●Introduction 285
●Pathophysiology 285
●Principles of management 286●Diet in diabetes mellitus 286
●Drugs used to treat diabetes mellitus 286CHAPTER 37
37 Diabetes mellitus
INTRODUCTION
Before the discovery of insulin, type 1 diabetes – where insulin
deficiency can lead to ketoacidosis – was invariably fatal. Since
the introduction of insulin, the therapeutic focus has broadened
from treating and preventing diabetic ketoacidosis to preventing
long-term vascular complications. Type 2 diabetes – where
insulin resistance and a relative lack of insulin lead to hyper-
glycaemia – not only causes symptoms related directly to hyper-
glycaemia (polyuria, polydipsia and blurred vision – see below),
but is also a very powerful risk factor for atheromatous disease.
Glucose intolerance and diabetes mellitus are increasingly
prevalent in affluent and developing countries, and represent a
major public health challenge. Addressing risk factors distinct
from blood glucose, especially hypertension, is of paramount
importance and is covered elsewhere (Chapters 27 and 28). In
this chapter, we focus mainly on the types of insulin and oral
hypoglycaemic agents.
PATHOPHYSIOLOGY
Insulin is secreted by β-cells (also called B-cells) of the islets of
Langerhans. It lowers blood glucose, but also modulates the
metabolic disposition of fats and amino acids, as well as carbo-
hydrate. It is secreted together with inactive C-peptide, which
provides a useful index of insulin secretion: its plasma concen-
tration is low or absent in patients with type 1 diabetes, but
very high in patients with insulinoma (an uncommon tumour
which causes hypoglycaemia by secreting insulin). This should
not be confused with ‘C-reactive peptide’ (CRP) which is an
acute phase protein synthesized by the liver and used as a non-
specific index of inflammation. C-peptide concentration is not
elevated in patients with hypoglycaemia caused by injection of
insulin.
Diabetes mellitus (fasting blood glucose concentration
of 7 mmol/L) is caused by an absolute or relative lack of
insulin. In type 1 diabetes there is an absolute deficiency of
insulin. Such patients are usually young and non-obese at
presentation. There is an inherited predisposition. However,
concordance in identical twins is somewhat less than 50%, so
it is believed that genetically predisposed individuals must
also be exposed to an environmental factor. Viruses (including
Coxsackie and Echo viruses) are one such factor and may ini-
tiate an autoimmune process that then destroys the islet cells.
In type 2 diabetes there is a relative lack of insulin secretion,
coupled with marked resistance to its action. The circulating
concentration of immunoreactive insulin measured by stand-
ard assays (which do not discriminate well between insulin
and pro-insulin) may be normal or even increased, but more
discriminating assays indicate that there is an increase in pro-
insulin, and that the true insulin concentration is reduced.
Such patients are usually middle-aged or older at presentation,
and obese. Concordance of this form of diabetes in identical
twins is nearly 100%. Type 2 diabetes is rarely if ever associated
with diabetic ketoacidosis, although it can be complicated by
non-ketotic hyperosmolar coma or, rarely (in association with
treatment with a biguanide drug such as metformin, see
below), with lactic acidosis.
An increased concentration of glucose in the circulating
blood gives rise to osmotic effects:- diuresis (polyuria) with consequent circulating volume
reduction, causing thirst and polydipsia;
2.the refractive index of a high glucose concentration
solution in the eye differs from healthy aqueous humour,
causing blurred vision.
In addition, glycosuria predisposes to Candidainfection, espe-
cially in women. The loss of calories in the urine is coupled
with inability to store energy as glycogen or fat, or to lay down
protein in muscle, and weight loss with loss of fat and muscle
(‘amyotrophy’) is common in uncontrolled diabetics.
Both types of diabetes mellitus are complicated by vascular
complications. Microvascular complications include retino-
pathy, which consists of background retinopathy (dot and
blot haemorrhages and hard exudates which do not of them-
selves threaten vision), and proliferative retinopathy which