Co-morbidity of type 1 diabetes and endometriosis: bringing a new paradigm into focus

in Journal of Endocrinology
Correspondence should be addressed to R C M Simmen: simmenrosalia@uams.edu

Type 1 diabetes mellitus and endometriosis separately affect millions of women worldwide. Reproductive-age women diagnosed with type 1 diabetes may also suffer from endometriosis, but the asymptomatic pre-clinical period of highly variable duration for each condition can lead to challenges in the timely recognition of co-morbid disease onset and misdiagnosis. While knowledge of the pathogenesis of each condition has grown substantially, co-morbid endometriosis and type 1 diabetes has not been widely considered and much less addressed. This review discusses the molecular rationale for the likelihood of their co-existence, and prospects for improvements in therapeutic strategies and reduced complications, if this paradigm is included as a significant variable in disease management.

Abstract

Type 1 diabetes mellitus and endometriosis separately affect millions of women worldwide. Reproductive-age women diagnosed with type 1 diabetes may also suffer from endometriosis, but the asymptomatic pre-clinical period of highly variable duration for each condition can lead to challenges in the timely recognition of co-morbid disease onset and misdiagnosis. While knowledge of the pathogenesis of each condition has grown substantially, co-morbid endometriosis and type 1 diabetes has not been widely considered and much less addressed. This review discusses the molecular rationale for the likelihood of their co-existence, and prospects for improvements in therapeutic strategies and reduced complications, if this paradigm is included as a significant variable in disease management.

Introduction

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, resulting from the destruction of insulin-producing β-cells of the pancreatic islets of Langerhans, which leads to a state of hypoinsulinemia and hyperglycemia. In 2015, 1.25 million Americans suffered from T1DM, with an annual economic cost of ~$14B (https://beyondtype1.org/type-1). With 40,000 new cases diagnosed annually, the prediction that 5 million people will have T1DM by 2020 is disconcerting. The incidence of T1DM has also increased by ~3% per year globally, albeit with some geographical preferences (Maahs et al. 2010). Mortality risks are higher in individuals with T1DM than in the general population (Collier et al. 2018). While T1DM is often diagnosed at childhood and may have early life origins (Knip et al. 2017), the condition has later onset in many adults. In such cases, the condition is often mistaken for type 2 diabetes, leading to inappropriate management and a life-threatening state (Thomas et al. 2019).

Endometriosis (ENDO), a chronic estrogen-dependent disease, characterized by the implantation and growth of endometrial tissues predominantly in the peritoneal cavity and the ovary, affects 6–10% of all reproductive-age women (average age 13–45 years) (Burney & Giudice 2012). Debilitating pelvic pain, infertility in 50% of afflicted patients, considerable morbidity, and an economic burden of ~$50B a year in the United States alone accompany this condition. ENDO is often subject to delayed diagnosis, has no known effective treatment and is recurrent.

T1DM and ENDO share similar pathophysiology since both are associated with chronic inflammation triggered by overactivation of the immune response (Cabrera et al. 2016, Symons et al. 2018). The predominance of ENDO in women with T1DM remains unknown; however, women (and young girls upon initiation of menses) with T1DM may suffer from ENDO during their reproductive years. Considering the significant health and economic burdens related to T1DM and ENDO singly and the prospect of their co-incidence, an increased understanding of their risks and predisposition are imperative. This review aims to address why these two conditions may co-exist and how awareness of this possibility may improve clinical management and quality of life in affected women.

