Nerves (3) Autonomic
Diabetic neuropathy is not a singular condition, it is the term used to describe a multitude of problems that arise as a result of nerve damage caused by the effects of diabetes. Neuropathies are frequently referred to simply as being either somatic (sensorimotor) or autonomic, however classifications found in the medical literature more fully describe the multitude of problems that can arise. The Summary Table in the introduction section for these pages on neuropathy gives a list of conditions caused by diabetes-related nerve damage, and shows one way in which diabetic neuropathies can be classified.
Autonomic neuropathy is a serious and far-reaching complication of diabetes that is frequently glossed over when it comes to patient information. There are many conditions that can arise as a result of autonomic neuropathy, and a single web page on the subject cannot cover each of these in sufficient detail – it is therefore my intention that these pages will expand into a more comprehensive resource as time goes on…
What’s covered on this page
? Confused by the terminology – all the technical language and the various medical terms used? Let me know!
Diabetic autonomic neuropathy (DAN) is a sub-type of peripheral neuropathy*(see footnote). Most organ systems within the body are controlled by two sets of nerves that together control the organ function without the need for any concious input from the brain (the autonomic nervous system is essentially based on a system of reflexes).
To illustrate the point, let’s consider heart rate – how fast or slow the heart beats. One set of nerves is programmed to tell the heart to beat faster. The other set of nerves is programmed to tell the heart to beat more slowly. These different nerve types have different effects on the “target organ” – the heart in this case – by releasing different substances or chemical messengers. Damage to either of the different nerve types affects the automatic functioning of major organs – that which is largely beyond our control.
>> More detail on the autonomic nervous system
Autonomic neuropathy often occurs alongside other complications of diabetes and the many combinations are numerous. Widespread damage to peripheral nerves and small blood vessels (microvascular damage – see “Hyperglycaemia and Long Term Complications“) together makes almost all of the body’s organ systems vulnerable to malfunction in people with long-standing diabetes.
Footnote *This may sound confusing if you have read elsewhere that “diabetic neuropathy may be either peripheral or autonomic”. The structure of the nervous system is divided into two parts – the central nervous system, and the peripheral nervous system. The central nervous system comprises the brain and spinal cord. The peripheral nervous system basically comprises everywhere else in the body. Thus, the term “peripheral neuropathy” – when correctly used – covers both somatic and autonomic neuropathies occurring in people with diabetes.
Signs and symptoms
Signs and symptoms of autonomic neuropathy depend on which parts of your autonomic nervous system are affected. Autonomic neuropathy is the root cause of many common problems suffered by people with long-standing diabetes.
Cardiovascular autonomic neuropathy (CAN)
Stomach, digetsive and bowel problems (Gastrointestinal)
Sexual and urinary problems (Genitourinary)
Cardiovascular Autonomic Neuropathy (CAN)
Cardiovascular autonomic neuropathy (CAN) results from damage to the autonomic nerve fibres that innervate the heart and the blood vessels. This damage causes abnormalities in the control of heart rate and blood vessel p is associated with autonomic neuropathy and a number of heart conditions.roperties. This means that the heart and circulation system are not as able to adapt to changing circumstances.
Loss of Heart Rate Variablility (HRV) can lead to a number of conditions that are recognised as clinical consequences of autonomic neuropathy:
Exercise intolerance – the heart rate and blood presssure do not change appropriately in response to a change in activity level. The heart should automatically pump harder during exercise in order to get more oxygen and nutrients to the muscle tissue that need them; this doesn’t happen properly in people with CAN.
It has been suggested that people with diabetes and CAN should undergo cardiac stress testing before starting an exercise programme.
Orthostatic hypotension – this is dizziness and fainting upon standing, caused by a drop in blood pressure.
People with orthostatic hypotension may notice dizziness, weakness, tiredness, blurred vision or neck pain, but many patients do not have any noticable symptoms.
