DIABETES MELLITUS - Clinical features, Investigations

Glucose metabolism

Blood glucose levels are closely regulated in health and rarely stray outside the range of 3.5-8.0 mmol/L (63-144 mg/dL), despite the varying demands of food, fasting and exercise. The principal organ of glucose homeostasis is the liver, which absorbs and stores glucose (as glycogen) in the post-absorptive State and releases it into the circulation between meals to match the rate of glucose utilization by peripheral tissues. The liver also combines 3-carbon molecules derived from breakdown of fat (glycerol), muscle glyco-gen (lactate) and protein (e.g. alanine) into the 6-carbon glucose molecule by the process of gluconeogenesis. Insulin is the key hormone involved in the storage of nutrients, in the form of glycogen in liver and muscle, and triglyceride in fat. During a meal insulin (derived from proinsulin after splitting off C-peptide) is released from the beta (P) cells of the pancreatic islets into the portal vein and facilitates glucose uptake by fat and muscle and sup-presses glucose production by the liver. In the fasting State insulin concentra-tions are low and it modulates glucose production from the liver. The counter-regulatory hormones, glucagon, adrenaline (epinephrine), cortisol and growth hormone, oppose the actions of insulin and cause greater produc-tion of glucose from the liver and less utilization of glucose in fat and muscle for a given plasma level of insulin.

Classification of diabetes

Diabetes mellitus is a common group of metabolic disorders that are char-acterized by chronic hyperglycaemia resulting from relative insulin deficiency, insulin resistance or both. Diabetes is usually primary but may be secondary to other conditions, which include pancreatic (e.g. total pancreatectomy, chronic pancreatitis, haemochromatosis) and endocrine diseases (e.g. acromegaly and Cushing's syndrome). It may also be drug induced, most commonly by thiazide diuretics and corticosteroids.

Primary diabetes is divided into type 1 and type 2 diabetes. In practice the two diseases are a spectrum, distinct at the two ends but overlapping in the middle (Table 15.1). At one end of the spectrum the type 1 diabetic is young, has insulin deficiency with no resistance and immunogenic markers. Type 1 diabetes is most prevalent in Northern European countries, particularly Finland, and the incidence is increasing in most populations, particularly in young children. Type 2 diabetes is common in all populations enjoying an affluent lifestyle and is also increasing in frequency, particularly in adolescents.

Table 15.1 The spectrum of diabetes: a comparison of type 1 and type 2 diabetes mellitus

Type 1

Type 2

Epidemiology

Younger (usually < 30 years of age)

Older (usually > 30 years of age)

Usually lean

Often overweight

Increased in those of North European ancestry

All racial groups, commoner in African/Asian

Heredity

HLa-DR3 or DR4 in >90%

No HLA links

30-50% concordance in identical twins

50% concordance in identical twins

Pathogenesis

Autoimmune disease

Islet cell antibodies
Insulitis
Association with other

autoimmune diseases

Immunosuppression after

diagnosis delays
β-cell destruction

No immune disturbance

Clinical

Insulin deíiciency

Partial insulin deíiciency Insulin resistance

May develop ketoacidosis

May develop hyperosmolar state

Always need insulin

Sometimes need insulin

Biochemical

Eventual disappearance of C-peptide

C-peptide persists

Aetiology and pathogenesis

Type 1 diabetes mellitus results from an autommune destruction of the pancreatic p cells. This process occurs in genetically susceptible individuals and is probably triggered by one or more environmental antigens. Autoantibodies directed against insulin and islet cell antigens (e.g. glutamic acid decarboxylase) predate the onset of clinical disease by several years. There is an association with other organ-specific autoimmune dis-eases, e.g. autoimmune thyroid disease, Addison's disease and pernicious anaemia.

Type 2 diabetes mellitus is a polygenic disorder; the genes responsible for the majority of cases have yet to be identified. However, the genetic causes of some of the rare forms of type 2 diabetes have been identified and include mutations of the insulin receptor and structural alterations of the insulin molecule. Environmental factors, notably Central obesity, trigger the disease in genetically susceptible individuals. The p-cell mass is reduced to about 50% of normal at the time of diagnosis in type 2 diabetes. Hypergly-caemia is the result of reduced insulin secretion (inappropriately low for the glucose level) and peripheral insulin resistance.

