Effect of normalization of fasting glucose by intensified insulin therapy and influence of eNOS polymorphisms on the incidence of restenosis after peripheral angioplasty in patients with type 2 diabetes: a randomized, open-label clinical trial
详细信息 查看全文
- 作者：Pier Marco Piatti (1)
Enrico Marone (2)
Manuela Mantero (3)
Emanuela Setola (1)
Elena Galluccio (4)
Pietro Lucotti (1)
Ermal Shehaj (1)
Valentina Villa (1)
Francesca Perticone (1)
Massimo Venturini (6)
Alessio Palini (7)
Flavio Airoldi (3)
Ezio Faglia (3)
Alessandro Del Maschio (6)
Antonio Colombo (5)
Roberto Chiesa (2)
Emanuele Bosi (1) (4)
Lucilla D. Monti (4) - 关键词：Intensified insulin therapy ; Type 2 diabetes ; Critical limb ischemia ; eNOS polymorphism ; Endothelial progenitor cells ; Restenosis ; Amputation
- 刊名：Acta Diabetologica
- 出版年：2013
- 出版时间：June 2013
- 年：2013
- 卷：50
- 期：3
- 页码：373-382
- 全文大小：306KB
- 参考文献：1. Ness J, Aronow WS, Ahn C (2000) Risk factors for symptomatic peripheral arterial disease in older persons in an academic hospital-based geriatrics practice. J Am Geriatr Soc 48:312-14
2. Soder HK, Manninen HJ, Jaakkola P et al (2000) Prospective trial of infrapopliteal artery balloon angioplasty for critical limb ischemia: angiographic and clinical results. J Vasc Interv Radiol 11:1021-031 CrossRef
3. Dorros G, Jaff MR, Dorros AM, Mathiak LM, He T (2001) Tibioperoneal (outflow lesion) angioplasty can be used as primary treatment in 235 patients with critical limb ischemia: 5?years follow-up. Circulation 104:2057-062 CrossRef
4. Aronow WS (2005) Management of peripheral arterial disease. Cardiol Rev 13:61-8 CrossRef
5. Boyko EJ (1996) Increased mortality associated with diabetic foot ulcer. Diabetes Med 13:967-72 CrossRef
6. Sarwar N, Gao P, Seshasai SR et al (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative metaanalysis of 102 prospective studies. Lancet 375:2215-222 CrossRef
7. Seshasai SR, Kaptoge S, Thompson A et al (2011) Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 364:829-41 CrossRef
8. Uchmanowicz I, Loboz-Grudzien K, Jankowska-Polanska B, Sokalski L (2011) Influence of diabetes on health-related quality of life results in patients with acute coronary syndrome treated with coronary angioplasty. Acta Diabetol. Mar 27 [Epub ahead of print]. PubMed PMID: 21442428
9. Gui MH, Li X, Lu ZQ, Gao X. (2012) Fasting plasma glucose correlates with angiographic coronary artery disease prevalence and severity in Chinese patients without known diabetes. Acta Diabetol. Jun 10 [Epub ahead of print]. PubMed PMID: 22684266
10. Lazzeri C, Valente S, Chiostri M et al (2011) The prognostic role of in-hospital peak glycemia in stemi patients with and withoutdiabetes. Acta Diabetol. Oct 19 [Epub ahead of print]. PubMed PMID:22008949
11. Lazzeri C, Valente S, Chiostri M, et al (2011) The glucose dysmetabolism in the acute phase of non-diabetic ST-elevation myocardial?infarction: from insulin resistance to hyperglycemia. Acta Diabetol. Oct 9.?[Epub ahead of print] PubMed PMID: 21984048
12. Monti LD, Barlassina C, Citterio L et al (2003) Endothelial nitric oxide synthase polymorphisms are associated with type 2 diabetes and the insulin resistance syndrome. Diabetes 52:1270-275 CrossRef
13. Galluccio E, Piatti PM, Citterio L et al (2008) Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis. Am J Physiol Endocrinol Metab 294:E978–E986 CrossRef
14. Aicher A, Heeschen C, Mildner-Rihm C et al (2003) Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 9:1370-376 CrossRef
15. Yu J, deMuinck ED, Zhuang Z, Drinane M et al (2005) Endothelial nitric oxide synthase is critical for ischemic remodelling, mural cell recruitment, and blood flow reserve. Proc Natl Acad Sci USA 102:10999-1004 CrossRef
16. Murohara T, Asahara T, Silver M et al (1998) Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest 101:2567-578 CrossRef
17. Hamed S, Benjamin B, Abassi Z, Aharon A, Deeb Daoud D, Roguinand A (2010) Hyperglycemia and Oxidized-LDL exert a deleterious effect on endothelial progenitor cell migration in type 2 diabetes mellitus. Thromb Res 126:166-74 CrossRef
