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It is well established that obesity, reduced physical activity, and aging
increase susceptibility to T2DM; however, many people exposed to
these risk factors do not develop the disease. Recent genome studies
95
have identified a number of genetic variants that explain some of the
inter-individual variation in diabetes susceptibility. In addition to the
95
genetic markers of T2DM there is also a growing body of evidence sug-
gesting a role for epigenetic factors (heritable changes in gene func-
tion that occur without a change in the nucleotide sequence) in the
complex interplay between genes and the environment (Figure 4). 95
Environmental factors of considerable note include persistent organic
pollutants (POPs), the presence of which have been shown to be re-
lated to the prevalence of diabetes (dose response relationship). 96, 97
It has also been suggested that as people become more overweight,
the retention and toxicity of POPs related to the risk of diabetes may
increase. 96, 97

Figure 4. The interplay between genetics, epigenetics and the environment in the
development of T2DM. 95

Understanding the underlying genetic and epigenetic defects in blood
sugar homeostasis and how these interact with environmental factors
(e.g. persistent organic pollutants) will help direct T2DM management,
perhaps drawing on new therapies with novel modes of action that
target specific defect(s). 34, 95

Drug development is promising to deliver a range of therapies that
will directly address a number of the unmet needs currently facing the
management of T2DM. Compounds such as the SGLT-2 inhibitors prom-
ise to deliver significant improvements in blood glucose levels as well

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