胃旁路术或可逆转衰老

亚特兰大——在本年度“肥胖周”(Obesity Week)大会上，来自美国加州斯坦福大学的减重外科医生John Morton博士报告称，胃旁路术与端粒延长有关，提示手术减重有可能逆转肥胖患者的衰老过程。

Morton博士在接受采访时说：“端粒是反映人体衰老的一种独特标志物，还与慢性病以及吸烟、抑郁等有关。对端粒有潜在影响的东西很多，但能产生积极影响的很少。”

Morton博士及其同事检测了51例胃旁路术患者(女性占77%，平均年龄49岁)的基线端粒长度、C反应蛋白(CRP)水平、胆固醇水平和空腹胰岛素水平。术前患者的平均体重指数为44 kg/m2。术后3、6和12个月再次检测这些指标。采用定量聚合酶链反应检测端粒长度。


John M. Morton博士

在所有患者中，术后12个月多余体重下降率平均为71%；提示炎症的CRP水平平均下降超过60%。空腹胰岛素水平从基线的24 uIU/mL降至术后1年的6 uIU/mL。Morton博士称，这些结果与既往研究的结果相符，但这项研究首次发现了这些变化与人体衰老生物标志物端粒之间的相关性。

意外的结果

在整个患者队列中，端粒长度无显著变化，但当根据CRP和LDL水平进行分析时，在CRP和LDL基线水平偏高的患者中发现端粒长度发生了显著的变化(P = .0387和P = .005)。在CRP基线水平偏高的患者中，端粒延长还与体重下降(P = .0498)和HDL胆固醇水平升高(P = .0176)之间呈现出显著的正相关关系。

Morton博士说，这一结果多少令我们感到有些意外。“最让我惊讶的是如果会有变化，应该是整个患者队列都一样；但却只在炎症标志物水平偏高的患者中观察到了差异。这是在一个非常特别的人群中获得的一个非常特别的结果。”

至少还有另一项纵向研究表明非手术干预措施，即饮食改变会影响端粒长度(PLoS One 2013;8:e62781[doi:10.1371/journal.pone.0062781])，但Morton博士指出，这项强调少吃红肉，多吃鱼类、新鲜蔬菜和橄榄油的研究得到的结果与我们的研究发现并没有什么明显的不同。“那项研究所采用的饮食方案，即地中海饮食，已知能够提高HDL。而在我们的研究中也观察到了端粒延长与HDL升高之间的相关性。要达到这样的目的真的很难。确实能影响这种‘好’胆固醇的药物并不多。”

胃旁路术的"独特作用"

这项研究没有评估端粒与其他类型的手术减重干预措施之间的相关性，但Morton博士说，未来还需针对其他减重手术方法，比如袖状胃切除术展开研究，以确定其是否具有与胃旁路术相同的效果。

Morton博士说：“胃旁路术对炎症的影响具有一定的独特性，这是独立于其他手术方法之外的。”他还提到了今年早些时候他在美国外科医师协会年会上报告的研究数据，讨论的是胃旁路术与糖尿病之间的关系。“我们的研究表明，与其他手术方法相比，胃旁路术后C反应蛋白下降更为明显。”

Morton博士说，在所有的手术干预措施中，胃旁路术对糖尿病的影响最大，并且与减重情况无关，提示我们可以把炎症作为未来研究的方向。“人们开始猜测2型糖尿病可能不仅仅涉及胰腺功能异常，可能还涉及许多炎症。”

Morton博士把减重手术称作是一个能帮助我们了解炎症与疾病过程之间关系的“研究平台”，不仅仅针对肥胖患者，而是整个一般人群。“我相信未来我们可以弄清楚其中一些过程，并且找到不同的干预措施，比如药物。”

Morton博士声明无相关经济利益冲突。

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By: WHITNEY MCKNIGHT, Clinical Endocrinology News Digital Network

ATLANTA – Gastric bypass was associated with the lengthening of telomeres, an indication that surgical weight loss may reverse aging in obese patients.

The most significant changes in telomere length occurred in patients with biomarkers indicative of higher levels of preoperative inflammation and cholesterol, according to findings presented by bariatric surgeon John Morton at this year’s Obesity Week.

"Telomeres are unique markers for aging and are linked to chronic diseases and things like smoking and depression," Dr. Morton said in an interview. "There are a lot of things that can potentially affect telomeres, but there aren’t a lot of things that can affect them in a positive sense."

Dr. Morton and his colleagues at Stanford (Calif.) University measured the baseline telomere length, weight, C-reactive protein (CRP) levels, cholesterol levels, and fasting insulin levels in 51 gastric bypass surgery patients (77% female, average age 49 years). The group’s mean body mass index was 44 kg/m2. The measurements were taken again at 3, 6, and 12 months. Telomere length was determined using quantitative polymerase chain reaction testing.
 
In all patients, excess body weight loss at 12 months averaged 71%; CRP levels, indicative of inflammation, dropped an average of more than 60%. Fasting insulin levels decreased from 24 uIU/mL at baseline to 6 uIU/mL when measured 1 year after surgery. These results were consistent with those of previous studies, but this study was the first to correlate such changes with the body’s biomarkers for aging, telomeres, Dr. Morton said.

Unexpected results

Telomere length did not change significantly across the cohort, but when analyzed according to CRP and LDL levels, significant changes in telomere length were found in patients whose levels of both were higher at baseline (P = .0387 and P = .005). In those whose baseline CRP was high, there also was a significant positive correlation between telomere lengthening and weight loss (P = .0498) and increases in HDL cholesterol level (P = .0176).

The results were somewhat unexpected. "The thing that surprised me the most was that if there were going to be changes, then they should be across the board," said Dr. Morton. "But where it really made a difference was in those who had [high levels of markers of] inflammation. It was a pretty specific result in a pretty specific population."

At least one other longitudinal study has shown the impact of nonsurgical intervention, namely a change in diet, on the length of telomeres (PLoS One 2013;8:e62781[doi:10.1371/journal.pone.0062781]), but Dr. Morton said the study, which emphasized eating less red meat and more fish, fresh vegetables, and olive oil did not demonstrate results that were notably different from his findings.

"One thing that study’s diet, the Mediterranean Diet, is known to do is to raise HDL," said Dr. Morton. "In our study we also saw a correlation between telomere lengthening and increases in HDL. That’s really hard to do. There aren’t a lot of medicines that can really affect the ‘good’ cholesterol."

‘Unique ability’ of gastric bypass

The study did not examine the relationship between telomeres and other kinds of surgical interventions for weight loss, but Dr. Morton said future studies on bariatric procedures such as the sleeve gastrectomy need to be conducted before they can be equated with bypass.

"Gastric bypass has a unique affect on inflammation that is independent of the other operations," said Dr. Morton, referring to data he presented earlier this year at the American College of Surgeons annual meeting, discussing the relationship between bypass and diabetes. "We have shown that C-reactive protein decreases more with gastric bypass than with other operations."

That of all the surgical interventions, gastric bypass has the greatest impact on diabetes, independent of weight loss, points to future research on inflammation, said Dr. Morton. "People are starting to think that type 2 diabetes is not just a burned-out pancreas, but that a lot of inflammation is involved."

Calling bariatric surgery a "platform for investigation" that can help [us] understand the connection between inflammation and the processes of disease in the general population, not just those with obesity, Dr. Morton said, "I think the future will elucidate some of those processes, and will come up with different interventions such as drugs."

Dr. Morton said he did not have any relevant financial disclosures.