Commonalities between T1DM and ENDO

Inflammatory status

Substantial evidence from human and animal studies indicates that dysfunction in local immune signaling contributes to the development and maintenance of ectopic lesions (EC) in ENDO (Ulukus & Arici 2005, Pabona et al. 2012, Greaves et al. 2014). A review on this topic (Symons et al. 2018) summarizes the cell populations of the innate immune system implicated in ENDO pathophysiology. Neutrophils, macrophages, and natural killer cells recruited to EC may promote ENDO in two ways. One mechanism for which the estrogen receptor-β (ESR2) signaling cascade has been implicated (Han et al. 2015), results in increased secretion of various cytokines that support the growth, invasion and angiogenic properties of lesions (Capobianco et al. 2011). A second mechanism occurs via the reduction in the phagocytic abilities of macrophages and natural killer cells, thus inhibiting the clearance of endometrial cells in the immediate environment of lesions (Chuang et al. 2010). In a murine model of ENDO, EC growth was associated with dendritic cells, which can attenuate (Stanic et al. 2014) or enhance (Pencovich et al. 2014) the process. Toll-like receptors (TLRs) are essential components of the innate immune system owing to their roles in mediating pattern recognition of and response toward pathogens and host-related antigens. In patients with peritoneal ENDO, higher expression of TLR3 and TLR4 in glandular epithelium of EC than of corresponding EU were noted (Allhorn et al. 2008, Hayashi et al. 2013). A potential mechanism for TLR4 promotion of ENDO has been described (Luo et al. 2015). In this scenario, TLR4 activation causes increased secretion of pro-inflammatory interleukin-8 (IL-8) and enhanced expression of IL-8 receptor C-X-C motif chemokine receptor-1 in endometriotic stromal cells, to bolster these cells’ invasive and proliferative potential.

In recent years, innate immunity in the pathogenesis of T1DM has gained substantial support and has linked TLRs in mediating islet inflammation (Lien & Zipris 2009, Alkanani et al. 2012, Cabrera et al. 2016). TLRs implicated in T1DM include TLR1, TLR2, TLR3, TLR7 and TLR9. Nonetheless, distinct TLRs may be protective or supportive of T1DM, suggesting contextual effects and differing mechanisms. For example, in non-obese diabetic mice, TLR4 deficiency accelerated the development of T1DM (Devaraj et al. 2011, Gülden et al. 2013), while loss of TLR9 reduced incidence of T1DM (Tai et al. 2013). Similar to ENDO, T1DM pathogenesis is associated with aberrant dendritic cell function. Many polymorphic loci identified by genome-wide and disease-association studies and which can potentially underlie susceptibility to T1DM have been linked to immune dysfunctions in dendritic cells such as in cytokine signaling, development and activation, all of which disrupt their tolerogenic properties (Hotta-Iwamura & Tarbell 2016). The recent identification of an insulin B peptide as a trigger of T-regulatory cells in the pancreas provides a promising prospect for targeting TLRs and dendritic cells to suppress autoimmunity in T1DM (Wang et al. 2019).

Risk for ovarian and other cancers

Epidemiological and molecular evidence indicate that while benign in its initial stages, ENDO is an independent risk factor for both clear-cell and endometroid ovarian carcinoma (reviewed in Lee et al. 2016, Bulun et al. 2019). Somatic mutations in key genes, primarily phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and Kirsten rat sarcoma (KRAS) in endometriotic epithelial cells have been suggested to contribute to the development of ovarian cancers (Er et al. 2016). However, mutations in these same genes have been detected in endometriosis with and without cancers (Anglesio et al. 2017). Moreover, epithelial cells isolated from ovarian endometriotic lesions and normal/benign uterine endometrium displayed mutations in both PIK3CA and KRAS, albeit at different allele frequencies, suggesting that these mutations are not sufficiently causal for ovarian cancers (Suda et al. 2018). In a comparison of gene expression patterns of normal (non-diseased) endometria with those of endometriosis (benign, atypical, concurrent with endometriosis) and endometriosis-associated ovarian cancer, Andersen et al. (2018) implicated the loss of estrogen receptor-α signaling and the development of endocrine resistance as contributing to the progression of ENDO to endometriosis-associated ovarian carcinoma. More detailed examination of coincident and multi-gene mutations occurring in endometriosis and ovarian cancers is undoubtedly needed to reinforce the ENDO-Ovarian cancer link.

