4. Once BG normal -> Small snack if next meal >1hr away
67
Treatment of severe hypoglycaemia?
1mg glucagon injection:
- Buttock
- Arm
- Thigh
68
What is the definition of impaired hypoglycaemia awareness?
When BG
69
During DKA what hormones increase in levels?
Counter-regulatory:
- Glucagon
- Adrenaline
- Cortisol
- GH
70
What does the activation of certain hormones in DKA cause?
```
Increased lipolysis
Decreased glucose utilization:
-> Hyperglycaemia
Increased proteolysis:
-> Hyperglycaemia
Increased gluconeogenesis:
-> Hyperglycaemia
```
71
What does hyperglycaemia result in?
Glycosuria
- > Electrolyte loss
- > Dehydration
- > Dehydration and Hyperosmolar state
72
What is the biochemical diagnosis of DKA?
1. Ketonaemia > 3mmol/L OR Ketonuria > ++
2. BG > 11.0mmol/L OR Known DM
3. Bicarbonate <15mmol/L OR venous pH <7.3
73
What can commonly precipitate DKA?
Infection
Drugs/Alcohol
Non-adherence to therapy
Newly diagnosed DM
74
What signs and symptoms are caused by the following in DKA:
- Osmotic changes
- Ketone body related
```
Osmotic:
- Thirst
- Polyuria -> Dehydration
Ketone bodies:
- Flushing
- Vomiting
- Abdominal pain
- Kussmaul's respiration
- +/- Ketone breath
```
75
What other biochemical changes can be seen in DKA?
```
Potassim is often raise (> 5.5mmol/L)
Creatinine is often raised
Sodium is often decreased
Increased lactate
Ketones increased:
- β-hydroxybutarate in blood
- Acetoacetate in urine
```
76
What causes death in DKA?
```
Adults:
- Hypokalaemia
- Aspiration pneumonia
- ARDS
Kids:
- Cerebral oedema
```
77
How is DKA managed?
Replace losses:
- Fluid -> 0.9% NaCl
- > Dextrose when glucose
78
What HbA1c levels indicate the following:
1. Normal
2. Pre-diabetes
3. Diabetes
Normal:
- 48mmol/L
- >6.5%
79
What fasting glucose levels indicate the following:
1. Normal
2. Pre-diabetes
3. Diabetes
Normal:
| - 7.0mmol/L
80
What 2hr OGTT levels indicate the following:
1. Normal
2. Pre-diabetes
3. Diabetes
Normal:
| - 11.1mmol/L
81
What is the normal blood ketone level?
82
What is the typical biochemistry in Hyperglycaemia Hyperosmolar Syndrome?
```
Higher glucose than DKA
Significant renal impairment
Increased sodium
Increased osmolarity (~400)
Less acidotic
```
83
Where does lactate originate from?
Erythrocytes
Skeletal muscle
Brain
Renal medulla
84
How is lactate cleared?
Hepatic uptake
| Aerobic conversion -> Pyruvate -> Glucose
85
What is the normal range for lactate?
0.6-1.2mmol/L
86
How do we calculate the anion gap?
[Na+ + K+] - [HCO3- + Cl-]
87
What is the normal ion gap?
10-18mmol/L
88
What causes of acidosis present with a normal ion gap?
```
Diarrhoea
RTA
Addison's
Reason:
- Bicarbonate is reduced
- Cl- is raised
```
89
What causes of acidosis present with a high ion gap?
```
MUDPILES
Reason:
- Bicarbonate reduced
- Replaced by sulfate, phosphate
- Cannot be replaced sufficiently
```
90
What is Type A lactic acidosis?
```
Associated with tissue hypoxia:
- Infarct
- Cardiogenic shock
- Hypovolaemic shock
> Sepsis
> Haemorrhage
```
91
What is Type B lactic acidosis?
Liver disease
Leukaemia
Associated with DM:
- Metformin in illness/renal failure
92
What are the targets for each of the following in DM?
