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Introduction
Diabetic microvascular complications (DMC) develop in all types of diabetes. This review focuses on DMC in patients with type 2 diabetes. Diabetic retinopathy can lead to impaired vision, increased risk of falls, and, ultimately, blindness. Diabetic nephropathy can lead to severe chronic kidney disease (CKD), need for renal replacement therapy, and possibly death. Diabetic autonomic neuropathy and diabetic peripheral neuropathy (DPN) can lead to orthostatic hypotension, dysautonomy, foot ulcers, and limb amputations. 1 All three DMC impair function and quality of life, lead to disability, and decrease employment chances and productivity. 1 2
National and international guidelines stress timely and intensive interventions early in the disease, individualizing targets, agents, and approach. Detecting and treating complications of diabetes are major components for these interventions. 3 4 5 Strong evidence supports the need to achieve and maintain proper glycemic control to prevent the incidence (primary prevention) or progression (secondary prevention) of microvascular complications.
This review excludes the well established role of glycemic control for DMC prevention and focuses on all other potentially successful interventions. Notably, cellular damage created by hyperglycemia and other factors may be shared in the three types of DMC. These include biochemical and molecular pathways, such as increased polyol pathway flux, increased advanced glycation end products formation, activation of protein kinase C isoforms, and increased hexosamine pathway flux. 6
This review focuses on evidence published in the past decade on interventions for the primary and secondary prevention of DMC in type 2 diabetes (box 1). It also discusses upcoming trials, gaps in knowledge, and emerging strategies, providing a practical framework to guide specialists and academic clinicians who treat patients with DMC.
Box 1: Primary and secondary prevention of microvascular complications in patients with type 2 diabetes
Primary prevention: to prevent or delay onset of complications
Prevention and management of known modifiable risk factors: improving lifestyle behaviors and pharmacologic interventions for hypertension, dyslipidemia, obesity, and smoking
Screening for disease pre-stages, leading to interventions to prevent onset*
Secondary prevention: to reduce progression and damage from established complications
Screening for early stages of disease, leading to early detection and intensive interventions to slow progression
Continuation of interventions aimed at known risk factors. Specific targets may be proposed (for example, rather than prevention of hypertension or treatment...