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Other risk factors

A number of other factors are known to increase the risk of developing
T2DM. For example, individuals with impaired glucose tolerance (IGT)
or impaired fasting glucose (IFG) are at an increased risk of developing
this disease. IGT and IFG are pre-diabetic states characterised by the
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same pathophysiological abnormalities of T2DM, only milder in degree.

A history of gestational diabetes mellitus is known to increase the risk
of developing T2DM later on in life. In around 3-8% of pregnancies,
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impaired glucose tolerance or full gestational diabetes can develop.
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The reason for this is not clear, but it is thought that the hormones pro-
duced during pregnancy, notably progesterone, can worsen insulin
resistance in susceptible individuals, resulting in raised blood glucose
levels. The transient demand on glucose-regulating mechanisms may
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contribute to T2DM later on. Additionally, an abnormal metabolic intra-
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uterine milieu affects foetal development by permanently modifying
expression of key genes regulating β-cell development (Pdx1) and
glucose transport (Glut4) in muscle. Ultimately, this can lead to the
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development of T2DM in adulthood. This observation reinforces the
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importance of epigenetics in the development of T2DM (see Genetic
predisposition section earlier in this chapter).

Women with polycystic ovarian syndrome are also at an increased risk
of developing T2DM. It is thought the hormonal imbalances associ-
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ated with this condition, notably the overproduction of androgens can
impair carbohydrate metabolism, ultimately leading to impaired glu-
cose tolerance and T2DM. 59

T2DM complications

Underlying aetiology

T2DM causes a number of complications that together account for
much of the morbidity, mortality and burden associated with this dis-
ease. These complications can be broadly divided into two categories:
microvascular and macrovascular. Regardless of the classification, all
complications of T2DM are a consequence of chronic hyperglycae-
mia and the other metabolic and haemodynamic abnormalities that
accompany this disease such as central obesity, dyslipidaemia and
hypertension. Several of these diabetic complications can also occur
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in patients with normal glucose tolerance and prediabetes. 28

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