Pathophysiology of diabetes mellitus complications: Metabolic events and control

Abstract

Background: Diabetes mellitus (DM) is a metabolic disorder that is characterized by hyperglycemia and glucose intolerance, which is associated with impaired insulin secretion and peripheral sensitivity and eventual b-cell dysfunction. This review summarized the major metabolic pathways leading to both microvascular and macrovascular complications in DM, with a view of highlighting the enzymes involved and the possible inhibition of the enzymes facilitating these processes as a measure of diabetic control. Methods: Data used in writing this review were sourced online from scientific search engines such as Google Scholar, Scopus, EMBASE, PubMed, ResearchGate, Mendeley, Medline, and SpringerLink, using keywords such as 'diabetic complications', 'hyperglycemia-induced diabetic mechanisms', 'diabetic enzymes' and 'diabetic enzyme inhibitors'. A total number of 109 references published online between 1990 and 2020 were generated and cited in this review. Results: The most scourging and dilapidating effects of DM as well as associated vascular complications are classified into four categories viz.: nephropathy, retinopathy, neuropathy and cardiovascular disease. Hyperglycemia, which is associated with uncontrolled DM, elicits abnormal metabolism such that the enzymes involved in metabolic events leading to diabetic complications are expressed and amplified. The disorders associated with DM are linked to various metabolic pathways facilitated by enzyme activities of the polyol pathway, hexosamine biosynthetic pathway, glucose autoxidation as well as increased synthesis of advanced glycation end-products (AGEs), hexokinase-2 driven glycolytic overload, increased activities of the cyclooxygenase (COX), lipoxygenase (LOX) and pyruvate kinase (PKC) enzymes. The inhibition of the enzymes involved in these pathways could serve to mitigate and arrest diabetic complications. Conclusion: Thus, suitable inhibitors for enzymes involved in DM metabolic events could serve as panaceas against DM complications, which will add to the growing list of new and more efficacious antidiabetic drugs.