Conclusion
Increasingly we have learned that the microvasculature within different tissues serves multiple functions beyond being a conduit for exchange of respiratory gases, nutrients, and metabolic waste. Consequently, microvascular injury can express common and unique changes at different sites. The dynamic between microvascular injury and repair determines the manifestation of tissuespecific injury. Diabetes affects both injury and repair processes in a manner distinct from other vascular diseases. We have summarized both the general molecular processes involved in diabetic microvascular disease and many of their tissue-specific expressions. Clearly, there is much we still do not understand, and consequently, our ability to successfully intervene to prevent or reverse microvascular disease is quite limited. Insights gained by the use of newer tools, including genetic, proteomic, metabolomics, and other analyses, will certainly add new insights in the basic functioning of microvascular cells, and these insights will light the way to improved therapies.
Acknowledgments
Weacknowledge science writer Eric Vohr for the contribution to this scientific statement.
Financial Support
S.C.'s contributions were in part supported by NIH P30 AG 049638.
Abbreviations
Aβ, amyloid β; ACCORD, Action to Control Cardiovascular Risk in Diabetes; ACE, angiotensin-converting enzyme; ACEi, angiotensin-converting enzyme inhibitor; AD, Alzheimer's disease; ADP, adenosine 5′-diphosphate; ADVANCE, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; AGE, advanced glycation end product; ALA, α-lipoic acid; Ang II, angiotensin II; APC, activated protein C; AR, aldose reductase; ARB, angiotensin II receptor blocker; ATPase, adenosine trisphosphatase; BBB, blood-brain barrier; BK, bradykinin; BK1R, BK1 receptor; BK2R, BK2 receptor; BM, basement membrane; BP, blood pressure; C1-INH, C1-inhibitor; CBF, cerebral blood flow; CI, confidence interval; CKD, chronic kidney disease; CMB, cerebral microbleed; CMI, cerebral microinfarct; CNS, central nervous system; CVD, cardiovascular disease; DAG, diacylglycerol; DCCT, Diabetes Control and Complications Trial; DKD, diabetic kidney disease; DN, diabetic nephropathy; DPN, diabetic peripheral neuropathy; DR, diabetic retinopathy; DSPN, distal symmetric polyneuropathy; DTI, diffusion tensor imaging; ECM, extracellular matrix; EDIC, Epidemiology of Diabetes Interventions and Complications;\eGFR, estimated glomerular filtration rate; eNOS, endothelial nitric oxide synthase; EPC, endothelial progenitor cell; EPVS, enlarged perivascular space; ER, endoplasmic reticulum; ESKD, end-stage kidney disease; ET-1, endothelin 1; FA, fatty acid; FDG, fludeoxyglucose F18 ligand; FLT-1, fms-like tyrosine kinase 1; GFR, glomerular filtration rate; GLP-1, glucagon-like peptide 1; GSH, glutathione; GWAS, genome-wide association studies; HbA1c, hemoglobin A1c; IAPP, islet amyloid polypeptide; iNOS, inducible NOS; IRS 1/2, insulin receptor substrate 1/2; KD, kidney disease; Keap, Kelch erythroid cell-derived protein with CNC homolog-associated protein; KKS, kallikrein-kinin system; LDL, lowdensity lipoprotein; MAPK, mitogen-activated protein kinase; MRI, magnetic resonance imaging; mRNA, messenger RNA; MTI, magnetization transfer imaging; NAD, nicotinamide adenine dinucleotide; NADPH, nicotinamide adenine dinucleotide phosphate; NCV, nerve conduction velocity; NF-κB, nuclear factor κ light chain enhancer of activated B cells; NO, nitric oxide; NOS, nitric oxide synthase; Nrf2, NF-E2–related factor 2; OR, odds ratio; PDGF, platelet-derived growth factor; PET, positron emission tomography; PI3K, phosphatidylinositol 3-kinase; PKC, protein kinase C; QOL, quality of life; RAAS renin-angiotensin aldosterone system; RAGE, receptor for AGE; RAS, reninangiotensin system; RBF, retinal blood flow; RBX, ruboxistaurin; RCT, randomized controlled trial; ROS, reactive oxygen species; RVP, retinal vascular permeability; SHP-1, Src homology-2 domain-containing phosphatase-1; SNP, single-nucleotide polymorphism; STZ, streptozotocin; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; TGFβ, transforming growth factor β; UKPDS, United Kingdom Prospective Diabetes Study; VEGF, vascular endothelial growth factor; WESDR, Wisconsin Epidemiologic Study of Diabetic Retinopathy; WMH, white matter hyperintensity.
J Clin Endocrinol Metab. 2017;102(12):4343-4410. © 2017 Endocrine Society
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