Diabetes Flashcards
1
Q
Are severe insulin resistance syndromes autosomal dominant or recessive
A
Dominant
2
Q
Causes of insulin resistance
A
- Central adiposty
- Acromegaly ⇒ GH resistance
- Pheochromocytoma of adrenal glands
- Cushing’s disease
3
Q
Effect of visceral fat on insulin resistance
A
Produced adipokines that affect action of insulin
4
Q
HbA1c in acute T1DM
A
NORMAL
5
Q
Will HbA1c be higher or lower in pregnant women
A
Lower
6
Q
When is OGTT often used for identifying T2DM
A
IN gestational diabetes
7
Q
How does T1 DM usually progress
What are the 3 stages and when does clinical onset happen?
A
Genetic susceptibility to immune dysfunction
Stage 1-> Insulitits, inflammatory infiltration of islet, B cell destruction by T cells, autoantibodies present in blood, BGL STILL NORMAL
Stage 2-> loss of first phase insulin secretion, IGT
Stage 3- clinical onset when 80% of islets destroyed, overt diabetes
8
Q
What antibodies can be detected for type 1 diabetes
A
GAD, IA2, ICA, ZnT8
9
Q
What symptoms in T1DM are not common in T2DM
A
Weight loss, kussmaul breathing
10
Q
Diagnostic tests for Type ! DM
A
High blood glucose, DKA , antibodies, elevated HbA1c in some cases
11
Q
autoimmune disorders associated with diabetes
A
thyroid, pernicious anaemia, coeliac, addison’s, vitiligo
12
Q
drugs that can cause hypos and what is their MOA
A
Sulphonylureas - Encourage beta cells to produce more insulin
Binds to SUR1 receptor on cell membrane which closes K+ channels and leads to depolarisation of the cell and opening of voltage dependent ca2+ channels , leading to release of insulin
13
Q
What are the first few hormones to rise as counter regulation for hypoglycaemia
A
epinephrine and glucagon, which result in gluconeogenesis in liver ( epinephrine also stimulates kidneys and reduces glucose use in kidneys)
14
Q
What hormones are secreted when epinephrine and glucagon fail to sufficiently raise blood glucose levels
A
Cortisol and GH
15
Q
What are autonomic symptoms of hypoglycaemia
A
Sweating, shaking, palpitations, hunger
16
Q
What are neuroglycopenic symptoms of hypo
A
Confusion, driwsiness, difficulty speaking, odd behaviour and incoordination
17
Q
What are non-specific (malaise) symptoms of hypo
A
Nausea and headache
18
Q
What is whipple’s triad and what does it do
A
Diagnosis of hypos
- Typical symptoms
- Biochemical confirmation (no agreed cut-off) but usually below 4
- Symptoms resolve with carbohydrates
19
Q
What is the management of hypos
alert
Not alert
Follow up
A
- If alert and has safe swallow , give oral carbs ⇒ sweet drink or dextrose tablet (20g CHO)
- If not alert give 20% dextrose iv
- If can’t get iv access and unsafe swallow, give 1mg im glucagon plus sweet drink (not effective in alcoholic hypo or liver disease)
- Follow-up rapid acting carbs with slow release (complex) carbs
- 10% glucose IV infusion if long-acting insulin or SU.
20
Q
How often should drivers test glucose
A
Before driving (2h). every 2h while on long journey Do not drive if below FIVE
21
Q
How long to wait before continuing driving if hypo
A
45 mins
22
Q
When must drivers inform DVLA
A
more than 1 severe hypo while awake, impaired hypo awareness, hypo while driving
23
Q
How does DKA develop
A
Body unable to utilise glucose, so FFA is mobilised instead and lipolysid occurs -> ketogenesis-
24
Q
Why is glucose so high in DKA
A
profound insulin deficiency -> muscle proteinolysis->lactate and arginine gluconeogenesis
25
how does DKA affect GFR
decreases GFR due to osmotic diuresis and hypovolemia
26
What are the clinical signs of DKA
JVP, BP decreased, HR increased, 5L fluid deficit, significant electrocyte deficit, abdominal pain, nausea and vomiting due to ketone bodies, kussmaul resp, ketotic breath, muscle cramps
27
What is the management of dKA?
Fluids to rehydrate- fast (rapid iv fluids in firs hour)initially then slower
IV insulin in first hour to switch off ketone body production
1-4 hrs:
need to monitor K+ as hypokalaenia common as insulin given
Add 10% glucose once blood glucose is 14 or less to continue giving IV insulin
28
Treatment of DKA patient once they are eating and drinking
Swap to subcutaneous inulin, but must give basal insulin 1h before IV inslin ustops
29
How to deal with CVD risk in patients with T2DM
Statins like atorvastatin to any T1DM patient above 40yo,T2M patients with Q Risk Score above 10
30
What do monocytes form in the arteriar wall
Differentiate into macrophages which accumulate oxidised lipids to form foam cells
31
How do foam cells lead to atherosclerosis
foam cells stimulate macrophage proliferation and attraction of T lymphocytes, in turn inducing smooth muscle proliferation in the arterial walls and collagen accumulation.
