DIABETES: BASIC FACTS

What is diabetes?

A definition of diabetes from a societal perspective would

include the burden that the disease places on health economies,
in terms of both the costly treatment and the premature morbidity
and mortality.
From the patients perspective, diabetes is a lifelong condition
requiring daily attention to diet, lifestyle and monitoring of blood
and/or urine, and is associated with varying degrees of anxiety
and multiple visits to health-care providers.

Sean F Dinneen

How is diabetes classified?

There are two main forms of diabetes type 1 and type 2.
In type 1 diabetes, pancreatic -cells are destroyed, usually by
autoimmune inflammatory mechanisms.
Type 2 diabetes is a complex metabolic disorder associated
with -cell dysfunction and with varying degrees of insulin resistance. The latter is found in other metabolic conditions, including
hypertension, obesity and polycystic ovary syndrome, and these
often occur in patients with type 2 diabetes.
The genetic basis of type 2 diabetes is not well understood,
but several other types have been characterized genetically. The
most common of these is maturity-onset diabetes of youth, which
is a familial form of diabetes inherited in an autosomal dominant
manner and associated with mutations in certain -cell or hepatic
enzymes (e.g. glucokinase). Other well-characterized forms are
often termed secondary diabetes and include diabetes associated
with pancreatic insufficiency, with steroid (or other) hormone
excess and with certain drugs (e.g. protease inhibitors in HIV
infection, atypical antipsychotics in schizophrenia).
Gestational diabetes is a separate form of diabetes and is defined
as diabetes occurring or first recognized in pregnancy.

Diabetes mellitus is not a single disorder. It represents a series of

metabolic conditions associated with hyperglycaemia and caused
by defects in insulin secretion and/or insulin action.
Exposure to chronic hyperglycaemia may result in microvascular
complications in the retina, kidney or peripheral nerves. Although
these are characteristic of diabetes, they cannot be used to define
the disorder because they take too long to manifest. The so-called
macrovascular complications of diabetes (myocardial infarction,
stroke, peripheral ischaemia) occur more commonly. It has been
suggested that diabetes should be defined as premature atherosclerosis with associated hyperglycaemia, thereby emphasizing
the clinical problems to which most patients succumb.

How is diabetes diagnosed?

Sean F Dinneen is Senior Lecturer in Medicine at the National University

of Ireland, Galway, Ireland and Consultant in Diabetes and Endocrinology
at University College Hospital, Galway. Conflicts of interest: none
declared.

Diabetes is diagnosed by documentation of hyperglycaemia of

a certain degree in the fasting state or in a (usually 75 g) oral
glucose tolerance test (OGTT). In the presence of the classical

Diagnostic thresholds for diabetes and lesser degrees of impaired glucose regulation
Category
Normal1
IFG
IGT
Diabetes2

Fasting plasma glucose

< 6.1 mmol/litre (< 110 mg/dl)
6.16.9 mmol/litre (110125 mg/dl)

7.0 mmol/litre ( 126 mg/dl)

2-hour plasma glucose

< 7.8 mmol/litre (< 140 mg/dl)

7.811.0 mmol/litre (140199 mg/dl)

11.1 mmol/litre ( 200 mg/dl)

IFG, impaired fasting glucose;

IGT, impaired glucose tolerance
When both tests are performed, IFG or IGT should be diagnosed only when diabetes is not diagnosed by the other test.
The Expert Committee of the American Diabetes Association published a follow-up report in November 2003, in which they recommended
that the fasting plasma glucose used to diagnose IFG be reduced from 6.1 mmol/litre to 5.6 mmol/litre. This recommendation has not yet been
endorsed by the WHO.
2
The diagnosis of diabetes must be confirmed on another day.
1

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DIABETES: BASIC FACTS

Classification of diabetes mellitus

Type 1 diabetes
Immune mediated
Idiopathic

Drug or chemical induced

Vacor
Pentamidine
Nicotinic acid
Glucocorticoids
Thyroid hormone
Diazoxide
-adrenergic agonists
Thiazides
Clozapine
Protease inhibitors
Others
Infections
Congenital rubella
Cytomegalovirus
Others
Uncommon forms of immune-mediated diabetes
Stiff man syndrome
Anti-insulin receptor antibodies
Others
Other genetic syndromes sometimes associated with diabetes
Downs syndrome
Klinefelters syndrome
Turners syndrome
Wolframs syndrome
Friedreichs ataxia
Huntingtons chorea
LawrenceMoonBiedel syndrome
Myotonic dystrophy
Porphyria
PraderWilli syndrome
Others

Type 2 diabetes
Other specific types
Genetic defects in -cell function
HNF-4 (MODY 1)
Glucokinase (MODY 2)
HNF-1 (MODY 3)
IPF-1 (MODY 4)
HNF-1 (MODY 5)
NeuroD1 or BETA 2 (MODY 6)
Mitochondrial DNA
Others
Genetic defects in insulin action
Type A insulin resistance
Leprechaunism
RabsonMendenhall syndrome
Lipodystrophic diabetes
Others
Diseases of the exocrine pancreas
Pancreatitis
Trauma/pancreatectomy
Neoplasia
Cystic fibrosis
Haemochromatosis
Fibrocalculous pancreatic diabetes
Others
Endocrinopathies
Cushings syndrome
Acromegaly
Glucagonoma
Phaeochromocytoma
Somatostatinoma
Aldosteronoma
Hyperthyroidism
Others

Gestational diabetes mellitus

MODY, maturity-onset diabetes of youth
Source: Diabetes Care 1997; 20: 118397, with permission.

symptoms of hyperglycaemia (polydipsia, polyuria, weight loss),

a single elevated reading is sufficient for the diagnosis. If the
patient is asymptomatic, a confirmatory test must be undertaken
on another day.
The diagnostic criteria established by an Expert Committee of
the American Diabetes Association (ADA) in 1996 and ratified by
the WHO are outlined in Figure 1. The ADA recommended use of
a fasting glucose measurement rather than the more cumbersome
OGTT to establish the diagnosis. The diagnostic cut-off points of
7.0 mmol/litre (fasting) and 11.1 mmol/litre (OGTT 2-hour value)
are based on the levels at which retinopathy begins to appear in a
population. The upper end of the normal range is 6.1 mmol/litre
(fasting) and 7.8 mmol/litre (OGTT 2-hour value).

MEDICINE 34:2

The intermediate zones between normal and overt diabetes

are termed impaired fasting glucose and impaired glucose tolerance, respectively. These states of milder hyperglycaemia are
not clinical disorders, though the term pre-diabetes has been
used to describe them. Pre-diabetes (dysglycaemia) is important,
because it is a strong risk indicator for the development of diabetes in the future. In addition, the increased cardiovascular risk
associated with overt diabetes appears to extend into the range of
pre-diabetes.
It has been suggested that populations at increased risk of type 2
diabetes should undergo screening to identify these intermediate
degrees of hyperglycaemia, to enable interventions to prevent (or
delay) the onset of diabetes.

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2006 Elsevier Ltd