T1DM patients of both genders show increased risks for several cancers (stomach, kidney, liver, and pancreas) (Shu et al. 2010, Carstensen et al. 2016). In women, T1DM increased predisposition to ovarian and endometrial cancers, but unlike type 2 diabetes, did not influence breast cancer risk (Liaw et al. 2015, Wise 2016). Two recent epidemiological studies provide support for an association between T1DM and increased ovarian cancer risk. In a study conducted in the United Kingdom, ovarian cancer risk was significantly elevated in younger-onset T1DM patients (standard incidence ratio of 2.14) (Swerdlow et al. 2005). Another study conducted in Taiwan of 14,610 female patients with T1DM showed a significant positive association between T1DM patients and risk for ovarian cancer (Hsu et al. 2015). Mechanistically, the association maybe explained in part, by high levels of glucose that promote tumor growth (Kellenberger & Petrik 2018). However, no studies to date have linked ovarian cancer risk in women with co-morbid T1DM and ENDO.

Vascular dysfunctions

ENDO is an independent risk factor for venous thromboembolism, a major cause of maternal mortality, during pregnancy and post-partum (Abe et al. 2019, Sugiura-Ogasawara et al. 2019). Increased cardiovascular disease is also associated with infertility (Mahalingaiah et al. 2017), a co-morbidity of ENDO.

Cardiovascular disease is the leading cause of death in T1DM patients. Serum concentrations of cardiovascular disease biomarkers (e.g., soluble intracellular adhesion molecule 1, soluble endothelial selectin) are higher in T1DM than in healthy women (Lebkowska et al. 2017). Branchial distensibility, an independent risk factor for cardiovascular disease, showed a steeper decline with age in T1DM that in non-diabetic, women (Ljunggren et al. 2016). Interestingly, women with T1DM have higher risks of fatal and non-fatal vascular events than males with T1DM (Huxley et al. 2015).

Compromised reproductive health

Infertility, dysmenorrhea and pelvic pain are common symptoms of reproductive-age women with ENDO (Burney & Giudice 2012). Women with ENDO are predisposed to increased early pregnancy loss and later pregnancy complications such as placenta previa, antepartum and post-partum hemorrhage, small-for-gestational-age births and cesarean delivery (Saraswat et al. 2017, Zullo et al. 2017).

Women with T1DM manifest delayed puberty and menarche, oligomenorrhea, mild hyperandrogenism, and in some cases, earlier menopause (Codner et al. 2012). Increased risk of infertility in women with T1DM compared to women without T1DM, was also noted, despite adjustments for irregular menses (Kim et al. 2018). The compromised reproductive function in T1DM females may have early developmental origins since diabetic girls showed delayed uterine development (length and volume of uterus) at puberty relative to non-diabetic counterparts, although this difference largely equalized post puberty (Gurr et al. 1986). Perturbations in leptin and kisspeptin signaling have been associated with defective reproductive function in women with T1DM (Castellano et al. 2009).

T1DM complicates a relatively small percentage of pregnancies (~1 of 200). Nevertheless, women with T1DM experience fewer livebirths (Lin et al. 2018), higher early pregnancy terminations (Sjöberg et al. 2017) and a greater risk for preterm births (Ludvigsson et al. 2019) than the general population. Increased infiltration and adhesion of monocytes to placental bed endothelium leading to inflammation and reduction of placental blood flow have been suggested to partly underlie these poor birth outcomes in women (Galettis et al. 2004) and were mechanistically confirmed in non-obese diabetic mice (Burke et al. 2007).

In a number of T1DM patients, islets transplantation is a course of treatment, and patients undergo immunosuppression therapy (Cure et al. 2004). Adverse outcomes of these regimen include menstrual cycle alterations and emergence of ovarian cysts (Alfadhli et al. 2009), which can further contribute to diminished reproductive status of TIDM patients.

