MET3 Revision: Diabetes II Flashcards
Describe why diabetic complications occur [3]
Long term exposure to hyperglycaemia:
- causes mircroaneurysms and venous beading (where the walls of the veins are no longer straight and parallel and look more like a string of beads or sausages)
- vessel closure: hypoxia & nutrients decreased
- vessel permeability: damaged vessels dilate and leak
Which is the strongest risk factor for diabetic complications? [1]
Name 3 others [3]
1st: Smoking
2nd: HTN
3rd: Dysplidaemia
4th: Hyperglycaemia
Describe the pathophysiology of diabetic retinopathy [3]
Chronic hyperglycemia causes:
- basement membrane thickening
- loss of pericytes
- endothelial cell damage in retinal blood vessels (microaneurysms & venous beeding
Describe the three classifications of diabetic retinopathy? [2]
non-proliferative diabetic retinopathy (NPDR) marked by:
- microaneurysms
- retinal haemorrhages (dot haemorrhages)
- hard exudates (yellowish deposits of lipid due to vessel leakage)
proliferative diabetic retinopathy (PDR) (more advanced and severe stage), is characterized by:
- the proliferation of new, fragile blood vessels that can bleed into the vitreous, leading to vision loss due to VEGF upregulation
- can be new vessels on disc (NVD) OR new vessels everywhere (NVE)
Diabetic maculopathy:
- Presence of any retinopathy within 1 disc diameter around macula:
Can be:
- Focal
- Diffuse
- Ischaemic
How can you prevent diabetic retinopathy? [3]
Good BP control - most important
Good glycaemic control
Annual screening
What does this yellow arrow depict in non-proliferative diabetic retinopathy? [1]
Hard exudates
What does the yellow arrow on the image of non-proliferative retinopathy depict? [1]
Lipid exudates
Describe what the arrows & circle depict on this image of non proliferative diabetic retinopathy [3]
intraretinal microvascular abnormality (IRMA; green arrow)
venous beading and segmentation (blue arrow)
cluster haemorrhage (red circle)
featureless retina suggestive of capillary non-perfusion (white ellipse)
How can PDR lead to blindness? [4]
- New blood vessels are very fragile; easily break and leak
- Retinal haemorrhage can lead to acute blindness
- If repeated; leads to fibrosis & scarring
- Can lead to: tractional retinal detachment: when scar tissue or other tissue grows on your retina and pulls it away from the layer underneath
Which pathology is depicted? [1]
Diabetic maculopathy: hard exudates near to the macula
What is depicted in this image? [1]
Proliferative diabetic retinopathy:
extensive vitreous haemorrhage obscuring most of fundus (white circle)}
What is the management of diabetic retinopathy? [5]
Laser photocoagulation
Anti-VEGF medications such as ranibizumab, bevacizumab & Aflibercept
Vitreoretinal surgery (keyhole surgery on the eye) may be required in severe disease or a vitrectomy may be necessary to clear severe vitreous hemorrhage or to relieve tractional retinal detachment.
Corticosteroids: (triamcinolone, dexamethasone implant) can also be used, particularly in refractory DME.
Pan-retinal photocoagulation (PRP): laser used to make small burns evenly across the peripheral retina - should make blood vessels shrink and dissapear
What are the different types of diabetic neuropathy? [5]
- Periperal sensory neuropathy
- Autonomic neuropathy
- Proximal motor neuropathy (amyotrophy; femoral nerve neuropathy - severe pain in anterior thigh & quadricep wasting)
- Cranial nerve palsies (CN III, VI & VII)
- Median nerve / Carpal tunnel syndrome
Which cranial nerves are particularly effected by diabetes? [3]
Cranial nerve palsies: CN III, VI & VII
Describe the treatment regime for diabetic peripheral neuropathy [4]
What are two additonal therapies if these don’t work? [2]
first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
tramadol may be used as ‘rescue therapy’ for exacerbations of neuropathic pain
topical capsaicin may be used for localised neuropathic pain
pain management clinics may be useful in patients with resistant problem
Describe the effects of diabetic autonomic neuropathy on genito-urinary [2]; GI [3] & CV [1] systems
Genito-urinary
- ED
- Atonic bladder: difficulty voiding / urinary incontinence
Gastrointestinal [3]:
- Gastroparesis: stomach doesn’t empty properly, causing outflow problems: recurrent vomiting & early satiety
- Chronic constipation & diarrhoea
- Gustatory sweating: severe sweating on eating
CV [1]:
- Postural hypotension
What is the clinical presentation triad of diabetic nephropathy? [3]
Hypertension
Albuminuria
Decline renal function
What does the green arrows point to? [1]
Kimmelstein-Wilson lesion
Describe the pathophysiology of diabetic nephropathy [4]
Oxidative stress consumes nitric oxide, which prevents flow-mediated dilation of blood vessels (endothelial dysfunction): subjecting the endothelium to injury
Leads to production of cytokines, acceleration of inflammation, worsening of blood vessel rigidity due to atherosclerosis, and further impairment of FMD and susceptibility to oxidative stress.
Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) mediate mesangial expansion and fibrosis via the stimulation of matrix protein (collagen and fibronectin) synthesis and decreased matrix degradation
Angiotensin II (ATII), elevated in DKD, constricts the efferent arteriole in the glomerulus, causing high glomerular capillary pressures, and also stimulates fibrosis and glomerular inflammation
How do you screen for microalbuminuria for suspected diabetic nephropathy patients? [2]
Measure urine albumin:creatinine ratio (ACR):
- Normal is < 2.5mg/mmol men; < 3.5 mg/mmol in women
- If evelated repeated x2: 2/3 positive microalbuminuria present
- (can be elevated by meat; running)
Describe the treatment regime for nephropathy (have microalbuminuria) [7]
Control BP:
- ACE inhibitor: captopril; elanapril; lisinopril; ramipril
- ARB if ACE inhibitor not tolerated; losartan; valsartan
- Add calcium-channel blocker amlodopine; felopdipine; nifedipine and/or thiazide-like diuretic: hydrochlorothiazide; and/or beta-blocker carvedilol; metaprolol
Optomise blood glucose control
Manage CV risk factors aggressivey
Manage lipid levels: atorvostatin
Stop metformin when eGFR < 30 mls/min
Refer to specialist if eGFR < 45 mls/min
Renal transplant if giving pancreatic transplant
When should you stop prescribing metformin a patient suffering from diabetic nephropathy? [1]
Stop metformin when eGFR < 30 mls/min
Refer to specialist if eGFR < 45 mls/min
What are common skin presentations of diabetes? [6]
- Oral / genital candidiasis
- Skin abcesses
- Rhinocerebral mucormycosis infection
- Fungal nail infections
- Aconthosis nigricans (sign of insulin resistance)
- Bullosis Diabeticorum (blisterng)
- Granuloma annulare
- Necrobiosis Lipoidica Diabeticorum (pink skin lesion on lower legs)
What is this skin condition associated with diabetes? [1]
Necrobiosis Lipoidica Diabeticorum
What is the name of this skin complication of diabetes? [1]
Granuloma annulare
What is the name for this diabetic skin complication? [1]
Bullosis Diabeticorum
Describe the two rheumatological complications / manifestations of diabetes need to know?
Charcot neuroarthopathy: chronic, devastating, and destructive disease of the bone structure and joints in patients with neuropathy; it is characterized by painful or painless bone and joint destruction in limbs that have lost sensory innervation
Diabetic cheiroarthropathy: limited mobility of the joints of the hands
Name this complication of diabetes
Charcot neuroarthropathy
Name this sign [1] and disease [1] that is a complication of diabetes
Prayer sign; diabetic cheiroarthropathy
What is the most common cause of visual loss in patients with diabetes? [1]
Describe this [1]
Diabetic macular oedema (DMO)
DMO is the commonest cause of visual loss in patients with diabetes
DMO is characterised by oedematous changes in or around the macula. As the macula is responsible for central vision, affected patients tend to complain of blurred vision when reading or difficulty recognising faces in front of them. DMO is the commonest cause of visual loss in patients with diabetes.9
DMO can be subcategorised into three categories. Describe them [3]
Focal/diffuse macular oedema:
* the fluid that escapes from damaged vessels can be well-circumscribed (focal) or more widespread and poorly demarcated in nature (diffuse).
Ischaemic maculopathy:
- patients will be symptomatic with defects in visual acuity due to ischaemia at the site of the macula. These areas are best visualised with fluorescein angiography.
Clinically significant macular oedema (CSMO):
- CSMO describes significant changes associated with retinopathy, such as hard exudates and retinal thickening, found within a certain distance to the fovea or greater than a certain size.
