The harmonious and interdependent
functioning of the various systems in
the body requires the maintenance of a
very accurate environment within the
body, and a means of communication
between sometimes distant organs
and tissues. These homeostatic
functions are achieved extremely
efficiently and (in health) successfully
by two major bodily systems. In
temporal terms, the nervous system
effects this obligation in the short
term, while the endocrine system is
concerned with the longer term
execution of this essential task.
The nervous system and its abnormalities have
been covered in previous articles in this series
(Parts 1, 4a and 4b). The endocrine system
consists of various glands which secrete
hormones directly into the blood stream.
Hormones are either steroids (e.g. cortisol,
androgens) or proteins, e.g. insulin. They may
exert their effects at a site distant from the
secretory gland or may exert a more
generalised effect on different systems of the
body. Cells secreting protein hormones have a
very well developed, rough endoplasmic
reticulum (it is called rough because of the
presence of countless ribosomes on its surface;
ribosomes are the site of protein synthesis).
Preponderance of smooth (without ribosomes)
endoplasmic reticulum is typical of cells
secreting steroids. Both these types of cells
also possess well-developed mitochondria and
Golgi apparatus; the former are the power
houses of the cell and would generate the
energy required for the secretory activity. The
latter is concerned with the accumulation,
concentration and storage of secretions
(  ).
Hormone levels in the body and the
magnitude of their effects are finely controlled
by feedback mechanisms. For example, the
secretion of glucocorticoids from the adrenal
cortex is stimulated by adrenocorticotrophic
hormone (ACTH), which is released from the
pituitary gland – and as a feedback mechanism,
high levels of glucocorticoids in the blood
inhibit the release of ACTH from the pituitary.
In this way the levels of hormones in the blood
and at the target organ are finely tuned to
meet differing physiological demand.
Endocrine glands include the pituitary,
which secretes ACTH (see above), growth
hormone (GH), prolactin, follicle stimulating
hormone (FSH), and thyroid stimulating
hormone (TSH); the adrenal gland, which
secretes corticosteroids (cortex) and
catecholamines (medulla); the thyroid gland,
which secretes thyroxine (T4) and
tri-iodothyronine (T3); testes/ovaries, which
secrete androgens/oestrogens respectively; and
Islets of Langerhans of the pancreas, which
secrete insulin (B cells) and glucagon
(A cells).
When the tuning of the levels of hormone
breaks down, too much or too little hormone is
secreted, leading to a predictable syndrome.
Underactivity of an endocrine gland is treated
with the relevant hormone; overactivity by
administration of drugs which inhibit secretion
of that particular hormone, or by using an
antagonist of that hormone.
Diabetes mellitus
Diabetes mellitus is a disease of increasing
incidence which is only too familiar to
optometrists owing to its ocular complications
(see later). It is a disease which causes
considerable mortality and morbidity, including
cardiac complications, retinopathy, neuropathy
and nephropathy. The epidemiology is complex
but certain features are worthy of mention. The
disease is more common in certain races,
particularly in Indians living outside the subcontinent, e.g. in Malaysia, Singapore, Fiji and,
indeed, in the UK. It is rare in Eskimos.
Physiology of glucose metabolism 
Glucose is a monosaccharide, i.e. it is a simple
unit of sugar just like fructose and galactose.
Sucrose, maltose and lactose are disaccharides,
i.e. double units of sugars formed by the
combination, respectively, of two
monosaccharides (  ). Complex
carbohydrates or polysaccharides, such as
glycogen or starch, are long chains, sometimes
branched, of simple sugars. Glucose is an
important substrate required for the provision
of energy in many organs and tissues in the
body, e.g. the brain uses glucose as its
principal energy source.
Glucose levels in the body, and particularly
in the blood are maintained within a
very precise range in health, namely
80-100mg/100ml (≈4.5-6.5 mmoles/litre).
Certain processes affect the blood levels of
glucose. These include glycogenolysis,
gluconeogenesis, hepatic glucose synthesis,
extrusion out of cells, all of which tend to
increase blood glucose; and glycogenesis,
glucose utilisation and entry into cells which
tend to reduce blood levels. Insulin inhibits the
former and promotes the latter actions, thus its
26 August 16, 2002 OT
Figure 1
Structure of a cell from a gland secreting a protein-based
hormone, as seen under an electron microscope. Note the well
developed rough endoplasmic reticulum, Golgi complex and
mitochondria (only a few of these latter are shown here). A cell
from a gland secreting a steroid hormone would be similar
except that the smooth endoplasmic reticulum would be
abundant instead of the rough (also see text)
Understanding disease
Medicine and surgery for the optometrist
Part 6: Endocrine diseasewww.optometry.co.uk
has a hypoglycaemic effect, while glucagon has
the opposite effects (  ).