Clinical features

■ Acute presentation. Young people present with a 2- 6-week history of thirst, polyuria and weight loss. Polyuria is the result of an osmotic diu-resis that results when blood glucose levels exceed the renal tubular reabsorptive capacity (the renal threshold). Fluid and electrolyte losses stimulate thirst. Weight loss is caused by fluid depletion and breakdown of fat and muscle secondary to insulin deficiency. Ketoacidosis (see later) is the presenting feature if these early symptoms are not recognized and treated.

■ Subacute presentation. Older patients may present with the same symp-toms, although less marked and extending over several months. They may also complain of lack of energy, visual problems and pruritus vulvae or balanitis due to Candida infection.

■ With complications, e.g. retinopathy noted during a vist to the optician (see later).

■ In asymptomatic individuals diagnosed at routine medical examinations, e.g. for insurance purposes.

Investigations

The diagnosis of diabetes mellitus is made by demonstrating:

■ Fasting (no calorie intake for at least 8 hours) plasma glucose ≥7.0 mmol/L (126 mg/dL)

■ Random plasma glucose >11.1 mmol/L (200 mg/dL)

Table 15.2 The oral glucose tolerance test - WHO criteria

Fasting glucose

2 hour after glucose

Normal

<7.0 mmol/L

<7.8 mmol/L

Diabetes mellitus

>7.0 mmol/L

≥ 11.1 mmol/L

Impaired glucose tolerance (IGT)

<7.0

7.8-11.0 mmol/L

After an overnight fast 75 g of gỉucose is taken in 300 mL of water. Bỉood sampỉes are taken before and 2 hours after the gỉucose has been given. Resuỉts are for venous pỉasma- whoỉe bỉood vaỉues are ỉower.

■ One abnormal laboratory value is diagnostic in a patient with typical hyperglycaemic symptoms; two values are needed in asymptomatic people.

A glucose tolerance test (GGT, Table 15.2) is hardly ever used for clinical purposes except for screening for gestational diabetes when a random blood glucose is ≥ 7.0 mmol/L. It is mainly used for epidemiological studies. Glyco-suria does not necessarily indicate diabetes and may be found in normo-glycaemic subjects who have a low renal threshold for glucose excretion.

Other routine investigations at diagnosis include screening the urine for microalbuminuria (p. 684), full blood count, serum urea and electrolytes, liver biochemistry, and a fasting blood sample for cholesterol and triglyceride levels.

Impaired glucose tolerance

This is not a clinical entity but a risk factor for future diabetes and cardio-vascular disease. Obesity and lack of regular physical exercise make progres-sion to frank diabetes more likely.

Management

A multidisciplinary approach involving, among others, the hospital doctor, the general practitioner, nurse specialists, dieticians and chiropodists is neces-sary in management of this condition. It is essential that the patient under-stands the risks of diabetes, the potential benefits of good glycaemic control and the importance of maintaining a lean weight, stopping smoking and taking care of the feet. Education at diagnosis is the key to developing patient self-management with ongoing input from the healthcare professionals involved with care.

Management involves:

■ Achieving good glycaemic control

■ Advice regarding regular physical activity and reduction of bodyweight in the obese, both of which improve glycaemic control in type 2 diabetes

Table 15.3 Regular checks for patients with diabetes
Checked each visit
Review of monitoring results and current treatment
Talk about targets and change where necessary
Talk about any general or specific problems
Continued education
Checked at least once a year
Biochemical assessment of metabolic control (e.g. glycosylated haemoglobin test)
Measure bodyweight
Measure blood pressure
Measure plasma lipids (except in extreme old age)
Measure visual acuity
Examine state of retina (ophthalmoscope or retinal photo)
Test urine for proteinuria/microalbuminuria
Test blood for renal function (creatinine)
Check condition of feet, pulses and neurology
Review cardiovascular risk factors
Review self-monitoring and injection techniques
Review eating habits
Review and reinforce structured education

■ Aggressive treatment of hypertension and hyperlipidaemia, both of which are additional risk factors for long-term complications of diabetes

■ Regular checks of metabolic control and physical examination for evi-dence of diabetic complications (Table 15.3).

