Polyuria, polydipsia and nocturia

Acute hyperglycaemia causes increased urine excretion (polyuria) and, as a result, excessive thirst and water ingestion (polydipsia). These presenting symptoms of diabetes mellitus are also termed osmotic symptoms. Raised plasma glucose leads to increased renal tubular delivery of glucose, which then exceeds the resorptive capacity of the renal tubule, leading to glycosuria. Therefore, despite hyperglycaemia, people with an increased renal threshold for glucose may have no osmotic symptoms. Conversely, people with a low renal threshold for glucose may have glycosuria despite being normoglycaemic. It is for this reason that glycosuria is an unreliable feature in the diagnosis of diabetes mellitus. Nocturia is also common in patients presenting with osmotic symptoms of diabetes, and enquiry regarding the frequency of passing urine at night can be helpful in evaluating symptoms.

Other conditions can cause polyuria and polydipsia (Table 17.4). Diabetes insipidus (DI) is characterized by loss of renal concentrating capacity, owing to either loss of secretion of antidiuretic hormone (arginine vasopressin) from the posterior pituitary gland (cranial DI) or to poor renal tubular responsiveness to antidiuretic hormone (nephrogenic DI). This leads to loss of free water which, if uncorrected by increased water ingestion, can lead to severe dehydration and plasma hypertonicity. Electrolyte disturbance, such as hypercalcaemia or hypokalaemia, can impair antidiuretic hormone action and hence lead to polyuria and polydipsia. In addition, polyuria and nocturia are common symptoms of chronic renal failure.

Table 17.4 Causes of polyuria

Weight loss and lethargy

Loss of more than 5% of total body weight should be considered clinically important in a subject not deliberately attempting to lose weight. Weight loss is a common presenting symptom in people with type 1 diabetes, and occasionally in type 2 diabetes with marked hyperglycaemia. Loss of weight in diabetes is predominantly due to renal glucose loss as a result of lack of insulin to enable cellular uptake of glucose. The weight loss usually occurs despite a normal appetite and dietary intake. This is in contrast to the weight loss of malignant disease, which is usually associated with reduced appetite and oral intake, or thyrotoxicosis which is associated with increased appetite and oral intake.

Lethargy and fatigue are also common presenting symptoms of diabetes mellitus, particularly type 2, where the symptoms may have been present for some time.

Skin problems

Dermatological manifestations of diabetes are common at diagnosis, especially in patients with poor glycaemic control. Skin infections, such as staphylococcal infection leading to boils, carbuncles or abscesses, which are often recurrent, may occur. Severe infection itself can lead to hyperglycaemia, and a new diagnosis of diabetes should be reconsidered once the acute infection has cleared.

Oral and genital candidiasis can also be presenting features of diabetes mellitus. The presence of the characteristic white plaques on the tongue and oropharynx in a previously healthy person not on antibiotic therapy should alert the physician to the possibility of diabetes mellitus, although other conditions leading to immune paresis, such as HIV infection or haematological malignancy, can also lead to candidiasis. Genital candidiasis in women leads to a thick white discharge and vaginal soreness. Similarly, in men it can lead to a severe balanitis (inflammation of the glans penis). Always check the blood glucose in people with recurrent candidiasis.

Visual disturbance

Hyperglycaemia can lead to blurred vision, owing to osmotic changes within the aqueous humour of the lens of the eye. This can also occur when chronic hyperglycaemia is treated, causing further osmotic shifts in the lens. The symptom usually settles once normoglycaemia is achieved.

Other important aspects of a diabetic history

Home glucose testing

In a patient previously diagnosed with diabetes, assess his self-monitoring of glucose. This will enable a reasonable judgement of glycaemic control. Self-monitoring can be done by home capillary blood testing, or by urine testing for glycosuria (Fig. 17.1).

Figure 17.1 Home glucose testing is an important part of diabetes care.