32
How is platelet aggregation promoted in macrovascular complications
Impaired nitric oxide generation, increased free radical formation in platelets and altered calcium regulation all promote platelet aggregation
33
How is fibrinolysis impaired in macrovascular complications
Elevated levels of plasminogen activator inhibitor type 1 may also impair fibrinolysis
34
How to treat DKD
Check for microalbuminuria
ACE inhibitors and ARBS like losartan to reduce glomerular pressure and microalbuminuria
35
Treatment of diabetic foot
- Antibiotics
- Debridement ⇒ To reveal what is going on but also take away some of the infection
- Off loading ⇒ Take away pressure from toe
- Improved glycaemic control ⇒ To bring down Hb1Ac
- Vascular assessment ⇒ Feeling for pulses or imaging if lack of pulse
36
pathophysiology of retinopathy
- Aldose reductase may play role in development of diabetic complications
- Initial enzyme in intracellular coil pathway = glucose converted into sorbitol
- High glucose levels increases flux of sugar mol in the pathway and causes sorbitol accumulation in the cells.
- Osmotic stress from sorbitol accumulation may be a causes of diabetic microvascular complications
37
What is sorbitol accumulation in the eyes also linked to
- Linked to microaneurysm formation, thickening of basement membranes and loss of pericytes
- Cells are also thought to be injured by glycoproteins
38
What does proliferative retina disease mean
New vessel formation or preretina hemorrhage or tractional retinal detatchment
39
Treatment for diabetic retinopathy
Try to improve glycaemic control first, may use laser to improve (for proliferative diabetic retinopathy ⇒ new vessels in the eye to increase oxygen supply to the eyes)
Anti VEGF for macular oedema => treatment removes fluid
40
How does diabetes lead to diabetic nephropathy
- Initial constriction of the efferent arterioles and dilatation of the afferent
- Resultant glomerular HTN and hyperfiltration
- Gradually changes to hypotension through time
- Thickening of basement membrane
- Widening of podocytes
- Increased mesangial cells
- Eventually shutting off glomerular filtration
41
Ways to halt complications with diabetic nephropathy
- Improving glycaemic control
- ACEI (reducing BP within the glomerular capillaries)
- Haemodialysis or peritoneal dialysis
- Kidney transplant
42
What are the GI effects of diabetes and how to treat?
Can cause gastroparesis-- vomitting, not absorbing food
Metoclopramide or gastric pacemaker for GI symptoms
43
How to treat Erectile Dysfunction
Patient should lose weitght, can give testosterone replacement and PD 5 inhibitors like sildenafil
44
What is Hyperosmolar hyperglycemic state
Due to relative insulin deficiency affecting the ability for peripheral glucose to be taken into tissue, results in excess glucagon secretion to raise glucose levels, resulting in increase liberation of arginine and gluconeogenesis , as well as increased glycogenolysis
45
diagnoses of HHS and how to differentiate from DKA
- Hyperglycaemia (>30mmol/l, but often 60-90 mmol/l))
- Serum osmolality >320mmol/Kg
- No / mild ketoacidosis ⇒ since it is only due to RELATIVE insulin deficiency
- Severe dehydration (2x DKA) and pre-renal failure common
46
Symptoms of HHS
- nsidious onset
- Profound dehydration (9-10L deficit) 2x DKA
- Hypercoagulability (exclude CVA, DVT, PE)
- Hypercoagulable due to profound dehydration and raised osmolarity
- Confusion, coma, fits.
- Gastroparesis, N&V, hematemesis
47
Management of HHS and difference with DKA
-
- Slower, prolonged rehydration
- Gradual reduction in Na+
- Gentler glucose reduction
- Anticoagulation vital: Prophylactic sc heparin
48
When should Metformin not be given to patients
If eGFR is less than 30 or withdrawing fast
Withdraw during tissue hypoxia but can reinstate later
- ‘Shock’
- MI, significant CCF
- Sepsis
- Dehydration
- Acute renal failure
- Withdraw for 3 days after iodine-containing contrast medium given. Check U/E before reinstating 48h later'
- Withdraw 2 days before general anaesthetic and reinstate once renal function stable
49
What is the first line for diabetes lol
Metformin lmao
50
What is the mechanism of action of metformin
Reduces hepatic glucose output through effect on AMPK - reduces synthesis and increases glucose uptake, glycolysis, fatty acid oxidation and mitchondrial biogenesis
51
Is metformin weight neutral
Encourages weight loss/ neutral
52
What diabetic drug causes hypos
Only Sulphonylureas -- Gliclazide and glibenclamide
53
How do glicazides work
They cause insulin secretion independent of blood glucose level
54
Are sulphonylureas weight neutral
No, can cause modest increase in weight
55
What do glitazones/thiazolidinediones do?