18. Avogaro A, Albiero M, Menegazzo L, de Kreutzenberg SV, Fadini GP (2011) Endothelial dysfunction in diabetes. The role of reparatory mechanisms. Diabetes Care 34(Suppl. 2):S285–S290 CrossRef
19. Chen M-C, Sheu J-J, Wang P-W et al (2009) Complications impaired endothelial progenitor cell function in Type 2 diabetic patients with or without critical leg ischemia: implication for impaired neovascularization in diabetes. Diabetes Med 26:134-41 CrossRef
20. Fadini GP, Miorin M, Facco M et al (2005) Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 45:1449-457 CrossRef
21. Grollman J, Levin DC, Bettmann MA, et al (2000) Recurrent symptoms following lower extremity angioplasty: claudication and threatened limb. American College of Radiology. ACR Appropriateness Criteria. Radiology 215(Suppl.):95-9
22. Isner JM, Rosenfield K (1993) Redefining the treatment of peripheral artery disease: role of percutaneous revascularization. Circulation 88:1534-557 CrossRef
23. Corpus RA (2004) Optimal glycemic control is associated with a lower rate of target vessel revascularization in treated type II diabetic patients undergoing elective percutaneous coronary intervention. J Am Coll Cardiol 43:8-4 CrossRef
24. Briguori C, Condorelli G, Airoldi F et al (2005) Impact of microvascular complications on outcome after coronary stent implantations in patients with diabetes. J Am Coll Cardiol 45:464-66 CrossRef
25. Briguori C, Condorelli G, Airoldi F, Mikhail GW, Ricciardelli B, Colombo A (2004) Impact of glycaemic and lipid control on outcome after percutaneous coronary interventions in diabetic patients. Heart 90:1481-482 CrossRef
26. Exner M, Schillinger M, Minar E et al (2004) Interleukin-6 promoter genotype and restenosis after femoropopliteal balloon angioplasty: initial observations. Radiology 231:839-44 CrossRef
27. Mlekusch W, Exner M, Schillinger et al (2004) E-selectin and restenosis after femoropopliteal angioplasty: prognostic impact of the Ser128Arg genotype and plasma levels. Thromb Haemost 91:171-79
28. Mongiardo A, Curcio A, Spaccarotella C, Parise S, Indolfi C (2004) Molecular mechanisms of restenosis after percutaneous peripheral angioplasty and approach to endovascular therapy. Curr Drug Targets Cardiovasc Hematol Disord 4:275-87 CrossRef
29. Abizaid A (2001) Clinical and economic impact of diabetes mellitus on percutaneous and surgical treatment of multivessel coronary disease patients: insights from the arterial revascularization therapy study (ARTS) trial. Circulation 104:533-38 CrossRef
30. Romiti M, Albers M, Brochado-Neto FC, Durazzo AE, Pereira CA (2008) Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia. J Vasc Surg 47:975-81 CrossRef
31. Kosiborod M, Rathore SS, Inzucchi SE et al (2005) Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction. Circulation 111:3078-086 CrossRef
32. ACCORD Study Group (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545-559 CrossRef
33. Gerstein HC, Miller ME, Genuth S et al (2011) ACCORD Study Group. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 364:818-28 CrossRef
34. Song W, Ergul A (2006) Type-2 diabetes induced changes in vascular extracellular matrix gene expression: relation to vessel size. Cardiovasc Diabetol 5:3 CrossRef
35. Harris AK, Hutchinson JR, Sachidanandam K et al (2005) Type 2 diabetes causes remodelling of cerebrovasculature via differential regulation of matrix metalloproteinases and collagen synthesis: role of endothelin-1. Diabetes 54:2638-644 CrossRef
36. Kawasumi M, Tanaka Y, Uchino H et al (2006) Strict glycemic control ameliorates the increase of carotid IMT in patients with type 2 diabetes. Endocrine J 53:45-0 CrossRef
37. Fadini GP, de Kreutzenberg SV, Mariano V et al (2011) Optimized glycaemic control achieved with add-on basal insulin therapy improves indexes of endothelial damage and regeneration in type 2 diabetic patients with macroangiopathy: a randomized crossover trial comparing detemir versus glargine. Diabetes Obes Metab 13:718-25 CrossRef
38. Chen YH, Lin SJ, Lin FY et al (2007) High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes 56:1559-568 CrossRef
