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Published in: BMC Women's Health 1/2017

Open Access 01-12-2017 | Research article

Evaluating the role of race and medication in protection of uterine fibroids by type 2 diabetes exposure

Authors: Digna R. Velez Edwards, Katherine E. Hartmann, Melissa Wellons, Anushi Shah, Hua Xu, Todd L. Edwards

Published in: BMC Women's Health | Issue 1/2017

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Abstract

Background

Uterine fibroids (UF) affect 77% of women by menopause, and account for $9.4 billion in annual healthcare costs. Type-2-diabetes (T2D) has inconsistently associated with protection from UFs in prior studies. To further evaluate the relationship between T2D and UFs we tested for association between T2D and UF risk in a large clinical population as well as the potential differences due to T2D medications and interaction with race.

Methods

This nested case–control study is derived from a clinical cohort. Our outcome was UF case-control status and our exposure was T2D. UF outcomes and T2D exposure were classified using validated electronic medical record (EMR) algorithms. Logistic regression, adjusted for covariates, was used to model the association between T2D diagnosis and UF risk. Secondary analyses were performed evaluating the interaction between T2D exposure and race and stratifying T2D exposed subjects by T2D medication being taken.

Results

We identified 3,789 subjects with UF outcomes (608 UF cases and 3,181 controls), 714 were diabetic and 3,075 were non-diabetic. We observed a nominally significant interaction between T2D exposure and race in adjusted models (interaction p = 0.083). Race stratified analyses demonstrated more protection by T2D exposure on UF risk among European Americans (adjusted odds ratio [aOR] = 0.50, 95% CI 0.35 to 0.72) than African Americans (aOR = 0.76, 95% CI 0.50 to 1.17). We also observed a protective effect by T2D regardless of type of T2D medication being taken, with slightly more protection among subjects on insulin treatments (European Americans aOR = 0.42, 95% CI 0.26 to 0.68; African Americans aOR = 0.60, 95% CI 0.36 to 1.01).

