Diabetes: Science and Clinical Flashcards
(98 cards)
1
Q
The exocrine pancreas produces… [physiology]
A
watery, alkaline secretions and digestive enzymes to the duodenum
2
Q
The endocrine pancreas has 4 groups of cells which are: [physiology]
A
- beta cells (insulin)
- alpha cells (glucagon)
- D-cells (somatostatin)
- F cells (pancreatic polypeptide)
3
Q
Where are b-cells found? [physiology]
A
centrally within the islets of langerhans
4
Q
Role of somatostatin [physiology]
A
released in response to increased BG and amino acides. slows rate of digestion to prevent excess nutrients in the plasma
5
Q
Role of pancreatic polypeptide [physiology]
A
reduces appetite and food intake
6
Q
promotes the acitivity of which enzyme [Insulin]
A
Glycogen synthase
7
Q
inhibits the activity of which enzyme [Insulin]
A
lipase
8
Q
[carbohydrates] insulin has 4 effects on carbohydrates
A
- facilitates transport into cells via GLUT 4
- stimulates glycogenesis
- inhibits glycogenolysis
- inhibits gluconeogenesis
9
Q
[fat] insulin has 4 effects on fat
A
- increases fatty acid uptake into adipose tissue
- increased transport of glucose into adipose tissue via GLUT 4
- Promotes use of fatty acid in reactions
- inhibits lipolysis
10
Q
[proteins] insulin has 3 effects on protein
A
- promotes active transport of amino acids into muscles
- increases amino acid incoporation into protein
- inhibits protein degradation
11
Q
main driver of release of insulin [insulin; physiology]
A
an increase in blood sugr
12
Q
5 steps of insulin release in the cell [insulin; cellular release]
A
- glucose enters b-cell via GLUT 2 facilitated diffusion
- glucose is metabolised to G-6-P and then to ATP
- ATP:ADP ratio increases causing ATP-K sensitive channel to close
- reduced K exit depolarises cell and opens VGCC
- Ca enters b-cell and stimulates release of insulin
13
Q
insulin is produced as a polymer with what other protein [insulin]
A
C-peptide
*this can be measured in T1 diabetics to monitior the decrease in insulin production however may take 3-4 years to disappear so is not a reliable indicator
14
Q
what is the physiological difficulty with diabetes mellitus? [DM; physiology]
A
An inability to produce any or sufficient endogenous insulin
15
Q
Why do complications occur in DM? [DM; physiology]
A
As a result of high blood sugar as insulin is the only hormone able to reduce BG
16
Q
Criteria for diagnosis from a random BG [DM; diagnosis]
A
> 11.1 mmol/L with symptoms OR
7.8 - 11 mmol/L on two occassions with symptoms
17
Q
Criteria for diagnosis from 2hr OGTT [DM; diagnosis]
A
> 11.1mmol/L and above
7.8-11 is pre-diabetes
18
Q
Criteria for diagnosis from FG [DM; diagnosis]
A
> 7.0mmol/L
19
Q
Criteria for diagnosis from HbA1c [DM; diagnosis]
A
48 mmol/L and above
20
Q
Three forms of microvascular complications [DM; complications]
A
Retinopathy, neuropathy, nephropathy
21
Q
Process underlying retinopathy [DM; Complications]
A
- formations of microaneurysms in the eye.
2. proteins cause the BM of the eye to become thickened and more permeabel –> fibrous response –> destroys the retina
22
Q
Process underlying nephropathy [DM; Complications]
A
Vascular disease in the kidney leads to kidney failure
23
Q
Process underlying neuropthy [DM; Complications]
A
PVD may affect the nerves causing a loss of sensation and higher chance of foot ulcers
24
Q
Forms of macrovascular complications [DM; Complications]
A
MI, Stroke and CVD - need to tightly control blood pressure as all vascular disease is accelerated, 50-70% of diabetics die from CVD
25
Pathophysiology of T1DM [T1DM]
Autoimmune destruction of the pancreatic b-cells leading to inability to produce insulin and control blood sugar. Usually occurs in adolescence but can occur at any age
26
Genetics associated with T1DM [T1; Science]
90% of T1DM carry HLA DR3+DR4; those with a first degree relative with T1DM have a 5-6% chance of developing the disease
27
Autoantibodies associated with T1DM [T1; science]
ICA (islet cell antibodies) and GAD (anti-glutamic acid decarboxylase)
28
What is LADA? [T1; science]
A form of T1 that presents in adults but presents with a slower onset and slower progression to insulin dependence
29
Symptoms associated with T1 (5/9 for 5*) [T1; symptoms]
Polyuria; polydipsia; weight loss; tiredness; ketosis; thirst; thrush; many and persistent infections; blurred vision
30
Treatment of T1 [T1; Treatment]
Insulin regimes, DAFNE
31
Example of long acting insulin [T1; treatment]
lantus
32
Example of rapid acting insulin [T1; treatment]
novorapid
33
A finger prick before a meal informs the patient of the long/short acting dose? [T1; treatment]
A long acting dose is monitored before a meal
34
A finger prick after a meal informs the patient of the long/short acting dose? [T1; treatment]
A short acting dose is monitored after the meal
35
What sort of adjustment might be made to insulin when exercising for a short period and why? [T1; treatment; physiology]
Increased dose of insulin as a short burst of exercise will increase the amount of adrenalin produced. Adrenaline pushes BG up and thus more insulin is required to counteract this.
