新技术可改善糖尿病控制

《内科学文献》7月10日在线发表的一项系统综述显示，与常规血糖监测和胰岛素给药方法相比，实时动态血糖监测仪和胰岛素泵可更有效地优化一些1型糖尿病患者的血糖控制。此外，这些昂贵的新技术还可改善治疗满意度和生活质量。

约翰•霍普金斯大学的Hsin-Chieh Yeh博士及其同事对入选1型或2型糖尿病儿童、青少年或成人患者的试验进行了评价。排除连续皮下胰岛素输注(CSII)组使用胰岛素的试验，因为这不是临床首选治疗方法。纳入每日多次注射(MDI，每日至少注射3次)胰岛素组使用长效及速效类似物和(或)中性鱼精蛋白锌胰岛素及常规胰岛素的试验，因为这两种方法均为临床现行方法。纳入评价了过程指标、中期预后、生活质量或重度低血糖的试验及设有评价微血管或大血管预后或死亡率的同期对照组的随机对照试验和观察性试验。由2名研究者独立对试验纳入标准进行评价。最终纳入33项随机对照试验，其中19项对CSII与MDI进行比较，10项对实时动态血糖监测(rt-CGM)与自我监测血糖(SMBG，每日手指采血至少3次)进行比较，4项对传感器增强型胰岛素泵与MDI和SMBG进行比较。

分析结果显示，与MDI相比，CSII有助于改善1型糖尿病成人患者的血糖控制，并且这两种方法预防低血糖的效果一样好。结果还显示，rt-CGM(与SMBG相比)和传感器增强型胰岛素泵(与MDI/SMBG相比)均可改善血糖控制，并且不增加低血糖风险。

在1型糖尿病儿童和青少年患者中，随访≥16周后CSII组HbA1c相对基线的改变与MDI组无差异。同样，在2型糖尿病成人患者中，这两个给药组的血糖控制情况和重度低血糖发生率也相似。在1型糖尿病成人患者中，CSII控制血糖的效果较好，但研究者认为该结果受到以下因素的影响，即在一项研究中受试者入组时的HbA1c较高，导致观察到的HbA1c降幅大于受试者入组时HbA1c接近目标值的其他研究中观察到的降幅。

比较rt-CGM和SMBG的疗效发现，rt-CGM组HbA1c降幅达到统计学意义，但无临床意义。在传感器依从性≥60%的研究中，这一效应稍大。此外，在年龄≤18岁的患者中，rt-CGM组的HbA1c水平低于MDI组，这在一定程度上支持了近期对8岁以上儿童应用rt-CGM的建议。

在1型糖尿病患者中，与MDI/SMBG组相比，传感器增强型胰岛素泵组HbA1c降幅更大，且具有统计学和临床意义，但没有充分证据支持得出有关重度低血糖或生活质量的明确结论。

该系统评价存在一些局限性：各对比较的试验数量较少，并且作者可能遗漏了未发表的试验。此外，评价结果不能外推至所有糖尿病患者，因为CSII和rt-CGM治疗通常仅限于大型医疗机构和积极性高的患者。该系统综述也未探讨可获得性、费用和医保范围等可能妨碍新技术应用的因素。

尽管MDI和以速效类似物为基础的CSII强化胰岛素治疗在降低1型糖尿病患者HbA1c水平方面的有效性相似，并且低血糖发生率也相似，但rt-CGM降低1型糖尿病患者HbA1c 水平的作用优于SMBG，且不增加重度低血糖风险，在依从使用rt-CGM监测仪的患者中尤其如此，这一结果提示，在SMBG和强化胰岛素治疗基础上增加这种监测方法有助于该患者人群血糖达标。

作者声明无相关经济利益冲突。该系统综述获卫生保健研究与质量管理局(AHRQ)支持。

爱思唯尔  版权所有

By: DIANA MAHONEY, Clinical Endocrinology News Digital Network

Real-time continuous glucose monitoring devices and insulin pumps more effectively optimize blood sugar control in some individuals with type 1 diabetes who use the devices as prescribed compared with conventional blood sugar monitoring and insulin delivery methods, a study has shown.

The newer, more expensive technologies are also associated with improvements in treatment satisfaction and quality-of-life measures, although they may be limited to highly motivated patients in expert settings, Hsin-Chieh Yeh, Ph.D., of Johns Hopkins University in Baltimore and her colleagues reported online July 10 in Annals of Internal Medicine (2012 July 10).

