The influence of diabetes and antidiabetic medications on the risk of pancreatic cancer: a nationwide population-based study in Korea

Lee, Da Young; Yu, Ji Hee; Park, Sang‐Hyun; Han, Kyungdo; Kim, Nam Hoon; Yoo, Hye Jin; Choi, Kyung Mook; Baik, Sei Hyun; Seo, Ji A

doi:10.1038/s41598-018-27965-2

Cited by 35 publications

(57 citation statements)

References 28 publications

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“…A similar risk of PDAC is also reported with use of sulfonylureas (insulin secretagogues) routinely used in DM treatment [13, 5, 6]. Recently, these observations seem to be confirmed by Lee et al , who analyzed a Korean population-based cohort of subjects with and without DM and reported that risk of PDAC increases in patients after initiating therapy with sulfonylureas (HR, 1.73) and insulin (HR, 2.86) compared to no drug exposure group [17]. Some have speculated a direct causal relationship between insulin and PDAC occurrence secondary to anabolic effect of insulin on tumor cells [18].…”

Section: Insulin Use and Risk Of Pdacmentioning

confidence: 82%

Pancreatic Cancer and Diabetes Mellitus

Sharma

Chari

2018

Curr Treat Options Gastro

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Studies report that while some anti-diabetic medications (e.g., metformin) may decrease the risk of PDAC, others (insulin, sulfonylureas and incretin-based therapies) may increase the risk. However, these observations may be subject to protopathic biases. Metformin's anti-tumor activity may have influence overall survival of PDAC, but epidemiological reports have largely been inconsistent to defend these findings due to heterogeneous methodologies. There is congruent data to support the association between DM and PDAC, with an inverse relationship to DM duration. Older subjects with new-onset DM are the only known high-risk group for PDAC, and strategy using this group for early detection has led to development of clinical risk prediction models that define a very high-risk PDAC group. Role of anti-diabetic medication in PDAC risk modification or survival is controversial. With successful efforts to distinguish type 2-DM from PDAC-DM using risk-stratifying models, there is an opportunity to initiate screening protocols for early detection of PDAC in a sub-set of DM subjects.

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Section: Insulin Use and Risk Of Pdacmentioning

confidence: 82%

Pancreatic Cancer and Diabetes Mellitus

Sharma

Chari

2018

Curr Treat Options Gastro

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“…Unfortunately, even in this case, no definitive conclusions have as yet been reached. It is not entirely clear whether, how much, and in which direction diabetes treatments affect the association between diabetes and PDAC [ 23 , 25 , 64 , 65 , 66 , 67 ]. To give a couple of examples, the protection provided by metformin, the most commonly drug used to treat T2DM, is currently under vigorous discussion, together with its mechanistic implications [ 67 , 68 , 69 , 70 , 71 , 72 , 73 ], and even the increased risk of PDAC observed in insulin-treated patients in some case-control studies [ 27 , 74 ] can be misleading [ 26 , 72 ].…”

Section: Relationship Between Diabetes and Pancreatic Cancermentioning

confidence: 99%

Diabetes and Pancreatic Cancer—A Dangerous Liaison Relying on Carbonyl Stress

Menini

Iacobini

Vitale

et al. 2021

Cancers

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Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity. Accumulating evidence demonstrates that diabetes promotes pancreatic ductal adenocarcinoma (PDAC) in experimental models of T2DM, a finding recently confirmed in a T1DM model. The carbonyl stress markers advanced glycation end-products (AGEs), the levels of which are increased in diabetes, were shown to markedly accelerate tumor development in a mouse model of Kras-driven PDAC. Consistently, inhibition of AGE formation by trapping their carbonyl precursors (i.e., reactive carbonyl species, RCS) prevented the PDAC-promoting effect of diabetes. Considering the growing attention on carbonyl stress in the onset and progression of several cancers, including breast, lung and colorectal cancer, this review discusses the mechanisms by which glucose and lipid imbalances induce a status of carbonyl stress, the oncogenic pathways activated by AGEs and their precursors RCS, and the potential use of carbonyl-scavenging agents and AGE inhibitors in PDAC prevention and treatment, particularly in high-risk diabetic individuals.

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“…In 2018, a population-based study was performed to evaluate the effects of T2DM and antidiabetic medications on the risk of PC by Lee D Y et al93 It was shown that among antidiabetic medications, metformin was an independent association with a reduced risk for future PC (HR=0.86, 95% CI=0.77–0.96) and subjects with dual exposure history to metformin plus thiazolidinedione or metformin plus dipeptidyl peptidase-4 inhibitor had a lower risk of PC compared to metformin-only treated subjects, which implicated that metformin could decrease the risk of PC. Pusceddu S et al, made a study in 2018 to figure out the association between metformin use and PC 94.…”

Section: Relationship Between Drug Therapy For T2dm and Pcmentioning

confidence: 99%

“…In 2018, Lee D Y et al, undertook a population-based study to find out the effects of T2DM and antidiabetic medications on the risk of PC 93. It was concluded that among antidiabetic medications, insulin exposure was with an increased risk of PC (HR=2.86, 95% CI=1.43–5.74) compared to subjects with no drug exposure, which implicated that insulin could increase the risk of PC.…”

Section: Relationship Between Drug Therapy For T2dm and Pcmentioning

confidence: 99%

<p>The relationship between pancreatic cancer and type 2 diabetes: cause and consequence</p>

Li¹,

Bian²,

Wei³

et al. 2019

CMAR

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Pancreatic cancer (PC) is a devastating and lethal malignant disease and it is well known that there is a complex bidirectional relationship between PC and type 2 diabetes mellitus (T2DM). In order to more deeply summarize the relationship between them, this article summarizes the epidemiological data on the relationship between PC and T2DM in the past 5 years, and further explains the mechanism of interaction between them. Meanwhile, it also summed up the effects of drug therapy for T2DM on PC and the impact of T2DM on surgical resection of PC. Epidemiological studies clearly indicate that the risk of PC is increased in patients with T2DM. But increasing epidemiological data points out that PC also acts as a cause of T2DM and new-onset T2DM is sign and consequence of PC. Insulin resistance, hyperinsulinemia, hyperglycemia, and chronic inflammation are the mechanisms of T2DM-Associated PC. Metformin decreases the risk of PC, while insulin therapy increases the risk of PC. Besides, studies have shown that T2DM decreases the survival in patients with PC resection.

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The influence of diabetes and antidiabetic medications on the risk of pancreatic cancer: a nationwide population-based study in Korea

Cited by 35 publications

References 28 publications

Pancreatic Cancer and Diabetes Mellitus

Pancreatic Cancer and Diabetes Mellitus

Diabetes and Pancreatic Cancer—A Dangerous Liaison Relying on Carbonyl Stress

<p>The relationship between pancreatic cancer and type 2 diabetes: cause and consequence</p>

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