Genomic Medicine and DM management

As per the current updates on diabetes, it was revealed that there are some genetic variants responsible
for increased risk in both type 1 and type 2 diabetes. Over 50 loci related with an increased genetic risk
of DM type 1 were identified with genome-wide association studies. For DM type 2, several probable
genes for increased risk of developing it have been also identified. These include PPARγ2, ACE, MTHR,
FABP2), and fat mass and obesity associated gene or FTO (Abbas S et. al., 2013)

With the use genetic test, subgroups of patients with specific molecular defects who otherwise are
classified under the broad umbrella of type 1 diabetes or type 2 diabetes can be identified. Doing this
will provide the basis for most suitable and optimal preventive or therapeutic management. Facilitating
genetic testing increases the precision effectively in diagnosing and selecting the treatment for patients
with known monogenic diabetes including MODY and neonatal diabetes.

It is now feasible to detect causal mutations in >80% of patients with monogenic diabetes by doing
comprehensive testing using sequencing. This serves as a promising outline for precision medicine in
diabetes (De Franco E. et al.,2013).

There are also genomic studies that revealed that some variants causing DM are known to cause or
more prone to the complication in diabetes. In a large‐scale case–control analysis of Caucasians, it was
noted the following gene mutations in CNTNAP2, PTPN13and AFF3 were associated with CKD in type 1
diabetes (Sandholm N et. al.,2017). Such genomic findings tell us that individuals with these genetic
predispositions might require to be treated a target‐specific therapies or be monitored and managed
more intensively to reduce the complication risk.

In terms of application of pharmacogenomics, it is also possible to predict individual response and ADE
to drugs. For instance, a patient with genetic variants related with increased responsiveness to
metformin and Sulfonylureas as a result of decreased clearance might also be at risk of side‐effects with
renal dysfunction, while a patient with genetic variants linked with increased responsiveness to TZD
might have advantage from the drug, in spite of this drug class not being prescribed often now.

References:

Abbas S, Raza ST, Ahmed F, et al. Association of genetic polymorphism of PPARγ-2, ACE, MTHFR, FABP-2
and FTO genes in risk prediction of type 2 diabetes mellitus. J Biomed Sci. 2013;20(1):80

De Franco E, Flanagan SE, Houghton JA, et al The effect of early, comprehensive genomic testing on
clinical care in neonatal diabetes: an international cohort study. Lancet 2015; 386: 957–963.,

Sandholm N, Van Zuydam N, Ahlqvist E, et al The genetic landscape of renal complications in type 1
diabetes. J Am Soc Nephrol 2017; 28: 557–574.