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Metformin reduces the risk of cancer in patients with type 2 diabetes: An analysis based on the Korean National Diabetes Program Cohort.

ABSTRACT: The epidemiological literature suggests that insulin resistance, hyperinsulinemia, and increased levels of insulin-like growth factors place patients with type 2 diabetes mellitus (T2DM) at greater risk of cancer. The association between cancer incidence and the use of antidiabetic medications in patients with T2DM has been recently examined. There have been conflicting reports regarding an association between metformin and cancer risk. The aim of this study was to investigate the relationship between metformin use and the incidence of cancer in Koreans with T2DM.Data from The Korean National Diabetes Program (KNDP, 2006-2014), a nationwide, large-scale, prospective, multicenter cohort study in Korea, were used to study patients with T2DM. Patients ?30 years old whose complete medical records were available were included in this study. Patients with a history of any cancer on KNDP registration or those who had been diagnosed with any type of cancer within 1 year of metformin use were excluded. Survival curves with respect to the incidence of cancer were plotted using the Kaplan-Meier method. Hazard ratios and 95% confidence intervals for cancer were estimated in a Cox proportional hazards regression analysis.During a mean 5.8 years of follow-up, 164 of the 1918 study patients (335 metformin nonusers and 1583 metformin users) developed cancer. The incidence per 1000 person-years was 21.8 in metformin nonusers and 13.2 in metformin users. Metformin users had a reduced risk of cancer, even after adjustment for demographic characteristics, metabolic parameters, diabetic complications, and other antidiabetic medications (hazard ratio 0.513, 95% confidence interval 0.318-0.826, P?=?.0060). Subgroup analysis of metformin users showed a reduced risk of cancer in males, patients?

SUBMITTER: Kim HJ

PROVIDER: S-EPMC5841986 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Metformin reduces the risk of cancer in patients with type 2 diabetes: An analysis based on the Korean National Diabetes Program Cohort.

Kim Hae Jin HJ Lee SooJin S Chun Ki Hong KH Jeon Ja Young JY Han Seung Jin SJ Kim Dae Jung DJ Kim Young Seol YS Woo Jeong-Taek JT Nam Moon-Suk MS Baik Sei Hyun SH Ahn Kyu Jeung KJ Lee Kwan Woo KW

Medicine 20180201 8

The epidemiological literature suggests that insulin resistance, hyperinsulinemia, and increased levels of insulin-like growth factors place patients with type 2 diabetes mellitus (T2DM) at greater risk of cancer. The association between cancer incidence and the use of antidiabetic medications in patients with T2DM has been recently examined. There have been conflicting reports regarding an association between metformin and cancer risk. The aim of this study was to investigate the relationship b ...[more]

PMID: 29465545

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Project description:Aims/hypothesisPreterm birth (gestational age <37 weeks) has been associated with insulin resistance early in life. However, no large population-based studies have examined risks of type 1 and type 2 diabetes and potential sex-specific differences from childhood into adulthood. Clinicians will increasingly encounter adults who were born prematurely and will need to understand their long-term risks. We hypothesised that preterm birth is associated with increased risks of type 1 and type 2 diabetes into adulthood.MethodsA national cohort study was conducted of all 4,193,069 singletons born in Sweden during 1973-2014, who were followed up for type 1 and type 2 diabetes identified from nationwide diagnoses and pharmacy data to the end of 2015 (maximum age 43 years; median age at the end of follow-up 22.5 years). Cox regression was used to adjust for potential confounders, and co-sibling analyses assessed the influence of shared familial (genetic and/or environmental) factors.ResultsIn 92.3 million person-years of follow-up, 27,512 (0.7%) and 5525 (0.1%) people were identified with type 1 and type 2 diabetes, respectively. Gestational age at birth was inversely associated with both type 1 and type 2 diabetes risk. Adjusted HRs for type 1 and type 2 diabetes at age <18 years associated with preterm birth were 1.21 (95% CI, 1.14, 1.28) and 1.26 (95% CI, 1.01, 1.58), respectively, and at age 18-43 years were 1.24 (95% CI, 1.13, 1.37) and 1.49 (95% CI, 1.31, 1.68), respectively, compared with full-term birth. The associations between preterm birth and type 2 (but not type 1) diabetes were stronger among females (e.g. at age 18-43 years, females: adjusted HR, 1.75; 95% CI, 1.47, 2.09; males: 1.28; 95% CI, 1.08, 1.53; p < 0.01 for additive and multiplicative interaction). These associations were only partially explained by shared genetic or environmental factors in families.Conclusions/interpretationIn this large national cohort, preterm birth was associated with increased risk of type 1 and type 2 diabetes from childhood into early to mid-adulthood. Preterm-born children and adults may need early preventive evaluation and long-term monitoring for diabetes.

Project description:ImportanceDiabetes is an established risk factor for developing cancer. A limited body of evidence also suggests that cancer can increase the risk of developing new cases of diabetes, but the evidence is inconclusive.ObjectiveTo evaluate whether the development of cancer is associated with increasing risk of subsequent diabetes.Design, setting, and participantsThis cohort study included a nationally representative sample of the Korean general population observed for up to 10 years (January 1, 2003, to December 31, 2013). A total of 524?089 men and women 20 to 70 years of age without diabetes and with no history of cancer at baseline were included.ExposuresIncident cancer (time-varying exposure).Main outcomes and measuresIncident type 2 diabetes using insurance claim codes.ResultsDuring 3?492?935.6 person-years of follow-up (median follow-up, 7.0 years) in 494?189 individuals (50.0% female; mean [SD] age, 41.8 [12.5] years), 15?130 participants developed cancer and 26?610 participants developed diabetes. After adjustment for age, sex, precancer diabetes risk factors, metabolic factors, and comorbidities, the hazard ratio (HR) for diabetes associated with cancer development was 1.35 (95% CI, 1.26-1.45; P?<?.001). The excess risk for diabetes was highest in the first 2 years after cancer diagnosis, but it remained elevated throughout follow-up. By cancer type, development of pancreatic (HR, 5.15; 95% CI, 3.32-7.99), kidney (HR, 2.06; 95% CI, 1.34-3.16), liver (HR, 1.95; 95% CI, 1.50-2.54), gallbladder (HR, 1.79; 95% CI, 1.08-2.98), lung (HR, 1.74; 95% CI, 1.34-2.24), blood (HR, 1.61; 95% CI, 1.07-2.43), breast (HR, 1.60; 95% CI, 1.27-2.01), stomach (HR, 1.35; 95% CI, 1.16-1.58), and thyroid cancer (HR, 1.33; 95% CI, 1.12-1.59) was associated with a significantly increased risk of diabetes.Conclusions and relevanceIn this large Korean cohort, cancer development increased the risk of subsequent diabetes. These data provide evidence that cancer is associated with an increased risk of diabetes in cancer survivors independent of traditional diabetes risk factors. Physicians should remember that patients with cancer develop other clinical problems, such as diabetes, with higher frequency than individuals without cancer, and should consider routine diabetes screening in these patients.

Dataset Information

Metformin reduces the risk of cancer in patients with type 2 diabetes: An analysis based on the Korean National Diabetes Program Cohort.

Publications

Metformin reduces the risk of cancer in patients with type 2 diabetes: An analysis based on the Korean National Diabetes Program Cohort.

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