Symptoms of macrovascular disease

The features of ischaemic heart disease are described elsewhere (see Ch. 11). People with diabetes have fewer, less severe symptomatic chest pains, possibly due to autonomic neuropathy leading to reduced deep pain sensation – so-called silent ischaemia. Thus, the only symptom of ischaemic heart disease in a diabetic subject may be breathlessness.

Peripheral vascular disease presents with claudication (Ch. 11). In addition, in patients with diabetes, a combination of peripheral neuropathy and peripheral vascular disease can lead to foot ulceration, particularly at sites of pressure (Fig. 17.2).

Figure 17.2 Diabetic neuropathic ulcer in a patient with Charcot neuroarthropathy.

Cerebrovascular disease in diabetic patients can present with any stroke syndrome (Ch. 14). Transient ischaemic attacks are common.

Symptoms of microvascular disease

Diabetic retinopathy is frequently asymptomatic until it causes significant visual loss, which may be acute in onset (e.g. owing to a sudden retinal haemorrhage) or insidious (e.g. owing to cataract or maculopathy). Diabetic nephropathy is similarly asymptomatic until renal dysfunction becomes so severe that uraemia ensues (see Ch. 18). Uraemic symptoms include fatigue, breathlessness and tachypnoea, pleuritic chest pain due to pericarditis and pruritus. Heavy proteinuria may lead to the development of a nephrotic syndrome.

In contrast, diabetic neuropathy can manifest in a number of ways. Chronic peripheral sensory neuropathy is the commonest form, affecting around 5% of patients with diabetes. This can present with symptoms varying from numbness, a feeling of ‘walking on cotton wool’ and paraesthesiae (pins and needles) to burning, sharp and shooting pains. The latter is a feature of selective involvement of small pain fibres. Typically the symptoms start distally and spread up in a stocking distribution, and are characteristically worse at night, frequently leading to insomnia.

Proximal motor neuropathy (diabetic amyotrophy, or femoral neuropathy) is uncommon, but is seen predominantly in middle-aged men with type 2 diabetes. The condition is characterized by severe, deep pain and paraesthesiae in the upper anterior thigh, followed by weakness and wasting of the quadriceps muscle. The condition is often unilateral, generally short-lived (around 3 months) and usually resolves spontaneously. Associated weight loss and cachexia are common.

Mononeuropathies, particularly affecting the median nerve of the hand (carpal tunnel syndrome; see Ch. 14) are common in patients with diabetes. This frequently presents with paraesthesiae and numbness in the median nerve distribution of the hand (lateral two-and-half digits) and is again worse at night. Similar symptoms may occur in the foot (tarsal tunnel syndrome). Cranial mononeuropathies are rare, but palsies of cranial nerves III, VI and VII are seen in patients with diabetes, leading to blurred or double vision due to ophthalmoplegia, or a lower motor neurone facial palsy (Ch. 14). The pupillomotor fibres are usually spared in diabetic third nerve palsy.

Diabetes can cause autonomic neuropathy, the symptoms of which can be very troublesome. They include impotence, gustatory sweating (severe facial sweating on tasting food), urinary retention or incontinence, dizziness or syncope due to postural hypotension, constipation or diarrhoea (so called diabetic diarrhoea) and recurrent nausea and vomiting due to diabetic gastroparesis.

General assessment

Patients with diabetes can present with acute metabolic decompensation, leading to diabetic ketoacidosis (DKA), hyperosmolar hyperglycaemic syndrome (HHS) or, in treated patients, hypoglycaemia. Thus, it is mandatory for all patients presenting with coma or reduced conscious level to have their blood glucose checked immediately.

Characteristically, the cardinal symptoms of severe polyuria, polydipsia and weight loss will have been present for some time prior to coma; such symptoms should never be ignored in a diabetic person. Patients with acute hyperglycaemic crises are frequently severely dehydrated, with hypotension (including postural hypotension), tachycardia, dry mucous membranes and reduced skin turgor. Other signs of DKA include rapid deep sighing respiration (Kussmaul breathing – a respiratory compensation for metabolic acidosis) and ketones on the breath (a sweet odour reminiscent of nail polish remover). Diabetic ketoacidosis can occasionally present with symptoms of an acute abdomen.

