Student Pages

Lecturer: Craig Payne

This lecture will cover:

Complications of diabetes

Diabetic neuropathy

Complications of diabetes

Complications of Diabetes

Acute complications:
- ketoacidosis, hypoglycaemia, hyperosmolar non-ketotic coma, intercurrent illness
Chronic complications:
- retinopathy, nephropathy, neuropathy, macrovascular disease, other

Prevalence of complications:
Liebl et al (2002) reported a prevalence’s in those with type 2 diabetes of myocardial infarction (10.6%); stroke (6.6%); foot ulcer (3.97%); amputation (2.3%); blindness (1.34%).
Williams et al (2002) reported that at leats 72% of those with type 2 had at least one complication; 19% had only a microvascular complication; 10% had only a macrovascular complication; 24% had both a microvascular and macrovascular complication. The macrovascular complications were – peripheral vascular disease (18%); angina (17%); heart failure (12%); myocardial infarction (9%). The microvascular complications were – neuropathy (28%); renal damage (20%); retinopathy (20%); needing treatment for an eye complication (6%).

Hypoglycaemia
- Most "hypo's" are minor and easily treated
- Prolonged and repeated attacks can result in permanent damage.
- Symptoms occur when blood glucose level drops to about 3.00mmol/l.
- Commonly precipitated by diet changes (eg missed meals, delayed meals, not eating enough), exercise, inappropriate insulin doses.

- More common in those on insulin than sulphonylurea drugs.
- Fictitious or deliberately induced hypoglycaemic attacks may occur for psychological reasons.

Risk factors - older person; change in hypoglycaemic treatment; type of sulphonylurea; male; tight glycaemic control; polypharmacy; renal disease; high alcohol consumption

Clinical features of hypoglycaemia:
Most patients recognise the symptoms (except during sleep) - sweating, tremor/trembling, palpitations/pounding heart, anxiety, tiredness, pallor, headache, hunger, dizziness, irritability, blurred vision, irritability, aggressive behaviour, slurred speech, confusion, drowsiness, convulsions, coma

In longstanding cases - develop a hypoglycaemic unawareness (especially in presence of autonomic neuropathy) and have difficulty recognising the symptoms.

Consequences of serious and/or repeated hypoglycaemic attacks:
Coma, convulsions, impaired cognitive function, intellectual decline, cardiac arrythmias, eye damage, hypothermia, accidents (eg motor vehicle)

Management:
Give food containing glucose (soft drink; honey; jelly beans etc); nothing by mouth if unconscious - use glucagon or IV dextrose; determine cause

Diabetic ketoacidosis (DKA)
- Life threatening - result of severe insulin deficiency - leading to a release of free fatty acids into the circulation and hepatic fatty acid oxidation à forms ketone bodies.
- Biochemical features - hyperglycaemia, hyperketonaemia and metabolic acidosis

Aetiology:
New presentation; intercurrent infection (loose appetite - stop taking insulin); illness (eg stroke); withdrawal of insulin; major dietary indiscretion; significant emotional stress.

Clinical features:
Develops over a few days; polyuria; thirst; weight loss; weakness; leg cramps; hypotension; tachycardia; nausea; vomiting; abdominal pain and tenderness; dehydration; kussmaul respiration; blurred vision; ketotic breath; hypothermia; confusion; coma

Consequences of ketoacidosis - cerebral oedema; acute respiratory distress syndrome; thromboembolism; disseminated intravascular coagulation

Management:
Hospitalisation; fluids; insulin (IV infusion); electrolyte balance (especially potassium); determine cause; antibiotics if infection

Other acute complications:

- Hyperosmolar non-ketotic coma - significant hyperglycaemia and dehaydration not associated with ketosis

- Intercurrent illness - illness affects blood glucose control and need for insulin

Retinopathy
- Main cause of blindness in adults in developed countries.
- Almost all those with diabetes will eventually develop some form of retinopathy (especially those with Type 1).
- Up to 20% of those with Type 2 at time of diagnosis of the diabetes.
- Two basic pathophysiological mechanisms - increased capillary permeability and closure of retinal capillaries vascular leakage retinal oedema and accumulation of lipids seen as hard exudate in the retina and retinal ischaemia.

