Cancer Specific Mortality in Insulin-Treated Type 2 Diabetes Patients

Abstract

AimsTo test the hypothesis that cumulative exposure to insulin and long-acting insulin analogs might be associated with cancer mortality in diabetes patients.MethodsAll consecutive diabetes patients aged over 40 years, residing in a major urban area were screened at their first diabetes outpatient visit between 01/01/2001-12/31/2008 (n = 79869). Exclusion criteria were insulin treatment at screening, no insulin treatment until 12/31/2008, less than 6 months of glucose-lowering treatment alone before insulin initiation, insulin prescription before glargine became available, age <40/≥80 years at first insulin prescription, and <6 months of insulin exposure. A total 4990 subjects were followed-up for death based on death certificate, until 12/31/2011. Adjusted time-dependent competing risk regression analysis, with daily updates of treatment modalities was performed. Results are expressed for every 10,000 IU of cumulative dose or one year of cumulative time exposure to insulin.ResultsMean baseline age was 62±9 years, and follow-up 4.7±1.9 years. Glargine cumulative dose was associated with lower cancer mortality risk (subhazard ratio, SHR: 0.94 (95%CI 0.89–0.99, p = 0.033)). Cumulative exposure limited to that attained one year prior to death revealed lower SHRs for cumulative time (0.94 (95%CI 0.89–0.99, p = 0.018)) and cumulative dose of glargine (0.92 (95%CI 0.86–0.98, p = 0.014)). Glargine cumulative time and cumulative dose were significant predictors for lower pancreatic and breast cancer mortality, but not for deaths from lung, colorectal, female genital, liver, and urinary tract cancer. No increased hazards were found for any other subtypes of insulins.ConclusionsThe cumulative dose exposure to insulin glargine was associated with a lower risk of cancer mortality in general, and of breast and pancreatic cancer in particular. This effect remained even after additional “fixed” cohort or propensity score analyses.

Insulin and GH–IGF-I axis: endocrine pacer or endocrine disruptor?

“…This has been confirmed by other several large studies [147][148][149]. In particular, the use of glargine was not associated with either an increased mortality for cancer [147] or a higher incidence of malignancies [148,149].…”

“…Really, several subsequent clinical studies did not confirm these data, and a specific large randomized controlled trial, designed to test cardiovascular and cancer risk of glargine, did not show any increase in cancer risk in patients treated with glargine [146]. This has been confirmed by other several large studies [147][148][149]. In particular, the use of glargine was not associated with either an increased mortality for cancer [147] or a higher incidence of malignancies [148,149].…”

A Prognostic Model to Predict Mortality among Non–Small-Cell Lung Cancer Patients in the U.S. Military Health System

“…Large cell histology has also been reported to be associated with worse survival compared to other histologic types (12, 14). The associations between type II diabetes mellitus and high risk of mortality in lung cancer patients have been reported in previous studies 30–33 although the association was not consistently observed in other studies 34 . Peripheral vascular and cerebrovascular diseases are among the most commonly found comorbidities among lung cancer patients that contributed to decreased survival in NSCLC patients 35, 36 .…”

Type 2 diabetes, insulin treatment and prognosis of breast cancer

“…Other publications demonstrated that insulin treatment did not influence breast cancer survival significantly . One study even reported that insulin treatment was a favourable factor for breast cancer patients . In summary, there was large variation in the abovementioned studies, and the effect of insulin therapy on the prognosis of breast cancer is still a mystery.…”