Diagnosis, Pathophysiology and Management of Microvascular Dysfunction in Diabetes Mellitus

Abstract

Microcirculation is an essential system that regulates oxygen and nutrients to cells and tissues in response to various environmental stimuli and pathophysiological conditions. Diabetes mellitus can cause microvascular complications including nephropathy, neuropathy, and retinopathy. The pathogenesis of microvascular dysfunction in diabetes is associated with hyperglycemia and the result of an interplay of various factors. Research studies have demonstrated that functional microvascular dysfunction appears much earlier than structural alterations in vasculature in diabetes. This finding of the progression from microvascular dysfunction to macrovascular disease establishes a foundation for the screening and early diagnosis of diabetes by assessing the microvascular function. This comprehensive review discusses technologies (laser Doppler, transcutaneous oximetry, infrared thermography and near-infrared spectroscopy) with computational methods (linear (time and frequency domains), nonlinear and machine learning approaches) for diagnosing microvascular dysfunction in diabetes. Pathophysiological changes of microvascular dysfunction leading to impaired vasomotion and blood flow oscillations in diabetes are reviewed. Recent findings in managing microvascular dysfunction using lifestyle modifications and force-based modulations are evaluated. A consensus endorsed by the American Diabetes Association has been reached that an effective exercise program would greatly slow down the progression of microvascular dysfunction and its impact on diabetic foot ulcers, muscle fatigue and weakness and peripheral neuropathy. However, it is imperative to determine the dose-response relationship of exercise and microvascular responses in patients with diabetes. Research studies have demonstrated that local vibration and whole-body vibration can improve microcirculation in various pathological conditions, including diabetes. Due to the complex nature of microvascular regulation, various computational methods have been developed to shed light on the influence of diabetes on microvascular dysfunction. This comprehensive review will contribute to the diagnosis and management of microvascular dysfunction in diabetes.

Keywords: diabetic foot ulcers; diabetic peripheral neuropathy; endothelial; exercise; laser Doppler; near-infrared spectroscopy; oximetry; vasomotion.