Cancer replaces vascular disease as leading cause of excess death in diabetes

A large epidemiological analysis shows cancer has replaced vascular disease as the leading cause of excess death among people with diabetes, suggesting improved lifestyle habits and cardiovascular disease prevention efforts may be working.

“One of the things we have observed generally is life expectancy for people with diabetes is increasing,”Jonathan Pearson-Stuttard, MD, FRSPH,a Wellcome Trust clinical research fellow and epidemiologist with Imperial College London School of Public Health and vice chair of the Royal Society for Public Health, told Healio. “There has been some evidence from the U.S. that this has led to a diversification in cause of death. But studies to date, including those done in the U.S., have not been as granular as ours — with less information on what makes up 'other' non-vascular, non-cancer causes of death.”

For the past 30 years, deaths attributable to vascular disease have declined overall globally due to a combination of factors, such as reduction of salt and saturated fat intake, lower smoking rates, blood pressure control, improvements in therapeutics and better survival rates after myocardial infarction. A new primary care database analysis, published in February inThe Lancet Diabetes & Endocrinology,揭示了这些改善对于糖尿病患者而不是没有的人。

皮尔森·斯图塔德（Pearson-Stuttard）说：“如果您问糖尿病领域的任何人，他们说血管疾病是患有糖尿病患者的最大风险。”“好消息是，我们一直在做的事情，对于糖尿病患者而言，更是如此。”

The flip side, according to the data, is gains in cancer mortality have been much more modest. Additionally, unlike vascular disease, where the best improvements have been observed among people with diabetes, the reverse was true for cancer.

“Cancer gains have been slower and more slow among people with diabetes compared with those without diabetes,” Pearson-Stuttard said. “When you look at the data by age group, we see that, among older adults, there is no improvement, and perhaps a worsening among people with diabetes.”

Primary care data

在对初级保健记录的流行病学分析中，Pearson-Stuttard及其同事分析了2001年至2018年之间313,907名糖尿病成年人的数据，使用了与英国国家统计死亡率数据链接的临床实践研究Datalink的数据。研究人员使用泊松回归模型来估计所有原因的死亡率，以及糖尿病男性和女性的12个特定原因，还估计了与同一数据集中没有糖尿病的年龄和性别匹配的成年人的死亡率。

From 2001 to 2018, researchers found that total mortality declined by 32% in men with diabetes and 31% in women with diabetes, with similar trends for those without diabetes — a 41% decline for men and a 33% decline for women.

对于糖尿病患者，特定死亡原因的绝对下降最大的是缺血性心脏病（每1000人年死亡7.2人死亡），中风（每1000人年死亡3.6人死亡）和糖尿病（每1000人年死亡2.8人死亡）;男性和女人的改善相似。研究人员观察到没有糖尿病患者的类似模式。

Cancer deaths decreased for those with and without diabetes; however, declines in cancer-related mortality were much larger for those without diabetes. Researchers observed declines of 0.4 deaths per 1,000 person-years for diabetes-related cancers and 2.1 deaths per 1,000 person-years for all other cancers among those without diabetes, vs. declines of 0.2 deaths per 1,000 person-years and 0.5 deaths per 1,000 person-years for those with diabetes.

血管疾病死亡率的大幅下降导致从血管原因向癌症的过渡，这是糖尿病患者死亡率的主要因素以及患有和没有疾病患者之间死亡率的差距。

Michael Bergman, MD, FACP,NYU Grossman医学院医学和人口健康临床教授兼NYU糖尿病预防计划主任指出，绝对癌症死亡的数量相对较少，这排除了对研究中死亡率的精确癌症的识别。

伯格曼告诉Healio：“这两个人群的癌症死亡都在下降，但糖尿病人口和非糖尿病人口的下降较少，因此可归因的死亡率是高的两倍，但数量仍然相对较小。”“显然，癌症取代了血管疾病，原因是导致死亡过多的原因。然而，其他因素似乎与糖尿病​​有关，这些因素也增加了死亡率，包括肝病和痴呆症，这可能与增加的寿命和其他因素有关。”

代谢障碍，癌症之间的联系

In commentary accompanying the study,Mingyang歌曲，MBBS，SCD,assistant professor of clinical epidemiology and nutrition at the Harvard T.H. Chan School of Public Health, noted that cancer has traditionally been considered a distinct spectrum of disease from diabetes. Increasing evidence supports the importance of metabolic disturbances in the cause of cancer, he said.

