Prior to the development of type 2 diabetes, glucose levels increase into the prediabetic states of isolated impaired fasting
glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), or combined IFG/IGT. A better understanding of the aetiology
and pathophysiology of the prediabetic states might give a basis for the development of individualised prevention and treatment
strategies for type 2 diabetes. Several studies have examined mechanisms and potential aetiological factors leading to the
development of the different prediabetic states. The pathophysiology of i-IFG seems to include the following key defects:
reduced hepatic insulin sensitivity, stationary beta cell dysfunction and/or chronic low beta cell mass, altered glucagon-like
peptide-1 secretion and inappropriately elevated glucagon secretion. Conversely, the prediabetic state i-IGT is characterised
by reduced peripheral insulin sensitivity, near-normal hepatic insulin sensitivity, progressive loss of beta cell function,
reduced secretion of glucose-dependent insulinotropic polypeptide and inappropriately elevated glucagon secretion. Individuals
developing combined IFG/IGT exhibit severe defects in both peripheral and hepatic insulin sensitivity as well as a progressive
loss of beta cell function. The aetiologies of i-IFG and i-IGT also seem to differ, with i-IFG being predominantly related
to genetic factors, smoking and male sex, while i-IGT is predominantly related to physical inactivity, unhealthy diet and
short stature. Since the transition from the prediabetic states to overt type 2 diabetes is characterised by a non-reversible
vicious cycle that includes severe deleterious effects on glucose metabolism, there are good reasons to use the well-established
aetiological and pathophysiological differences in i-IFG, i-IGT and IFG/IGT to design individualised preventive strategies.
Keywords Beta cell dysfunction - Environmental factors - Genetic factors - Impaired fasting glycaemia - Impaired glucose tolerance - Insulin resistance - Pathophysiology - Prevention - Review - Treatment