Diabetes mellitus and ovarian cancer: More complex than just increasing risk

Abstract

Objective Diabetes mellitus (DM) is a risk factor for endometrial cancer and is associated with poorer outcomes in breast and colon cancers. This association is less clear in epithelial ovarian cancer (EOC). We sought to examine the effect of DM on progression-free (PFS) and overall survival (OS) in women with EOC. Methods A retrospective cohort study of EOC patients diagnosed between 2004 and 2009 at a single institution was performed. Demographic, pathologic and DM diagnosis data were abstracted. Pearson chi-square test and t test were used to compare variables. The Kaplan-Meier method and the log rank test were used to compare PFS and OS between non-diabetic (ND) and DM patients. Results 62 (17%) of 367 patients had a diagnosis of DM. No differences in age, histology, debulking status, or administration of intraperitoneal chemotherapy between ND and DM patients were present, although there were more stage I and IV patients in the ND group (p=0.04). BMI was significantly different between the two groups (ND vs. DM, 27.5 vs. 30.7 kg/m2, p < 0.001). While there were no differences in survival based on BMI, diabetic patients had a poorer PFS (10.3 vs. 16.3 months, p=0.024) and OS (26.1 vs. 42.2 months, p=0.005) compared to ND patients. Metformin use among diabetic patients did not appear to affect PFS or OS. Conclusions EOC patients with DM have poorer survival than patients without diabetes; this association is independent of obesity. Metformin use did not affect outcomes. The pathophysiology of this observation requires more inquiry.

Metabolic risk factors and mechanisms of disease in epithelial ovarian cancer: A review

“…This was partially attributed to co-morbidities frequently present in diabetics; however, a multivariable analysis confirmed that the presence of diabetes was an independent risk factor for death with regard to overall survival (HR 2.04, 95% CI 1.31–3.17, p = 0.002) [10]. A retrospective cohort study (n = 367) mirrored these findings, with diabetic patients exhibiting both poorer PFS (10.3 vs. 16.3 months) and OS (26.1 vs. 42.2 months) [4]. It has been postulated that survival differences may be partially attributable to different treatment approaches in diabetic patients due to comorbidities and dose limiting chemotherapy toxicities such as neuropathy.…”

“…Metformin usage is another confounding variable when assessing the correlation of diabetes to ovarian cancer. Some reports suggest that metformin reduces cancer mortality [25], whereas others have reported no survival difference among patients taking metformin [4]. …”

“…However, in one single institution study diabetic patients were not less likely to receive optimal surgical cytoreduction or to undergo complete surgical staging and they were equally as likely to undergo neoadjuvant treatment than non-diabetics [10]. Furthermore, the frequency with which diabetics receive intraperitoneal (IP) chemotherapy was equivalent to their non-diabetic counterparts in a single-institution study [4]. Diabetic patients may experience dose-limiting toxicities during chemotherapy that could contribute to their poorer survival, most commonly development or worsening of neuropathy.…”

“…The incidence of neuropathy in diabetic patients is approximately 30%, with an increased risk with increasing age, duration of disease, and poorer glycemic control [26, 27]. Bakhru et al demonstrated that diabetics with EOC were more likely to be older (59.9 vs. 54.7 years old in non-diabetics) and postmenopausal [10], conflicting with findings from Shah et al, which found no difference in the age of diabetic vs. non-diabetic patients with EOC (64.6 vs. 63.2) [4]. Findings by Shah et al suggest that in those with early stage disease, diabetic patients have a worse prognosis.…”

“…Among adults with DM, approximately 60% also have obesity and 80% have a BMI > 25 [8]. The link between DM and EOC incidence is debated [9]; however, DM has been clearly associated with poorer outcomes and shorter survival in EOC [4,10]. MetS is defined by the presence of three of the five following metabolic derangements in an individual: elevated waist circumference (population and country specific cutoffs), elevated triglycerides (≥150 mg/dL), reduced high-density lipoprotein cholesterol (<40 mg/dL in males, <50 mg/dL in females), hypertension (systolic ≥ 130, diastolic ≥ 85), and elevated fasting glucose (≥ 100 mg/dL) [11].…”