Diabetes mellitus Flashcards
1
Q
Microvascular complications of diabetes mellitus? (specific to diabetes)
A
Retinopathy, nephropathy, neuropathy (foot)
2
Q
Macrovascular complications of diabetes mellitus?
A
Cerebrovascular, ischaemic heart disease, peripheral vascular disease (foot)
3
Q
Difference between type 1 a and b?
A
1a is destruction of beta cells due to an AI response
1b is idiopathic
4
Q
Hallmark of type 1?
A
Absence of C-peptide
5
Q
MODY 1-7 =
A
Monogenic diabetes
6
Q
Genetic defects in insulin action:
A
Type a insulin resistance
Leprechaunism
Rabson-Meldenhall syndrome
7
Q
Diabetes can develop secondary to which conditions?
A
Other endocrine conditions e.g. Cushing’s or acromegaly
8
Q
Endocrine causes of diabetes?
A
Glucocorticoids and thyroxine
9
Q
Infectious causes of diabetes?
A
Congenital rubella
CMV
10
Q
Stiff man =
A
Antibodies to the insulin receptor
11
Q
Osmotic symptoms of diabetes?
A
Thirst, polyuria and polydipsia
12
Q
Associated genetic syndromes:
A
Down’s
Huntington’s
13
Q
Proteolysis and lipolysis in marked/complete insulin insufficiency leads to…
A
Weight loss
Ketogenesis and ketosis leading to acidosis resulting in vasodilation and causing (along with dehydration) hypotension
14
Q
Mononeuritis in diabetes?
A
Diplopia
15
Q
Neuropathies:
A
Peripheral - numbness/pain/tingling in hands and feet
Autonomic - sweating, gastroparesis, postural dizziness, erectile dysfunction, diarrhoea and incontinence
Radiculopathy - pain and wasting
Mononeuritis - diplopia
Compression - carpal tunnel, ulnar nerve, lateral popliteal nerve
16
Q
Diagnosis of diabetes mellitus (symptomatic):
A
Diabetes symptoms (e.g. polyuria or weight loss in type 1) and any one of:
1) Random venous plasma glucose > 11.1mmol/L
2) Fasting plasma glucose concentration > 7mmol/L, whole blood > 6.1mmol/L
3) Two hour plasma glucose > 11.1mmol/L after 75g glucose in an oral glucose tolerance test
17
Q
Diagnosis of diabetes mellitus (asymptomatic):
A
Absence of any symptoms with raised venous plasma glucose with a raised fasting plasma glucose or OGTT on a seperate day
18
Q
Diagnosis with HbA1c:
A
Pre-diabetes = 6.1-6.4% (43-47 mmol/L)
Diabetes = 6.5% (48 mmol/L)
A value of less than 6.5% does not exclude diagnosis of diabetes with glucose tests
19
Q
When is HbA1c not an appropriate diagnostic tool?
A
All children and young people Suspected type 1 Diabetes symptoms < 2 months High risk acutely ill patients Patients taking any medications that can cause rapid glucose rise e.g. antipsychotics or steroids Acute pancreatic damage Pregnancy Other influencing factors on HbA1c
20
Q
Features of the oral glucose tolerance test (OGTT):
A
180gm CHO for 3 days before Overnight fast Sedentary during test Fasting venous plasma glucose 75g anhydrous glucose over 5 minutes 2 hour venous plasma glucose
21
Q
Clinical features of type 1:
A
Insulin deficient Ketosis prone HLA markers Autoimmune (other AI conditions) Peak of onset in adolescence Weight loss
22
Q
Clinical features type 2:
A
Insulin resistant and deficient Not ketosis prone Polygenic South Asians > Africans and Carribeans > Europeans Increases with ageing Associated with central obesity
23
Q
Genetic markers of type 1 diabetes:
A
HLA-DR3 HLA-DR4 DQalpha and beta IDDM2 IDDM12
24
Q
Can a patient with a HbA1c under 6.5% be diagnosed with diabetes?
