糖尿病并发症发生率因患者年龄和病程而异

据12月9日在线发表于《美国医学会杂志•内科学》上的一篇有关“糖尿病与老化研究”的报道，在60岁至80多岁的成人中，患者年龄和2型糖尿病的病程均独立决定着该病的临床经过。

该研究的研究者、芝加哥大学的Elbert S. Huang医生及合作者称，糖尿病心血管并发症是所有年龄段患者最常见的也是最严重的并发症，而通过关注血糖控制预防这些并发症一直是糖尿病管理的基础。但这项大型队列研究显示，在年龄较大的患者中以及那些病程较长的患者中，低血糖发生率接近冠状动脉疾病。这意味着对于相当多的年龄较大的糖尿病患者而言，把重点放在血糖控制上是不合理的。低血糖是治疗引起的不良反应，从这个意义上说，它的出现让人们对医源性疾病的接受限度产生了严重的顾虑。

鉴于目前对2型糖尿病临床经过的了解大多数是基于20世纪90年代的研究，而糖尿病治疗从那时起又有所发展，因此Huang医生及其同事在较年长的成人中研究了该病的临床经过。他们分析了凯撒医疗集团（Kaiser Permanente）北卡罗来纳州糖尿病注册研究的数据，共涉及72,310例在2004年研究基线时年龄≥60岁的糖尿病患者。患者的平均年龄为71岁，约75%的受试者年龄≥80岁。该队列为多种族性，并且接受医疗保健的机会相等，大多数患者在合理的接受他汀类药物和血管紧张素转化酶（ACE）抑制剂治疗。研究者对这些受试者进行了7年的随访（平均随访时间，5.4年），随访的监测内容包括因急性高血糖事件而住院；因急性低血糖事件而到急诊科就诊或住院；严重眼病、终末期肾病、外周血管病变以及截肢等微血管并发症；心肌梗死、冠状动脉旁路移植术、血管成形术、缺血性或出血性卒中、颈动脉内膜切除术以及充血性心力衰竭等非致死性心血管并发症；以及任何类型的致死性并发症。

结果显示，患者年龄和2型糖尿病病程显著并独立影响着哪些并发症有可能出现。最值得关注的是，低血糖风险会随着年龄和糖尿病病程的增加而显著上升，因此会赶超冠状动脉和脑血管事件，即该人群中最常见的严重并发症。”低血糖在较年轻的患者中相当多见，是60多岁患者第四大常见的并发症，是70多岁患者中第三大常见的并发症。低血糖事件发生率的范围是从年龄最小、病程最短的患者中的3.0/1,000（人•年）到年龄最大、病程最长的患者中的19.6/1,000（人•年），冠状动脉疾病事件相应的发生率范围内是8.5~24.1/1,000（人•年）。这表明，强化血糖控制可能不是一项有意义的治疗目标，甚至对后一组患者有害。另外，在糖尿病病程长（超过10年）的年龄最大的患者中，急性高血糖事件的发生率仅为2.35/1,000（人•年），这也提示对于这类患者通过强化血糖控制预防高血糖事件可能并无助益(JAMA Intern. Med. 2013 Dec. 9 [doi: 10.1001/jamainternmed.2013.12956])。

本研究的观察结果为重新定位老年糖尿病患者的护理重点，而非继续以强化血糖控制作为管理的核心工作提供了进一步的支持。不同的患者分层均有着不同的临床经过，这支持在老年患者中制定个体化的血糖目标的建议。

糖尿病与老化研究由美国国家糖尿病、消化病及肾病研究所和芝加哥大学资助。作者们无经济利益冲突的报告。

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By: MARY ANN MOON, Cardiology News Digital Network

Both patient age and the duration of type 2 diabetes independently determine the clinical course of the disease among adults aged 60 to 80-plus years, according to a report published online Dec. 9 in JAMA Internal Medicine.

The cardiovascular complications of diabetes are considered the most common as well as the most serious complications in patients of all ages, and preventing them by concentrating on glycemic control has been the mainstay of diabetes management. But this large cohort study showed that among older patients and those with longer disease duration, hypoglycemia rates approached those of coronary artery disease, said Dr. Elbert S. Huang of the University of Chicago and his associates in the Diabetes and Aging Study.

This means that the core focus on glycemic control is inappropriate for a substantial number of older diabetes patients. "To the extent that hypoglycemia is an adverse effect of treatment, its emergence as a dominant ‘complication’ raises serious concerns about the acceptable limits of iatrogenesis," they noted.

Dr. Huang and his colleagues examined the clinical course of type 2 diabetes in older adults because "most of our current understanding" is based on studies from the 1990s," and diabetes care has evolved since that time.

They analyzed data from the Kaiser Permanente Northern California Diabetes Registry concerning 72,310 diabetes patients aged 60 years and older at baseline in 2004. These study participants were followed for up to 7 years (mean follow-up, 5.4 years) for acute hyperglycemic events requiring hospitalization; acute hypoglycemic events requiring emergency department visits or hospitalization; microvascular complications such as severe eye disease, incident end-stage renal disease, peripheral vascular disease, and amputation; nonfatal cardiovascular complications such as myocardial infarction, coronary artery bypass graft surgery, angioplasty, ischemic or hemorrhagic stroke, carotid endarterectomy, and congestive heart failure; and fatal complications of any kind.

The mean patient age was 71 years, and about 15% of the study population was aged 80 years and older. The cohort was ethnically diverse and had equal access to health care, and most patients were receiving statins and angiotensin-converting enzyme (ACE) inhibitors appropriately.

Both patient age and duration of type 2 diabetes had a significant, independent effect on which complications were likely to arise. "Most notably, the risk of hypoglycemia rose markedly" with increasing age and duration of disease, so that it outpaced both coronary and cerebrovascular events as the most common serious complication in this subset of the population, the investigators reported (JAMA Intern. Med. 2013 Dec. 9 [doi: 10.1001/jamainternmed.2013.12956]).

Hypoglycemia was even fairly frequent among younger patients: It was the fourth most common complication among patients in their 60s and the third most common among patients in their 70s.

The rate of hypoglycemic events ranged from a low of 3.0 per 1,000 person-years among the youngest patients with the shortest duration of disease to a high of 19.6 per 1,000 person-years among the oldest patients with the longest duration of disease. (The corresponding rates of coronary artery disease events were 8.5 and 24.1 per 1,000 person-years.) This suggests that intensive glycemic control may not be a helpful treatment goal and may even be harmful to the latter group.

In addition, among the oldest patients who had a long duration of diabetes (more than 10 years), the rate of acute hyperglycemic events was only 2.35 per 1,000 person-years. This also suggests that intensive glycemic control to guard against hyperglycemic events may not be helpful in such patients.

"Our observations ... provide additional support for the reorientation of care of older patients with diabetes away from intensive glycemic control as the core focus of management. The distinctive clinical course of different patient strata supports recommendations to individualize glycemic targets among older people," Dr. Huang and his associates said.

The Diabetes and Aging Study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of Chicago. No financial conflicts of interest were reported.