Clinical features:
- Earliest feature is microaneurysms (small discrete dark red spots near retinal vessels); haemorrhages; hard exudate (appear as spots in perimacular area); soft exudate (appear as 'cotton wool' spots) venous dilation; new vessel formation
- Presence is best detected with ophthalmoscope through dilated pupils
- Factors associated with worsening diabetic retinopathy:
- Later age of onset of diabetes; poor control of diabetes; longer duration of diabetes; associated hypertension or nephropathy; insulin treatment; pregnancy; smoking.

Factors associated with worsening diabetic retinopathy:

Management:
- DCCT showed intensive treatment for tight control of blood glucose levels reduces risk by 76%. UKPDS showed a 25% overall reduction in microvascular complications in the intensive group versus the conventional group. Both studies show that good glycaemic control does not prevent retinopathy, but it does reduce the risk.
- Laser photocoagulation is very helpful to destroy areas of retinal ischaemia, seal leaking microaneurysms and obliterate new vessels - importance of regular screening for those at risk.
- Several cost effectiveness analyses have shown that screening for diabetic retinopathy saves vision for a relatively low cost.

Other eye conditions in diabetes:
• cataract – develop earlier in those with diabetes; higher risk if also taking corticosteroids
• glaucoma – more common in those with diabetes
• a transient visual disturbance is also common due to osmotic changes

Nephropathy
- Important cause of morbidity and mortality in those with diabetes.
- Commonest cause of end stage renal failure/disease (ESRF/ESRD) in developed countries.
- Nephropathy is symptom free until it is moderately advanced.
- First sign is a microalbuminuria and elevated blood pressure - progresses to a macroproteinuria with a decline in renal function.

Management:
- Routine urinalysis is often advised at diagnosis of Type 2 for possible albuminuria
annual screening is advisable.
- Intensive insulin therapy (DCCT showed reduction in risk of developing of 50%); reduction of protein intake; ACE inhibitors; reduce cardiovascular risk factors (especially hypertension); calcium channel blockers.
- Later need dialysis and maybe transplant.

Macrovascular disease
Risk for coronary heart disease, cerebrovascular disease and peripheral vascular disease is higher in those with diabetes - due to premature and accelerated atherosclerosis (major cause of morbidity and mortality).

In type 2 diabetes 'clock starts ticking' for macrovascular disease well before the clinical onset of diabetes due to insulin resistance and dyslipidaemia.

Autonomic neuropathy can reduce the symptoms of chest pain associated with angina and other cardiac complications.

Glycaemic control is a risk factor for atherosclerosis. Those with proteinuria are at an even greater risk (hypothesised that the presence of microalbuimuria is a marker for the generalised endothelial dysfunction that predisposes to atherosclerosis). The effects of dyslipidaemia, hypertension and cigarette smoking on atherosclerosis are amplified in those with diabetes. The atherosclerosis tends to more diffuse in those with diabetes than those without diabetes.

Dyslipidaemia increases the risk for macrovascular disease differently in type 1 and 2:
• in type 1 – total and LDL cholesterol is normal; triglycerides are normal or decreased; HDL cholesterol is normal of increased ? this possibly an anti-atherogenic profile. However, there may be changes in structure of lipoproteins (eg glycation)
• in type 2 – triglycerides and VLDL are increased; HDL is decreased; increase in small dense LDL particles (these particles are very atherogenic) ? this profile is often called ‘diabetic dyslipidaemia’

In those with diabetes, the peripheral vascular disease is more common in younger age groups; progresses more rapidly; affects many segments; has a predilection for tibial vessels; tends to spare vessels in the foot; tends to be bilateral; and has more involvement of vessels adjacent to occlusions.

Other complications
- Gastrointestinal
- Sexual dysfunction
- Skin (necrobiosis lipidica diabeticorum; granuloma annulare; diabetic dermathy)
- Pregnancy (insulin resistance increases during pregnancy; higher incidence of larger babies)
- Infections
- Dyslipidaemia

- Hypertension

- Musculoskeletal changes (limited joint mobility; gout is more common; decreased bone mineral density)

- Psychosocial

Online resources:

ePodiatry's links to online articles on diabetes complications

How To Treat Skin Conditions In Diabetic Patients - Full text article from Podiatry Today

American Diabetes Association clinical practice guidelines:

Diabetic Nephropathy

Diabetic Retinopathy

Management of Dyslipidemia in Adults With Diabetes

Hyperglycemic Crises in Patients With Diabetes Mellitus

Treatment of Hypertension in Adults With Diabetes

Diabetic Neuropathy

Diabetic neuropathy is a descriptive term covering many clinical types or syndromes of neural damage. It is the most common chronic complication of diabetes and is responsible for a large amount of morbidity

‘Subclinical neuropathy’ – is found on electrophysiological testing, but no evidence of it on clinical examination. Progression is through initial biochemical abnormalities in the nerve (accumulation of sorbitol, oedema, depletion of myo-inositol) to impairment in nerve conduction (asymptomatic) to clinical neuropathy.

