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.

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Data availability

Data is available via CESQIP.org and by written request. These data were previously presented in limited fashion at the virtual CESQIP session hosted by the American Association of Endocrine Surgeons (AAES) on May 18, 2020.

Abbreviations

ACC:

Adrenocortical carcinoma

CESQIP:

Collaborative Endocrine Surgery Quality Improvement Program

DM:

Diabetes mellitus

DFCI:

Dana Farber Cancer Institute

AAES:

American Association of Endocrine Surgeons

BMI:

Body mass index

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Acknowledgements

The authors would like to thank the AAES research committee of CESQIP, particularly Dr. Dave Schneider for making these data available. We would like to thank Lia Wrenn MD for her critical appraisal of the manuscript and for her support.

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Authors

Contributions

Sean Wrenn: Study conception and design, drafting of manuscript, analysis and interpretation of data, and critical revision of manuscript. TK Pandian: Study conception and design and critical revision of manuscript. Rajshri Gartland: Analysis and interpretation of data and critical revision of manuscript. Zhi Ven Fong: Analysis and interpretation of data and critical revision of manuscript. Matthew Nehs: Study conception and design, analysis and interpretation of data, drafting of manuscript, and critical revision of manuscript.

Corresponding author

Correspondence to Sean M. Wrenn.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

This article does not contain any studies with animals performed by any of the authors.

Informed consent

Given the retrospective nature of this research, a waiver of informed consent was obtained by the Institutional Review Board.

Disclaimer

“CESQIP and the hospitals participating in CESQIP are the source of the data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors. The conclusions, findings, and opinions expressed by the authors do not necessarily reflect the official position of the AAES or CESQIP. Use of CESQIP data does not imply endorsement by any of the groups named above.”

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Wrenn, S.M., Pandian, T.K., Gartland, R.M. et al. Diabetes mellitus and hyperglycemia are associated with inferior oncologic outcomes in adrenocortical carcinoma. Langenbecks Arch Surg (2021). https://doi.org/10.1007/s00423-020-02061-0

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Keywords

  • Adrenal gland
  • Adrenocortical carcinoma
  • Endocrine surgery
  • Surgical metabolism
  • Quality
  • Outcomes
  • Diabetes mellitus
  • Hyperglycemia
  • Warburg effect