近日，美国糖尿病协会（ADA）和欧洲糖尿病研究协会（EASD）联合发布了一份立场声明，其中强调了2型糖尿病患者的个体化降糖治疗。这份新指南于2012年4月19日发表在 Diabetes Care和Diabetologia的在线版中。

ADA医学和科学主席、美国杜兰大学医学院的Vivain Fonseca博士在电话采访中介绍说：“所有指南的更新都是以最新的资料为基础，并于每年一月对整体治疗标准进行更新。”据他介绍。上一份针对高血糖管理的指南是在大约4-5年前发布的，本次的新指南中加入了其后的最新进展情况。

目前，患有2型糖尿病患者的血糖控制日益复杂并越来越具有争议，因此是推动这次新指南发布的主要原因。使血糖控制复杂的原因有很多，比如，药物潜在副作用，强化血糖控制对于大血管病变效果的不确定性。

目前，2型糖尿病的血糖管理日趋复杂，而且存在一定争议，这正是推动制定新指南的主要原因。导致血糖管理复杂化的原因很多，如药物潜在不良反应及强化血糖控制对大血管并发症的影响的不确定性。

Fonseca 解释说，在血糖控制的最佳目标方面做了些微小的调整。基于ACCORD和其他研究结果，ADA认为HbA1c的一般目标应为7%，但在某些情况下这一目标应个体化。“例如，对于患晚期心血管疾病、预期寿命较短以及合并多种疾病的患者，血糖控制目标应该更宽松，”Fonseca说，“对于新诊断且意向积极治疗的患者，血糖控制目标可以相对严格一些。”

促使新指南的制定还有另一个潜在原因：近期人们认识到，很多糖尿病患者将需要应用多种药物进行治疗。例如，在上一版的高血糖指南发布之后，在可选择的药物中增加了二肽基肽酶-4（DPP-4）抑制剂。

以患者为中心的管理模式

新指南更多地强调以患者为中心的管理模式，而弱化了被动接受医生处方的模式。指南建议根据患者的个体情况如年龄、患者需求等制定个体化的治疗方案。其他个体化治疗的考量因素还包括：不同患者的不同病情表现、并发症情况、体重、种族、性别以及生活方式。

“我们推荐首先从二甲双胍起始，如果患者在三个月内未达标，我们会根据患者的个体情况调整治疗方案。”Fonseca博士说到。“目前还没有权威的研究比较各种治疗策略的优劣。所以我们根据患者是否愿意自行注射胰岛素以及患者的减肥意愿等个人因素来选择治疗策略。如果治疗不成功，我们再试用其他治疗方案。由于我们目前的治疗方案更多是以患者为中心，所以与以往的推荐相比，不那么清晰明确。”

这项声明指出，所有的医生或医疗机构都应该负责对糖尿病患者的健康教育。其内容应该包括饮食干预、适当加强体育锻炼以及适度控制体重。

新指南建议如下：

1、必须根据患者具体特点制定个体化的血糖控制目标和降血糖方案；
2、所有2型糖尿病治疗方案的基础仍然是饮食、运动和患者教育；
3、在无禁忌证的情况下，二甲双胍是首选的一线降糖治疗药物；
4、除二甲双胍外的其他降糖药物的应用尚缺乏足够资料，合理的做法是在二甲双胍基础上增加1到2种口服药物或注射药物进行联合治疗，并尽可能减少副反应的发生；
5、为了维持血糖控制，很多患者最终需要接受单纯胰岛素治疗或胰岛素联合口服降糖药治疗；
6、  应使患者尽可能参与到所有的治疗决策中来，制定决策时考虑患者自己的喜好、需求和利益；
7、 全面降低心血管风险是降糖的一个主要目标。

该声明的编写小组组长--耶鲁大学糖尿病中心主任Silvio E. Inzucchi博士指出，对于2型糖尿病患者，除了应重视血糖控制之外，还应重视对其他心血管危险因素的管理，如降压和调脂治疗、抗血小板治疗和戒烟治疗等。
Inzucchi博士指出，以患者为中心的治疗是对患者喜好、需求和价值的尊重和回应，这种方法尤其适用于2型糖尿病患者，因为在2型糖尿病的治疗中，采取何种生活方式最终仍由患者自己决定。另外，让患者参与治疗决策也有助于提高其对治疗的依从性。

新指南的其他建议包括：

血糖控制--糖化血红蛋白A1c的控制目标仍为低于7%，与既往无异。然而，根据个体患者考虑因素可适当调整目标，包括：患者态度和预期治疗力度、低血糖相关风险、其他不良事件、病程、预期寿命、重要合并症、血管并发症、资源和支持系统。