39. Krankel N, Adams V, Linke A et al (2005) Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells. Arterioscler Thromb Vasc Biol 25:698-03 CrossRef
40. Quyyumi AA (2004) Circulating endothelial progenitor cells as novel biological determinants of vascular function and risk. Can J Cardiol 20:44B-8B
41. Landmesser U, Engberding N, Bahlmann FH, Schaefer et al (2004) Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation 110:1933-939 CrossRef
42. Tepper OM, Galiano RD, Capla JM et al (2002) Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106:2781-786 CrossRef
43. Ceriello A, Ihnat MA, Thorpe JE (2009) The “metabolic memory- is more than just tight glucose control necessary to prevent diabetic complications? J Clin Endocrinol Metab 94:410-15 CrossRef
44. Boussageon R, Saadatian-Elahi M, Lafont S et al (2011) Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 343:1-2 CrossRef
45. Phung OJ, Scholle JM, Talwar M, Coleman CI (2010) Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA 303:1410-418 CrossRef - 作者单位：Pier Marco Piatti (1)
Enrico Marone (2)
Manuela Mantero (3)
Emanuela Setola (1)
Elena Galluccio (4)
Pietro Lucotti (1)
Ermal Shehaj (1)
Valentina Villa (1)
Francesca Perticone (1)
Massimo Venturini (6)
Alessio Palini (7)
Flavio Airoldi (3)
Ezio Faglia (3)
Alessandro Del Maschio (6)
Antonio Colombo (5)
Roberto Chiesa (2)
Emanuele Bosi (1) (4)
Lucilla D. Monti (4)
1. Cardio-Metabolism and Clinical Trials Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science Division, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
2. Vascular Surgery Division, Cardio-Thoraco-Vascular Department and Cardiovascular Science Division, San Raffaele Scientific Institute, Milan, Italy
3. Cardiovascular Department, Multimedica IRCCS, Milan, Italy
4. Cardio-Diabetes and Core Lab Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science Division, San Raffaele Scientific Institute, Milan, Italy
6. Department of Radiology and Center for Experimental Imaging, San Raffaele Scientific Institute, Milan, Italy
7. Flow Cytometry Resource Laboratory, San Raffaele Scientific Institute, Milan, Italy
5. Interventional Cardiology Division, Cardio-Thoraco-Vascular Department and Metabolic and Cardiovascular Science Division, San Raffaele Scientific Institute, Milan, Italy - ISSN：1432-5233
文摘
Primary objective was to evaluate whether an intensified insulin therapy (IIT) incorporating the target of normal fasting glucose and HbA1c levels could halve the incidence of restenosis/amputation/SCA/death at 6?months after peripheral angioplasty compared with standard care (SC) in patients with type 2 diabetes (DMT2) affected by critical limb ischemia (CLI). Forty-six consecutive patients with DMT2 and CLI were randomly assigned to a parallel, open-label study with IIT (basal-bolus glulisine?+?glargine administrations) or SC (glargine administration?+?oral antidiabetic drugs). A SNP of eNOS (rs753482-A>C) and circulating CD34+ and CD34+KDR+ progenitor cells were determined. At the end of the study, although HbA1c levels were lower in IIT than in SC (6.9?±?1.3?% vs. 7.6?±?1.2?%, p?<?0.05), IIT did not reduce the cumulative incidence of restenosis/amputation/SCA/death (52 and 65?%, respectively, odd ratio 0.59; CI 95?%: 0.21-.62, p?=?0.59). rs753482AC+CC as compared with rs753482AA increased the cumulative incidence of restenosis/amputation/SCA/death (79 and 42?%; odd ratio 5.3; CI 95?%: 1.41-9.5, p?<?0.02). Baseline CD34+KDR+ were higher in rs753482AA (166.2?±?154.0?×?106 events) than in rs753482AC+CC (63.1?±?26.9?×?106 events, p?<?0.01). At the end of the study, the highest circulating CD34+KDR+ were found in IIT rs753482AA (246.9?±?194.0?×?106 events) while the lowest levels were found in SC rs753482AC+CC (70.9?±?45.0?×?106 events). IIT did not decrease the cumulative incidence of restenosis/amputation/SCA/death in DMT2 and CLI patients. These patients correspond to a class of fragile subjects at high risk of cardiovascular events, and new predictors of restenosis should be contemplated, such as of eNOS polymorphism, (rs753482-A>C SNP) and circulating endothelial progenitor cells.