Complications of type 2 diabetes

Abstract

Diabetes, a disease of the endocrine system diagnosed by abnormally high blood glucose levels, is one of the most common and fastest growing diseases worldwide, projected to affect 693 million adults by 2045, a >50% increase from 2017. Vascular complications of both the macro- and microvascular systems (cardiovascular disease [CVD], diabetic kidney disease [DKD], diabetic retinopathy [DR], and neuropathy) are the leading cause of morbidity and mortality in individuals with diabetes, carrying enormous financial burden with unequal healthcare expenditure and access to treatment between developed and developing countries. While the precise mechanisms of hyperglycemia-induced vascular damage are both complex and not fully understood, it is thought that high levels of intracellular glucose increase the production of reactive oxygen species altering a series of critical downstream pathways, including polyol pathway flux, advanced glycation end product formation and activation, protein kinase C activation, and hexosamine pathway flux. Diabetes is not a single disease, but rather a group of conditions broadly categorized by a single diagnostic criterion – hyperglycemia, the final common pathway on which disparate metabolic derangements converge. It is becoming increasingly evident that even type 2 diabetes (T2D), the predominant diabetes subtype making up 90–95% of cases, is itself heterogeneous in terms of both the mechanisms of action and the relationships with health outcomes