Principles of treatment

All patients with diabetes require diet therapy. Regular exercise is encouraged to control weight and reduce cardiovascular risk. Insulin is always indicated in a patient who presents in ketoacidosis, and is usually indicated in those under 40 years of age. Insulin is also indicated in other patients who do not achieve satisfactory control with oral hypoglycaemics. Treatment of type 2 diabetes is summarized in Figure 15.1.

Diet The diet for people with diabetes is no different from the normal healthy diet recommended for the rest of the population. Recommended food should:

■ Be low in sugar (though not sugar-free)

■ Be high in starchy carbohydrate (especially foods with a low glycaemic index, e.g. pasta, which is slowly absorbed and prevents rapid fluctua-tions in blood glucose). Carbohydrate should represent about 40-60% of total energy intake

Fig. 15.1 Suggested treatment pathway for type 2 diabetes mellitus. Discussion of lifestyle changes and compliance should be undertaken at every stage. All patients require BP control, statin therapy and low dose aspirin. BMI = body mass index.

■ Substitute artificial sweeteners instead of sugar and limit intake of fruit juices, confectionary, cakes and biscuits

■ Be low in fat (especially saturated fat) which should represent less than 35% of total energy intake

■ Include protein representing about 15% of total energy intake (1 g per kg ideal bodyweight).

The nutrient load should be spread throughout the day (three main meals with snacks in between and at bedtime), which reduces swings in blood glucose. The overweight or obese should be encouraged to lose weight by a combination of changes in food intake and physical activity.

Tablet treatments for type 2 diabetes These are used in association with diet and lifestyle changes when this alone has failed to control hyper-glycaemia (Fig. 15.1):

■ Biguanide. Metformin is the only biguanide available (p. 698). It reduces glucose production by the liver and sensitizes target tissues to insulin. It is usually the first line treatment in patients who have not achieved optimal glucose control with diet alone, particularly in overweight patients (unlike the sulphonylureas, appetite is not increased). It is the only oral agent shown to reduce cardiovascular risk in diabetics. Metformin is also used in combination treatment when single agent use has failed to control diabetes. Side-effects include anorexia and diarrhoea. Lactic acidosis has occurred in patients with severe heart failure, liver disease or renal disease (serum creatinine > 150 |imoI/L), in whom its use is contraindicated.

■ Sulphonylureas promote insulin secretion. Glibenclamide is the most popular choice, but is best avoided in elderly people and in those with renal failure because of its relatively long duration of action (12-20 hours) and renal excretion. Tolbutamide, which is shorter acting and metabolized by the liver, is a better choice in these patient groups. The most common side-effect of sulphonylureas is hypoglycaemia, which may be prolonged. Meglitinides, e.g. repaglinide and nateglinide, are also insulin secreta-gogues. They have a rapid onset of action and short duration of action and are administered shortly before each main meal.

■ Incretins are agents that mimic the effect of two peptide hormones -glucose-dependent insulinotrophic peptide (GIP) and glucagon-like peptide-1 (GLp-1) - that are released from the pancreas and promote insulin release after an oral glucose load. In addition to its insulinotropic effect, GLp-1 inhibits glucagon release, prolongs gastric emptying and leads to a decrease in body weight. Exenatide and liraglutide are long-acting GLp-1 analogues given by subcutaneous injection and are used as an alternative to insulin, particularly in the overweight. Sitagliptin and vildagliptin inhibit dipeptidyl peptidase 4, the enzyme which inactivates GLp-1, and thus potentiates the effects of endogenous GLp-1. Their role in the management of type 2 diabetes has yet to be established.

