Diabetes mellitus and hyperglycemia are associated with inferior oncologic outcomes in adrenocortical carcinoma

Abstract

Purpose: Prior literature suggests that cancer patients with hyperglycemia and type 2 diabetes mellitus (DM) exhibit worse oncologic and overall outcomes. Tumor metabolism and anabolism pathophysiology may explain this association, although this has not been adequately studied in adrenocortical carcinoma (ACC). We hypothesized that DM would be associated with worse oncological outcomes in ACC, and we utilized data from a national database and institutional sources for multimodal analysis.

Methods: Both a multi-institutional database (the Collaborative Endocrine Surgery Quality Improvement Program or CESQIP) and a single-center longitudinal cohort (Dana Farber Cancer Institute or DFCI) were queried as unique retrospective cohorts to identify patients with ACC. Patient demographics, tumor characteristics, DM-specific variables, and oncologic outcome data were assessed. Results were analyzed via univariate analysis and multivariable linear regression analysis. Statistical significance was defined as p < 0.05.

Results: Forty-eight CESQIP patients met inclusion criteria; 16 (33.0%) had DM. DM patients had a higher frequency of recurrence on longitudinal follow-up (12.5% v 0.0%, p = 0.04). Persistent disease was observed in 68.8% of DM patients and 40.6% of non-DM patients (p = 0.06). Patients in the DFCI cohort with lower average glucose values (< 110 mg/dL) had a significant survival benefit (p < .0001). A mean serum glucose > 110 mg/dL had increased risk (HR 36.3, 95% confidence interval 1.6, 831.3) for all-cause mortality.

Conclusions: This multi-institutional, multimodal analysis suggests that patients with DM have worse oncologic and overall outcomes for ACC. While further study is warranted, consideration should be given among clinicians to optimize glycemic control as part of their ACC management.

Keywords: Adrenal gland; Adrenocortical carcinoma; Diabetes mellitus; Endocrine surgery; Hyperglycemia; Outcomes; Quality; Surgical metabolism; Warburg effect.