所有糖尿病患者均可能发生低血糖

《Diabetes Care》7月30日在线发表的一项研究称，美国北加州糖尿病研究(DISTANCE)调查表明，接受治疗的2型糖尿病患者无论血糖控制水平高低，低血糖事件都常常发生。

美国耶鲁大学的Kasia J. Lipska博士及其同事报告称，共有9,094例年龄介于30~77岁的2型糖尿病成年患者参与了这项调查，受试者均为Kaiser Permanente北加州糖尿病登记库成员。研究者于2005~2006年调查了这些接受降糖治疗的患者的重度低血糖发作情况，比如导致患者晕厥和/或需要医疗救助的低血糖发作。

结果显示，11%的患者称其在过去1年内曾发生重度低血糖事件，其中又有将近1/4(24%)自称在同期内发生过3次以上的重度低血糖事件(Diabetes Care 2013 July 30 [doi: 10.2337/dc13-0610])。

研究者指出，以下患者报告低血糖发作的几率更高：女性；因慢性病使用4种以上药物治疗者；观察期前使用了胰岛素或胰岛素促泌剂的患者；病程较长、既往有低血糖发作史以及存在多种合并症的患者。但在针对各种潜在效应修饰因素分析低血糖事件的发生率之后，研究者并没有发现任何显著的相互作用。

未经校正的分析显示，HbA_1c水平最高者和最低者发生低血糖事件的几率最高。研究者解释道，与HbA_1c水平“较好”(7.0%~7.9%)的患者相比，HbA_1c水平“接近正常”(＜6%)的患者发生低血糖的相对风险为1.25，HbA_1c水平“非常好”(6.0%~6.9%)的患者的相对风险为1.01，HbA1c水平“不理想”(8.0%~8.9%)的患者的相对风险为0.99，HbA_1c水平“非常差”(≥9%)的患者的相对风险为1.16。

但研究者指出，只有在HbA_1c水平≥9%的患者中，升高的相对风险才有统计学意义。研究者还补充道，虽然针对人口统计学参数进行校正后并没有“改变总体相关性”，虽然血糖控制水平最高者和最低者的低血糖风险点估值仍然较高，但在全面校正模型中，每个HbA_1c分组与参照组之间的风险差异都没有达到统计学显著性水平。

研究者称，传统观念认为只有HbA_1c水平最低的患者才会发生低血糖，但上述研究结果对此提出了挑战。过去关于血糖控制水平与低血糖事件之间相关性的研究得出的结果并不一致，而这项研究的结果表明“无论HbA1c水平高低，均有可能发生低血糖，只是血糖控制水平接近正常或非常差的患者的低血糖风险更高。”

研究者说，这一结果很重要，因为多项研究表明遭遇了重度低血糖事件的患者发生各种不良健康结局的风险也会增加，包括痴呆、跌倒、跌倒相关骨折、心血管事件、健康相关生活质量差，而且死亡率也会增加。研究者指出，除了要尽量控制过度治疗的不良影响并改善患者结局之外，还需要考虑各种降糖治疗用于HbA_1c水平偏高患者的安全性。“糖尿病控制不佳可能导致糖尿病并发症风险增加和治疗相关低血糖风险增加。因此，必须权衡好改善血糖水平的治疗需求与降糖治疗的安全性之间的关系。”

研究者总结道，虽然这项研究存在一些局限性，比如低血糖事件是患者自我报告的，并没有经过实验室验证；受试者的年龄跨度较大，因而对于老年糖尿病患者的适用性有限等等，但在这种常规治疗环境下获得的结果显然凸显了改善降糖治疗安全性的重要意义。这对于已经达到强化血糖控制的患者以及病情控制不良的患者都很重要。研究者指出：“未来还需开展进一步的分析以确定可降低低血糖风险的管理策略和治疗因素。”

这项DISTANCE调查由多项经费支持，包括美国国立衰老研究所和国立心肺血液研究所给作者个人或其所在单位提供的研究经费。

爱思唯尔版权所有  未经授权请勿转载

By: SHARON WORCESTER, Clinical Endocrinology News Digital Network

Hypoglycemia is common among patients being treated for type 2 diabetes, regardless of their level of glycemic control, according to findings from the Diabetes Study of Northern California (DISTANCE) survey.

