每当糖化血红蛋白上升1%,心血管疾病风险就会上升约17%~18%。[20]Goff DC, Gerstein HC, Ginsberg HN, et al. Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007;99:4i-20i.http://www.ncbi.nlm.nih.gov/pubmed/17599424?tool=bestpractice.com[21]Selvin E, Marinopoulos S, Berkenblit G, et al. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med. 2004;141:421-431.http://www.ncbi.nlm.nih.gov/pubmed/15381515?tool=bestpractice.com[22]Andersson C, van, Gaal L, Caterson ID, et al. Relationship between HbA1c levels and risk of cardiovascular adverse outcomes and all-cause mortality in overweight and obese cardiovascular high-risk women and men with type 2 diabetes. Diabetologia. 2012;55:2348-2355.http://www.ncbi.nlm.nih.gov/pubmed/22638548?tool=bestpractice.com
有越来越多的证据表明,强化血糖控制可降低1型糖尿病患者心血管疾病的风险,还可降低2型糖尿病患者微血管疾病(视网膜病、肾病或神经病)的风险。
对于1型糖尿病,糖尿病控制和并发症试验(DCCT)和糖尿病干预和并发症流行病学(EDIC)研究发现,相比于接受常规治疗(平均糖化血红蛋白76mM/mol[9.1%])的1型糖尿病患者,接受强化治疗(平均糖化血红蛋白54mM/mol[7.2%]))的1型糖尿病患者的心血管疾病会减少50%。[23]Nathan DM, Cleary PA, Backlund JY, et al; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353:2643-2653.http://www.nejm.org/doi/full/10.1056/NEJMoa052187#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/16371630?tool=bestpractice.com
在 2 型糖尿病中,没有证明血糖控制能够降低大血管并发症的风险,而只能减少微血管终点(例如视网膜光凝术)。
在一些试验中,特定的降糖药物 [二甲双胍、利拉鲁肽和依帕列净 (empagliflozin)] 可降低心血管风险。[24]UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-853.http://www.ncbi.nlm.nih.gov/pubmed/9742976?tool=bestpractice.com[25]Holman R, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577-1589.http://www.nejm.org/doi/full/10.1056/NEJMoa0806470#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/18784090?tool=bestpractice.com[26]Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128.http://www.nejm.org/doi/full/10.1056/NEJMoa1504720#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/26378978?tool=bestpractice.com[27]Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322.http://www.nejm.org/doi/full/10.1056/NEJMoa1603827#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/27295427?tool=bestpractice.com
若干大型随机对照试验已发现,对于2型糖尿病和心血管疾病患者来说,非常严格的血糖控制(目标糖化血红蛋白42mM/mol~48mM/mol[6%至6.5%])不会对死亡率产生有益或有害影响,并会增加低血糖风险。[28]Gerstein HC, Miller ME, Byington RP, et al; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559.http://www.nejm.org/doi/full/10.1056/NEJMoa0802743#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/18539917?tool=bestpractice.com[29]Patel A, MacMahon S, Chalmers J, et al; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560-2572.http://www.nejm.org/doi/full/10.1056/NEJMoa0802987#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/18539916?tool=bestpractice.com[30]Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129-139.http://www.nejm.org/doi/full/10.1056/NEJMoa0808431#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/19092145?tool=bestpractice.com[31]Kelly TN, Bazzano LA, Fonseca VA, et al. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med. 2009;151:394-403.http://annals.org/article.aspx?articleid=744809http://www.ncbi.nlm.nih.gov/pubmed/19620144?tool=bestpractice.com[32]Gerstein HC, Miller ME, Genuth S et al; ACCORD Study Group. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364:818-828.http://www.nejm.org/doi/full/10.1056/NEJMoa1006524#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/21366473?tool=bestpractice.com[33]Ismail-Beigi F, Craven T, Banerji MA, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376:419-430.http://www.ncbi.nlm.nih.gov/pubmed/20594588?tool=bestpractice.com[34]Zhang CY, Sun AJ, Zhang SN, et al. Effects of intensive glucose control on incidence of cardiovascular events in patients with type 2 diabetes: a meta-analysis. Ann Med. 2010;42:305-315.http://www.ncbi.nlm.nih.gov/pubmed/20429797?tool=bestpractice.com一项强化血糖控制(HbA1c 中位值为 6.9% 与 8.4%)长期随访研究的确显示,强化血糖控制能够减少每 1000 人-年的主要心血管事件,但没有改善总生存期。[35]Hayward RA, Reaven PD, Wiitala WL, et al; VADT Investigators. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;37:2197-2206.http://www.nejm.org/doi/full/10.1056/NEJMoa1414266#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/26039600?tool=bestpractice.com并且,一项比较强化与标准血糖控制(<6.0% 与 7.0%-7.9%)的 ACCORD 试验随访结果显示,在强化组中,心肌梗死、冠脉血运重建和不稳定性心绞痛的发生率频率低于标准治疗组。[36]Gerstein HC, Miller ME, Ismail-Beigi F, et al; ACCORD Study Group. Effects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial. Lancet. 2014;384:1936-1941.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397008/http://www.ncbi.nlm.nih.gov/pubmed/25088437?tool=bestpractice.com建议将 HbA1c 控制到<53 mmol/mol (<7%),以预防微血管并发症。[1]American Diabetes Association. Standards of medical care in diabetes - 2017. Diabetes Care. 2017;40(suppl 1):S1-S129.http://care.diabetesjournals.org/content/40/Supplement_1