Frontiers in Endocrinology

內分泌學前沿

2022, Volume 13, Article 800995

The Relationship Between Diabetes Mellitus and Cancers and Its Underlying Mechanisms

The link between diabetes and cancer has been proposed for more than 100 years.

糖尿病和癌癥之間的聯(lián)系已被提出100多年。

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The risk of cancers appears to be increased in both type I diabetes mellitus and type 2 diabetes mellitus.

1型和2型糖尿病似乎都會增加癌癥風險。

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Cancer incidence of liver, pancreas, kidney, esophagus, stomach, lung, thyroid, squamous cell carcinoma, and leukaemia significantly increased for both sexes with T1DM. Incidence of non-Hodgkin’s lymphoma and colon cancer significantly increased for men; while incidence of the ovary, esophagus, endometrium, vulva and vagina, and thyroid cancer significantly increased for women. On the contrary, incidences of prostate cancer and testis cancer significantly decreased in men with T1DM in comparison with the general population. Women with T1DM had significantly lower risk for breast cancer, melanoma, and Hodgkin’s lymphoma.

1型糖尿病患者的肝臟、胰腺、腎臟、食道、胃、肺、甲狀腺、鱗狀細胞癌和白血病的癌癥發(fā)病率顯著增加。男性非霍奇金淋巴瘤發(fā)病率顯著增肌，女性卵巢癌、食管癌、子宮內膜癌和甲狀腺癌發(fā)病率顯著增加。

但相反地，與普通人相比，男性1型糖尿病患者前列腺癌癥和睪丸癌的發(fā)病率顯著降低，女性患者患乳腺癌癥、黑色素瘤和霍奇金淋巴瘤的風險顯著降低。

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But, there was evidence of heterogeneity in risk of some cancers by country, and TIDM duration.

但是，有證據(jù)表明，某些癌癥的風險因國家和1型糖尿病持續(xù)時間而異。

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Significant positive associations between T2DM and mortality from cancers were observed for the cancers of stomach, colorectum, oral cavity, gallbladder, bile duct, liver, pancreas, ovary, endometrium, breast, thyroid, prostate, lung, kidney, bladder, and lymphoma. Controversially, some studies reported a null association between T2DM and the risk of death from cancers of the lung, bladder, stomach, cervix, esophagus, as well as leukaemia, suggesting that the role of diabetes in these site cancer needs further clarification.

在胃癌、結直腸癌、口腔癌、膽囊癌、膽管癌、肝臟癌、胰腺癌、卵巢癌、子宮內膜癌、乳腺癌、甲狀腺癌、前列腺癌、肺癌、腎臟癌、膀胱癌和淋巴癌的病例中，觀察到了2型糖尿病與癌癥死亡率的顯著正相關。

有爭議的是，一些研究報告稱，2型糖尿病與肺癌、膀胱癌、胃癌、宮頸癌、食道癌以及白血病死亡風險之間沒有關聯(lián)，上述作用需進一步澄清。

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Genetic factors have been identified as contributing to the associations between diabetes and some cancers. For instance, individuals who have a family history of pancreatic cancer often have a higher risk of developing pancreatic cancer.

遺傳因素已經(jīng)被確定為糖尿病與某些癌癥之間關聯(lián)性的因素。

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It is well known that most patients with prediabetes or T2DM have overweight or obesity. A large cohort study which included 900 000 individuals with an over 16-year duration of follow-up reported that severe obesity was associated with a significantly increased mortality from cancers of the liver, pancreas, colon and rectum, kidney, non-Hodgkins lymphoma, esophagus, and multiple myeloma. The greatest influences were observed in cancers of liver, colon and rectum, and pancreas.

眾所周知，大多數(shù)糖尿病前期或2型糖尿病患者都有超重或肥胖。一項包括60萬名隨訪時間超過16年的研究報告稱，嚴重肥胖與肝癌、胰腺癌、結腸癌和直腸癌、腎癌、非霍奇金淋巴瘤、食道癌和多發(fā)性骨髓瘤的死亡率顯著增加有關，肝癌、結腸癌、直腸癌和胰腺癌的影響最大。

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Epidemiological data have shown that hyperglycemia is related to higher risk of colorectal, liver, gastric, lung and pancreatic cancer. Normally, cells differentiates rely on mitochondrial oxidative phosphorylation to provide the energy to cellular processes, while cancer cells tend to use a less efficient glycolytic pathway for proliferation. Cancer cells therefore require increased glucose uptake to generate sufficient energy hence meet their proliferation needs.

流行病學數(shù)據(jù)表明，高血糖與結直腸癌、肝癌、胃癌、肺癌和胰腺癌的高風險相關。正常情況下，細胞在分化過程中依賴線粒體氧化磷酸化提供能量，而癌癥細胞一般使用效率較低的糖酵解進行增殖。因此，癌細胞需要更多葡萄糖攝取，以產生足夠的能量，滿足其增殖需要。

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Numerous clinical studies and meta-analyses have demonstrated that diabetes exposure to metformin was associated with a significantly decreased cancer incidence and mortality.

大量臨床研究和薈萃分析表明，糖尿病患者使用二甲雙胍可顯著降低癌癥發(fā)病率和死亡率。

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The use of DPP-IV inhibitor sitagliptin or the GLP-I analog exenatide was associated with a significant increase in the incidence of pancreatic cancer.

使用DPP-IV抑制劑西他列汀或GLP-I類似物艾塞那肽與胰腺癌發(fā)病率顯著增加相關。

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There is a complicated association between diabetes mellitus and cancers. In summary, the risk a number of cancers and cancer mortality is increased in T1DM and T2DM. On the other hand, some kinds of cancer and cancer therapies are associated with the increased risk of diabetes mellitus. Additionally, genetic factors, obesity, inflammation, oxidative stress, hyperglycemia, hyperinsulinemia, cancer therapies, insulin and some oral hypoglycemic drug appear to play a role in the crosstalk between diabetes mellitus and cancers. Thus, we suggest that cancer screening should be conducted in patients with diabetes, and precautions for diabetes should be taken in patients suffering from cancer. Further researches are merited to explore on the associations between these different diseases.

糖尿病和癌癥之間有著復雜的關系。1型/2型患者患多種癌癥的風險和癌癥死亡率增加。另外，某些類型癌癥和癌癥治療與糖尿病風險增加有關。此外，遺傳因素、肥胖、炎癥、氧化應激、高血糖、高胰島素血癥、癌癥治療、胰島素和一些口服降糖藥物似乎在糖尿病和癌癥之間相互影響中發(fā)揮了作用。對糖尿病患者進行癌癥篩查、對癌癥患者采取糖尿病預防措施都是值得建議的。