Long and Short term effects of Diabetes + Psychology

Question 1

What is Diabetic Keto-acidosis?

• describe the pathogenesis

Answer 1

• this is a diabetic emergency that presents with
  
  • hyperglycaemia
    
    • due to insulin deficiency –> glycogenolysis
  • Dehydration
    
    • osmotic diuresis - the osmotic force of unreabsorbed glucose holds water in tubules
  • high anion gap metabolic acidosis
    
    • due to the dissociation of ketone bodies into hydrogen ion and anions
  • and ketonaemia
    
    • hyperglucagonaemia –> decreases malonyl co A production and increases carnitine palmitoyltransferase I –> free fatty acids are converted to ketones rather than triglycerides
• this is mostly associated with T1DM (increasing prevalence in T2DM)

Question 2

What are the precipitating events that lead to a DKA?

Answer 2

• Infection (30-40%)
• New-onset diabetes (25%)
• Inadequate insulin treatment or non-compliance (20%)
• MI/ Stroke
• Acute Pancreatitis
• Trauma
• Drugs: clozapine/olanzapine, cocaine, lithium, terbutaline

Question 3

Describe the physiological effects insulin deficiency has on adipose tissue

Answer 3

• Increased lipolysis and reduced esterification of fat due to
  
  • Insulin deficiency
  • Glucagon/adrenaline excess
  • Results in excess FFA and glycerol from breakdown triglycerides
• FFA substrate are used for hepatic synthesis of ketone bodies
  
  • Acetoacetate/Hydroxybutyrate – strong organic acids (Acetone)
  • Rate of ketogenesis is linked to rate of gluconeogenesis
• Muscle and brain can utilise ketones as main energy substrate
• Ketoacidosis results when ketone body production exceeds rate of utilisation in peripheral tissues (brain and muscle) and renal clearance

Question 4

What compensatory mechanisms does the body take to manage acidosis?

Answer 4

• Intracellular buffering - H+ / K+ exchange
  
  • Potassium hydrogen ion pump
• Respiratory compensation – hyperventilation
  
  • H+ stimulates respiratory centres
  • Breathe off CO2 (H⁺ + HCO₃^- H₂O + CO₂)
• Renal excretion of H+ (slow response)

Question 5

Give a clinical overview of DKA

• Age:
• Precipitating causes:
• Serum sodium:
• Blood glucose:
• Serum bicarbonate/pH:
• Serum ketones:
• Mortality:
• Subsequent course:

Answer 5

• Age: Mostly young T1DM
• Precipitating causes: Relative or absolute insulin deficiency
• Serum sodium: Normal or low
• Blood glucose: Usually <40mmol/l
• Serum bicarbonate/pH: <14mmol/l / pH<7.3
• Serum ketones: high +++++
• Mortality: 5% depending on age
• Subsequent course: Insulin dependent

Question 6

What are some symptoms and signs of DKA?

• what causes these?

Answer 6

• Thirst and polyuria | Weakness and malaise | Drowsiness, confusion
  
  • caused by Hyperglycaemia + dehydration, seen via
    
    • Dry mouth, Sunken eyes, Postural or supine hypotension, Hypothermia & Coma
• Nausea and vomiting | Abdominal pain | Breathlessness
  
  • caused by Acidosis seen via
    
    • Facial flush, Hyperventilation, Smell of ketones on breath and ketonuria

Question 7

What is the management plan for DKA?

• 5 steps

Answer 7

1. Confirm diagnosis and check for precipitating causes
2. Rehydrate & monitor fluid balance
   
   • Iv fluids - saline with added potassium
   • Consider urinary catheter
3. Lower glucose
   
   • Intravenous insulin – fixed-rate 0.1Unit/kg/hr
4. Monitor electrolytes
   
   • Potassium (and sodium)
5. Prevent clots
   
   • Prophylactic low molecular weight heparin

Question 8

Apart from the 5 management steps what else needs to be considered in treating DKA?

