Microvascular complications of diabetes

There are 3 main microvascular complications of diabetes:

• Diabetic retinopathy
• Diabetic neuropathy
• Diabetic nephropathy

The microvascular complications tend to manifest themselves 10-20yrs after diagnosis in young patients. They present earlier in older patients, probably because these have had unrecognized diabetes for months or even years prior to diagnosis.

The natural history of retinopathy:

• Diabetes causes thickening of the basement membrane and increased permeability of the retinal capillaries.
• Aneurysmal dilatation may occur in some vessels, whilst others may become obstructed.
• After 20 yrs of IDDM, almost all patients have some retinopathy and 60% progress to sight-threatening retinopathy

Stages of retinopathy:

There are 4 types of diabetic retinopathy, each discussed below.

Background retinopathy:

• Most common form
• Hard exudates (caused by cholesterol)
• Microaneurysms (dot haemorrhages)
• Managed by improving blood glucose control

Pre-proliferative retinopathy:

• Cotton wool spots (‘soft’ exudates). Indicate the 1^st stages of neovascularisation – an indication of retinal ischaemia
• If left alone, the vessels will grow and may bleed.
• We treat with pan-retinal photocoagulation

Proliferative retinopathy:

• Visible new blood vessels over the surface of the retina
• Treat with pan-retinal photocoagulation

Maculopathy:

• Hard exudates near the macula
• May threaten direct vision
• Treat with a grid of photocoagulation

The diabetic kidney:

The kidney may be damaged by diabetes in 3 main ways:

• Glomerular damage
• Ischaemia (resulting from hypertrophy of afferent and efferent arterioles)
• Ascending infection

Diabetic glomerulosclerosis:

• Manifests itself 15-25 yrs after dx
• Affects 25-35% of patients diagnosed before the age of 30 yrs
• Leading cause of premature death in young diabetics

Pathophysiology:

• Initial structural lesion in the glomerulus is thickening of the basement membrane
• We get a progressive leakage of large molecules (particularly protein) into the urine
• Earliest evidence of protein in the urine is ‘microalbuminuria’ (amounts of urinary albumin so small as to be undetectable by dipsticks)
• Microalbuminuria may progress to persistent proteinuria

At the stage of persistent proteinuria:

• Plasma creatinine may be normal but the patient is 5-10 yrs from ESRF
• A rise in plasma creatinine is a late feature
• Patients typically have a normochromic normocytic anaemia and hypertension

Ischaemic lesions of the diabetic kidney:

Arteriolar lesions, with hypertrophy and hyalinization of the vessels, affect both afferent and efferent arterioles.

The appearances are similar to those of hypertensive disease but are not necessarily related to the BP in patients with DM.

Infective lesions of the diabetic kidney:

• Ascending infection may occur because of bladder stasis resulting from autonomic neuropathy
• Infections are able to establish themselves more easily in damaged renal tissue

Diagnosis of diabetic nephropathy:

• The urine of ALL diabetics should be checked regularly for the presence of protein.
• Many centres also screen for the presence of microalbuminuria, since there is good evidence that meticulous glycaemic control or antihypertensive treatment at this stage may delay the onset of frank proteinuria

Diabetic neuropathy:

There are two proposed mechanisms for the damage of peripheral nerve tissue:

1. Vascular hypothesis. This postulates occlusion of the vasa nervorum
2. Metabolic hypothesis. Hyperglycaemia leads to increased formation of sorbitol and fructose in Schwann cells, accumulation of these disrupts function and structure.

There are 6 main types of diabetic neuropathy:

• Symmetrical (mainly sensory) polyneuropathy
• Acute painful neuropathy
• Mononeuropathy and mononeuritis multiplex
• Cranial nerve lesions
• Isolated peripheral nerve lesions
• Radiculopathy
• Autonomic neuropathy
• Diabetic amyotrophy

Symmetrical (mainly sensory) polyneuropathy:

Early clinical signs include loss, from the feet, of:

• Vibration sense
• Pain (deep before superficial
• Temperature

At later stages patients may complain of:

• A feeling of ‘walking on cotton wool’
• Loss of balance when washing the face or in the dark (owing to loss of proprioception)

Involvement of the hands is much less common.

Complications include unrecognised trauma, beginning as blistering (e.g. due to an ill-fitting shoe) and leading to ulceration.

Acute painful neuropathy:

The patient describes burning or crawling pains in the feet, shins and anterior thighs.

The pain is worse at night and pressure from bedclothes may be intolerable. It usually remits within 3-12 months if good glycaemic control is maintained.

Mononeuritis and mononeuritis multiplex (multiple Mononeuropathy):

Any nerve in the body can be involved in diabetic mononeuritis; the onset is abrupt and sometimes painful.

Radiculopathy (i.e. involvement of a spinal nerve root) may occur.

Isolated palsies of nerves to the external eye muscles (especially the 3^rd and 6^th nerves) are more common in diabetes. A characteristic feature of diabetic 3^rd nerve palsy is that pupillary reflexes are retained owing to sparing of pupillomotor fibres.

Full spontaneous recovery is the rule for most episodes of mononeuritis.

Diabetic amyotrophy:

• Usually seen in older men with diabetes
• Presentation is with painful wasting (usually asymmetrical) of the quadriceps muscles
• The wasting may be very marked
• Affected area is usually extremely tender

Diabetic amyotrophy is usually associated with periods of poor glycaemic control and may be present at dx. It often resolves with time and careful control of blood glucose.

Autonomic neuropathy – cardiovascular system:

• Vagal neuropathy results in tachycardia at rest and loss of sinus arrhythmia
• At a later stage, the heart may become denervated (resembling a transplanted heart)
• Postural hypotension occurs owing to loss of sympathetic tone to peripheral arterioles
• A warm foot with a bounding pulse is sometimes seen in a polyneuropathy as a result of a peripheral vasodilatation

Autonomic neuropathy – gastrointestinal tract:

• Vagal damage can lead to gastroparesis (often asymptomatic) but rarely leading to intractable vomiting
• Diarrhoea often occurs at night accompanied by urgency and incontinence
• Diarrhoea and steatorrhoea may occur owing to bacterial overgrowth. Treatment is with antibiotics

Autonomic neuropathy – bladder involvement:

The following may occur:

• Loss of tone
• Incomplete emptying
• Stasis (predisposing to infection)

These factors may, ultimately, result in an atonic, painless, distended bladder

Autonomic neuropathy – impotence:

• Common
• The first manifestation is incomplete erection which may, in time, progress to impotence

However, impotence in diabetes is not always due to autonomic neuropathy. Other causes include:

• Depression
• Alcohol excess
• Drugs
• Primary or secondary gonadal failure
• Hypothyroidism
• Inadequate vascular supply owing to atheroma in the pudendal arteries