To determine whether the mode of intensive insulin therapy has a differential effect on outcomes in individuals with type 1 or type 2 diabetes, and whether outcomes differ by monitoring strategy, the investigators conducted a systematic review to evaluate the effectiveness of blood sugar sensors that constantly monitor glucose levels and pumps that deliver insulin around the clock as needed relative to glucose self-monitoring via frequent finger sticks and multiple daily injections (MDI) of insulin.

Toward this end, they reviewed a total of 33 randomized controlled trials in children and adults, including 19 that compared continuous subcutaneous insulin infusion (CSII) with MDI, 10 that compared real-time continuous glucose monitoring (rt-CGM) with self-monitoring of blood glucose (SMBG), and 4 that compared a sensor-augmented insulin pump with MDI and SMBG. Their analysis showed that CSII had a favorable effect relative to MDI on glycemic control in adults with type I diabetes, and that both methods worked equally well in preventing hypoglycemia.

Their results also suggest that rt-CGM and sensor-augmented pumps improve glycemic control relative to SMBG and MDI/SMBG, respectively, without increasing individuals’ risk of hypoglycemia.

For the analysis, the investigators included studies of adults, adolescents, or children with type 1 or type 2 diabetes that compared CSII with MDI consisting of at least three injections per day; rt-CGM with SMBG consisting of at least three finger sticks per day; and sensor-augmented pumps with MDI/SMBG. "We excluded studies where insulin was used in the CSII arm, because this is not the preferred clinical practice," the authors wrote, noting that they included studies using long- and rapid-acting analogues and/or neutral protamine Hagedorn and regular insulin in the MDI arms, because both regimens are used in current practice.

Those studies that evaluated process measures, intermediate outcomes, quality of life, or severe hypoglycemia were included in the analysis, as were randomized controlled trials and observational studies with a concurrent comparison group that evaluated microvascular or macrovascular outcomes or mortality. Study eligibility was reviewed independently by two investigators, the authors wrote.

With respect to the comparative effectiveness of CSII versus MDI in children and adolescents with type 1 diabetes, "our meta-analysis showed no difference between groups in the HbA1c change from baseline after 16 or more weeks of follow-up," the authors reported. Similarly, the delivery methods appeared to have similar effects on glycemic control and the incidence of severe hypoglycemia in adults with type 2 diabetes. In contrast, CSII showed favorable effect on glycemic control in adults with type 1 diabetes, although the authors acknowledged that this result was influenced by a single study in which participants had higher hemoglobin A1c values at enrollment, "allowing for greater HbA1c lowering compared with other studies where participants were closer to the HbA1c target at enrollment."

Evaluation of the comparative effectiveness of rt-CGM and SMBG showed that the former was associated with the achievement of a lower HbA1c that reached statistical significance but was not clinically meaningful. The effect was slightly greater in studies where sensor compliance was at least 60% or greater, the authors wrote. "We also found that rt-CGM was associated with a lower HbA1c level compared with MDI in individuals 18 years of age or younger," a finding that provides modest support for a recent recommendation in favor of rt-CGM use in children older than 8 years, they stated.

Finally, sensor-augmented pump use was associated with a statistically and clinically significant greater reduction in HbA1c compared with MDI/SMBG use in individuals with type 1 diabetes, but there was not enough evidence to draw definitive conclusions about severe hypoglycemia or quality of life, they authors wrote.

The findings of the systematic review are limited by a number of considerations. The number of studies for each of the comparisons was small, and the authors may have missed unpublished studies, according to the authors. Further, the data are not generalizable to all diabetes patients, "as the management of CSII and rt-CGM are often limited to expert settings and highly motivated patients," and the study did not address the availability, costs, and insurance coverage of the various new technologies, which could be obstacles to their use, they acknowledged.

Although intensive insulin therapy delivered by MDI and rapid-acting analogue–based CSII were similarly effective in lowering HbA1c levels with similar rates of hypoglycemia in patients with type 1 diabetes, the finding that rt-CGM was superior to SMBG in lowering HbA1c levels without increasing the risk of severe hypoglycemia in type 1 diabetes patients – particularly those who are compliant with using the device – suggests "the addition of this monitoring method to SMBG and intensive insulin therapy can assist in achieving glycemic targets" in this patient population, the authors wrote.

The authors disclosed no relevant conflicts of interest. The research was supported by the Agency for Healthcare Research and Quality (AHRQ).