In the non-acute setting, measurement of weight and height to ascertain the body mass index (BMI) is of great importance in the assessment of the diabetic patient (Box 17.3). It is desirable for all patients with diabetes to undergo a full medical assessment once a year – the so-called diabetic annual review (Box 17.4).

Skin, nails and hands

Dermatological manifestations of diabetes are common. Fungal nail infections, particularly of the feet, are common, as are dermatophyte infections of the skin of the feet (tinea pedis). Staphylococcal skin infections leading to pustules, abscesses or carbuncles can also be seen. Other skins lesions seen in diabetes include necrobiosis lipoidica diabeticorum (Fig. 17.3). This is a rare complication of diabetes, predominantly seen in young women aged 15-40 years. This presents as a painless red macule, usually over the anterior shin, which then heals with scarring to form a yellowish/brown lesion. The condition can be unsightly, and little effective treatment is available. Vitiligo is seen in a small number of patients with type 1 diabetes, reflecting its autoimmune nature.

Figure 17.3 Necrobiosis lipoidica diabeticorum.

Diabetic dermopathy is characterized by brown macules on the lower legs that heal to form atrophic, shiny white scars. A further skin lesion seen in patients with diabetes is granuloma annulare, pale, shiny rings and nodules usually seen on the hands (Fig. 17.4). Bullosis diabeticorum is a rare manifestation, characterized by tense blistering, mainly on the feet. Acanthosis nigricans is characterized by a dark velvety appearance in the axillae or neck of people with insulin resistance (Fig. 17.5) and frequently accompanies type 2 diabetes, but may occur in people with insulin resistance in the absence of diabetes.

Figure 17.4 Granuloma annulare.

(Courtesy of Dr David Peterson.)

Figure 17.5 Acanthosis nigricans.

Diabetic patients treated with insulin should have their injection sites examined for signs of lipohypertrophy (a physiological response to insulin injected near fat cells) (Fig. 17.6) or lipoatrophy (an allergic response to non-human insulins – now rarely seen) (Fig. 17.7).

Figure 17.6 Lipohypertrophy.

(Courtesy of Dr David Peterson.)

Figure 17.7 Lipoatrophy.

(Courtesy of Dr David Peterson.)

Diabetic cheiroarthropathy, or ‘stiff hand syndrome’ or ‘limited joint mobility’, is seen in some patients with longstanding diabetes. It is characterized by skin thickening and sclerosis of the tendon sheaths, leading to reduced joint mobility and the characteristic prayer sign (Fig. 17.8). Examination of the hands for signs of carpal tunnel syndrome (Ch. 14) is important if the patient has suggestive symptoms. Thus, the presence of Tinel’s sign (Fig. 17.9) and Phalen’s sign (Fig. 17.10) should be sought. Thenar eminence wasting may also be seen.

Figure 17.8 The prayer sign in diabetic cheiroarthropathy.

Figure 17.9 Tinel’s sign in carpal tunnel syndrome: tapping on the median nerve at the wrist induces pain in the median nerve distribution.

Figure 17.10 Phalen’s sign in carpal tunnel syndrome: hyperflexion of the wrist leads to pain in the median nerve distribution.

Eyes

Examination of the eyes is mandatory in patients with diabetes. External examination may indicate signs of dyslipidaemia (corneal arcus and xanthelasmata; Fig. 17.11). A reduced pupillary response to light may indicate autonomic neuropathy. Visual acuity should be assessed yearly with a Snellen chart, and unexplained loss of acuity should be investigated. Funduscopy should be undertaken with pharmacological dilatation of the pupils in order to obtain an adequate view. Loss of the red reflex on funduscopy may indicate cataract formation, and the lens should be assessed for opacities (Fig. 17.12). The vitreous and retina should be examined carefully, starting from the optic disc and radiating into each quadrant of the eye. The macula is examined last, as this can be quite uncomfortable for the patient. The use of green light may aid the detection of microaneurysms. Ideally, all patients with diabetes should have annual fundal photography. A classification of diabetic retinopathy is shown in Box 17.5 (and see Figs 17.13–17.17).