Clinically, orthostatic hypotension is defined as a fall in blood pressure of
>20mmHg for systolic and/or
>10mmHg for diastolic blood pressure
in response to a change in posture (e.g. going from lying down to standing up)
[ >> see “Hypertension”Page for more on blood pressure]
Education for patients that experience orthostatic hypotension is important in order to reduce further complications, especially fainting and/or falls.
Resting tachycardia – this is a high resting heart rate.
The condition is usually defined as a heart rate of >100 beats per minute. You may experience your heart racing whilst you are sitting down and supposedly ‘relaxed’.
Silent myocardial ischaemia – cardiac denervation syndrome – this relates to a reduced appreciation by the person of angina or heart pain caused by a reduced supply of oxygen to the heart muscles.
In other words, a part of your heart is starved of oxygen and you don’t feel the pain that you should. The cause of this condition is still a bit controversial, but it is often put down to autonomic neuropathy. The consequence of the condition is that angina or even a heart attack may go unnoticed.
Potential problems during surgery – Intraoperative cardiovascular lability – in surgery, the heart and circulation system do not sufficiently compensate for the effects of the anaesthetic on the circulation system.
Another problem that has been noted during surgery of diabetic patients with cardiovascular autonomic neuropathy is that the body temperature goes down. This is known as intraoperative hypothermia and has been associated with reduced wound healing and decreased drug metabolism (drugs aren’t processed and removed so effectively from the body).
The Valsalva Maneuver
The Valsalva maneuver is performed by forcibly exhaling against a closed airway. Variations of the maneuver can be used either in medicine, as a test of cardiac function and autonomic nervous control of the heart (or to ‘clear’ the ears and sinuses (equalize pressure) when ambient pressure changes, as in diving or when coming up or going down in an airplane).
The normal physiological response effected by the Valsalver Maneuver consists of 4 phases:
Initial pressure rise: On application of expiratory force, pressure rises inside the chest forcing blood out of the pulmonary circulation into the left atrium. This causes a mild rise in blood pressure.
Reduced venous return and compensation: Return of systemic blood to the heart is impeded by the pressure inside the chest. The output of the heart is reduced and blood pressure falls. This occurs from 5 to about 14 seconds in the illustration. The fall in blood pressure reflexively causes blood vessels to constrict with some rise in pressure (15 to 20 seconds). This compensation can be quite marked with pressure returning to near or even above normal, but the cardiac output and blood flow to the body remains low. During this time the pulse rate increases.
Pressure release: The pressure on the chest is released, allowing the pulmonary vessels and the aorta to re-expand causing a further initial slight fall in pressure (20 to 23 seconds) due to decreased left ventricular return and increased aortic volume, respectively. Venous blood can once more enter the chest and the heart, cardiac output begins to increase.
Return of cardiac output: Blood return to the heart is enhanced by the effect of entry of blood which had been dammed back, causing a rapid increase in cardiac output and of blood pressure (24 seconds on). The pressure usually rises above normal before returning to a normal level. With return of blood pressure, the pulse rate returns towards normal.
Deviation from this response pattern signifies either abnormal heart function or abnormal autonomic nervous control of the heart.
Stomach, digestive & bowel problems (Gastrointestinal)
Gastrointestinal symptoms are relatively common in people with diabetes. (NOTE: Sometimes symptoms are due to factors other than autonomic neuropathy.)
It is reported that approximately 50% of people with longstanding diabetes (> 20 yrs) have delayed gastric emptying (gastroparesis) but in many people it goes unrecognised.
Treatment of diabetic diarrhoea should always be based on the use of a prokinetic agent, rather than a constipating agent which can precipitate or worsen cycles of diarrhoea and constipation.
Gallbladder atony and enlargement are a potential complication of autonomic neuropathy too.
What’s going on?
Signs and symptoms
Disordered peristalsis — this is a disruption to the wave-like contractions that move food along;
Abnormal lower sphincter function — this means that the circular band of muscle (sphincter) – that closes the last few centimeters of the oesophagus to prevent the backward flow of stomach contents – doesn’t work properly.