宋告诉Healio：“在某种程度上，癌症会超过血管疾病，这是普通人群和糖尿病患者的主要死亡原因。”“令我最惊讶的是差距的幅度。如果您查看总癌症死亡人数的数量，几乎是血管疾病的两倍。这种范围强调了这个问题的紧迫性。”

Compared with people without diabetes, those with diabetes are nearly twice as likely to develop liver and pancreatic cancer, 1.5 to two times more likely to develop endometrial and gallbladder cancer and 1.1 to 1.4 times more likely to develop kidney, colorectal, bladder and breast cancer, Song wrote. Globally, an estimated 5.7% of all incident cancers in 2012 were attributable to the combined effects of adiposity and diabetes.

“癌症正在成为一个重要的问题with diabetes, as obesity is such a strong risk factor for some cancers,” Song said. “This is a problem we should not neglect. This needs to be a focus in the clinic when providers talk to patients.”

癌症筛查的价值

Current recommendations for cancer screenings do not differ for people with or without diabetes. Additionally, there are no specific screening tests that have been shown to reduce deaths from most of the cancer types associated with diabetes, according toEmily Gallagher, MD，博士，MRCPI,assistant professor of endocrinology, diabetes and bone disease and associate program director for the internal medicine residency program at the Icahn School of Medicine at Mount Sinai.

“We need to conduct studies to see if screening for specific diabetes-related cancers, specifically in people with diabetes, reduces cancer mortality in this population,” Gallagher, who studies links between obesity, type 2 diabetes and cancer, told Healio. “Additionally, we also need to study preventive strategies.”

Gallagher说，与代谢综合征和糖尿病前期有关的胰岛素抵抗的过程在高血糖和公开2型糖尿病发生之前已经发生了多年，表明预防癌症预防策略也可能早期开始。

“如评论中所述，在某些研究中，与糖尿病有关的癌症风险增加了糖尿病诊断后约8年达到峰值，然后下降，这表明正是与糖尿病前期的高胰岛素血症和代谢综合征有关对于癌症，”加拉格尔说。“这意味着在糖尿病发展之前需要制定癌症预防策略。”

Bergman said enhanced cancer surveillance for specific cancers associated with diabetes is worth considering.

“We don’t know the cost for increasing cancer surveillance, particularly in the diabetic population,” Bergman said. “But it makes sense to look at this very carefully. Also worth noting is that prediabetes, a precursor to type 2 diabetes affecting well over 80 million people in the U.S., is also associated with an increased risk for cancer, but that risk is approximately 50% lower than in people with overt diabetes. It is logical that the same cancers associated with type 2 diabetes, are also associated with prediabetes.”

Data spur questions

Experts agree that many open research questions remain regarding cancer and diabetes.

“We know people with diabetes have a higher risk for vascular disease, and we have prevention-specific actions in their care pathways, but we do not have any specific screening or prevention approaches in cancer,” Pearson-Stuttard said. “What is difficult about that is it is very unlikely that every single person with diabetes has that increased risk for cancer. We are not quite sure what that driving mechanism is. It is probably high insulin levels or insulin-like growth factor I levels, but the evidence isn’t there yet to inform new, specific measures.”

最近的研究还表明，糖尿病药物二甲双胍可能受益于癌症。加拉格尔说，这些新数据可能只会加剧讨论。

“患者经常询问二甲双胍的潜在抗癌作用，虽然我告诉他们没有大型随机对照试验绝对显示出对二甲双胍有益的好处，但没有研究对癌症结果产生负面影响，”加拉格说。“正如无论如何是糖尿病管理作为一线疗法的指示，我绝对倡导。问题是，对于糖尿病前的人，我们应该早些时候开处方吗？”

As research continues, Song said clinicians should “bring the cancer perspective” into the discussion when talking with patients.

“Motivate the patient to do more with lifestyle changes,” Song said. “Regarding the research side, there is a lot that can be done. Should people with diabetes be considered a high-risk group that warrants earlier cancer screenings? More work still needs to be done to answer that question. As the obesity rate rises, this problem will become greater in the clinic.”

References:

Pearson-Stuttard J, et al.柳叶刀糖尿病内分泌。2021; doi：10.1016/s2213-8587（20）30431-9。

歌M。柳叶刀糖尿病内分泌。2021; doi：10.1016/s2213-8587（21）00016-4。

For more information:

Michael Bergman, MD, FACP,can be reached atmichael.bergman@nyulangone.org。

Emily Gallagher, MD，博士，MRCPI,can be reached atemily.gallagher@mssm.edu。

Jonathan Pearson-Stuttard，博士，can be reached atj.pearson-stuttard@imperial.ac.uk。

Mingyang歌曲，MBBS，SCD,can be reached atmis911@mail.harvard.edu。