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258 Cardio Diabetes Medicine 2017

Role of Oxygen Insufficiency

in the Onset & Development of

Vascular Complications of Diabetes

Dr. V.N. Rajasekaran, MD PhD; DTM&H
Dr. R. Sudhir, DNB (General Medicine)

ABSTRACT MECHANISMS OF VASCULAR
Diabetes mellitus is a chronic metabolic disorder, COMPLICATIONS
which when not controlled adequately, is compli- Some of the most studied mechanisms include in-
cated by damage to several organs, primarily due creased polyol pathway flux causes excessive accu-
to dysfunction and changes in the vascular tree. mulation of sorbitol causing a raised osmotic stress
Vascular changes, both micro- and macro-vascular, on tissues causing Advanced Glycation End prod-
are influenced by several factors. Hypoxia has been ucts. Metabolism of the excess sorbitol to fructose.
quoted as a significant factor in the onset and devel- produces decreased availability of reduced NADH
opment of these vascular complications. This article and alters the NADH/ NAD+ ratio, essential factors
briefs on the possible and confirmed mechanisms by in many redox reactions, thereby inducing a state
which hypoxia as a result of hyperglycemia induced of pseudohypoxia, wherein essential NADH is not
destabilization of the vascular milieu, brings about available for mitochondria for other metabolic cas-
the vascular complications in patients with diabetes cades, This leads to reduced levels of Glutathione,
mellitus and its clinical implications. NO and myo-inositol , There may also be an ath-
eroscelortic plaque obstruction causing a state of
COMPLICATIONS OF DIABETES true hypoxia, further aggravating the problem. Hy-
Complications involving the end organs are the ma- perglycemia induced activation of the diacylglycerol
jor cause of morbidity and mortality in patients with (DAG)/protein kinase C (PKC) pathway alters vascu-
diabetes. Microvascular complications include reti- lar permeability,contractility, extra cellular matrix, cell
nopathy, nephropathy and neuropathy, are leading growth, angiogenesis, leucocyte adhesion and cyto-
causes of blindness, end-stage renal disease and kine production. Reactive Oxygen Species induced
various painful neuropathies; whereas macrovascu- Oxidative stress and its subsequent casade causes
lar complications encompass atherosclerosis related vascular dysfunction Genetic factors also have been
diseases, such as coronary artery disease, peripher- suggested as important risk markers for developing
3
1
al vascular disease and stroke . Two large studies, diabetic complications . It is thus evident that there is
the Diabetic Control and Complications Trial (DCCT) a complex interplay of factors in the pathogenesis of
and the United Kingdom Prospective Diabetes Study vascular dysfunction leading to tissue hypoxia on a
(UKPDS) clearly showed that intensive control of hy- metabolic level which when combined with mechani-
perglycemia could reduce the progression of diabetic cal obstruction in the form of atherosclerotic plaques
microvascular complications. These clinical observa- causes major organ damage.
tions indicate that hyperglycemia is a major factor
responsible for the pathogenesis of diabetic compli- ENDOTHELIAL DYSFUNCTION
cations. In contrast, it is known that multiple factors, The endothelium is a monolayer of cells covering the
such as fatty acid, lipid, insulin resistance, inflamma- vascular lumen. The importance, this cell layer is now
tory cytokines in addition to hyperglycemia induced gaining recognition, and now it is known to play vi-
derangement of various metabolic pathways interact, tal roles in maintaining vascular homeostasis by its
increasing the risk for atherosclerosis in diabetes . paracrine, endocrine and autocrine functions, Endo-
2,3

GCDC 2017