Lancet Diabetes Endocrinol. 2015 Nov;3(11):866-75. doi: 10.1016/S2213-8587(15)00291-0. Epub 2015 Sep 13.
Effective prevention is needed to combat the worldwide epidemic of type 2 diabetes. We investigated the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention, originally shown during the 3-year Diabetes Prevention Program (DPP), and assessed whether these interventions reduced diabetes-associated microvascular complications.
The DPP (1996-2001) was a randomised trial comparing an intensive lifestyle intervention or masked metformin with placebo in a cohort selected to be at very high risk of developing diabetes. All participants were offered lifestyle training at the end of the DPP. 2776 (88%) of the surviving DPP cohort were followed up in the DPP Outcomes Study (DPPOS, Sept 1, 2002, to Jan 2, 2014) and analysed by intention to treat on the basis of their original DPP assignment. During DPPOS, the original lifestyle intervention group was offered lifestyle reinforcement semi-annually and the metformin group received unmasked metformin. The primary outcomes were the development of diabetes and the prevalence of microvascular disease. For the assessment of microvascular disease, we used an aggregate microvascular outcome, composed of nephropathy, retinopathy, and neuropathy.
During a mean follow-up of 15 years, diabetes incidence was reduced by 27% in the lifestyle intervention group (hazard ratio 0·73, 95% CI 0·65-0·83; p<0·0001) and by 18% in the metformin group (0·82, 0·72-0·93; p=0·001), compared with the placebo group, with declining between-group differences over time. At year 15, the cumulative incidences of diabetes were 55% in the lifestyle group, 56% in the metformin group, and 62% in the placebo group. The prevalences at the end of the study of the aggregate microvascular outcome were not significantly different between the treatment groups in the total cohort (placebo 12·4%, 95% CI 11·1-13·8; metformin 13·0%, 11·7-14·5; lifestyle intervention 11·3%, 10·1-12·7). However, in women (n=1887) the lifestyle intervention was associated with a lower prevalence (8·7%, 95% CI 7·4-10·2) than in the placebo (11·0%, 9·6-12·6) and metformin (11·2%, 9·7-12·9) groups, with reductions in the lifestyle intervention group of 21% (p=0·03) compared with placebo and 22% (p=0·02) compared with metformin. Compared with participants who developed diabetes, those who did not develop diabetes had a 28% lower prevalence of microvascular complications (relative risk 0·72, 95% CI 0·63-0·83; p<0·0001).
Lifestyle intervention or metformin significantly reduced diabetes development over 15 years. There were no overall differences in the aggregate microvascular outcome between treatment groups; however, those who did not develop diabetes had a lower prevalence of microvascular complications than those who did develop diabetes. This result supports the importance of diabetes prevention.
National Institute of Diabetes and Digestive and Kidney Diseases.
需要有效的预防措施来应对全球 2 型糖尿病的流行。我们研究了生活方式干预和二甲双胍对糖尿病预防的长期有益效果，这些效果最初在为期 3 年的糖尿病预防计划（DPP）中得到了证实，并评估了这些干预措施是否降低了糖尿病相关的微血管并发症。
DPP（1996-2001 年）是一项随机试验，比较了强化生活方式干预或二甲双胍与安慰剂在一个非常高的糖尿病风险队列中的效果。所有参与者在 DPP 结束时都接受了生活方式培训。2776 名（88%）幸存的 DPP 队列成员参加了 DPP 结果研究（DPPOS，2002 年 9 月 1 日至 2014 年 1 月 2 日），并根据他们最初的 DPP 分配进行了意向治疗分析。在 DPPOS 期间，最初的生活方式干预组每半年接受一次生活方式强化治疗，而二甲双胍组则接受未掩饰的二甲双胍治疗。主要结局是糖尿病的发展和微血管疾病的流行。为了评估微血管疾病，我们使用了一种综合微血管结局，包括肾病、视网膜病变和神经病变。
在平均 15 年的随访中，与安慰剂组相比，生活方式干预组的糖尿病发病率降低了 27%（风险比 0.73，95%CI 0.65-0.83；p<0.0001），二甲双胍组降低了 18%（0.82，0.72-0.93；p=0.001）。随着时间的推移，两组之间的差异逐渐减小。在第 15 年，生活方式组的累积糖尿病发病率为 55%，二甲双胍组为 56%，安慰剂组为 62%。在总队列中，治疗组的综合微血管结局的患病率在研究结束时没有显著差异（安慰剂组 12.4%，95%CI 11.1-13.8；二甲双胍组 13.0%，11.7-14.5；生活方式干预组 11.3%，10.1-12.7）。然而，在女性（n=1887）中，与安慰剂组（11.0%，9.6-12.6）和二甲双胍组（11.2%，9.7-12.9）相比，生活方式干预组的患病率较低（8.7%，7.4-10.2），与安慰剂组相比降低了 21%（p=0.03），与二甲双胍组相比降低了 22%（p=0.02）。与发生糖尿病的参与者相比，未发生糖尿病的参与者的微血管并发症患病率降低了 28%（相对风险 0.72，95%CI 0.63-0.83；p<0.0001）。
生活方式干预或二甲双胍在 15 年内显著降低了糖尿病的发生。治疗组之间在综合微血管结局方面没有总体差异；然而，那些没有发生糖尿病的患者微血管并发症的患病率低于那些发生糖尿病的患者。这一结果支持了糖尿病预防的重要性。
美国国立卫生研究院糖尿病、消化和肾脏疾病研究所。
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