Name a complication of diabetic retinopathy [1]
Diabetic retinopathy is one of several causes of neovascular glaucoma: a type of secondary glaucoma.
Neovascularization can occur within the iris and its trabecular meshwork (rubeosis) causing a narrowing and closure of the drainage angle and therefore increased intraocular pressure.
Diabetic ketoacidosis: once blood glucose is < 14 mmol/l due to NaCl and fixed rate insulin has been given. What is the next appropriate step? [1]
Diabetic ketoacidosis: once blood glucose is < 14 mmol/l an infusion of 10% dextrose should be started at 125 mls/hr in addition to the saline regime
When are SGLT-2 inhibitors indicated in diabetes patients? [4]
the patient has ahigh risk of developing cardiovascular disease (CVD, e.g. QRISK ≥ 10%)
the patient has established CVD
the patient has chronic heart failure
SGLT-2 inhibitors should also be started at any point if a patient develops CVD (e.g. is diagnosed with ischaemic heart disease), a QRISK ≥ 10% or chronic heart failure
metformin should be established before introducing the SGLT-2 inhibitor
If metformin is contraindicated in a diabetic patient, what should a patient be prescribed if:
- the patient has a risk of CVD, established CVD or chronic heart failure [1]
- if the patient doesn’t have a risk of CVD, established CVD or chronic heart failure [2]
if the patient has a risk of CVD, established CVD or chronic heart failure:
* SGLT-2 monotherapy
if the patient doesn’t have a risk of CVD, established CVD or chronic heart failure:
* DPP‑4 inhibitor or pioglitazone or a sulfonylurea
* SGLT-2 may be used if certain NICE criteria are met
If a patient is presenting with Diabetic ketoacidosis: [] should be used initially, even if the patient is severely acidotic [1]
What is the following treatment? [3]
Diabetic ketoacidosis: isotonic saline should be used initially, even if the patient is severely acidotic
an intravenous insulin infusion should be started at 0.1 unit/kg/hour
once blood glucose is < 14 mmol/l an infusion of 10% dextrose should be started at 125 mls/hr in addition to the 0.9% sodium chloride regime
potassium may therefore need to be added to the replacement fluids
Name 4 non medical causes of hypoglycaemia [4]
Exercise with too much insulin or not enough carbs
Alcohol – can cause hypoglycaemia even in non-diabetic people
Vomiting
Breastfeeding
State 4 medical causes of hypoglycaemia [4]
Liver disease
Progressive renal impairment
Hypoadrenalism (is associated with Type 1 diabetes)
Hypothyroidism
Hypopituitarism (rare)
Insulinoma (rare)
Autonomic symptoms occurs at a glucose level of ~ [] mmol/L [1]
Name 6 symptoms
Autonomic symptoms – Glucose ~ 3.6 mmol/L
Sweating
Shaking or tremor
Anxiety
Palpitations
Hunger Nausea
Neuroglycopenic symptoms occurs at a glucose level of ~ [] mmol/L [1]
Name 5 symptoms
Neuroglycopenic symptoms– Glucose ~ 2.7 mmol/L
Confusion
Drowsiness
Slurred speech
Aggression
Visual disturbances
How can you reverse hypoglycaemic unawareness? [3]
May be improved by “hypo holiday”:
Strict hypoglycaemia avoidance by relaxing glycaemic control
Use of analogue insulin
Continuous Subcutaneous Insulin Infusion (insulin pump therapy)
Treatment of mild [2], moderate [2] and severe [4] hypoglycaemia?
Mild:
Sugary drink, e.g. lucozade, ordinary coke, orange juice
5-7 glucose tablets, or 3-4 heaped teaspoons of sugar in water
Moderate:
Glucogel® – 1-2 tubes buccally (into cheek), or jam, honey, treacle massaged into the cheek.
