Ebook Textbook of diabetes: Part 2
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Ebook Textbook of diabetes: Part 2
7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2xpartments o( Medicine and Endocrinology, Albert Einstein College of Medkine, NY, USAKeypoints•Mkrovasaiar complicaticns are caused by prolonged exposure to hyperglycemia.•Hypergyceria damages cell types that carrot downregulate glucose uptake, causing intracellular hyperglycemia.•Intracellular hype Ebook Textbook of diabetes: Part 2rglycemia damages tissues by fire majw mechanisms: Increased flux of glucose and other sugars through the polyol pathway; Increased intracellular tormEbook Textbook of diabetes: Part 2
atdn cf advanced glycation end-products (AGES); Increased expression of the receptor for AGES and its actuating ligands; actuation of protein kinase c7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2these mechanisms.•Persistent consequences of hyperciycemia-induced mitochondrial seperoxide producton may also explan the continuing progression oftissue damage after improrement of glycemic lerels (• hyperglycemic memory").•Different intWduai susceptibility to mKroMScưar complications hare been lin Ebook Textbook of diabetes: Part 2ked to polymorphisms in the superoxide dismutase 1 gene.•Hyperglycemia-induced mitochondrial reactive oxygen species production impairs the necvasojlaEbook Textbook of diabetes: Part 2
r response to ischemia by blunting hypcaia-inducitle factor 1 transaction.•Hypertension accelerates mkrovascular damage by increasing intracellular hy7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2clude transketolase activators, pcl)Ebook Textbook of diabetes: Part 2
brain and lower extremities. As a consequence of its diseasespecific pathology, diabetes mellitus is now the leading cause of new blindness in people7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2s is half that of those without diabetes. More than 60% of patients with diabetes are affected by neuropathy, which includes distal symmetrica) polyneuropathy, mononeuropathies and a variety of autonomic neuropathies causing erectile dysfunction, urinary incontinence, gastroparesis and nocturnal dia Ebook Textbook of diabetes: Part 2rrhoea. Diabetic accelerated lower extremity arterial disease in conjunction with neuropathyTcxrtwk of Diabrtci. 4th edition. Edited by R. Holt. c. CoEbook Textbook of diabetes: Part 2
ckram, A. Flyvbierg and B. GoklMdn. o 2010 Blackwell Publishingaccounts for 50% of all non-traumatic amputations in the USA. Diabetes and impaired glu7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2n (MI) have diabetes and 35% hare impaired glucose tolerance. Finally, new blood vessel growth in response to ischemia is impaired in diabetes, resulting in decreased collateral vessel formation in ischemic hearts, and in non-healing foot ulcers. The focus of this chapter is on the microvascular com Ebook Textbook of diabetes: Part 2plications comprising retinopathy, nephropathy and peripheral neuropathy.Much of the impact of chronic diabetes falls on the microcirculation 11,2|. WEbook Textbook of diabetes: Part 2
ith long-standing disease, there is progressive narrowing and eventual occlusion of vascular lumina, resulting in impaired perfusion, ischemia and dys7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2owing extravasation of plasma proteins that accumulate as periodic acid-Schiff-positive deposits in the vessel walls. In addition, the extracellular matrix elaborated by perivascular cells such as pericytes (retina) and mesangial cells (glomerulus) is increased, brought about by changes in synthesis Ebook Textbook of diabetes: Part 2 and turnover of its component proteins and glycosaminoglycans. As a result, the basement membrane B thickened in many tissues, including retinal capiEbook Textbook of diabetes: Part 2
llaries and the Visa nervorum, while mesangial matrix is55$Part / Microvascular Complications in Diabetesexpanded in the renal glomerulus. Hypertrophy7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2ity of the blood and adhesion of platelets and leukocytes to the endothelial surface lead to microthrombus formation and luminal occlusion.The progressive narrowing and blockage of diabetic microvas-cular lumina are accompanied by loss of microvascular cells. In the retina, diabetes induces apoptosi Ebook Textbook of diabetes: Part 2s of Muller cells and ganglion cells |3|, pericytes and endothelial cells |4|. In the glomerulus, widespread capillary occlusion and declining renal fEbook Textbook of diabetes: Part 2
unction are associated with podocyte loss. In the vasa nervorum of diabetic nenes, endothelial cell and pericyte degeneration occur |5| and appear to 7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2ominent feature of diabetic micro-vascular tissue damage |7-111 and may also cause damage to adjacent cells.Role of hyperglycemia in microvascular complications Overall, diabetic microvascular complications are caused by prolonged exposure to high glucose levels. This has been established by large-s Ebook Textbook of diabetes: Part 2cale prospective studies for both type 1 diabetes (T1 DM) by the Diabetes Control and Complications Triab'Epidemiology of Diabetes Interventions and CEbook Textbook of diabetes: Part 2
omplications Study ỊDCCT/ EDIC] [ I2| and for type 2 diabetes (T2DM) by the UK Prospective Diabetes Study IUKPDS1 113|). Similar data have been report7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2erglycemia selectively damage some cell types and not others? The targeting of specific cell types by generalized hyperglycemia reflects the failure of those cells to downregulate their uptake of glucose when extracellular glucose concentrations are elevated, oils that are not directly susceptible t Ebook Textbook of diabetes: Part 2o direct hyperglycemic damage such as vascular smooth muscle show an inverse relationship between extracellular glucose concentrations and glucose traEbook Textbook of diabetes: Part 2
nsport. In contrast, vascular endothelial cells, a major target of hyperglycemic damage, show no significant change in glucose transport rate when glu7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2ences in expression and function of different glucose transporter (GLUT) proteins 115).Mechanisms of hyperglycemia-induced damageThere are nearly 2000 publications supporting five major mechanisms by which hyperglycemia causes diabetic complications:1Increased flux of glucose and other sugars throug Ebook Textbook of diabetes: Part 2h the polyol pathway;(a)Smooth muscle cells5.522Medium glucose (mmol/L)Figure 35.1 Lack cf dowregulatcn of gkxose BJT6f>oit by hyperglycemia in cellsEbook Textbook of diabetes: Part 2
affected by diatecc compliiaticns. (a) 2-Deoxygbcose uptake n vascular smooth musde cells (xe-eiposed to 5.5 or 22mmdit glucose, (b) 2-Dec»yglx05e upt7 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ix Ebook Textbook of diabetes: Part 2at Differential regulation of glucose transport and transporters by glucose in vascular endothHia’ and smooth musde cells. Dứteces 1993.42:80-89.2Increased intracellular formation of advanced glycation endproducts (AGEs); Ebook Textbook of diabetes: Part 27 Microvascular Complications in Diabetes35Pathogenesis of Microvascular ComplicationsFerdinando Giacco & Michael BrownleeDiabetes Research Center. ixGọi ngay
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