生活方式干预--旨在增加活动量及优化食物摄入的生活方式干预是任何2型糖尿病治疗方案的基础。建议对所有患者提供标准化的一对一或集体式普通糖尿病教育。

药物选择--与既往指南一样，该声明也认为二甲双胍是最佳的一线药物，除非存在禁忌证。另外，加用1~2种口服或注射药物也较为合理，不过需尽可能减少副作用。为了维持血糖控制，许多患者需要接受单纯胰岛素治疗或在胰岛素治疗基础上加用其他药物。

该声明建议考虑在二甲双胍基础上加用其他主要类别的降糖药物(磺脲类、噻唑烷二酮类、DPP-4抑制剂、GLP-1受体拮抗剂和胰岛素)，以及过渡至单独使用胰岛素和各种基于胰岛素的方案。
患者考量--需考虑的患者因素包括年龄、体重、性别/种族/遗传差异、合并症和低血糖。近期研究发现低血糖的危害比既往认为的要大得多，因此对2型糖尿病患者的低血糖应给予更为密切的关注。

该声明最后呼吁进行更高质量的降糖药疗效对比研究，并加强对生活质量议题、避免并发症和血糖控制的重视。另外，还需获取有关药物基因组学的临床数据，以明确表型和患者/疾病特异性特征是如何影响药物选择的。由于对所有药物组合进行头对头比较需要非常大的样本量，不太可行，因此在治疗上有赖于临床医生的经验判断。

原文：

ADA/EASD issue new hyperglycemia management guidelines

Alexandria, VA and Düsseldorf, Germany - The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have issued a joint position statement emphasizing patient-specific treatment of hyperglycemia in those with type 2 diabetes [1]. The new guidelines are reported online April 19, 2012 in Diabetes Care and Diabetologia.

"All guidelines are in a state of evolution based on new information, and the overall standard of care is updated every January," Dr Vivian Fonseca (Tulane University School of Medicine, New Orleans, LA), ADA president of medicine and science, said in a telephone interview.

The last guidelines specific to management of hyperglycemia were published about four to five years ago, and more recent developments have been incorporated into the new guidelines, he said.

The impetus underlying the new guidelines was the growing complexity and controversy surrounding contemporary glycemic management in patients with type 2 diabetes. Factors complicating management include the increasing number and variety of available pharmacotherapy, issues regarding potential adverse effects, and new uncertainties concerning the effects of intensive glycemic control on macrovascular complications.

Fonseca explained that there has been a small change in what the optimal blood glucose goal should be. On the basis of findings from ACCORD and other studies, the ADA has set the HbA1c goal at 7% in general, but with some individualization.

"For patients with advanced cardiovascular disease, reduced life expectancy, and multiple medical problems, for example, the goal may be higher," Fonseca said. "For patients who are newly diagnosed and very motivated, the goal may be lower."

Another recent change underlying the new guidelines is the recognition that many people with diabetes will need multiple agents. For example, the dipeptidyl peptidase-4 (DPP4) inhibitors have become available since the last hyperglycemia guideline was published.

Patient-centered management

Rather than using clearly defined algorithms, the new guidelines are less prescriptive and more patient-centered. Recommendations are tailored to individual patient needs, preferences, and tolerances and are based on differences in age and disease course. Other factors affecting individualized treatment plans include specific symptoms, comorbid conditions, weight, race/ethnicity, sex, and lifestyle.

"We start with metformin, and if the patient is not meeting goal in three months, we change therapy based on patient-specific factors," said Fonseca, who was not involved in writing the new guidelines.

"There have been no good studies comparing all available treatment strategies, so we base the decision on individual factors such as willingness to self-inject or need for weight loss. If that fails, we try another option. There is no clear-cut decision tree as there was in the previous hyperglycemia guideline, because this guideline is more patient-centric."

The position statement mandates diabetes education for all patients, to be administered to individuals or groups. The curriculum should highlight dietary intervention and the key role of increased physical activity and weight management, when appropriate.

Key points

Key recommendations in the new ADA/EASD statement include the following:

Glycemic targets and treatments to lower glucose must be individualized according to specific patient characteristics.

The mainstay of any type 2 diabetes treatment program is still diet, exercise, and education.

Metformin is the preferred first-line drug, in the absence of contraindications.

Data are limited regarding use of agents other than metformin. A reasonable approach is combination therapy with one to two additional oral or injectable agents, with the goal of minimizing side effects to the extent possible.

To maintain glycemic control, many patients will ultimately need insulin monotherapy or in combination with other medications.

Whenever possible, the patient should participate in all treatment decisions, focusing on their preferences, needs, and values.

A major treatment goal must be comprehensive cardiovascular risk reduction.

"The new guideline should actually be easier for physicians to implement because there is greater flexibility in management, offering a road map rather than a single path," Fonseca concluded. "The ADA guidelines in general are already fairly widely implemented, and we are seeing benefits from that. Over the past 10 to 15 years, HbA1c has been dropping, and over the past year, there has started to be a drop in rates of diabetes-related blindness, retinopathy, dialysis, and amputation. But there still remain a large number of patients with these outcomes, so we still have a ways to go."