Microvascular Complications of Diabetes - Neuropathy

Question 1

what are the chronic complications of diabetes

Answer 1

macrovascular: IHD and stroke (risk x2)

microvascular

cognitive dysfunction/dementia

erectile dysfunction

psychiatric

Question 2

traditionally, what did diabetes lead to

Answer 2

blindness, amputation and dialysis

Question 3

what are the most important interventions in the long term care of DM

Answer 3

control blood pressure - use an ACE (reduces intraglomerular pressure)

vascular disease is the chief cause of death - use a statin for ALL

adress other risk factors eg diet

renal damage may be preventable with good BP and glycaemic control

Question 4

pathophysiology

Answer 4

non-enzymatic glycolysation (glucose simply sticking to proteins in blood) of proteins leads to accumulation of AGE causing injury and inflammation via stimulation of proinflammatory factors

Poyol pathway

Question 5

Poyol pathway

Answer 5

• becomes active in raised intracellular glucose (nerves and blood vessels etc are insulin independent so cannot regulate glucose influx) as aldose reductase has a higher K_M for glucose.
• the metabolism of glucose by aldose reducatse leads to the accumulation of sorbitol and fructose
• this causes disruption in structure and function of eg nerves
• increase in total body Na which predisposes one to hypertension

Question 6

neuropathy - pathophysiology

Answer 6

occlusion of the vasa nervorum (small arteries that provide blood supply to peripheral nerves)

hyperglycaemia (Poyol pathway) leads to increased formation of sorbitol and fructose in Schwann cells - accumulation of these disrupts function and structure

Question 7

risk factors for neuropathy

Answer 7

increased length of diabetes

poor glycaemic control

type 1 (>type 2)

high cholesterol/lipids

smoking

alcohol

inherited traits

mechanical injury

Question 8

functional and histological changes in nerves

Answer 8

delayed conduction velocity

segmental demyelination caused by damage to Schwann cells (due to accumulation of sorbitol and fructose (Poyol pathway))

• in the early stages the axons are preserved (recovery?), but at a later stage irreversible axonal degeneration develops

Question 9

symptoms of neuropathy

Answer 9

sensorimotor:

numbness/insensitivity

tingling/burning

sharp pains or cramps

sensitivity to touch

loss of balance and coordination

Question 10

peripheral neuropathy

Answer 10

• eg pain/loss of feeling in feet and hands
• Commonly gives plantar ulcers
• Often not noticed by patient in the early stages, early clinical signs are loss of vibration sense, temperature and pain sensation
• At later stages patient can lose balance due to loss of proprioception

Question 11

what can peripheral neuropathy lead to

Answer 11

interosseous muscle wasting

Question 12

autonomic neuropathy

Answer 12

affects the nerves that regulate heart rate and blood pressure, as well as control of internal organs eg gastric motility, respiratory function, urination, sexual function and vision

Question 13

autonomic neuropathy: digestive system

Answer 13

• Gastric slowing/frequency and constipation/diarrhoea often accompanied by urgency and incontinence
• Oesophagus nerve damage can make swallowing difficult
• Can lead to weight loss
• Vagal damage can lead to gastroparesis (slowing of stomach emptying) causes persistent nausea and vomiting, bloating and loss of appetite
  
  • This can make blood glucose levels fluctuate widely, due to abnormal food digestion
• Diarrhoea and steatorrhoea may occur owing to small bowel bacterial overgrowth

Question 14

treatment of gastroparesis

Answer 14

• improved glycaemic control
• dietary - small portions, low in fat and fibre (can lead to bezoar formation)
• promotility drugs
• anti nausea medications
• botulinum toxin injection
• gastric pacemaker

Question 15

promotility drugs used in gastroparesis

Answer 15

metoclopramide, domperidone

Question 16

anti nausea medications used in gastroparesis

Answer 16

prochlorperazine and serotonin antagonists (eg ondansetron)

Question 17

abdominal pain treatment in gastroparesis

Answer 17

NSAIDs, low dose tricyclic antidepressants, gabapentin , tramadol

Question 18

botulinum toxin injection

Answer 18

inhibits the release of ACh and causes transient paralysis when injected into gastric smooth muscle

Question 19

autonomic neuropathy: bladder

Answer 19

• loss of tone, incomplete emptying and stasis predisposes one to infections
• May ultimately result in atonic, painless and distended bladder