- BMI
- HbA1c
- BP
- Total cholesterol
- LDL
- Triglycerides
BMI -> 25
HbA1c -> 7% (75mmol/mol)
BP ->
93
How do we treat T2DM in the following situations:
- BMI >25
- BMI
BMI >25:
- Metformin up to 1g tds
BMI
94
What anti-lipid therapies are recommended in diabetes?
```
Statins:
- Increase dose to lower cholesterol
Fibrates
Ezetimibe
Cholestyramine:
- Unpleasant
```
95
What is peripheral neuropathy?
Pain/Loss of feeling in:
- Hands
- Feet
96
What is autonomic neuropathy?
```
Changes in bowel habit
Bladder function
Sexual response
Sweating
HR/BP/Hypoglycaemic unawareness
```
97
What is proximal neuropathy?
Pain in thigh/hips/buttocks:
| - Leg weakness (Amyotrophy)
98
What factors precipitate neuropathy?
```
Increased length of DM
Poor glycaemic control
T1DM > T2DM
Increased cholesterol
Smoking/Alcohol/Genetics
```
99
A diabetic patient presents with numbness, tingling and sharp pains in their foot. It is very sensitive to touch and they have lost their balance.
Peripheral nerve damage
100
What complications can peripheral neuropathy result in?
Infections/Ulcers
Charcot foot
Deformities
Amputations
101
What is the step up treatment for painful neuropathy?
1. Simple analgesia
2. TCAs (amitryptiline at night)
3. Gabapentin
4. Oxycodone/Tramadol
102
A patient presents with constipation, nausea, bloating and a loss of appetite. He has difficulty swallowing and has known, poorly controlled DM.
Autonomic neuropathy
103
How can gastroparesis be treated?
Metoclopramide
Domperidone
Erythromycin
Gastric pacemaker
104
What is diabetic nepropathy also known as?
Kimmelsteil-Wilson Syndrome
| Nodular Glomerulosclerosis
105
What can result in diabetic nepropathy?
Hypertension
Decreased renal function:
- GFR down by 1ml/min/month
Accelerated vascular disease
106
How is diabetic nephropathy screened for?
Urinary albumin creatinine ratio (ACR)
Confirm with EMU
Dipstick
U+Es -> eGFR
107
What is a normal ACR?
Male:
| -
108
What is defined as microalbuminuria?
30-300mg/L of urine
109
What is macroalbuminuria?
> 300mg/L of urine
110
What can cause a false positive urinary albumin excretion rate? (UAER)
```
Menstruation
Vaginal discharge
UTI
Pregnancy
Illness
Renal discharge
```
111
What are cotton wool spots a sign of in diabetic retinopathy?
Ischaemia
112
What are hard exudates a sign of in diabetic retinopathy?
Lipid break down products
113
Which of the following drugs doesn't cause erectile dysfunction:
- Thiazides
- Beta blcoerks
- Antidepressants
- Analgesics
- NSAIDs
NSAIDs
114
Put the following steps in atheroslcersosis development in order:
- Macrophages ingest LDL to become foam cells
- Fibrous cap forms from smooth muscle migration
- Cap rupture
- Monocytes migrate into epithelium
- Smooth muscle degenerated by activated macrophages
- Cytokines produced result in smooth muscle migration
- Platelets aggregate at site of rupture and thrombus forms
1. Monocytes migrate into epithelium (become macrophages)
2. Macrophages ingest LDL to become foam cells
3. Cytokines produced result in smooth muscle migration
4. Fibrous cap forms from smooth muscle migration
5. Smooth muscle degenerated by activated macrophages
6. Cap rupture
7. Platelets aggregate at site of rupture and thrombus forms
115
How do we diagnose diabetes?
1. Symptomatic and:
- One-time fasting glucose >7.0mmol/L OR
- One-time random glucose >11.1mmol/L
OR
2. Two time results of:
- Fasting glucose >7.0mmol/L OR
- OGTT >11.1mmol/L OR
- Random glucose >11.1mmol/L
OR
3. HbA1c >48mmol/L (>6.5%)