Reduce insulin resistance => Can stop the drug and still have effects for 6 months due to long lasting action
56
Side effects of metformin
In people with renal impairment ⇒ Possible nausea, kidney interactions like **lactic acidosis**
- Hold metformin for patients with low GFR
57
What glitazone/thiazolidinedione side effects are there and what are the contraindications
Cause fluid retention and may lead to CHF, affect bone mineral density, IHD is contraindication
58
what do GLP 1 agonists and DDP4 agonists do
Increase incretins and therefore insulin secretion
GLP 1 agonists increase insulin secretion while DDP4 agonists reduce incretin breakdown
59
Effect of incretin mimetics on weight loss
Increases as it encourages secretion of insulin as you eat, GLP 1 agonists delay gastric emptying
60
Side effects of incretin mimetics
GI symptoms
61
When should incretin mimetics be used
To be used in combination with other medications when other choices have failed
62
Does SGLT 2 inhibitor cause hypos
Only if really low in blood sugar
63
How do SGLT2 inhibitors reduce hyperglycaemia
- Stop reabsorption of glucose through urine - may have excess glucose in urine
- Bacterial infection, thrush, UTI
64
Contraindications of SGLT2 inhibitors
Don’t use in patients with eGFR < 40
65
What are the main causes of secondary diabetes
CF, diabetes secondary to pancreatitis ( alcohol intake) , acromegaly, cushing's , Drugs like Corticosteroids eg. prednisolone ⇒ Exogenous glucocorticoids exacerbates insulin resistance
haemochromatosis ⇒ iron overload (deposited in liver)
- Primary pancreatic tumours
- Pancreatectomy
- Trauma
- Haemochromatosis
66
What test to do for diabetes secondary to pancreatitis
C peptide
67
What gene defects are there in MODY, what inheritance
Single gene defects, autosomal dominant
68
Is MODY early onset? Insulin dependent?
Early onset BUT not insulin dependent
69
Most common MODY>
HNF 1 a
70
What does HNF 1B mutation lead to
Cystic formation in kidneys, insulin requiring diabetes and early onset kidney failure
71
How to test for MODY
C-peptide, check if insulin is being produced, if low, is more likely to be type 1
72
What hormone does the delta cell secrete
Somatostatin
73
What kind of enzymesdoes insulin stimulate
Synthesis enzymes like acetyl CoA carboxylase and glycogen synthase
74
What kind of hormones does glucagon stimulate
breakdown enzymes like TAG lipase and glycogen phosphorylase
75
What channels are involved in secretion of Insulin
GLUT 2
76
What does influx of glucose in B cells result in
Increase in metabolism and production of ATP which results in membrane depolarization due to closing of K+ channels causing less leakage of K+ ions. The depolarization of the channels results in opening of Ca2+ channels and exocytosis of the insulin vesicles
77
What is the action of insulin when it binds to cell membranes ( and of what cells?)
It causes the translocation of GLUT4 to cell membranes in fat and allows insulin-dependent glucose uptake into cells
78
Effect of insulin on glucose
- Increased glucose uptake in fat and muscle
- Increased glycogenesis in liver and muscle
- Decreased gluconeogenesis from C3 precursors in Liver
- Decreased Glycogenolysis in liver and muscle
79
Effect of insulin on protein
Increased amino acid uptake in muscle ⇒ increased protein synthesis
80
Effect of insulin on fats
- Increased lipogenesis in adipose tissue
- Decreased lipolysis in adipose tissue
81
Effect of insulin on ketones
Decreases ketogenesis in liver from aminoacids and fats
82
What is the effect of T1DM and T2DM on action of insulin
T1DM basically reverses it, T2DM reverses almost everything but decreases lipolysis and increases TAG
83
Actions of glucagon
- Glucagon favours glycogenolysis and gluconeogenesis
- **Inhibits glycolysis**
84
Effect of cortisol on glucos, protein and fats
Synergistic with glucagon and adrenalin and increases protein breakdown
85
Effect of glucagon and adrenaline wrt insulin
bascially opp
86
Difference in metabolic changes in starvation and trauma
Decreased BMR in starvation but increased in trauma, increase BG in trauma but not in starvation
87
What are medical disorders associated with T2DM
- Obstructive Sleep Apnoea
- Polycystic Ovarian Disease
- Hypogonadotropic Hypogonadism in men
- Non-Alcoholic Fatty Liver Disease
88
What is a renal complication of HHS
Pre renal failure