A
Yes
25
What are the hyperglycaemic diabetic emergencies?
Diabetic ketoacidosis
| Hyperosmolar hyperglycaemic state
26
Triad of DKA:
Hyperglycaemia, hyperketonaemia, metabolic acidosis
27
Diagnosis of DKA:
Blood glucose > 11mmol/L or known diabetes
Blood ketones > 3mmol/L or ketonuria > 2+
Bicarbonate < 15mmol/L and/or venous pH < 7.3
28
Which hormones can cause DKA?
Stress hormones - catecholamines, cortisol
29
Why can DKA cause disordered potassium?
Insulin causes K to move into cells
Insulin deficiency means that K moves into the blood (hyperkalaemia) and is lost in the urine - whole body loss
Acidosis causes similar effect as H and K compete
30
Problem with treating DKA?
K moves from the blood to the intracellular compartment too quickly and can cause arrhythmias
31
What can cause DKA?
Infection
Poor compliance
Newly diagnosed/failure of care
32
Complications of DKA:
```
Cerebral oedema (fluid shift)
Adult respiratory distress syndrome/acute lung injury
PE (dehydration)
Arrhythmias
Multi-organ failure (acidosis)
Co-morbid state
```
33
Symptoms of DKA:
Blurred vision not due to retinopathy but due to fluid-shifts
Leg cramps
Weakness
Osmotic symptoms
34
Signs of DKA:
```
Kussmaul respiration (laboured and deep, hyperpnoea)
Ketotic fetor (sweet smell on breath)
Dehydration
Tachycardia
Hypotension
Mild hypothermia
Confusion, drowsiness, coma
```
35
Step 1 of treating DKA:
Fluid replacement
IV 0.9% saline
Perfuse the kidneys to normalise the acid-base balance
36
Step 2 of treating DKA:
Insulin replacement
| Fixed rate IV 0.1 units/kg/hour
37
Step 3 of treating DKA:
Potassium replacement
| Replace the K as soon as in normal range as serum K falls very rapidly post fluid and insulin correction
38
Step 4 of treating DKA:
Address cause of the DKA
39
Step 5 of treating DKA:
VTE prophylaxis - LMWH
40
Step 6 of treating DKA:
Monitor - HDU
41
Type 2 diabetic emergency?
Hyperosmolar hyperglycaemic state (HHS)
42
HHS osmolality and glucose =
Hyperosmolality > 320 mosmol/kg
| Hyperglycaemia > 30 mmol/L
43
HHS pathology:
Severe dehydration and hypovolaemia
Without ketonaemia
Without acidosis
44
HHS complications:
```
Cerebral oedema
Osmotic demyelination syndrome
Seizures
Arterial thrombosis - MI, CVA, strokes
VTE, PE
Multiorgan failure
Foot ulceration
Co-morbid condition
```
45
Clinical features of HHS:
```
Osmotic symptoms
Blurred vision
Weakness
Dehydration
Tachycardia
Hypotension
Confusion, drowsiness and coma
```
46
What is the potentially life-threatening complication of not gradually normalising HHS?
Cerebral oedema
47
How is HHS treated?
The exact same protocol as for DKA except a lower fixed rate of insulin at 0.05 units/kg/hour
(Still have to give LMWH for VTE risk)
48
When do you give an extra short-acting insulin bolus?
| sick day rules
If CBG > 13mmol/L
| If blood ketones >1.5mmol/L
49
Why are sick day rules necessary?
When ill, glucose levels and insulin requirements go up causing ketones to rise as well
50
Sick day rules:
Never stop background long-acting insulin
Check cap BG every 2-4 hours
100ml/hour fluid
Bolus for carbohydrate
Med help if start vomiting, CBG/ketones not improving, hypos
51
Definition of a hypo:
<3.5mmol/L (<4 in hospital)
52
Main effect of sever hypo:
Confusion, seizure, coma and death (neuro)
53
Drug induced hypo:
Side effect of insulin or sulphonylureas
54
Symptoms of hypos:
Autonomic: sweaty and palpitations
Neuro: confusion, visual disturbances, circumoral paraesthesia
Hunger
55
Treatment for hypo with conscious patient who can walk?