Answer 8

• Is the patient conscious?
  
  • assess GCS –> potentially call ICU
• Are they at risk of aspiration?
  
  • consider NG tube
• Recovery needs to be monitored regularly
  
  • Glucose, ketones, pH, potassium - hourly

Question 9

What is Hyperosmolar Hyperglycaemic State (HHS)?

-

Answer 9

• similar to DKA caused by insulin deficiency and glucagon excess however there is
  
  • little or no ketoacid accumulation
  • serum glucose conc. often exceeds 50mmol/ L
  • plasma osmolality may reach 280mosmol/kg
  • neurological abnormalities are frequently present
• there is enough insulin to present lipolysis but not enough to allow appropriate levels of glucose utilisation
  
  • hence no ketonacids accumulating

Question 10

Give an overview of the clinical features for HHA (HONK)?

• Age:
• Precipitating causes:
• Serum sodium:
• Blood glucose:
• Serum bicarbonate/pH:
• Serum ketones:
• Mortality:
• Subsequent course:

Answer 10

• Age: usually >40yrs
• Precipitating causes: previously undiagnosed, steroids, diuretics, sugar
• Serum sodium: usually high
• Blood glucose: often >40mmol/l
• Serum bicarbonate/pH: normal/ pH 7.4
• Serum ketones: 0
• Mortality: 30% (thromboses)
• Subsequent course: Diet/tablet controlled

Question 11

What is the management plan for HHS?

• 5 key points

Answer 11

Correct the profound dehydration

1. Confirm diagnosis and check for precipitating causes
2. Rehydrate & monitor fluid balance
   
   • Iv fluids - saline with added potassium
   • Consider urinary catheter
3. Lower glucose (once glucose not improving with fluids)
   
   • Intravenous insulin – fixed rate 0.05Unit/kg/hr
4. Monitor electrolytes
   
   • Potassium (and sodium)
5. Prevent clots
   
   • Treatment low molecular weight heparin

Question 12

What is Hypoglycaemia?

Answer 12

• Hypoglycaemia is a biochemical term and exists when blood sugar < 4mmol/l but is often used to describe a clinical state.
• The clinical syndrome associated with hypoglycaemia develops as the nervous system becomes glucose deficient or ‘neuroglycopenic’.
• Can be classified as
  
  • Asymptomatic: awake, sleeping
  • Mild symptomatic
  • Severw symptomatic
  • Coma and convulsions

Question 13

What are symptoms of Hypoglycaemia?

• autonomic
• neuroglycopenic

Answer 13

• Autonomic – sympathomedullary activation
  
  • Sweating, feeling hot
  • Trembling or shakiness
  • Anxiety
  • palpitations
• Neuroglycopenic
  
  • Dizziness, light-headedness
  • Tiredness
  • Hunger, nausea
  • Headache
  • Inability to concentrate, confusion, difficulty speaking, poor coordination, behavioural change, automatism
  • Coma and convulsions, hemiplegia

Question 14

What are the causes of Hypoglycaemia?

Answer 14

• Insulin
  
  • excessive doses
  • not eating or insufficient CHO
• Sulfonylureas (diabetes medication)

Question 15

What is the treatment for minor hypoglycaemic episodes?

Answer 15

• 20g CHO as a sugary drink, fruit juice, glucose tablets, glucose gels
  
  • followed by something ‘starchy’ to eat

Question 16

What is the treatment of a hypoglycaemic coma?

Answer 16

• IM or IV glucagon 1mg
• IV dextrose 25g (150ml 10% glucose)

Question 17

What are the types of long term complications that accompany diabetes?

• Microvascular
• Macrovascular

Answer 17

Microvascular

• Retinopathy
• Nephropathy
• Neuropathy

Macrovascular

• IHD
• CVD
• PVD

Question 18

What can be seen through pathological investigations in those presenting with Diabetic retinopathies?