Question 20

autonomic neuropathy: sweat glands

Answer 20

nerves that control sweating are affected - body cannot regulate its temperature

can get profuse sweating at night and when eating - gustatory sweating

extremes of ani and hyper hidrosis occur

Question 21

treatment of excess sweating due to autonomic neuropathy

Answer 21

topical glycopyrrolate (decrease sweating - increase risk of heat related illness)

clonidine (decrease sweating)

botulinum toxin

Question 22

autonomic neuropathy: heart and blood vessels

Answer 22

• Cardiovascular system nerve damage interferes with the body’s ability to adjust blood pressure and heart rate.
• CV reflexes, e.g. Valsalva manoeuvre, are impaired
• Blood pressure may drop sharply after sitting or standing, causing a person to feel light-headed or faint (postural hypotension) due to loss of sympathetic tone to peripheral arterioles
• Vagal neuropathy results in tachycardia at rest and loss of sinus arrhythmia
• Heart rate may stay high, instead of rising and falling in response to normal body functions and physical activity.

Question 23

proximal neuropathy

Answer 23

eg pain in the thighs, hips or buttocks leading to weakness in the legs

amyotrophy - painful wasting of the quadriceps and other pelvifemoral muscles

Question 24

who is proximal neuropathy more common in

Answer 24

elderly

Question 25

what is proximal neuropathy often associated with

Answer 25

marked weight loss

Question 26

focal neuropathy

Answer 26

* **E.g. mononeuritis and mononeuritis multiplex** * Onset is typically abrupt and sometimes painful * Radiculopathy may occur * eg carpal tunnel, foot drop, bell's palsy, cranial nerve palsy * eg inability to focus eye, double vision, aching behind eye * pain on outside of foot, pain in thigh, chest etc

Question 27

what is a classical sign of CNIII palsy in DM

Answer 27

* A characteristic feature of CNIII palsy is that pupillary reflexes are retained owing to sparing of pupillomotor fibres

Question 28

foot screening tool

Answer 28

FRAME - e learning resource that helps to standardise diabetic foot screenings performed by heath care professionals

Question 29

diagnostic tools for neuropathy

Answer 29

nerve conduction studies/EMG (can determine type/extent of nerve damage and how well the muscles respond to electrical signals transmitted by nerves) heart rate variability (show response to deep breathing and changes in BP and posture) ultra sound (of bladder/UT eg to see if bladder empties completely after urination) gastric emptying studies

Question 30

what does a foot examination entail

Answer 30

* monofilament testing at 5 sites on each foot * palpation of pedal pulses * tuning fork

Question 31

charcot foot

Answer 31

complication that follows on from severe neuropathy thought to be initiated by injury to the foot and increased mechanical stress on the foot, which patients with diminished sensation in the foot are prone to injuries accumulate, and bone density is reduced and joints are destroyed

Question 32

what is found on examination of Charcots foot

Answer 32

gross deformity and insensate foot

Question 33

what is found on an X ray of Charcots foot

Answer 33

bag of bones appearance

Question 34

foot ulcer

Answer 34

typically a painless, punched out ulcer in an area of thick callus ± superadded infection treatment by nursing, podiatry care, offload of pressure, wound care, debridement

Question 35

what type of trauma often occurs

Answer 35

painless

Question 36

what class of medications are used in the treatment of neuropathic pain

Answer 36

it is found that medications used to treat depression and epilepsy are far more effective than paracetamol/ibuprofen etc

Question 37

name some medications used to treat neuropathy

Answer 37

amitryptline, duloxetine, gabapentin, pregabalin (combinations are not recommended, titrate up as needed)

Question 38

what is the choice of medications based on

Answer 38

patient preference and co-morbidities

Question 39

if there is localised neuropathic pain and the patient wishes to avoid/cannot tolerate oral treatments, what is the management

Answer 39

topical Capsaicin cream

Question 40

metoclopramide action

Answer 40

* increases gastric peristalsis and lower oesophageal sphincter tone * blocks D2 receptors in CTZ in brain - anti emetic * crosses the BBB unlike domperidone

Question 41

erectile dysfunction

Answer 41

* is common - occurs in half of all diabetic men, particuarly those over the age of 60 * The first sign is incomplete erection which may in time progress to total failure

Question 42

contributing risk factors for erectile dysfunction

Answer 42

* Chronic renal failure * Hepatic failure * Multiple sclerosis * Severe depression * Spinal cord injuries * Pelvic and urogenital surgery and radiation * Substance abuse * Alcohol * Smoking amplifies other risk factors * Medications (25% of all ED)

Question 43

which medications can cause ED

Answer 43

* All capable * Commonly, thiazides and ß blockers. * Uncommonly, Ca²⁺ channel blockers, alpha-adrenergic blockers and ACE inhibitors.