Fast-acting carbohydrate oral 15-20g
| Check in 10 mins, if still hypo then repeat and then check again in 5 minutes
56
Treatment for severe hypo with unconscious patient?
IV glucose 20% 75-100ml or 1mg SC/IM
Re-check and repeat if need be
If they can swallow and it is severe but two glycogen tablets in the inner cheek
57
Treatment after initial management of the hypo?
Eat 15-20g long acting carbohydrate like one slice of bread or two biscuits, do not omit insulin injection and address the cause
58
Effect of somatostatin?
Blocks both insulin and glucagon release
59
Example of a biguanide:
Metformin
60
Effect of Metformin?
Decreases hepatic gluconeogenesis (+gene expression)
Also activates AMPK which increases GLUT4 expression in muscle cells
Stimulates glycolysis in tissues
Decreases carbohydrate reabsorption in the gut
Stimulates lactate production
Lowers LDL and VLDL
Reduces microvascular complications
61
Benefits of Metformin?
Does not stimulate appetite
Does not cause hypos
Does not cause weight gain
62
Side-effects of Metformin?
Metallic taste
Diarrhoea, nausea
Decreased B12 and folate absorption
Rare: lactate acidosis
63
Features of Metformin:
Not bound to plasma protein
t(1/2) = 3hours
Absorbed in the small intestine
64
Sulphonylureas:
-mide/-zide
e.g. Glibendamide, Glipizide
(Old: carbutamide, tolbutamide, chlorpropramide)
65
Effect of Sulphonylureas?
Bind to KATP channels causing depolarisation of Beta cells and release of insulin
Decrease hepatic clearance of insulin
66
Features of Sulphonylureas?
Plasma protein bound so displace other plasma bound drugs and increase their plasma concentration e.g. NSAIDs, MAO inhibitors and Abx
Excreted in urine with enhanced effect in elderly/renal impairment
67
Main side-effect of sulphonylureas?
Hypos
| May need IV glucose, glucagon or adrenaline
68
Meglitinides:
Rapaglinide and Nateglinide
| t(1/2) = 1 hour
69
Effect on meglitinides?
Close KATP channels selective in beta cells
70
Guidelines for meglitinides:
Can be used as monotherapy
| Take just before meal
71
Comparison between sulphonylureas and meglitinides?
Meglinitides are less potent but more rapid and are less prone to causing hypos
72
Glutaziones:
Pioglitazone (risk of bladder cancer)
73
Effect of glutaziones:
Nuclear receptor (PPARgamma and RXR) agonists
Decrease insulin resistance in peripheral tissues
Reduces hepatic gluconeogenesis
Increases uptake and potentiates action of insulin
74
Side-effects of glutaziones:
Increased food intake in the brain
Decrease in bone density
Increase in sodium and water retention in the kidney
Increased growth and lipid storage in the heart
Increases adipocyte no. and lipogenesis so weight
75
Directions for glutaziones:
The t(1/2) = 7 hours, 24 hours for the active metabolite
Give with metformin or other hypo drugs
6-12 weeks of therapy for the maximum effect
76
Incretins:
Glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors
77
Effect of incretins?
Incretins are gut derived peptides that stimulate insulin release, decrease glucagon release
In the brain they reduce appetite so help lose weight
They slow glucose absorption in the gut by slowing gastric emptying
Stimulate an increase in beta cells
78
Guidance for incretins:
Must be given IV as an injection
No effect on weight or hypos however Loraglutide has been given at a high dose as a weight loss drug (daily injections)
Possible increase in cancer
DPP-4 breaks down GLP-1 so glistens inhibit this
Reduce risk of microvascular and renal outcomes
79
alpha-glucosidase inhibitors:
Acarbose - inhibits alpha-glucosidase at the intestinal brush border
80
Effect of alpha-glucosidase inhibitors?