Poor appetite for solid foods
Nonobstructive impairment of gastric emptying — this is the slowed emptying of the stomach and reduced wave-like contractions that are supposed to move gastrointestinal contents along at a healthy rate;
Brady/tachygastria — electrical signals for the exit of food from the stomach are either too slow or too fast;
Pylorospasm — spasmodic contraction of the ring of muscle that controls exit of food from the stomach.
Severe gastroparesis can cause:
Early satiety (your hunger is soon satisfied)
Impaired motility of the small bowel – bacterial overgrowth syndrome — the transit of food is slowed down and bacteria grow (need antibiotics);
Increased motility and secretory activity – pseudocholeretic diarrhoea — this means that the propulsion or movement of material is increased, and that bile production by the liver is increased.
Bowel movements may occur up to 20 times or more a day.
Stools are often watery.
There may be an alternation between diarrhoea and constipation.
Dysfunction of intrinsic and extrinsic intestinal neurons, decreased or absent gastrocolic reflex.
Bowel movements may be limited to 3 times per week.
Abnormal internal anal sphincter tone, impaired rectal sensation, abnormal external sphincter.
Inability to control bowel movements.
Stools may leak from the rectum/anus unexpectedly, sometimes when passing wind.
Sexual and urinary problems (Genitourinary)
Signs and Symptoms
Neurogenic bladder (diabetic cystopathy)
Loss of vaginal lubrication
Loss of orgasm?
The Neurogenic Bladder (Diabetic Cystopathy)
Certain aspects of urinating are under control of the autonomic nervous system. Nerves detect the ‘fullness’ of the bladder – where urine collects – and nerves control the muscles that control the flow of the urine out of the body.
Early problems may be caused by sensory abnormalities (damage to afferent nerves) that result in impaired bladder sensation, an increased threshold for starting to urinate, and therefore an increased bladder capacity and retention.
Damage to other (efferent) nerves involved may result in hesitancy to urinate, and the tendancy for a weak flow and to ‘dribble’. The clinical consequences of this are listed in the box below.
Clinical consequences of damage to efferent parasympathetic fibres to the bladder:
inclomplete bladder emptying
increased postvoid residual
decreased peak urinary flow rate
People with diabetes with any type of bladder dysfunction are at increased risk of developing urinary tract infections (UTIs). This includes pyelonephritis, which may accelerate or worsen renal failure (see pages on “Nephropathy”).
Erectile Dysfunction (Impotence)
Erectile dysfunction (ED) is defined as the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. ED is a common complication of diabetes, with about half of diabetic men experiencing it at some time in their lives.
Retrograde ejaculation into the bladder may also occur.
ED often responds well to a combination of lifestyle changes and drug treatment.
Lifestyle changes may include:
drink less alcohol
Drug treatment will usually be with a PDE-5 inhibitor (phosphodiesterase-5 (PDE-5) inhibitor); these drugs rarely cause serious side effects, and are generally well tolerated.
Cycling for more than 3 hours per week has been identified as an independent risk factor for erectile dysfunction, possibly due to nerve damage caused by contact with the saddle. As this damage is usually reversible, a break from cycling is recommended, in order to facilitate nerve repair.
Sildenafil (Viagra®), tadalafil (Cialis®), and vardenafil (Levitra®) are essentially equally effective, but personal circumstances or experience may affect the choice:
Sildenafil and vardenafil work for about 4 hours. They are suitable for occasional or as required use.
Tadalafil acts for up to 24 hours. It is suitable for use for longer periods (e.g. over a weekend).