The findings challenge the conventional wisdom that hypoglycemia occurs only among those with the lowest hemoglobin A1c levels, reported Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and colleagues. The study was published online July 30 in Diabetes Care.

Among 9,094 adults with diabetes who participated in the survey, 11% reported experiencing severe hypoglycemia in the past year, with nearly 1 in 4 (24%) reporting more than three events during that time period. In an unadjusted analysis, those with HbA1c at the highest and lowest levels were most likely to experience hypoglycemia, the investigators said (Diabetes Care 2013 July 30 [doi: 10.2337/dc13-0610]).

Compared with those with "good" HbA1c levels of 7.0%~7.9%; the relative risk of hypoglycemia was 1.25 in those with "near normal" levels of less than 6%, 1.01 in those with "very good" levels of 6.0%-6.9%, 0.99 in those with "suboptimal" levels of 8.0%-8.9%, and 1.16 among those with "very poor" levels of 9% or greater, they explained.

However, the elevated relative risk was statistically significant only for those with HbA1c of 9% or greater, they noted, adding that while adjustment for demographic variables did not "alter the shape of the relationship," and while the point estimates for hypoglycemia risk remained higher at the two extremes of glycemic control, the differences in risk between each HbA1c category and the reference group did not differ significantly in the fully adjusted model.

Study participants were patients with type 2 diabetes aged 30-77 years, who were members of the Kaiser Permanente Northern California Diabetes Registry. The patients, who were using glucose-lowering therapy, were surveyed during 2005-2006 about episodes of severe hypoglycemia, such as episodes during which they passed out and/or required medical assistance.

Patients most likely to report hypoglycemic episodes were women; those taking more than four medications for chronic conditions; those using either insulin or a secretagogue during the preobservation period; and those with longer duration of disease, prior history of hypoglycemia, and multiple comorbidities, the investigators noted.

After examining the prevalence of hypoglycemia across potential effect modifiers, however, they found no significant interactions.

Prior studies have resulted in inconsistent findings about the relationship between glucose control and hypoglycemic events, but findings from the current study suggest that "hypoglycemia occurs across all levels of HbA1c, with higher risk associated with near-normal or very poor glycemic control," the investigators said.

The findings are important, they said, because several studies have shown that patients who experience severe hypoglycemia are at increased risk for a number of unfavorable health outcomes, including dementia, falls, fall-related fractures, cardiovascular events, poor health–related quality of life, and increased mortality. The researchers noted that in addition to efforts to limit adverse effects of overtreatment and to improve patient outcomes, efforts to consider the safety of the various glucose-lowering therapies in patients with higher HbA1c levels are needed.

"Poorly controlled diabetes appears to be associated with both higher risk of diabetic complications and higher risk of treatment-related hypoglycemia. Therefore, quality improvement efforts must balance the need to improve glucose levels with safety of antihyperglycemic therapy in this group," they said.

Though limited by a number of factors, including self-reporting of hypoglycemia without laboratory confirmation and a wide age range of participants, which limits applicability to elderly patients with diabetes, the findings in this usual-care setting nonetheless underscore the importance of directing efforts to improve the safety of glucose-lowering therapies. Such efforts must be directed not only to patients achieving intensive glucose control, but also to those with poorly controlled disease, the investigators concluded, noting that "future analyses are needed to identify management strategies and treatment factors that may mitigate hypoglycemia risk."

The DISTANCE survey was funded by numerous grants, including grants to individual authors or their employers from the National Institute on Aging and the National Heart, Lung, and Blood Institute.