Answer 18

• Loss of pericytes
• Basement membrane thickening
• Capillary closure
• Ischaemia
  
  • Vascular endothelial growth factor (VEGF) production
  • Increased capillary permeability, due to hyperglycaemia increasing mean arterial pressure

Question 19

What are the clinical stages of Retinopathy?

Answer 19

• Non-proliferative
  
  • background
  • pre-proliferative
• Proliferative
• Macular Oedema
  
  • sight-threatening
  • non-sight threatening

Question 20

Explain Background Retinopathy (R1)

Answer 20

• death of retina pericytes, thickening of the retinal basement membrane –> impairment of function
• this is associated with the formation of microaneurysms and increased vascular permeability
  
  • leads to the leakage of hard exudate (proteinaceous material)
• vascular occlusion and rupture may be caused by preceding cycles of cell death and renewal involving
  
  • intraluminal proliferation
  • changes in platelet function
  • erythrocyte aggregation
  • high plasma fibrinogen levels

Question 21

Explain Preproliferative Retionpathy (R2)

Answer 21

• Intraretinal microvascular abnormalities (IRMAs): these are dilated capillaries that occur in response to retinal ischaemia
• This is the occurrence of intraretinal infarcts - cotton wool spots or soft exudate - distal to the microvascular occlusion
• further growth of the endothelial cells of retinal veins –> venous calibre abnormalities
  
  • venous bleeding
  • loops and dilation

Question 22

Explain Proliferative Retinopathy (R3)

Answer 22

• continuous microvascular occlusion and retinal ischaemia –> increased release of vaso-proliferative substances
  
  • IGF-1 and VEGF (vascular endothelial growth factor)
• ​these factor promote neo-vascularization, forming mesh of fibrous tissue connecting them.
• New vessel formation is associated with the following risk
  
  • ​Pre-retinal or vitreous haemorrhage: due to fragility
  • Retinal detachment: with new vessel maturation the fibrous component becomes more prominent resulting in contraction/ detachment from the choroid
• new vessel formation can also occur on the surface of the iris or the interior chamber –> glaucoma by blocking the outflow of the virtuous humour

Question 23

What pathology is this?

Answer 23

• Vitreous haemorrhage
• due to new arteries and veins being fragile and prone to rupture

Question 24

What pathology is this?

Answer 24

diabetic maculopathy with haemorrhages and circinate exudates

• associated with a best visual acuity of 6/12 or less

Question 25

Explain what Maculopathy is

Answer 25

• this is when there are exudates within one disc diameter of the centre of the fovea
• microaneurysms or haemorrhage within one disc diameter of the centre of the fovea associated with visual acuity of 6/12 or less
• retinal thickening within one disc diameter of the centre of the fovea

Question 26

What is Macular Oedema?

• presenting
• exams to confirm

Answer 26

• retinal thickening due to leaky blood vessels - can develop at any stage of retinopathy
• presents with gradual onset of blurring of near and distant vision
• referred to an ophthalmologist for
  
  • slit-lamp examination: detects thickening
  • fluorescein angiography: detects local leakage associated with oedema

Question 27

What measures can be taken to reduce the risk and progression of Retinopathies?

Answer 27

• Glycaemic control
  
  • lowering HbA1c: 1% decreases reduces risk by 37%
• Controlling blood pressure
  
  • Lisinopril (ACE inhibitor): used in normotensive T1DM patients was seen to be effective in reducing the progression of retinopathy
• Multifactorial lifestyle change (diet, therapy, exercise, smoking cessation etc.)
• Fenofibrate therapy + Antiplate agents show some efficacy, further study needed
• Regular screening needed in pregnancy due to increased risk

Question 28

What treatment is there for established retinopathy?