Intramuscular glucagon if needed
Severe (unconscious)
Do not put anything in the mouth
Place the person in the recovery position Administer 0.5-1mg glucagon IM
If carer is unable to administer glucagon, call 999
In hospital, administer iv glucose:
- Ideally 75mls of 20% glucose or 150mls 10% glucose over 15 mins
- 50mls 50% glucose can be given, but take care with veins – extravasation can cause chemical burns
What is the dose of IV glucose for hypoglycaemia? [2]
75mls of 20% glucose or 150mls 10% glucose over 15 mins
Name a risk of giving glucogel orally? (For moderate hypoglycaemia) [1]
Risk of causing aspirational pneumonia
Patients with diabetes who wake up with which symptoms may indicate they have nocturnal hypoglycaemia? [2]
How do you confirm this diganosis? [1]
High blood glucose levels (rebound hyperglycaemia)
Headaches – feels “hungover” despite no alcohol!
Confirm by advising testing blood glucose levels during the night (3.00am), or using continuous glucose monitoring sensor (CGMS), which monitors glucose over 5 days subcutaneously
Management of nocturnal hypoglycaemia? [4]
Analogue insulins
Pre bed snack
Change timing of insulin
Insulin pump therapy
Symptoms of DKA? [5]
Often a short history:
Abdominal pain and vomiting is common – can present as an acute abdomen
Kussmaul’s respiration – deep sighing respirations due to acidosis
Ketones on breath (remember ~40% people cannot smell these)
Drowsiness, confusion
Dehydration and Tachycardia
State 5 triggers of DKA [5]
Insulin omission (see notes later on “sick day rules”)
Infection
Pregnancy
Myocardial Infarction
Intoxication / drugs
Diagnosis of DKA?
Venous blood gases [2]
CBG [1]
Ketones? [1]
Venous blood gases:
- show acidosis (pH < 7.35, bicarb < 15)
Capillary Blood Glucose (CBG)
- usually over 14 mmol/L, but can be lower (euglycaemic ketosis or alcoholic ketosis)
Raised Urea and Creatinine
Urine or plasma ketones
- elevated: above 3 mmol/L
Describe fluid therapy provided for DKA patients:
Sodium chloride:
- What %? [1]
- How many litres, over what time period? [4]
Glucose:
- What %? [1]
- What level CBG mmol/L is required before giving? [1]
- How much ml/hr? [1]
Sodium chloride 0.9%
* 1 Litre stat
* 1 Litre in 1 hour
* 1 Litre over 2 hours (+20 mmol potassium chloride) 1 Litre over 4 hours (+potassium chloride)
* 1 Litre over 4 hours (+potassium chloride)
5% or 10% Glucose
* Start when the CBG is < 12 mmol/L and continue at 125ml/hr
* 10 % glucose may be necessary to increase insulin infusion Increase infusion rate if glucose falls below 6.0 mmol/L`
When is potassium provided in DKA fluid therapy? [1]
What levels of K are provided for patients with serum K of:
* < 3.5 [1]
* 3.5-5.5 [1]
* > 5.5 [1]
For the first 1-2 bags fluid, give no potassium as fluid is given too rapidly
For every subsequent bag of NaCl 0.9% or glucose 5% use a bag of fluid containing KCl as follows according to serum K+:
- < 3.5: May need additional K+ and delay insulin
- 3.5-5.5: 20-40 mmol/l
- > 5.5: none
Describe the overall management plan for DKA
- Fluid therapy: 0.9% NaCl; 5/10% glucose at a rate of 125 ml/hour (when serum glucose is below 14 mmHg
- IV Insulin therapy: 0.1 units/kg/hr
- Monitor Electrolytes: Insulin treatment will decrease plasma potassium levels leading to profound hypokalaemia.
Most common cause of death from DKA? [1]
Cerebral oedema
Explain the pathophysiology of Hyperglycaemic hyperosmolar state (HHS) [6]
Relative lack of insulin is coupled with a rise in counter-regulatory hormones (e.g. cortisol, growth hormone, glucagon) that leads to a profound rise in glucose.
These patients retain a certain level of insulin, which prevents the development of ketosis that epitomises DKA. However, the level of insulin is inadequate to prevent profound hyperglycaemia.
The excessive glucose leads to massive osmotic diuresis within the kidneys with the loss of essential electrolytes such as sodium and potassium.
This is because the proximal tubules within the kidneys only have a certain capacity for reabsorption of glucose. Once this is reached, the remaining glucose is passed through the renal nephrons causing diuresis
As water is lost, there is profound dehydration and reduced circulating volume, resulting in hyperosmolarity and marked hyperglycaemia. Patients with HHS may have up to a 9 litre deficit of water
The increase in osmolality increases compensatory mechanisms such as release of anti-diuretic hormone (ADH) and stimulation of thirst. However, if this cannot compensate for the renal water loss (e.g. elderly patients with co-morbidities) then hypovolaemia develops with progression to acute kidney injury, electrolyte disturbances, hypotension and coma.