■ Thiazolidinediones (‘glitazones'), e.g. and pioglitazone, bind to and acti-vate peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear receptor which regulates large numbers of genes including those involved in lipid metabolism and insulin action. They reduce hepatic glucose production and enhance peripheral glucose uptake. They are used alone or in combination with other agents but their place in the routine therapy of type 2 diabetes remains unclear. Side-effects are weight gain, fluid retention and heart failure, anaemia and osteoporosis. They are contraindicated in patients with heart failure.

■ Other therapies:

■ Acarbose inhibits intestinal a-glucosidases and impairs carbohydrate digestion and slows glucose absorption. Postprandial glucose peaks are reduced. Gastrointestinal side-effects, e.g. flatulence, bloating and diarrhoea, are common and limit the dose and acceptability of this treatment.

■ Weight loss is associated with improved diabetic control and even remission of diabetes. Orlistat is an intestinal lipase inhibitor and reduces the absorption of fat from the diet. It promotes weight loss in patients under careful dietary supervision on a low fat diet. Gastric banding and gastric bypass surgery should be offered to those with marked obesity unresponsive to 6 months intensive attempts at dieting and graded exercise.

Insulin treatment Almost all insulin now used in developed countries is synthetic (recombinant) human insulin. Insulin is administered by an injec-tion into the fat below the skin (subcutaneous) on the abdomen, thighs or upper arm. The injection site should be changed frequently to prevent areas of lipohypertrophy (fatty lumps). Patients who are started on insulin have a legal duty to inform the Driver and Vehicle Licensing Agency (DVLA). In addi-tion, those who experience complications of insulin such as frequent hypogly-caemic episodes or impaired awareness of hypoglycaemia may be unfit to drive.

There are three main types of insulin:

1. Short-acting (soluble) insulins start working within 30-60 minutes and last for 4-6 hours. They are given 15-30 minutes before meals in patients on multiple dose regimens and by continuous intravenous infusion in labour, during medical emergencies, at the time of surgery and in patients using insulin pumps.

2. Short-acting insulin analogues. The human insulin analogues (insulin aspart, insulin lispro, insulin glulisine) have a faster onset and shorter duration of action than soluble insulin but overall do not improve diabetic control. They have a reduced carry-over effect compared to soluble insulin and are used with the evening meal in patients who are prone to nocturnal hypoglycaemia.

3. Longer-acting insulins. Insulins premixed with retarding agents (either protamine or zinc) precipitate crystals of varying size according to the conditions employed. These insulins are intermediate (12-24 hours) or long acting (more than 24 hours). The protamine insulins are also known as isophane or NPH insulins, and the zinc insulins as lente insulins. Insulin glargine is a structurally modified insulin that precipitates in tissues and is then slowly released from the injection site.

In young patients a reasonable starting regimen is subcutaneous injection of an intermediate-acting insulin, 8-10 units administered half an hour before breakfast and before the evening meal. In many patients who present acutely with diabetes there is some recovery of endogenous insulin secretion soon after diagnosis ('the honeymoon period') and the insulin dose may need to be reduced. Requirements rise thereafter, and a multiple injection regimen (often using a ‘pen injector' device), which may improve control and allows greater meal flexibility, is then appropriate for most younger patients. An example of this is soluble insulin administered before each meal and an intermediate-acting insulin given at bedtime. Target blood values should normally be 4-7 mmol/L before meals and 4-10 mmol/L after meals. An alternative to multiple injections is to use a small pump strapped to the waist, which delivers a continuous subcutaneous insulin infusion (CSII). Meal-time doses are delivered when the patient presses a button on the side of the pump.

In many patients with type 2 diabetes who eventually require insulin, a twice-daily regimen of premixed soluble and isophane insulin (e.g. Mixtard) is suitable.

Complications of insulin therapy

■ Hypoglycaemia is the most common complication of insulin treatment (see below)

■ At the inịection site - lipohypertrophy (see above), local allergic reactions and rarely injection site abscesses

■ Insulin resistance - most commonly mild and associated with obesity

■ Weight gain - insulin makes patients feel hungry and it essential they maintain a careful dietary regimen to prevent weight gain.