Answer 28

• Laser Photocoagulation
  
  • only advised for more advanced retinopathy except in treating macular oedema
  • reduces the risk of visual loss, needs aggressive monitoring and treatment
• Inravetriol steroids
  
  • used to treat macular oedema, repeated injections usually necessary
• Vitrectomy
  
  • used to preserve useful vision
  • followed by removal of the vitreous humour and photocoagulation can restore some functional vision
• Growth factor inhibitors
  
  • VEGF inhibitors

Question 29

What is Diabetic Neuropathy?

• types of neuropathy

Answer 29

• this is caused by the loss of myelinated and unmyelinated nerve fibres due to vascular and metabolic factors that impair nerve repair mechanisms

They include

• Peripheral neuropathy
• Mononeurotherapy
• Autonomic neuropathy

Question 30

How does Peripheral neuropathy present?

• what are other signs it presents with

Answer 30

• distal sensory loss or paraesthesia
  
  • a sensation of numbness, tingling, burning, or sharpness
  • this starts at the feet and spreads proximally
• some patients experience neuropathic pain,
  
  • usually at night and in the lower extremities
• Signs: loss of the following sensations
  
  • pinprick sensations
  • temperature
  • vibration
  • joint position
  • with diminished ankle reflexes

Question 31

What is the presentation of Mononeuropathy

Answer 31

• motor weakness in a single cranial or peripheral nerve
  
  • III, IV, VI, VII,
  • median, ulnar, peroneal nerve
• most common is ptosis and ophthalmoplegia
  
  • due to cranial nerve III palsy
• may present with mononeuropathy multiplex

Question 32

How does Autonomic Neuropathy present itself?

Answer 32

• due to longstanding diabetes that leads to dysfunction involving the cholinergic, noradrenergic and peptidergic system
• Cardiovascular
  
  • postural hypotension
  • resting tachycardia
• Gastrointestinal
  
  • gastroparesis (delayed gastric emptying)
    
    • may present with anorexia, N&V early satiety, bloating
  • diarrhoea or constipation
  • gustatory sweating
• ​​Genitourinary
  
  • bladder dysfunction, incontinence
  • recurrent UTI
  • erectile & female dysfunction, reduced libido
• Hyperhidrosis & anhidrosis

Question 33

What are the pathological findings of those with Diabetic Nephropathy?

Answer 33

• Basement membrane thickening
  
  • Loss of negative charge
• Podocyte loss
  
  • Loss of integrity of the filtration barrier
• Glomerular sclerosis
• Mesangial expansion

Question 34

What are the clinical stages of Diabetic Nephropathy?

• dipstick tests

Answer 34

Question 35

How can Diabetic nephropathy be treated or it’s progression reduced?

• ABCD

Answer 35

• ACE inhibitor and ARBs
  
  • ACE inhibitors decrease microalbuminuria and hence risk of developing proteinuria in T1 +2 DM
• Blood pressure control
• Control of glycaemia
• Diet: protein restriction

Question 36

What is Diabulimia?

• aetiology

Answer 36

• Insulin omission
  
  • seen in 40% of T1 adolescents
• poorer outcomes fro diabulimia
• due to secondary and scute risk of DKA
• can be hours away from fatality even if they don’t appear obviously unwell

Question 37

What are the signs of Diabulimia?

Answer 37

• Symptoms of untreated diabetes
• Severe Fluctuations in weight/ Severe weight loss/Rapid weight gain/anorexic BMI
• Fear of injecting or extreme distress at injecting
• Co-occurrence of depression, anxiety or other psychological disturbance such as Borderline Personality Disorder
• Anxiety/ distress over being weighed at appointments
• Frequent Requests to switch meal plans
• Encyclopaedic knowledge of carbs

in serious conditions, they should be handled by a MDT + MH services

Question 38

What is the physical and psychological effect of diabetes on sex?

Answer 38

• Due to microvascular damage there is
  
  • loss of sensation
  • vaginal dryness & erectile dysfunction
    
    • 35-70% of men, 33% of women
• Psychological damage
  
  • fear of hypos during sex
  • body image & devices
  • shame