Some drugs that may contribute to ED
Diuretics – Thiazides (e.g. bendroflumethiazide), spironolactone
Antihypertensives – Methyldopa, clonidine, beta-blockers (e.g. propranolol), verapamil
Fibrates – Clofibrate, gemfibrozil
Antipsychotics – Phenothiazines (e.g. chlorpromazine), butyrophenones (e.g. haloperidol)
Antidepressants – Tricyclics (e.g. amitripyline), monoamine oxidase inhibitors (e.g. phenelzine), selective serotonin reuptake inhibitors (e.g. fluoxetine), lithium H2-antagonists§ Cimetidine, ranitidine
Hormones and hormone-modifying drugs – Oestrogens (e.g. oestradiol), progesterone, corticosteroids (e.g. prednisolone), cyproterone acetate, 5-alpha reductase inhibitors (e.g. finasteride)
Cytotoxics – Cyclophosphamide, methotrexate Anti-arrhythmics and anticonvulsants Disopyramide, carbamazepine
Sexual dysfunction in women
Females with diabetes have been reported to have decreased sexual desire and increased pain during intercourse. Such women may also experience decreased sexual arousal and inadequate vaginal lubrication. These problems may be partly due to the effects of autonomic neuropathy.
The flow of blood just under the skin is under the control of the autonomic nervous system and can be affected by diabetes. Often the rhythmic contration of the small arteries is disturbed and defective blood flow results.
Signs and symptoms:
Heat intolerance – Sweating abnormalities, especially decreased sweating, mean that the body can’t regulate its temperature effectively.
Gustatory sweating – Excessive sweating is often experienced, and sometimes after eating
Dry skin with loss of sweating may lead to the development of cracks or fissures in the skin, which are open to invasion by microorganisms – infectious ulcers or gangrene may result.
Defective microvascular blood flow may be associated with decreased responsiveness to mental arithmetic, cold pressor, handgrip and heating. The defect is reported to resemble premature aging.
Autonomic neuropathy may also lead to increased osteoclastic activity – meaning that bony tissue is destroyed, and bone density is reduced.
The follow-on from this is an incresed risk of Charcot neuroarthropathy (see section on “Feet”).
People with DAN may show a delayed or absent reflext response to light. Pupillomotor function impairment (i.e. decreased diameter of the dark-adapted pupil) may also be present. The sluggish pupil reaction, makes it difficult to adjust from light to dark and may cause difficulties with driving at night.
The relationship between DAN and hypoglycaemia unawareness is complex. Different research studies have implied different things and to go into the detail is beyond the scope of this webpage.
It is now widely recognized that some patients with long-standing diabetes lose their ability to secrete the major counterregulatory hormones, glucagon and epinephrine, and fail to have hypoglycemia-related autonomic warning symptoms. Many investigators focused initially on the role of autonomic neuropathy, assuming that the latter might explain the diminished epinephrine response to hypoglycemia and the blunted adrenergic warning signs. Although these studies confirmed that patients with advanced diabetic autonomic neuropathy have attenuated counterregulatory hormonal responses to hypoglycemia, many patients with inadequate counterregulatory hormone secretion lack the typical signs, symptoms, or cardiovascular reflex abnormalities typical of diabetic autonomic neuropathy. These patients may have a new variant of diabetic autonomic failure that selectively affects the central and peripheral autonomic mechanisms, which initiate epinephrine secretion and the defense against hypoglycemia. A potentially reversible cause for the failure of the counterregulatory hormone response to hypoglycemia has also been recently described.In this instance, the central nervous system fails to recognize hypoglycemia. The brain does not activate counter-regulation, and the patient develops no symptoms of hypoglycemia. Decreased central recognition of hypoglycemia results from either strict antecedent control or from a recent hypoglycemic event.
Robert D. Hoeldtke and Guenther Boden. Epinephrine Secretion, Hypoglycemia Unawareness, and Diabetic Autonomic Neuropathy. Anals of Internal Medicine 1994 | Volume 120 Issue 6 | Pages 512-517
It has been shown that people with Type 1 diabetes, early nephropathy and symptomatic autonomic neuropathy have inappropriately low levels of erythropoietin (EPO). This is a hormone produced by the kidney that promotes the formation of red blood cells in the bone marrow. These individuals can still produce enough EPO when stimulated by hypoxia (low oxygen) – and this makes red blood cell formation, resulting in anaemia.