Hypoglycaemia during insulin treatment This may also occur in patients taking sulfonylureas. Insulin or sulfonylurea therapy for diabetes accounts for the vast majority of cases of severe hypoglycaemia encountered in an accident and emergency department; other causes of hypoglycaemia are much less common.

Symptoms of sympathetic overactivity usually develop when blood glucose levels fall below 3.0 mmol/L and include hunger, sweating, pallor and tachy-cardia. Untreated, the symptoms of neuroglycopenia develop and later there is personality change, fits, occasionally hemiparesis, and finally coma. In patients with longstanding diabetes and autonomic neuropathy the early ‘adrenergic features' may be absent and as a result patients go from feeling normal to developing severe hypoglycaemia without warning.

Immediate diagnosis and treatment are essential. A blood glucose con-firms the diagnosis but treatment should begin immediately (while waiting for the result) if hypoglycaemia is suspected on clinical grounds. A rapidly absorbed carbohydrate, e.g. 50-100 mL fizzy non-diet drink (e.g. lemonade or coke) or GlucoGel (40% dextrose gel) should be given orally if possible. In unconscious patients, treatment is with intravenous dextrose (50 mL of 50% dextrose into a large vein though a large-gauge needle) followed by a flush of normal saline, as concentrated dextrose is highly irritant. Intramuscular glucagon (1 mg) acts rapidly by mobilizing hepatic glycogen and is particu-larly useful where intravenous access is difficult. Oral glucose is given to replenish glycogen reserves once the patient revives. Hypoglycaemia may recur after treatment, particularly if it is a result of treatment with longacting insulin preparations or sulfonylureas. These patients should be monitored with hourly (4-hourly when stable) blood glucose readings and may require a 10% dextrose drip to prevent recurrent hypoglycaemia.

Whole pancreas and pancreatic islet transplantation

Whole pancreas transplantation is sometimes performed, usually in diabetic patients who require immunosuppression for a kidney transplant. Lasting graft function can be achieved, but the procedure adds to the risks of renal transplantation. Islet transplantation is also performed by harvesting pancre-atic islets from cadavers and injecting these into the portal vein. These then seed themselves into the liver. While results are improving, this form of treatment remains experimental.

Measuring the metabolic control of diabetes

Patients may feel well and be asymptomatic even if their blood glucose is consistently above the normal range. Self-monitoring at home is therefore necessary because of the immediate risks of hyper- and hypoglycaemia, and because it has been shown that persistently good control (i.e. near normo-glycaemia) reduces the risk of progression to retinopathy, nephropathy and neuropathy in both type 1 and type 2 diabetes.

Home testing

■ Most patients, especially those on insulin, are taught to monitor control by testing finger-prick blood samples with reagent strips and reading these with the aid of a meter. Patients are asked to take regular profiles (e.g. four times daily samples on 2 days each week) and to note these in a diary or record book.

■ Urine testing for glucose (using Stix) is a crude measure of glycaemic control because glycosuria only appears above the renal threshold for glucose (which varies between a blood glucose of 7 and 13 mmol/L) and because urine glucose lags behind blood glucose. It is usually reserved for patients who will not perform capillary blood glucose monitoring at home.

■ Urine ketones, also measured with Stix (Ketostix), are useful if the patient is unwell, because ketonuria indicates potentially serious metabolic derangement.

Hospital (clinic) testing Single random blood glucose measurements are of limited value:

■ Glycosylated haemoglobin (HbA1c) is produced by the attachment of glucose to Hb. Measurement of this Hb fraction (expressed as mmol per mol of haemoglobin without glucose attached) is a useful measure of the average glucose concentration over the life of the Hb molecule (approxi-mately 6 weeks). The non-diabetic reference range is 20-42 mmol/mol. The target value for a diabetic patient is HbA1c of 48-59 mmol/mol. Pursuing lower HbA1c values risks hypoglycaemia, curtailing quality of life in the effort to achieve the target.

■ Glycosylated plasma proteins (fructosamine) are less reliable than HbA1c but may be useful in certain situations, e.g. thalassaemia where haemo-globin is abnormal.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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