Several types:
  1) Polyneuropathy
       b) Sensorimotor
           a) Acute
           b) Chronic
       a) Autonomic
   2) Mononeuropathy
   3) Proximal motor neuropathy

Chronic sensorimotor neuropathy (distal symmetrical neuropathy)
- Most common type - usually given the term 'diabetic neuropathy'

- First affects most distal parts of the longest nerves.
- Affects up to 50% of those with diabetes after 25 years.
- There is a long asymptomatic latency period before clinically apparent.
- Most important permissive factor for diabetic foot complications (LOPS - loss of protective sensation)

Clinical features:
Predominantly sensory and symmetrical; first present in most distal aspects of the limbs; spreads in a 'stocking and glove' distribution; pain - may be sharp, stabbing or burning; skin tenderness (hyperaesthesia); paraesthesia and 'numbness'; useful early signs are decreased vibration sensation.

Sensory changes may be initially asymmetric; progress is usually slow; irreversible

If motor involvement:
- muscle wasting (especially intrinsics)
- claw toes (probably due to denervation of intrinsic muscles)
- often called the ‘intrinsic minus foot’

Possible aetiologies:
- hyperglycaemia - both the DCCT and UKPDS demonstrated the role that good glucose control had on progress
- abnormality in vasa nervosum causing a local ischaemia resulting in poor nerve conduction
- Polyol pathway - glucose is converted to sorbitol via aldose reductase during hyperglycaemic states
- Myoinositol - hyperglycaemia inhibits the neural uptake of myoinositol
- Advanced glycation end products, resulting in increased glycation of neural proteins
- abnormality in fatty acid metabolism
- antibodies to neural tissue has been demonstrated in those with diabetes - role is not known in aetiology

Risk factors:
O lder age, longer duration of diabetes, HLA-DR3/4, taller, hyperglycaemia, hypertension, dyslipidaemia, smoking, alcohol abuse

Treatment:
- many of risk factors are modifiable.
- intensive treatment (DCCT)
- aldose reductase inhibitors(?)
- gamma-linoleic acid (?)
- local applications of capsaicin and Opsite® dressings may help painful cases.

Acute sensory neuropathy
- Can occur with onset of insulin therapy; with ketoacidosis; following surgery; weight loss; normalisation of blood glucose levels following period of poor control
- Pain in extremities
- Recovery usually occurs - can take several months

Mononeuropathy or Focal Neuropathy:
Commonly cranial nerves (usually 3rd - orbital pain and/or headache), a carpel or tarsal tunnel neuropathy or a femoral neuropathy. Believed to be an acute ischaemic event to a nerve or nerve root; sudden onset; asymmetric; foot drop may be a complication that may need AFO; self limiting course – cranial nerve involvement usually resolves within 3 months.

Proximal motor neuropathy/Diabetic amyotrophy:
Progressive asymmetrical atrophy and weakness of thigh muscles (unilateral or bilateral); deep pain in quadriceps muscles; hypersensitivity of skin over thighs; absent knee reflex, and instability in walking - falls; pain often affects sleep. Onset is usually acute and unilateral is more common; usually no sensory symptoms. Most recover spontaneously. Management is symptomatic – analgesia, physiotherapy, good glycaemic control

Autonomic neuropathy
Common abnormalities in diabetes include:
Cardiovascular (eg postural hypotension); gastrointestinal (eg dysphagia, gastroparesis, constipation); genitourinary (eg impotence); sudomotor (eg gustatory sweating, nocturnal sweats); vasomotor (eg dependent oedema); eye (eg decreased pupil size, delayed response to light changes)

In foot the microcirculation control is affected by increased arteriovenous shunting; increased nutritive capillary flow at rest; reduced axon flare response; and impaired postural vasoconstriction.

Online resources:

ePodiatry's links to online articles on diabetic neuropathy

eMedicne's article on diabetic neuropathy

US Pharmacist's article on the treatment of diabetic neuropathy