Neuropathy

A predominant clinical feature of ENDO is chronic pelvic pain during menstruation. The mechanism(s) underlying the origin of this pain remains unknown, although endometriotic lesions display increased expression of neurotrophic and angiogenic factors and higher density of nerve fibers (Morotti et al. 2014). Moreover, women suffering from deep infiltrating ENDO and bowel ENDO, who experience more pelvic pain, present greater nerve fiber densities in ectopic lesions than women with peritoneal ENDO and endometrioma (Morotti et al. 2014). A rat model for leg pain in ENDO showed that the complexes (cysts) formed from the fusion of nerve fibers with endometrial tissues are highly infiltrated with macrophages, indicating inflammation and are prominently innervated by small diameter axons, which together could result in persistent neural discharge and thus, pain (Bove 2016).

Neuropathy and neuropathic pain are common complications of T1DM. In adults with longstanding T1DM, neuropathic pain was more prevalent in females than in males (Cardinez et al. 2018). Similar to ENDO-associated pain, the pathophysiology of neuropathic pain in T1DM is not well understood, although hyperglycemia is highly considered to play an important role in its development. A recent review on this topic provides a comprehensive summary of plausible mechanisms, which include stress, microvascular changes and glial activation (Schreiber et al. 2015).

Differences between TIDM and ENDO

Links with polycystic ovary syndrome (PCOS)

PCOS is a condition associated with insulin resistance, hyperandrogenism, oligomenorrhea and other morbidities including reduced fertility (Escobar-Morreale 2018). While both PCOS and ENDO are associated with compromised fertility, an increased risk for ENDO with PCOS and vice-versa, has not been established, supporting the notion of their differing pathogenesis and underlying mechanisms. A prime example of these differences relates to pro-inflammatory cytokines, whose systemic levels are elevated predominantly in PCOS as opposed to more locally in ENDO (Younis et al. 2014). Moreover, while the early events in ENDO are highly dependent on the innate immune system (Burns et al. 2012, 2018), those of PCOS are largely initiated by hyperandrogenism with epigenetic underpinnings (Escobar-Morreale 2018).

PCOS incidence is higher in T1DM women than in the general population (Escobar-Morreale & Roldán-Martín 2016). Adolescent girls with T1DM also displayed a greater prevalence of PCOS (Busiah et al. 2017). Insulin therapy in T1DM may result in hyperinsulinemia that can aggravate PCOS through hyperandrogenism (Shigiyama et al. 2016). One study compared the phenotypic characteristics, including general hormonal patterns, of PCOS women with and without T1DM. No differences were noted, suggesting that the enhanced subfertility of women with coincidence of T1DM and PCOS, relative to PCOS alone may not be directly dependent on mechanisms related to glycemic/metabolic control (Amato et al. 2014, Escobar-Morreale & Roldán-Martín 2016). However, another study reported that while hirsutism and hyperandrogenism as well as ovarian volume were comparable between PCOS women with and without T1DM (and higher than shown for the control group), T1DM/PCOS women displayed lower anti-mullerian hormone levels (which were correlated with ovarian follicle numbers) and higher ratios of luteinizing hormone to follicle-stimulating hormone, than PCOS women without T1DM (Codner et al. 2007). The resolution of these differences is yet to be addressed.

Predisposition and body mass index

ENDO is inversely associated with BMI across the life course and with more favorable morphometric indicators and body composition (Backonja et al. 2017, Farland et al. 2017). Specifically, lower BMI is suggested to constitute a risk factor for the development of ENDO and a predictive factor for severe ENDO. This association is counter-intuitive to the substantially supported and largely acknowledged notion that obesity is a risk factor for many chronic diseases and compromises fertility. Given that a causal association is yet to be established between ENDO and BMI, numerous studies continue to address this seeming paradoxical relationship. Taylor and colleagues (Goetz et al. 2016) showed that in a mouse model of ENDO, the presence of EC promoted low BMI due to dysregulation of hepatic metabolism, suggesting ENDO as a cause rather than a consequence of low BMI. In another mouse model of ENDO from our group (Heard et al. 2016), EC growth was increased by high-fat diet, in the absence of changes in body weight. Further, genome-wide enrichment analyses between ENDO and obesity-related traits indicated that body fat distribution rather than BMI is associated with ENDO (Rahmioglu et al. 2015).