36
What sort of adjustment might be made to insulin when exercising for a longer period and why? [T1; treatment; physiology]
Decreased dose of insulin as the prolonged exercise will deplete BG availability and thus less insulin is required
37
What sort of adjustment might be made to insulin when feeling unwell and why? [T1; treatment; physiology]
More insulin is likely to be required especially if the patient is not eating or is vomiting and becoming dehydrated. This is because the stress hormone cortisol is produced in higher quantities and is likely to push BG up. Not controlling insulin properly when unwell is more likely to result in DKA
38
What is ketoacidosis? [T1; phsyiology]
ketoacidosis is an alternative pathway used in the starvation states in order to produce energy. It is less efficient and produces acetone as a by-product.
39
What is diabetic ketoacidosis? [T1; physiology; complications]
In T1DM, blood glucose may be high, glucose cannot enter the cells without insulin. Thus the cells act as if in starvation state and use the ketosis pathway to generate energy
40
Typical signs and symptoms of DKA [T1; complications; symptoms]
1. Drowsiness
2. Vomiting and dehydration
3. Abdominal pain
4. Kussmaul Breathing
41
In which patients should you test BG? [Signs and symptoms; T1; complications]
Unexplained vomiting, abdominal pain, polyuria, polydipsia, lethargy, ketotic breath, dehydration, coma, anorexia, kussmaul breathing
42
What is Kussmaul breathing? [T1; complications; signs and symptoms]
Deep, laboured hyperventilation
43
What is the main driver of acidaemia in DKA? [T1; science]
beta-hydroxybutarate
44
3 criteria for diagnosis of DKA [T1; diagnosis; complications]
1. acidaemia
2. hyperglycaemia
3. ketonuria
45
Investigations to order in suspected DKA + justification [T1; complications; diagnosis; investigations]
1. ECG - cardiac cause
2. CXR - pulmonary cause
3. Urine dipstick - ketones, nitrates, leucocytes (infection)
4. capillary and lab glucose - hyperglycaemia (lab more accurate)
5. U&Es - monitor K+
6. HCO3
7. a-amylase - acute pancreatitis
8. ABG/VBG - acidosis
9. FBC
10. Cultures - sepsis/infection
46
Common complications of DKA [T1; complications]
Cerebral oedema (kids); aspiration pneumonia; hypokalaemia; hypomagnesia; hypophosphataemia; thromboembolism
47
Treatment steps of DKA (4/6 for 5*) [T1; complications; treatment]
1. 0.9% saline 500ml bolus (established IV access, may need to run more than one bolus)
2. when BG <15mmol/L switch to dextrose
3. contact senior help to start insulin regime (?0.1units/kg/hour?) 4. Start of LMWH heparin
5. monitor ABG/VBG and K+
6. continue fluids to rehydrate
* *caution with replacing bicarbonate as may increase risk of cerebral oedema**
48
Hypoglycaemia for any diabetic? [T1/T2; complications; diagnosis]
4mmol/L
49
Complication of persistent Hypo's [T1/2; complications]
those who have many hypos are less able to recognise them
50
Risk factor for becoming hypo and why [T1; complications; physiology]
binge-drinking as the liver does not create any glycogen stores at this time
51
Symptoms of hypos [T1/2; complications]
Usually rapid onset and may be preceeded by odd behaviour; sweating; tachycardia; seizures
52
Treatment of a hypo in a patient who is able to swallow [T1/2; complications; treatment]
15-20g of glucotabs; 60ml glucojuice; 170ml lucozade or a sugary alterantive
53
Treatment of a hypo in a patient who is concious but confused [T1/2; compliations; treatment]
1-2 tubes of glucogel
54
Treatment of a hypo in the unconcious patient [T1/2; complications; treatment]
IV glucose (10-20g) or 200-300ml of dextrose. 1mg IM Glucagon (500mg in kids)
55
Exceptions to use of IM Glucagon in hypos [T1/2; complications; treatment]
Patients who are frail, malnourished or have been drinking heavily
56
Follow up to initial treatment of hypo [T1/2; complications; treatment]
Re-check BG after 15 minutes and repeat steps if still hypo. After recovery to normal BG, patient should have a snack of something including complex carbs and the insulin regime should be reviewed if necessary
57
Pathophysiology behind T2DM [T2; physiology]
Decreased insulin secretion AND/OR increased insulin resistance
58
Associations of T2DM [T2; epidemiology]
obesity, lack of exercise, calorific excess and alcohol excess
59
Genetics associated with T2DM [T2; genetics]
strong genetic component; 80% concordance with twins
60
Presentation of T2DM [T2; Signs and symptoms]
May be incidental finding or present similarly to T1
61
What is metabolic syndrome? [T2; risk factors]
