英国牛津丘吉尔医院Rury R Holman团队研究了2型糖尿病强化血糖控制随机对照试验的试验后监测从10年延长至24年的随访结果。相关论文于2024年5月17日发表在《柳叶刀》杂志上。

一项为期20年的英国前瞻性糖尿病研究显示，与传统血糖控制相比，新诊断的2型糖尿病患者随机分为磺脲类或胰岛素治疗或二甲双胍治疗的强化血糖控制组，具有主要临床益处。10年的试验后随访确定了持续和新出现的血糖和二甲双胍遗留治疗效果。该研究旨在通过将随访期再延长14年来确定这些影响是否会减弱。

1977年至1991年间招募的5102名患者，其中4209名（82.5%）参与者最初被随机分配接受强化血糖控制（磺酰脲或胰岛素，如果超重，则接受二甲双胍）或常规血糖控制（主要是饮食干预）。在为期20年的介入试验结束时，3277名存活的参与者进入了为期10年的试验后监测期，监测期持续到2007年9月30日。该研究的合格参与者均为试验后10年监测期结束时存活的参与者。通过将这些参与者与他们常规收集的国家医疗服务体系（NHS）数据联系起来，对他们进行了长达14年的长期随访。临床结局来源于死亡、入院、门诊就诊以及急诊室就诊记录。研究组在意向治疗的基础上，使用Kaplan–Meier事件时间和对数秩分析，通过随机血糖控制策略检查了七种预先指定的总临床结局（即任何糖尿病相关终点、糖尿病相关死亡、全因死亡、心肌梗死、中风、外周血管疾病和微血管疾病）。

2007年10月1日至2021年9月30日，1525名参与者中的1489人（97.6%）可能与常规收集的NHS行政数据有关。她们基线时的平均年龄为50.2岁（标准差8.0），41.3%为女性。截至2021年9月30日，存活者的平均年龄为79.9岁（SD 8.0）。从基线开始的个体随访时间为0至42年，中位数为17.5年（IQR为12.3-26.8）。总体随访增加了21%，从66972人年增加到80724人年。在试验结束后长达24年的时间里，血糖和二甲双胍的遗留效应没有减弱的迹象。与常规血糖控制相比，磺酰脲或胰岛素治疗的早期强化血糖控制显示，全因死亡的总体相对风险降低了10%（95%CI 2-17；p=0.015），心肌梗死的总体相对危险降低了17%（6-26；p=0.002），微血管疾病的总体相对危险降低了26%（14-36；p<0.0001）。相应的绝对风险分别降低了2.7%、3.3%和3.5%。与常规血糖控制相比，二甲双胍治疗的早期强化血糖控制显示，全因死亡的总体相对风险降低了20%（95%CI 5-32；p=0.010），心肌梗死的总体相对危险降低了31%（12-46；p=0.003）。相应的绝对风险降低率分别为4.9%和6.2%。在试验期间或试验后，两个强化血糖对照组的中风或外周血管疾病风险均未显著降低，二甲双胍治疗的微血管疾病风险也未显著降低。

研究结果表明，与传统的血糖控制相比，磺酰脲或胰岛素或二甲双胍的早期强化血糖控制似乎可以降低几乎终身的死亡和心肌梗死风险。在诊断后立即实现接近正常的血糖可能对于最大限度地降低糖尿病相关并发症的终身风险至关重要。

附：英文原文

Title: Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91)

Author: Amanda I Adler, Ruth L Coleman, Jose Leal, William N Whiteley, Philip Clarke, Rury R Holman

Issue&Volume: 2024-05-17

Abstract:

Background

The 20-year UK Prospective Diabetes Study showed major clinical benefits for people with newly diagnosed type 2 diabetes randomly allocated to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. 10-year post-trial follow-up identified enduring and emerging glycaemic and metformin legacy treatment effects. We aimed to determine whether these effects would wane by extending follow-up for another 14 years.

Methods

5102 patients enrolled between 1977 and 1991, of whom 4209 (82·5%) participants were originally randomly allocated to receive either intensive glycaemic control (sulfonylurea or insulin, or if overweight, metformin) or conventional glycaemic control (primarily diet). At the end of the 20-year interventional trial, 3277 surviving participants entered a 10-year post-trial monitoring period, which ran until Sept 30, 2007. Eligible participants for this study were all surviving participants at the end of the 10-year post-trial monitoring period. An extended follow-up of these participants was done by linking them to their routinely collected National Health Service (NHS) data for another 14 years. Clinical outcomes were derived from records of deaths, hospital admissions, outpatient visits, and accident and emergency unit attendances. We examined seven prespecified aggregate clinical outcomes (ie, any diabetes-related endpoint, diabetes-related death, death from any cause, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease) by the randomised glycaemic control strategy on an intention-to-treat basis using Kaplan–Meier time-to-event and log-rank analyses. This study is registered with the ISRCTN registry, number ISRCTN75451837.

Findings

Between Oct 1, 2007, and Sept 30, 2021, 1489 (97·6%) of 1525 participants could be linked to routinely collected NHS administrative data. Their mean age at baseline was 50·2 years (SD 8·0), and 41·3% were female. The mean age of those still alive as of Sept 30, 2021, was 79·9 years (SD 8·0). Individual follow-up from baseline ranged from 0 to 42 years, median 17·5 years (IQR 12·3–26·8). Overall follow-up increased by 21%, from 66972 to 80724 person-years. For up to 24 years after trial end, the glycaemic and metformin legacy effects showed no sign of waning. Early intensive glycaemic control with sulfonylurea or insulin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 10% (95% CI 2–17; p=0·015) for death from any cause, 17% (6–26; p=0·002) for myocardial infarction, and 26% (14–36; p<0·0001) for microvascular disease. Corresponding absolute risk reductions were 2·7%, 3·3%, and 3·5%, respectively. Early intensive glycaemic control with metformin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 20% (95% CI 5–32; p=0·010) for death from any cause and 31% (12–46; p=0·003) for myocardial infarction. Corresponding absolute risk reductions were 4·9% and 6·2%, respectively. No significant risk reductions during or after the trial for stroke or peripheral vascular disease were observed for both intensive glycaemic control groups, and no significant risk reduction for microvascular disease was observed for metformin therapy.

Interpretation

Early intensive glycaemic control with sulfonylurea or insulin, or with metformin, compared with conventional glycaemic control, appears to confer a near-lifelong reduced risk of death and myocardial infarction. Achieving near normoglycaemia immediately following diagnosis might be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible.

DOI: 10.1016/S0140-6736(24)00537-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00537-3/abstract