Diabetic microvascular disease in non-classical beds: the hidden impact beyond the retina, the kidney, and the peripheral nerves

Abstract

Diabetes microangiopathy, a hallmark complication of diabetes, is characterised by structural and functional abnormalities within the intricate network of microvessels beyond well-known and documented target organs, i.e., the retina, kidney, and peripheral nerves. Indeed, an intact microvascular bed is crucial for preserving each organ’s specific functions and achieving physiological balance to meet their respective metabolic demands. Therefore, diabetes-related microvascular dysfunction leads to widespread multiorgan consequences in still-overlooked non-traditional target organs such as the brain, the lung, the bone tissue, the skin, the arterial wall, the heart, or the musculoskeletal system. All these organs are vulnerable to the physiopathological mechanisms that cause microvascular damage in diabetes (i.e., hyperglycaemia-induced oxidative stress, inflammation, and endothelial dysfunction) and collectively contribute to abnormalities in the microvessels’ structure and function, compromising blood flow and tissue perfusion. However, the microcirculatory networks differ between organs due to variations in haemodynamic, vascular architecture, and affected cells, resulting in a spectrum of clinical presentations. The aim of this review is to focus on the multifaceted nature of microvascular impairment in diabetes through available evidence of specific consequences in often overlooked organs. A better understanding of diabetes microangiopathy in non-target organs provides a broader perspective on the systemic nature of the disease, underscoring the importance of recognising the comprehensive range of complications beyond the classic target sites.

Understanding the Clinical Relationship Between Diabetic Retinopathy, Nephropathy, and Neuropathy: A Comprehensive Review

“…Target tissues, such as the retina, kidney, and peripheral nerves, exhibit a heightened susceptibility to intracellular hyperglycemia toxicity due to the distribution of glucose transporters. Poorly controlled blood glucose levels exacerbate this vulnerability, increasing the risk of microangiopathy and subsequent complications [ 61 ].…”

“…Target tissues, such as the retina, kidney, and peripheral nerves, exhibit a heightened susceptibility to intracellular hyperglycemia toxicity due to the distribution of glucose transporters. Poorly controlled blood glucose levels exacerbate this vulnerability, increasing the risk of microangiopathy and subsequent complications [61]. DR, a prevalent microvascular complication in diabetes, stems from vision-threatening damage to the retina induced by hyperglycemia-mediated effects on the retinal microvasculature.…”

The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients

“…Under normal circumstances, the space between astrocyte end feet and blood vessels is extremely narrow (basement membrane width, approximately 20 nm), a critical factor enabling the rapid alteration of potassium concentration around the vascular wall ( Longden and Nelson, 2015 ). However, in diabetic mice, the end feet of astrocytes are separated from the blood vessel wall, which may impact the aforementioned process and is considered an expression of reactive astrocytes ( Mauricio et al, 2023 ).…”

Extrapulmonary Comorbidities Associated with Chronic Obstructive Pulmonary Disease: A Review

“… 42 Additionally, the damage to the endothelial cells in the pulmonary blood vessels can lead to connective tissue proliferation and subsequently reduce pulmonary compliance. 43 In addition, the advanced glycation end products (AGEs) associated with hyper glycaemia can trigger inflammation and attenuate alveolar retraction, thus exacerbating the patient’s ventilatory deficits. 44 At the same time, diabetic autonomic neuropathy can also dysregulate airway diastolic function.…”