| Summary: | Individuals with prediabetes or type 2 diabetes have an increased risk of diseases that are partly or entirely of microvascular origin (e.g. (lacunar) stroke, depression, cognitive decline, retinopathy, heart failure, chronic kidney disease, and neuropathy). These diseases are expressions of advanced microvascular dysfunction (MVD). Yet, MVD may develop already early and contribute to impaired insulin-mediated glucose uptake and subsequent metabolic insulin resistance, characterized by hyperglycemia. However, apart from hyperglycemia being a consequence of MVD, hyperglycemia can also (further) impair microvascular function, constituting a vicious cycle. In this review we shall discuss important evidence showing that MVD may precede and predict (pre)diabetes and related co-morbidities, and discuss the important determinants of early MVD. In addition, we shall discuss hyperglycemia being both a cause and consequence of MVD. Finally, we shall focus on prevention and treatment strategies for MVD.
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