Lancet：早期积极控制血糖是治疗糖尿病前期的关键

具有里程碑意义的“糖尿病预防计划(Diabetes Prevention Program，DPP)”的最新分析显示，及早让糖尿病前期患者恢复正常的血糖水平是预防疾病进展的关键所在，无论是通过生活方式干预还是药物治疗来实现。

美国科罗拉多大学的Leigh Perreault 博士及其同事报告称，事实上在参与DPP的受试者中，即便血糖水平短暂恢复正常也与糖尿病风险显著降低相关。DPP是一项比较减轻体重和调整饮食与药物治疗用于预防2型糖尿病的大规模多中心随机试验。该研究结果已于6月9日在线发表在《柳叶刀》上(Lancet 2012 June 9 [doi:10.106/S0140-6736(12)60525-X])。

在DPP中，基线时所有3,234例受试者均存在发生糖尿病的风险。经随机分组后，这些患者分别接受生活方式干预、二甲双胍或安慰剂治疗，干预期间的中位随访期为3.2年。

这项仍在进行中的名为“糖尿病预防计划结局研究(DPPOS)”的干预后观察性分析的中位随访期为5.7年。分析结果显示，与一直处于糖尿病前期的1,096例受试者相比，干预期间血糖调节恢复正常的894例受试者的糖尿病发病风险下降了56% (危险比[HR]，0.44)。并且，糖尿病发病风险降低与患者血糖调节达到正常的次数显著相关。具体来说，如果只达到了1次血糖调节正常，那么糖尿病发病风险下降47%(HR，0.53)；达到2次则下降61%(HR，0.39)；达到3次则下降67%(HR，0.33)。

研究者称，在干预期间血糖调节恢复正常的受试者中，糖尿病发病风险降低并不受分组情况的影响。在DPPOS中，与糖尿病发病风险增加相关的因素包括年龄小于45岁(HR，1.47)以及为非裔美国人(HR，1.77)。

研究者还指出，似乎矛盾的是，无论之前接受的是哪种干预措施，DPP期间体重明显减轻者的糖尿病发病风险反而更高(HR，1.26)。研究者认为这“很可能是因为在DPPOS中体重重新增加的患者比例很高，因而对糖尿病发病风险造成了负面影响”。

DPPOS开始时体重指数偏高也与DPPOS随访期间的糖尿病发病风险相关(HR，1.14)。β细胞功能和胰岛素敏感性偏高则具有保护意义(HR分别为0.80和0.83)。

对于DPP期间虽然接受了生活方式强化干预但仍然一直处于糖尿病前期的受试者，其在DPPOS中的糖尿病发病风险高于那些未处于糖尿病前期以及安慰剂组的受试者(HR，1.31)。研究者指出，这说明经严格生活方式干预后仍维持糖尿病前期状态提示糖尿病发病风险高，可能需要采取进一步的干预措施。

研究者还指出：“虽然大家一致同意预防糖尿病具有非常重要的意义，但在具体的干预措施方面尚未达成一致意见。上述分析结果表明，只要早期干预(从发现糖尿病前期即开始)，无论采用什么样的策略，都有可能恢复正常的血糖调节，哪怕只是短暂恢复。”

该研究由美国国立卫生研究院资助。作者声明无相关经济利益冲突。

Getting prediabetes patients to regain glucose control as early as possible provides the best shot at preventing disease progression, regardless of whether it is achieved through lifestyle interventions or drug therapy, according to the latest analysis from the landmark Diabetes Prevention Program.

In fact, even a transient reversion to normal glucose regulation was associated with a significantly reduced risk of diabetes among participants in the DPP, a major randomized trial comparing weight loss and dietary changes with drug therapy for preventing the onset of type 2 diabetes.

Compared with 1,096 participants in that multicenter trial who consistently had prediabetes, the risk of diabetes was 56% lower (hazard ratio, 0.44) among 894 individuals who had returned to normal glucose regulation during the intervention period, according to findings from the Diabetes Prevention Program Outcomes Study (DPPOS), an ongoing postintervention observational study, Dr. Leigh Perreault of the University of Colorado, Aurora, and her colleagues reported online in the June 9 Lancet.

“Diabetes risk reduction was strongly associated with the number of times normal glucose regulation was achieved. Specifically, diabetes risk was reduced 47% in DPPOS if normal glucose regulation was attained only once (HR, 0.53); 61% if it was reached twice (HR,0.39); and 67% if it was reached three times (HR, 0.33),” the investigators said (Lancet 2012 June 9 [doi:10.106/S0140-6736(12)60525-X]).

At baseline, all 3,234 participants were at risk for developing diabetes. They were randomized to receive lifestyle interventions, metformin treatment, or placebo, and were followed for a median of 3.2 years during the intervention.

The current analysis, at a median follow-up of 5.7 years, shows that the reduced risk for diabetes among those subjects who returned to normal glucose regulation during the intervention was not affected by group assignment, the investigators said.

Factors associated with increased diabetes risk during DPPOS included age younger than 45 years (HR, 1.47), and African American ethnic origin (HR, 1.77).

 “Paradoxically, increased weight loss during DPP adversely affected diabetes risk (HR, 1.26) in DPPOS independent of previous treatment,” the investigators also noted, adding that this was “probably because of the high rate of weight regain in DPPOS with associated adverse effects on diabetes risk.”

High body mass index at the beginning of DPPOS also related to diabetes risk during DPPOS follow-up (HR, 1.14). Higher beta-cell function and insulin sensitivity were protective (HR, 0.80 and 0.83, respectively).

Those who consistently had prediabetes during DPP – despite intensive lifestyle interventions – had an increased risk of developing diabetes during DPPOS, compared with those who didn’t have prediabetes and who were in the placebo group (HR, 1.31).

 “Although there is widespread consensus that diabetes prevention is crucially important, there is less agreement with respect to the particular intervention,” the investigators noted. “Results from the present analysis would contend that the strategy is unimportant as long as the intervention is early (when someone has prediabetes) and can restore normal glucose regulation, even if transiently.”

The findings also suggest that maintenance of prediabetes despite intensive lifestyle modification represents a high-risk state that may warrant additional interventions, she and her colleagues said.

“Together, these data serve as essential clinical information to support early and aggressive measures for long-term prevention of diabetes in people at risk,” they concluded.

This study was funded by the U.S. National Institutes of Health. The authors reported having no relevant financial conflicts.