Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum?

Abstract

Diabetes and related complications are associated with long-term damage and failure of various organ systems. The line of demarcation between the pathogenic mechanisms of microvascular and macrovascular complications of diabetes and differing responses to therapeutic interventions is blurred. Diabetes induces changes in the microvasculature, causing extracellular matrix protein synthesis, and capillary basement membrane thickening which are the pathognomic features of diabetic microangiopathy. These changes in conjunction with advanced glycation end products, oxidative stress, low grade inflammation, and neovascularization of vasa vasorum can lead to macrovascular complications. Hyperglycemia is the principal cause of microvasculopathy but also appears to play an important role in causation of macrovasculopathy. There is thought to be an intersection between micro and macro vascular complications, but the two disorders seem to be strongly interconnected, with micro vascular diseases promoting atherosclerosis through processes such as hypoxia and changes in vasa vasorum. It is thus imperative to understand whether microvascular complications distinctly precede macrovascular complications or do both of them progress simultaneously as a continuum. This will allow re-focusing on the clinical issues with a unifying perspective which can improve type 2 diabetes mellitus outcomes.

Comparative Study of Pulmonary Function Tests With Microvascular Complications, Retinopathy and Nephropathy in Type 2 Diabetes Mellitus and Correlation With Duration of Diabetes

“…Chronic hyperglycaemia is associated with long-term damage and failure of various organ systems mainly affecting eyes, nerves, kidneys, and heart. [4] The onset T2DM is often silent and insidious and chronic hyperglycaemia is usually found to be existing in most type 2 DM patients even before the diagnosis. Also at the onset most of the T2DM are usually treated with lifestyle modification, dietary advice and then followed by oral anti hyperglycemic drugs.…”

“…[3] Nephropathy, retinopathy and neuropathy are the most common microvascular complications in diabetes. [4] Longer the duration of diabetes, longer would be the persistence of hyperglycaemia. The long standing hyperglycaemic state in diabetes mellitus results in glucose, forming covalent adducts with plasma proteins through non-enzymatic process known as glycation.…”

“…[1] In initial stages, the illness remains silent and asymptomatic which delays the diagnosis and thereby increases the risk of complications. The actual onset of diabetic hyperglycaemia and clinical diagnosis has asymptomatic phase lasting for approximately [4][5][6][7] Correspondence: Dr. Arun Chutani, Assistant Professor, Dept of Physiology, MG Medical College & Hospital, Jaipur, Rajasthan. Email: docarun26@gmail.com years, resulting in 30-50% of population remaining undiagnosed.…”

“…[3] Microvascular complications include retinopathy, nephropathy, and neuropathy which has been well established in literature. [3,4] Many research studies conducted worldwide, have been conclusive of lung being target organ in diabetes mellitus [5,6] thus adding a further to the list of microvascular complications. The extensive pulmonary microvascular circulation and abundant connective tissue in lungs raises the possibility of it being involved in microvascular complications.…”

Complications of diabetes mellitus among patients attending the out-patient department of a tertiary care hospital

“…25 The mechanisms of hyperglycemia-induced polyol pathway, injury from advanced glycation end product (AGEs), and enhanced oxidative stress have been implicated in the pathogenesis of complications. 26 Chronicity of hyperglycemia is associated with long-term damage and failure of various organ systems mainly affecting the eyes, nerves, kidneys, and the heart.…”