The hyperosmolar state of the condition leads to hyperviscosity that increases the risk of arterial and venous thrombosis (e.g. stroke, DVT).
Describe the presentation of Hyperosmolar hyperglycemic state (HHS) [4]
Usually Type 2 diabetes
Longer subacute history
Hyperglycaemia often >40 mmol/L
NOT ketoacidotic, but may have lactic acidosis
Severe dehydration
Patient is often hypernatraemic
What are the treatments for Hyperosmolar hyperglycemic state (HHS)? [2]
Due to the significant fluid deficit, the initial management requires fluid resuscitation to restore circulating volume:
- 0.9% NaCl and at least 1 litre should be given over an hour (quicker in the presence of significant hypotension).
- Fluid replacement alone with 0.9% sodium chloride solution will result in falling blood glucose
- Further fluids can be given aiming for a positive fluid balance based on hourly measurement of urine output. A proposed target is 2-3 litres positive by 6 hours.
Insulin:
- IVI as for DKA – but consider slower fluids if elderly / heart failure
- much lower dose insulin – (maybe) no insulin for 1st 12 hours, then very low doses : rate of 0.05 units/kg/hour if blood ketones (beta-hydroxybutyrate) are ≤3.0 mmol/L and the patient is not acidotic
Why is fluid therapy given slowly when treating HHS? [1]
Rapid correction of the fluid deficit is not advisable as it can precipitate osmolar shifts leading to cerebral oedema (generally aim for 4 litres positive within the first 24 hour).
What K should be given for the following serum K levels when treating HHS & DKA?
Serum K+ > 5.5 mmol/L: [1]
Serum K+ 3.5-5.5 mmol/L: [1]
Serum K+ < 3.5 mmol/L: [1]
Serum K+ > 5.5 mmol/L: Nil potassium replacement
Serum K+ 3.5-5.5 mmol/L: 40 mmol potassium replacement
Serum K+ < 3.5 mmol/L: Senior review for more invasive potassium replacement
What pathology is a risk of rapid shift of glucose in HHS patient treatment? [1]
Why? [1]
Rapid shifts in glucose should be avoided due to risk of rapid fluid / sodium shifts, and risk of central pontine myelinolysis (CPM):
- destruction of the layer (myelin sheath) covering nerve cells in the middle of the brainstem (pons).
How long do you not give insulin for HHS treatment? [1]
Why? [1]
12hrs
Insulin treatment prior to adequate fluid replacement may result in cardiovascular collapse
as water moves out of the intravascular space, with a resulting decline in intravascular volume
Which other electrolytes are common to have a deficiency in HHS? [2]
Hypophosphataemia and hypomagnesaemia are common in HHS.
All patients should receive [] for the full duration of HHS admission unless contraindicated
Explain why [1]
All patients should receive prophylactic low molecular weight heparin (LMWH) for the full duration of admission unless contraindicated
Higher risk of VTE: (DM is a risk factor; hospitilisation; hypovolaemia)
Describe the different severities of NPDR [3]
Mild NPDR:
- Characterized by the presence of at least one microaneurysm. At this stage, the disease might not be apparent to the patient.
Moderate NPDR:
- More extensive microaneurysms are present, along with haemorrhages and hard exudates. The retina may also exhibit cotton-wool spots, which are areas of nerve fibre layer infarctions.
Severe NPDR:
- Defined by the ‘4:2:1 rule’. This means there are either more than 20 intraretinal haemorrhages in each of 4 quadrants (4), definite venous beading in 2 or more quadrants (2), or prominent intraretinal microvascular abnormalities (IRMA) in 1 or more quadrant (1).
Describe the difference between early and high risk PDR [2]
Early PDR:
- New vessels less than 1/3 of the disc area, no vitreous haemorrhage, and no tractional retinal detachment.
High-risk PDR:
- Characterized by any of the following: neovascularization of the disc (NVD) greater than or equal to 1/3 of the disc area, any NVD associated with vitreous or preretinal haemorrhage, or neovascularization elsewhere (NVE) greater than or equal to 1/2 disc area with vitreous or preretinal haemorrhage.