Figure 17.11 Corneal arcus and xanthelasmata in a patient with diabetic dyslipidaemia.

Figure 17.12 Diabetic cataract.

Figure 17.13 Background retinopathy (dot haemorrhages and microaneurysms) in the inferior nasal region.

(Courtesy of Dr Paul Dodson.)

Figure 17.14 Preproliferative changes with multiple dot and blot haemorrhages and cotton wool spots.

(Courtesy of Dr Paul Dodson.)

Figure 17.15 Retinal haemorrhage due to new vessel formation in severe proliferative retinopathy.

(Courtesy of Dr Paul Dodson.)

Figure 17.16 New vessel formation and laser photocoagulation burns in severe proliferative retinopathy.

(Courtesy of Dr Paul Dodson.)

Figure 17.17 Exudative diabetic maculopathy.

(Courtesy of Dr Paul Dodson.)

Cardiovascular system

Examination of the heart and vasculature is important in patients with diabetes. Palpation of peripheral pulses, especially of the feet, is extremely important, as is auscultation of the carotid and femoral arteries to detect bruits. Blood pressure should be measured frequently in patients with diabetes, to detect hypertension (classed at >140/80 mmHg in patients with diabetes) or postural hypotension (drop in systolic BP >20 mmHg on standing). A resting tachycardia, loss of sinus arrhythmia (reflex bradycardia on expiration) and loss of reflex bradycardia during a Valsalva manoeuvre can indicate autonomic neuropathy, although these are best assessed by electrocardiography (ECG).

Feet

The feet of patients with diabetes should be examined at least once a year. Signs of deformity, callus (a sign of excessive pressure at this site), fungal infection especially between the toes, nail care and ulceration should be carefully assessed. Peripheral pulses and nail-fold refill should be assessed for signs of peripheral vascular disease. Nerve function should be assessed by testing vibration sense at the great toe, medial malleolus and knee, and testing fine touch on the toes, metatarsal heads, heels and dorsum of the feet with a 10-g monofilament (Semmes Weinstein monofilament) (Fig. 17.18). Loss of ankle jerks is also a sign of early diabetic peripheral sensory neuropathy.

Figure 17.18 Testing for neuropathy using a Semmes Weinstein monofilament giving standard 10 g of fine touch.

A complication of diabetic peripheral neuropathy is the neuropathic joint – Charcot neuroarthropathy (see Fig. 17.2). This usually affects the ankle and presents with a painless, swollen, hot red joint, sometimes with a history of minor local trauma. The natural history is of progressive deformity until the process settles, usually over a few months. Untreated, the joint develops severe deformity, which then puts the foot at high risk of ulceration, infection and amputation. Treatment is with immobilization in a plaster-cast boot, and intravenous bisphosphonates.

Diabetic patients with signs of peripheral vascular disease or peripheral neuropathy, even if asymptomatic, should be classified as at high risk for ulceration and be given careful education on foot care by a podiatrist.

History

Lipid disorders rarely cause significant symptoms, unless the patient presents with an acute feature such as acute pancreatitis or myocardial infarction. Thus, any previous history of vascular disease or acute abdominal pain should be sought. Acute pancreatitis is a rare complication of severe hypertriglyceridaemia, and presents with acute severe generalized abdominal pain. Although alcohol and cholelithiasis are the commonest causes of acute pancreatitis, hypertriglyceridaemia is a well recognized and easily overlooked cause of the condition, and any patient presenting with acute pancreatitis should have his serum lipids checked.

