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Cardio Diabetes Medicine 2017 631

Susceptible and Prognostic Genetic Factors

Associated with Diabetic Peripheral Neuropathy:

A Literature Review

Dr. VHW Dissanayake, LBL Prabodha, ND Sirisena,

Human Genetics Unit, Faculty of Medicine,
University of Colombo,
Kynsey Road, Colombo 8, Sri Lanka.

ABSTRACT INTRODUCTION
Type 2 diabetes mellitus (T2D) is a disorder of glu- Diabetes mellitus is one of the foremost non-com-
cose metabolism. It is a complex process involving municable diseases of the current period affecting
the regulation of insulin secretion, insulin sensitivity, more than 387 million people worldwide [1]. Type 2
gluconeogenesis and glucose uptake at the cellular diabetes mellitus (T2D) is a disorder of glucose me-
level. Diabetic peripheral neuropathy (DPN) is one of tabolism. It is a complex process involving the reg-
the debilitating complications that presents in ap- ulation of insulin secretion, insulin sensitivity, gluco-
proximately 50% of diabetic patients. It is the prima- neogenesis and glucose uptake at the cellular level.
ry cause of diabetes-related hospital admissions and Dysregulation of one or more of these processes due
non-traumatic foot amputations. The pathogenesis to environmental or genetic factors can lead to al-
of diabetic neuropathy is a complex process that in- tered glucose metabolism causing diabetes mellitus
volves hyperglycaemia induced oxidative stress and [2,3]. More than 90% of cases of T2D show higher
altered polyol metabolism that changes the nerve incidence of insulin resistance. This phenomenon is
microvasculature, altered growth factor support acquired due to sedentary lifestyle in combination
and deregulated lipid metabolism. Recent literature with multifactorial genetic susceptibility. T2D is as-
has identified that there are several heterogeneous sociated with increased morbidity and mortality due
groups of susceptible genetic loci which clearly con- to its debilitating and progressive nature and asso-
tribute to the development of DPN. Several studies ciated complications. The condition usually leads to
reported that some patients with pre-diabetes de- multi-organ failure due to macrovascular and micro-
velop neuropathic complications, whereas others vascular involvement [2-5].
demonstrated little evidence of neuropathy even Uncontrolled T2D can complicate pregnancy out-
after long-standing diabetes. There is emerging ev- comes. Different kinds of birth defects are more
idence that genetic factors may contribute to the commonly seen in babies born to women with dia-
development of DPN. This paper aims to provide an betes [3].Twin studies can estimate the multifactorial
up to date review of the susceptible and prognostic genetic involvement in T2D more precisely and have
genetic factors associated with DPN. An extensive reported high degree of heritability of diabetes re-
search of scientific literature published in PubMed lated conditions such as disorders of first phase in-
using the search terms ‘Diabetic peripheral neurop- sulin response, basal and insulin stimulated glucose
athy/genetics’, ‘genome-wide association study’ was uptake [6]. There are different methods for mapping
carried out and most recent and relevant literature the genetic susceptibility loci in the pathogenesis of
was used for this review.
T2D. Candidate gene studies and genome-wide stud-
ies are commonly used to identify the association of
KEY WORDS susceptible genetic loci of T2D. The latter includes
Type 2 diabetes mellitus; Diabetic peripheral neu- both genome-wide linkage studies (GWL) and ge-
ropathy; Susceptible genetic loci, Prognostic genetic nome-wide association studies (GWAS) [6].With the
factors, Common genetic variants. advent of recent molecular genetic techniques and
rapid screening methods, the method of investi-

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