A syndrome including 3 of the following which puts an individual at significantly increased risk of CVD:
central obesity + BMI >30 + 2 of the following:
- BP >130/85
- Triglycerides >1.7 mmol/L
- HDL <1.03(M) or 1.29(F) mmol/L
- Fasting glucose >5.6 mmol/L
62
Overview of treatment for T2DM [T2; treatment]
Diet and exercise advice; podiatry and opthalmology screening; realistic HbA1c targetting; pharmacy
63
First line treatment in most T2 [T2; treatment]
Metformin
64
Mechanism of action of Metformin [T2; treatment; physiology]
biguanide that increases insulin sensitivity and aids weightloss - not associated with hypos
65
Dosing of metformin [T2; treatment]
500mg BD after food, may be increased to 1g BD
66
Contraindications to metformin [T2; treatment]
Renal disease
67
Side effects of metformin [T2; treatment]
nausea, diarrhoea, abdo pain
68
Example sulphonylurea [T2; treatment]
Gliclazide
69
Dose of Gliclazide [T2; treatment]
40mg OD
70
Mechanism of action of SUs [T2; treatment; physiology]
increases insulin action by acting on the K-ATP channel
71
Contraindications of SUs [T2; treatment]
Hepatic and renal impairement or if prone to hypos
72
Side effects of SUs [T2; treatment]
hypoglycaemia and weight gain
73
Example of a Glitazone [T2; treatment]
Pioglitazone
74
Mechanism of action of glitazone [T2; treatment; physiology]
PPARy agonist - acting on lipoprotein lipase and GLUT 4, only used in combination with Metformin or SUs
75
Contraindications of glitazone [T2; treatment]
hepatotoxicity, osteoporosis
76
Side effects of glitazones [T2; treatment]
hepatotoxicity, fractures, weight gain, fluid retention
77
Example of SGLT2 inhibitors [T2; treatment]
Dapagiflozin
78
Mechanism of action of SGLT2 inhibitors [T2; treatment; physiology]
Act to selectively block the reabsorption of glucose by SGLT2 in **PROXIMAL** tubule causing glucosuria and calorific loss; very good for those who need to lose weight and little chance of Hypos
79
Contraindications of SGLT2 inhibitors [T2; treatment]
avoid in those prone to UTIs
80
Example of DPP4 inhibitors [T2; treatment]
Sitagliptin
81
Mechanism of action of DPP4 inhibitors [T2; treatment, physiology]
inhibits the actions of DPP4 which inhibits GLP 1 however requires a certain number of b-cells to work
82
Side effects of DPP4 inhibitors [T2; treatment]
nausea
83
Examples of GLP-1 analogues [T2; treatment]
Exenatide
84
Mechanism of action of GLP-1 analogues [T2; treatment, physiology]
binds to receptors that increase IC cAMP conc. and increase insulin secretion, decrease glucagon secretion and slows gastric emptying leading to a decreased appetite ***modest weight loss and reduces hepatic fat accumulation
85
Administration of GLP-1 analogues [T2; treatment]
SC injection 2 x daily
86
Side effects of GLP-1 analogues [T2; treatment]
nausea, hypos, protentially pancreatitis
87
Example of a-glucosidase inhibitors [T2; treatment]
a-carbarose
88
Mechanism of action of a-carbarose [T2; treatment]
inhibits breakdown of starch to sugar via inhibition of a brush border enzyme
89
Side effects of a-carbarose [T2; treatment]
GI problems associated with excess glucose in intestine - not popular
90
Hyperosmolar Hyperglycaemic Non-ketotic Coma (HONK) compared to DKA [T2; complications]
Frequently occurs in older and T2 patients; history is longer than for DKA and has marked dehydration and glucose >35mmol/L; acidosis is absent as there is no switch to ketone metabolism
91
Signs and symptoms of HONK [T2; complications; signs and symptoms]
1. hypovolaemia
2. hyperglycaemia
3. hyperosmolar >320mosmol/kg
significant renal impairment is common
92
Calculation for osmolarity [T2; complications; science]
2 x [Na+/-K] + urea + glucose
93
2 x [Na+/-K] + urea + glucose [T2; complications; science]
Calculation for osmolarity
94
Calculation for osmolarity [T2; complications; science]
2 x [Na+/-K] + urea + glucose
95
2 x [Na+/-K] + urea + glucose [T2; complications; science]
Calculation for osmolarity
96
Normal osmolarity range [T2; complications; science]
285-295 mosmol
97
Medications that may predispose to HONK [T2; complications; causes]
steroids or diuretics
98
Treatment steps (4/6 for 5*) in HONK [T2; complications; treatment]
Caution not to fluid overload
1. 0.9% saline over 48 hours or 0.45% if fluctuating Na+
2. add K+ when urine starts to flow
3. care with insulin as may not need
4. LMWH unless contraindicated
5. screen for vascular events and sepsis as co-morbidities are likely
6. keep BG slightly higher for first 24 hours to avoid cerebral oedema
