血糖水平高者的痴呆风险也高

《新英格兰医学杂志》(New England Journal of Medicine) 8月8日发表的一项基于社区的队列研究表明，血糖水平升高与痴呆风险增加有关。

美国华盛顿大学的Paul K. Crane博士及其同事对来自一项前瞻性纵向研究的数据进行了分析；该前瞻性研究每2年随访一次受试者以统计偶发痴呆病例。共纳入2,067例随机抽样的老年男性和女性，所有受试者从上个世纪90年代开始，在每2年1次的体检中接受了多次血糖检测。

研究者称，在探讨葡萄糖代谢与痴呆风险间相关性的所有研究中，这是首个将血糖水平作为一种随时间变化的现象来进行评估的研究。研究者采用的是多层贝叶斯统计模型，以便将数年来获得的多项检测结果，包括随机血糖检测、空腹血糖检测和糖化血红蛋白检测，整合成一项能反映每位受试者葡萄糖暴露量的复合指标。

每位受试者平均接受了17次血糖监测和5次糖化血红蛋白检测。总共产生了35,264个空腹或随机血糖测值以及10,208个糖化血红蛋白测值。

研究者指出：“基于大量的临床实验室数据以及该队列的长期随访信息(随访期间出现了数百例痴呆病例)，这让我们有机会评价所观察到的整个血糖谱范围内的痴呆风险。”

在为期6.8年的中位随访期内，共有524例(25.4%)受试者出现了痴呆。这包括21.6%的糖尿病患者以及26.1%的非糖尿病受试者。大部分痴呆患者都很可能或可能患有阿尔茨海默病(403例)，其次是血管性痴呆 (55例)以及其他原因导致的痴呆(66例)。

在糖尿病患者中，与血糖水平较低者相比，血糖水平最高者发生痴呆的风险增加。Crane博士及其同事写道：“与[过去5年里]平均血糖水平为160 mg/dl的患者相比，平均血糖达到190 mg/dL的患者发生痴呆的校正危险比为1.40。”(N. Engl. J. Med. 2013 Aug. 8 [doi:10.1056/NEJMoa1215740])。

更令人惊讶的是，在非糖尿病受试者中，与血糖水平较低者相比，血糖水平最高但仍处于正常范围内的受试者发生痴呆的风险也会增加。研究者报告称：“与[过去5年里]平均血糖水平为100 mg/dl 的受试者相比，平均血糖为115 mg/dl的受试者发生痴呆的校正危险比为1.18。”

无论受试者的年龄或性别，在多项敏感性分析中这种相关性仍然具有统计学意义，并且与载脂蛋白E ε-4等位基因携带状态无关。

研究者总结道，无论是在糖尿病还是非糖尿病人群中，血糖水平升高都与这种不良效应相关。“这些数据表明，血糖水平升高可能对老化的大脑产生有害影响。”此外，“研究结果还强调了肥胖和糖尿病患者随时间变化的潜在结局，提示有必要采取合理的干预措施以降低血糖水平。”

研究者称，目前尚不十分清楚血糖水平升高导致痴呆风险增加的具体机制，不过急性和慢性高血糖、胰岛素抵抗以及中枢神经系统微血管病变可能都起到了一定的作用。

这项研究的部分经费由美国国立卫生研究院提供。Crane博士声明无相关经济利益冲突；另外4名作者声明与业界存在利益关系。

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By: MARY ANN MOON, Clinical Endocrinology News Digital Network

Higher glucose levels were associated with an elevated risk of dementia in a community-based cohort study reported Aug. 8 in the New England Journal of Medicine.

High glucose levels were linked to this adverse effect both in people who had diabetes and in people who did not. "These data suggest that higher levels of glucose may have deleterious effects on the aging brain," said Dr. Paul K. Crane of the University of Washington, Seattle, and his associates.

In addition, "our findings underscore the potential consequences of temporal trends in obesity and diabetes, and suggest the need for interventions that reduce glucose levels," they said.

Dr. Crane and his colleagues analyzed data from a prospective, longitudinal study in which participants were followed every 2 years to identify incident cases of dementia. The study involved 2,067 randomly sampled older men and women who underwent numerous glucose tests as part of their biennial work-ups, beginning in the 1990s.

The researchers described this as the first study among those investigating associations between glucose metabolism and the risk of dementia to evaluate glucose levels as a time-varying phenomenon. They used a hierarchical Bayesian statistical model that allowed them to incorporate multiple measurements taken over the course of several years – including random blood glucose tests, fasting blood glucose tests, and glycated hemoglobin tests – into a single composite estimate of glucose exposure for each study subject.

Each participant underwent an average of 17 measurements of blood glucose and 5 of glycated hemoglobin. This yielded a total of 35,264 values for fasting and random glucose levels and 10,208 values for glycated hemoglobin levels.

"The extensive clinical laboratory data available and the long-term follow-up of the cohort, in which there were hundreds of cases of dementia, afforded us the opportunity ... to evaluate risk across the entire spectrum of observed glucose levels," the investigators noted.

Overall, 524 (25.4%) of the study subjects developed dementia during a median follow-up period of 6.8 years. This included 21.6% of the subjects who had diabetes and 26.1% of those who didn’t have diabetes. Most of the patients with dementia had probable or possible Alzheimer’s disease (403), followed by dementia from vascular disease (55) and dementia from other causes (66).

In the subjects with diabetes, those who had the highest glucose levels were at increased risk of dementia, compared with those who had lower glucose levels. "For an average glucose level of 190 mg/dL [in the preceding 5 years], as compared with 160 mg/dL, the adjusted hazard ratio for dementia was 1.40," Dr. Crane and his associates wrote (N. Engl. J. Med. 2013 Aug. 8 [doi:10.1056/NEJMoa1215740]).

More surprisingly, in the subjects without diabetes, those who had the highest but still normal glucose levels were at increased risk of dementia, compared with those who had lower glucose levels. "For an average glucose level of 115 mg/dL [in the preceding 5 years], as compared with 100 mg/dL, the adjusted hazard ratio for dementia was 1.18," the researchers reported.

These associations remained significant in several sensitivity analyses, regardless of the subjects’ age or sex, and were independent of apolipoprotein E epsilon-4 allele status.

The mechanism(s) by which higher glucose levels may contribute to dementia risk have not yet been elucidated, but both acute and chronic hyperglycemia, insulin resistance, and microvascular disease of the CNS could all play a role, according to the researchers.

This study was supported in part by the National Institutes of Health. Dr. Crane reported no financial conflicts of interest; four other authors reported ties to industry sources.