Glycemic control was associated with nonprostate cancer and overall mortalities in diabetic patients with prostate cancer

Abstract

Background: Diabetes mellitus (DM) can worsen the prognosis or survival in prostate cancer (PC) patients. We investigated whether glycemic control impacts mortality in PC patients with existing diabetes. Methods: All PC patients with or without preexisting DM were enrolled from 2006 to 2017. Mean hemoglobin A1c (HbA1c) values (<7%, 7%-9%, ≥9%) were used to represent glycemic control. Major outcomes included all-cause, PC-specific, and non-PC mortalities. Statistical analyses were performed using Cox regression models with adjusted mean HbA1c and other related confounders. Results: A total of 831 PC patients were enrolled (non-DM group, n = 690; DM group with a record of mean HbA1c values, n = 141). Results showed that the DM group with mean HbA1c level ≥ 9% (n = 14) had significantly increased risk for all-cause and non-PC mortality (hazard ratio [HR], 3.09; 95% CIs, 1.15-8.32; p=0.025 and HR, 5.49; 95% CIs, 1.66-18.16; p = 0.005, respectively), but not for PC-specific mortality (HR, 1.03; 95% CIs, 0.13-8.44; p = 0.975), compared with the non-DM group. Conclusion: Our findings indicate that PC patients with DM who had a mean HbA1c level ≥ 9% had higher risks of all-cause and non-PC mortality compared with non-DM subjects. Further large and long-term studies are needed to verify the effect of glycemic control in PC patients with DM.

Glycemic control and outcome of cancer patients

“…The current study by Dr Lin also included this confounding factor-the use or no-use of metformin in PC patients with T2DM, and in their model 2 which included the use of metformin, all-cause mortality was positively correlated with poor glycemia control of T2DM and Gleason score; non-PC mortality was positively correlated with poor glycemia control of T2DM, and PC-specific mortality was positive correlated with Gleason score. 11 In conclusion, T2DM and cancer have a multifaceted relationship and may share regulatory mechanisms, although the biological links between T2DM and cancer are not completely understood. Metabolic dysregulation, dyslipidemia, hyperinsulinemia, hyperglycemia, abnormal secretion of local and systemic proinflammatory factors inducing chronic inflammation, excessive production of oxygen-free radicals through oxidative stress, abnormal levels of adipokines, such as leptin and adiponectin, overproduction of insulin-like growth factors, which are all found frequently in patients with T2DM, are also a factor in initiation, development, and progression of cancer.…”

“…It is well-known that T2DM has been associated with the risk of all-site and some site-specific cancers in several systematic reviews and meta-analysis, and cancer patients (liver, endometrium, pancreas, colon, breast, gastrointestinal tract, bladder, and leukemia) with T2DM have a 15%-225% higher risk of mortality, but conflicted results have also been reported in PC. 1,2,10,12,13 Lin et al 11 showed all-cause mortality was really increased in PC patients with T2DM, regardless whether glycemic control is good or poor compared to that in PC patients without. The trend is more apparent in patients with poor glycemic control (HbA1c ≥ 9%).…”

“…14,15 However, after adjusting all confounding factors, hormone therapy did not influence all-cause or cancer-specific mortality of PC patients in Dr. Lin's study. 11 Finally, antidiabetic agents and/or cholesterol-lowing medications, such as metformin and/or statins have been long-term considered as a protective factor for prevention and treatment of patients with various kinds of cancers, although the findings are not always consistent. 11,16,17 One study found that hydrophilic statins, and pravastatin in particular, are associated with improved disease free survival (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.53-0.95) as well as overall survival (HR 0.69, 95% CI 0.50-0.93, as well as HR 0.67, 95% CI 0.47-0.96).…”

“…11 Finally, antidiabetic agents and/or cholesterol-lowing medications, such as metformin and/or statins have been long-term considered as a protective factor for prevention and treatment of patients with various kinds of cancers, although the findings are not always consistent. 11,16,17 One study found that hydrophilic statins, and pravastatin in particular, are associated with improved disease free survival (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.53-0.95) as well as overall survival (HR 0.69, 95% CI 0.50-0.93, as well as HR 0.67, 95% CI 0.47-0.96). 17 Metformin, widely prescribed for T2DM patients, regulate blood sugar by inhibiting hepatic gluconeogenesis and promoting insulin sensitivity to facilitate glucose uptake by cells, mediated by AMP-activated protein kinase (AMPK) and non-AMPK pathways to exert effects beyond those related to T2DM treatment that might ameliorate cancer.…”

Molecular pathology-integrated clinicopathological prognostic factors

“…Finally, similar to many studies in the literature, the main limitation of the current article cannot avoid many confounding factors. 19,20 For example, in real-world clinical practice which is unlike to the well-established prospective, randomized clinical trial, it is hard to enroll the subjected with little heterogeneous characteristics; therefore, it is difficult to make a strong conclusion. 16 Additionally, retrospectivity in nature may also be a limit.…”