Insulin is secreted by the B cells of the
Islets of Langerhans in the pancreas (A cells
secrete glucagon). It is produced initially as a
polypeptide of 109 amino acid residues, called
preproinsulin, which is cleaved into two
peptides, one being proinsulin, consisting of 86
amino acid residues. Proinsulin is digested by
another proteolytic enzyme into insulin
(51 amino acids) and C-peptide (35 amino
acids) in the B cell granules. The insulin is then
released into the circulation. C-peptide has
some insulin-like activity and may, in fact, have
the capacity to modulate the actions of insulin,
by enhancing them at low insulin concentration
and dampening them at high insulin
concentration
1
.
Aetiology and pathogenesis
There are several factors which may play a part
in the causation of diabetes mellitus; these
interact with one another, and are different in
the two types of primary diabetes. Firstly
genetic factors are of considerable significance,
particularly in non-insulin dependant diabetes
mellitus (NIDDM). In this type, there is an
increased prevalence of the disease in the
relatives of sufferers; also the concordance
between monozygotic twins is nearly 100%,
suggesting that genetic factors play at least a
partial role in the aetiology of NIDDM. There is
some evidence that one gene defect in NIDDM
is located on chromosome 12
2
. A total of 80%
of NIDDM patients are overweight, so obesity is
another important factor. 
The basic defects of insulin physiology in
NIDDM have been shown to be both a reduced
release of insulin from B cells and a resistance
to insulin in the target organs. The latter has
been elucidated as being partly due to
reduction in the number of insulin receptors,
but also connected with a postreceptor
mechanism, possibly due to malfunction of the
transport effector proteins
3
. 
Three main factors appear to be involved in
the aetiology of IDDM – genetic, infective
(viral) and auto-immune.
The genetic tendency, although less evident
than in NIDDM, is borne out by the greater
frequency of certain histocompatibility antigens
in affected individuals. These are principally
HLA-B8, HLA-B15, HLA-DR3 and HLA-DR4 (no
specific HLA antigens have been identified in
NIDDM).
Diabetes can also occur secondary to other
conditions. In particular, when antagonists of
insulin are excessively produced,
hyperglycaemia results. This occurs in
hyperadrenalism, Cushing’s syndrome and
acromegaly, since adrenaline,
glucocorticosteroids and growth hormone,
respectively, are insulin antagonists.
Clinical features
The lack of insulin in IDDM results in
hyperglycaemia, and if the blood glucose level
exceeds the renal threshold (180mg/100ml),
glycosuria. Loss of calories in the urine results in
weight loss in the face of polyphagia (increased
appetite). The increased osmolarity of the urine
draws in water into the renal parenchyma
leading to polyuria followed, in turn, by
polydipsia due to dehydration. Fatigue and
infection are also commonly seen (  ). 
In IDDM, these symptoms occur abruptly,
with the patient often presenting with severe
ketoacidosis (accumulation of ketone bodies
like acetoacetate and hydroxybutyrate in the
blood and tissues) which may be accompanied
by coma. The peak age of incidence is 11 to 13
years, i.e. around puberty, although it can
occur earlier and young adults may contract it,
too. IDDM is unusual after the age of 40.
In NIDDM, polyuria, polydipsia and weight
loss occur over several weeks or months, and
dizziness, fatigue and blurred vision can also
occur. Ketosis is not a feature since some
insulin, or indeed excess of it, is usually
present. NIDDM usually occurs after the age of
40, and can be precipitated by pregnancy or
concurrent chronic illness. Since it may have
been present for some time before diagnosis,
retinopathy or nephropathy may be presenting
features.
Treatment
The control of diabetes is centred upon diet,
hypoglycaemic agents and insulin. The first
encompasses a good balance of the various
nutrients in food (high protein, moderate
amounts of complex carbohydrates, and very
low saturated fats), timing of meals and snacks
in relation to glucose levels and other therapy,
and caloric control. Hypoglycaemic agents are
useful in NIDDM, although some patients with
NIDDM may also require insulin. 
Drugs used include the sulphonylureas,
namely tolbutamide (RASTINON, which has a
short half-life and needs administration b.d. or
t.d.s.), glibenclamide (EUGLUCON), tolazamide
(TOLANASE), gliclazide (DIAMICRON), and
chlorpropamide (DIABINESE, once daily); and
the biguanide, metformin (GLUCOPHAGE).
Hypoglycaemic drugs have been traditionally
said to promote the release of insulin from
B cells. The mechanism of this release appears
to be by the closure of ATP-sensitive K
+
[K(ATP)]
channels, which results in opening of Ca
2+
channels and consequent exocytosis of insulin
Figure 2
The chemistry of the simple sugars; in the
intestine the physiological process is the
digestion of disaccharides to
monosaccharides
Figure 3
The various processes which modulate
blood glucose levels; actions probably
promoted by insulin are shown in red
Figure 4
Flow chart illustrating the pathophysiology of diabetes mellitus and the mechanism of
production of some of the clinical features