Decrease in carbohydrate breakdown and postprandial absorption
81
Features of alpha-glucosidase inhibitors:
Does not cause hypos
Used in both T1DM and T2DM
May cause flatulence and diarrhoea
82
SGLT2 inhibitors:
Dapagliflozin + empagliflozin are both SGLT2 inhibitors
Cangliflozin is an SGLT1 and an SGLT2 inhibitor
Xigduo = metformin + dapagliflozin
Vokanamet = metformin + canagliflozin
83
Effect of SGLT2 inhibitors?
SGLT2 is responsible for 80-95% of the glucose reabsorption in the proximal tubule
Inhibits glucose re-uptake in the kidney
Causes around 10% excretion of calorie intake
Decreases CVD secondary to diabetes
84
Effect of amylin analogues:
Inhibits glucagon release
Decreases gastric emptying
Promotes satiety
85
Features of amylin analogues:
Can cause amyloid aggregates - Alzheimer's
Pramlintide is an analogue that doesn't cause aggregates
Adjunct for both T1DM and T2DM
86
Which drugs increase insulin secretion?
Sulphonylureas
Meglitinides
Incretins
87
Which drugs decrease glucagon secretion?
Incretins
| Amylin analogues
88
Which drugs decrease appetite?
Incretins
| Amylin analogues
89
Which drugs decrease glucose reabsorption?
SGLT2 inhibitors
90
Which drugs increase cellular glucose uptake and utilisation?
Glutaziones (thiazolidinediones)
| Metformin
91
Which drugs decrease hepatic gluconeogenesis?
Glutaziones (thiazolidinediones)
| Metformin
92
Obesity treatment:
Serotonin uptake agonists help appetite control
93
What does U100 mean?
100 units of insulin per ml
94
Basal dose of insulin?
Long acting for whole day
One per day = glargine (acid solution in vial that precipitates at body pH)
Twice per day = detemir (attached to fatty acid as bigger molecules = longer action)
95
Prandial dose of insulin?
Fast acting dose before meal (e.g. monomers Lispro and Aspart)
96
What does insulin pump therapy provide (CSII)?
Basal and prandial spikes
97
Insulin for type 2 diabetes?
Long dose e.g. glargine once a day or mixed before breakfast and before dinner
98
CKD in diabetes type 2:
GFR can drop by 1ml a year (if 10 or over in a year then biopsy)
GFR can drop without proteinuria
SGLT2 inhibitor empagliflozin and incretin loraglutide improves renal outcomes
99
Side-effects of insulin?
Hypos increase risk of cardiac arrhythmias
Neuroglycopaenia
Higher risk of hypo if patient taking insulin has poor renal function
100
Weight reduction therapies:
Orlistat = weight reduction 5%, improves HbA1c
| Bariatric surgery = weight reduction 15-25%, diabetes remission
101
Reducing cholesterol:
Statins
| PSK9 inhibitors - Evolcumab
102
BP targets?
< 140/80
| < 130/80 if there are complications
103
Step 1 of drug BP control:
ACE inhibitor
| + CCB/diuretic if African/Carribean
104
Step 2 of drug BP control:
+ CCB/diuretic
105
Step 3 of drug BP control:
+ diuretic/CCB
106
Step 4 of drug BP control:
+ alpha-blocker/beta-blocker/K-sparing diuretic
107
Step 5 of drug BP control:
+ alpha-blocker/beta-blocker/K-sparing diuretic/refer to a specialist
108
When can reducing BP too much increase mortality risk?
Elderly patients >65 y/o
| Patients with reduced kidney function
109
Contraindication of glutaziones?
Heart failure (they caused oedema and heart failure)