In the assessment of patients with lipid disorder, it is important to enquire about symptoms of ischaemic heart disease (chest pain history, admissions for ischaemic heart disease and any cardiological/cardiothoracic interventions), peripheral vascular disease (intermittent claudication) and cerebrovascular disease (transient ischaemic attacks, amaurosis fugax and strokes). Other cardiovascular risk factors should also be assessed. The smoking history is very important and a family history of premature vascular disease (under the age of 55 years) should be carefully sought. In familial hypercholesterolaemia, half of men and a fifth of women die before the age of 60 from coronary heart disease. Possible symptoms of secondary causes should also be assessed. Thus, symptoms of hypothyroidism (Ch. 16), diabetes (above), renal failure or nephrotic syndrome (Ch. 18) and liver disease (Ch. 12) should be sought. Alcohol intake and dietary history should also be assessed.

Diagnostic criteria for familial hypercholesterolaemia are shown in Box 17.6.

Examination

The diagnostic hallmark of familial hypercholesterolaemia is tendon xanthomata. These are localized infiltrates of lipid-containing macrophages that resemble atherosclerotic plaques; they develop from the third decade onwards. The commonest sites are the Achilles tendon and the extensor tendons of the hands, particularly over the knuckles (Fig. 17.19). Other sites include the tibial tuberosities, at the site of insertion of the patellar tendon (subperiosteal xanthomata) or at the triceps tendon at the elbow.

Figure 17.19 Tendon xanthoma of the hands.

(Courtesy of Dr David Peterson.)

As the cholesterol deposition is deep within the tendon, and the swelling is fibrous, tendon xanthomata are felt as hard nodules along the length of the tendon. They occasionally become inflamed, and a tenosynovitis develops. On the extensor surface of the hands, they may overlie the knuckle and be very hard and quite easy to miss.

Xanthelasmata are deposits of lipid in the skin of the eyelids, more commonly the upper rather than the lower (see Fig. 17.11). Although a dramatic sign, they are not present in the majority of patients with familial hypercholesterolaemia. More common is a corneal arcus, seen as a rim of lipid deposit around the iris (Fig. 17.11). This can be seen at any age, although it is more common in older people; only in the minority is this sign associated with hypercholesterolaemia.

The characteristic sign of hypertriglyceridaemia is eruptive xanthomata (Fig. 17.20). These are yellow nodules or papules that usually appear on the extensor surface of the elbows, knees, buttocks and back. Striate palmar xanthomas are yellowish discoloration of the skin creases, usually seen best in the hands, and are due to hypertriglyceridaemia. In severe forms of hypertriglyceridaemia, hepatosplenomegaly may be seen. Funduscopy in severe hypertriglyceridaemia may show lipaemia retinalis, characterized by optic pallor and the retinal vessels appearing white (Fig. 17.21).

Figure 17.20 Eruptive xanthomata in severe hypertriglyceridaemia.

(Courtesy of Dr David Peterson.)

Figure 17.21 Lipaemia retinalis.

(Courtesy of Dr Paul Dodson.)

A careful cardiovascular examination should be performed in all patients with significant hyperlipidaemia, including a search for carotid or femoral bruits and signs of peripheral vascular disease. Patients with homozygous familial hypercholesterolaemia may have signs of aortic stenosis.

Investigation

All patients with lipid disorders should undergo a fasting lipid profile, comprising total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. In severe hypertriglyceridaemia, the serum may become turbid and take on the appearance of milk. Investigations to exclude secondary causes should include thyroid, liver and renal function and fasting glucose. Resting or exercise ECG may be checked to look for signs of ischaemic heart disease. Genotyping to determine the type of familial lipid abnormality may be required, especially for familial hypercholesterolaemia, although this is usually only available in specialist centres. Genotyping should be considered, depending on the parents’ wishes, to aid in antenatal diagnosis of familial monogenic hypercholesterolaemia.

Acute pancreatitis can be diagnosed using serum amylase, which is frequently very elevated in the condition. In severe hypertriglyceridaemia, however, falsely low serum amylase can lead to diagnostic confusion, as triglycerides interfere with the amylase assay. Severe hypertriglyceridaemia can lead to a pseudohyponatraemia, and care should be exercised when interpreting serum sodium levels in the condition.