Conclusions

These data, conducted in a large population of UF cases and controls, support prior studies that have found a protective association between diabetes presence and UF risk and is further modified by race. Protection from UFs by T2D exposure was observed regardless of medication type with slightly more protection among insulin users. Further mechanistic research in larger cohorts is necessary to reconcile the potential role of T2D in UF risk.
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Literature
1.
2.
go back to reference Marshall LM, Spiegelman D, Barbieri RL, Goldman MB, Manson JE, Colditz GA, et al. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet Gynecol. 1997;90:967–73.CrossRefPubMed Marshall LM, Spiegelman D, Barbieri RL, Goldman MB, Manson JE, Colditz GA, et al. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet Gynecol. 1997;90:967–73.CrossRefPubMed
3.
go back to reference Vollenhoven B. Introduction: the epidemiology of uterine leiomyomas. Baillieres Clin Obstet Gynaecol. 1998;12:169–76.CrossRefPubMed Vollenhoven B. Introduction: the epidemiology of uterine leiomyomas. Baillieres Clin Obstet Gynaecol. 1998;12:169–76.CrossRefPubMed
4.
go back to reference Day BD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188:100–7.CrossRef Day BD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188:100–7.CrossRef
5.
go back to reference Faerstein E, Szklo M, Rosenshein NB. Risk factors for uterine leiomyoma: a practice-based case–control study. II. Atherogenic risk factors and potential sources of uterine irritation. Am J Epidemiol. 2001;153:11–9.CrossRefPubMed Faerstein E, Szklo M, Rosenshein NB. Risk factors for uterine leiomyoma: a practice-based case–control study. II. Atherogenic risk factors and potential sources of uterine irritation. Am J Epidemiol. 2001;153:11–9.CrossRefPubMed
6.
go back to reference Faerstein E, Szklo M, Rosenshein N. Risk factors for uterine leiomyoma: a practice-based case–control study. I. African-American heritage, reproductive history, body size, and smoking. Am J Epidemiol. 2001;153:1–10.CrossRefPubMed Faerstein E, Szklo M, Rosenshein N. Risk factors for uterine leiomyoma: a practice-based case–control study. I. African-American heritage, reproductive history, body size, and smoking. Am J Epidemiol. 2001;153:1–10.CrossRefPubMed
7.
go back to reference Ojeda VJ. The pathology of hysterectomy specimens. N Z Med J. 1979;89:169–71.PubMed Ojeda VJ. The pathology of hysterectomy specimens. N Z Med J. 1979;89:169–71.PubMed
8.
go back to reference Moore AB, Flake GP, Swartz CD, Heartwell G, Cousins D, Haseman JK, et al. Association of race, age and body mass index with gross pathology of uterine fibroids. J Reprod Med. 2008;53:90–6.PubMed Moore AB, Flake GP, Swartz CD, Heartwell G, Cousins D, Haseman JK, et al. Association of race, age and body mass index with gross pathology of uterine fibroids. J Reprod Med. 2008;53:90–6.PubMed
9.
go back to reference Takeda T, Sakata M, Isobe A, Miyake A, Nishimoto F, Ota Y, et al. Relationship between metabolic syndrome and uterine leiomyomas: a case–control study. Gynecol Obstet Invest. 2008;66:14–7.CrossRefPubMed Takeda T, Sakata M, Isobe A, Miyake A, Nishimoto F, Ota Y, et al. Relationship between metabolic syndrome and uterine leiomyomas: a case–control study. Gynecol Obstet Invest. 2008;66:14–7.CrossRefPubMed
10.
go back to reference Baird DD, Travlos G, Wilson R, Dunson DB, Hill MC, D’Aloisio AA, et al. Uterine leiomyomata in relation to insulin-like growth factor-I, insulin, and diabetes. Epidemiology. 2009;20:604–10.CrossRefPubMedPubMedCentral Baird DD, Travlos G, Wilson R, Dunson DB, Hill MC, D’Aloisio AA, et al. Uterine leiomyomata in relation to insulin-like growth factor-I, insulin, and diabetes. Epidemiology. 2009;20:604–10.CrossRefPubMedPubMedCentral
12.
go back to reference Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 2010;33:1304–8.CrossRefPubMedPubMedCentral Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 2010;33:1304–8.CrossRefPubMedPubMedCentral
13.
go back to reference Bosco JL, Antonsen S, Sorensen HT, Pedersen L, Lash TL. Metformin and incident breast cancer among diabetic women: a population-based case–control study in Denmark. Cancer Epidemiol Biomarkers Prev. 2011;20:101–11.CrossRefPubMed Bosco JL, Antonsen S, Sorensen HT, Pedersen L, Lash TL. Metformin and incident breast cancer among diabetic women: a population-based case–control study in Denmark. Cancer Epidemiol Biomarkers Prev. 2011;20:101–11.CrossRefPubMed
14.
go back to reference Currie CJ, Poole CD, Jenkins-Jones S, Gale EA, Johnson JA, Morgan CL. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care. 2012;35:299–304.CrossRefPubMedPubMedCentral Currie CJ, Poole CD, Jenkins-Jones S, Gale EA, Johnson JA, Morgan CL. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care. 2012;35:299–304.CrossRefPubMedPubMedCentral
15.
go back to reference Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52:1766–77.CrossRefPubMed Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52:1766–77.CrossRefPubMed
16.
go back to reference Pulley J, Clayton E, Bernard GR, Roden DM, Masys DR. Principles of human subjects protections applied in an opt-out, de-identified biobank. Clin Transl Sci. 2010;3:42–8.CrossRefPubMedPubMedCentral Pulley J, Clayton E, Bernard GR, Roden DM, Masys DR. Principles of human subjects protections applied in an opt-out, de-identified biobank. Clin Transl Sci. 2010;3:42–8.CrossRefPubMedPubMedCentral
17.
go back to reference Feingold-Link L, Edwards TL, Jones S, Hartmann KE, Velez Edwards DR. Enhancing uterine fibroid research through utilization of biorepositories linked to electronic medical record data. J Womens. Health (Larchmt.) 2014;23:1027–1032. Feingold-Link L, Edwards TL, Jones S, Hartmann KE, Velez Edwards DR. Enhancing uterine fibroid research through utilization of biorepositories linked to electronic medical record data. J Womens. Health (Larchmt.) 2014;23:1027–1032.
18.
go back to reference Hartmann KE, Birnbaum H, Ben-Hamadi R, Wu EQ, Farrell MH, Spalding J, et al. Annual costs associated with diagnosis of uterine leiomyomata. Obstet Gynecol. 2006;108:930–7.CrossRefPubMed Hartmann KE, Birnbaum H, Ben-Hamadi R, Wu EQ, Farrell MH, Spalding J, et al. Annual costs associated with diagnosis of uterine leiomyomata. Obstet Gynecol. 2006;108:930–7.CrossRefPubMed
19.
go back to reference Ritchie MD, Denny JC, Crawford DC, Ramirez AH, Weiner JB, Pulley JM, et al. Robust replication of genotype-phenotype associations across multiple diseases in an electronic medical record. Am J Hum Genet. 2010;86:560–72.CrossRefPubMedPubMedCentral Ritchie MD, Denny JC, Crawford DC, Ramirez AH, Weiner JB, Pulley JM, et al. Robust replication of genotype-phenotype associations across multiple diseases in an electronic medical record. Am J Hum Genet. 2010;86:560–72.CrossRefPubMedPubMedCentral
20.
go back to reference Doan S, Bastarache L, Klimkowski S, Denny JC, Xu H. Integrating existing natural language processing tools for medication extraction from discharge summaries. J Am Med Inform Assoc. 2010;17:528–31.CrossRefPubMedPubMedCentral Doan S, Bastarache L, Klimkowski S, Denny JC, Xu H. Integrating existing natural language processing tools for medication extraction from discharge summaries. J Am Med Inform Assoc. 2010;17:528–31.CrossRefPubMedPubMedCentral
21.
go back to reference Xu H, Stenner SP, Doan S, Johnson KB, Waitman LR, Denny JC. MedEx: a medication information extraction system for clinical narratives. J Am Med Inform Assoc. 2010;17:19–24.CrossRefPubMedPubMedCentral Xu H, Stenner SP, Doan S, Johnson KB, Waitman LR, Denny JC. MedEx: a medication information extraction system for clinical narratives. J Am Med Inform Assoc. 2010;17:19–24.CrossRefPubMedPubMedCentral
22.
go back to reference Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009;32:1620–5.CrossRefPubMedPubMedCentral Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009;32:1620–5.CrossRefPubMedPubMedCentral
23.
go back to reference Ben SI, Le Marchand-Brustel Y, Tanti JF, Bost F. Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther. 2010;9:1092–9.CrossRef Ben SI, Le Marchand-Brustel Y, Tanti JF, Bost F. Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther. 2010;9:1092–9.CrossRef
24.
go back to reference Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle. 2009;8:88–96.CrossRefPubMed Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle. 2009;8:88–96.CrossRefPubMed
25.
Metadata
Title
Evaluating the role of race and medication in protection of uterine fibroids by type 2 diabetes exposure
Authors
Digna R. Velez Edwards
Katherine E. Hartmann
Melissa Wellons
Anushi Shah
Hua Xu
Todd L. Edwards
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Women's Health / Issue 1/2017
Electronic ISSN: 1472-6874
DOI
https://doi.org/10.1186/s12905-017-0386-y

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