T1DM individuals, in the absence of insulin therapy, experience poor metabolic control, which can lead to early death (Collier et al. 2018). With appropriate clinical management, however, T1DM females can lead relatively normal lives, despite the condition’s associated morbidities. T1DM patients typically have lower BMI than type 2 diabetes patients (Thomas et al. 2018). Sustained obesity (cumulative excess BMI ≥5 kg/m2) enhanced the risk for T1DM in pediatric and young women (<35 y-o) but the risk diminished with increasing age (Ferrara et al. 2017). While insulin resistance in T1DM patients occurs regardless of accompanying obesity or metabolic syndrome (Cree-Green et al. 2018), recent data indicate that a significant fraction (30%) of girls and adolescent females with T1DM are overweight or obese (Maffeis et al. 2018), which may have bearing on ENDO risk.

Molecular correlates in T1DM and ENDO

Table 1 provides a list of molecules independently implicated in ENDO and T1DM, based on studies with human patients and animal disease models. The parallel involvement of these molecules in both conditions reinforces the notion that T1DM and ENDO may not only co-exist but may promote each other’s occurrence. Pro-inflammatory molecules predominate the list, consistent with the inflammatory status associated with each condition. A recent review (Ahn et al. 2016) presents a comprehensive description of immune-inflammation genes associated with ENDO. Interferon-γ is a key molecule in ENDO (Mier-Cabrera et al. 2011, Gueuvoghlanian-Silva et al. 2018) and in T1DM (Driver et al. 2017, Osum et al. 2018), given its regulation of Th-1 cell development in autoimmunity. Tumor necrosis factor-alpha (TNF-α) is implicated in the pathogenesis of ENDO, since its levels are increased in peritoneal fluids of ENDO women by virtue of activated peritoneal macrophages infiltrating lesions and correlate with disease severity and with size and numbers of active lesions (Birt et al. 2013, Kocbek et al. 2016). Similarly, serum TNF-α levels are elevated in T1DM patients, regardless of age, disease duration, and ethnicity (Qiao et al. 2017). By using non-obese diabetic mice, Lee et al. (2005) demonstrated that TNF-α initiates T1DM autoimmunity by regulating the maturation of dendritic cells, leading to the activation of islet-specific pancreatic lymph node T-cells. Macrophage migration inhibitor factor-1 (MIF-1), another pro-inflammatory cytokine implicated in the innate immune system, showed significantly higher expression in EU of women with ENDO than in normal (control) endometrium, and its levels were highly upregulated by estrogen (Veillat et al. 2012, Rakhila et al. 2014). Expression of MIF’s specific receptor CD74 is also higher in human EC, where it is postulated to contribute to epithelial cell survival and enhanced IL-8 expression (Nothnick et al. 2018). MIF-1 is also associated with T1DM, where it is involved in the activation of macrophages and dendritic cells for inflammatory Th-1 response. By using wildtype and Mif-1 knockout mice administered streptozotocin to induce T1DM, Sánchez-Zamora et al. (2016) provided direct evidence to support MIF’s role in inducing hyperglycemia, inflammation, production of specific pancreatic antigen, and regulation of TLR expression, all of which characterize T1DM in humans. The transcription factor NF-κB is similarly implicated in the pathogenesis of ENDO and of T1DM, albeit in opposing manner. In pancreatic islet cells, NF-κB prevents TNF-α induced apoptosis by its upregulation of the anti-apoptotic protein TNF-induced protein 3 (Liuwantara et al. 2006, Kim et al. 2007), thus serving a protective role. By contrast, NF-κB promotes EC establishment, maintenance and progression by stimulating the synthesis of pro-inflammatory cytokines in ectopic endometrial cells and in macrophages that subsequently infiltrate these lesions (Veillat et al. 2009, Kaponis et al. 2012); these mechanisms were shown to be mediated by ESR2 (Gou et al. 2019). Nevertheless, it is currently unknown which condition (ENDO or T1DM) may occur first in the case of co-morbidity, since the diagnosis of each is subject to delay, owing in part to a lack of reliable non-intrusive biomarkers for ENDO and to the increasing adult onset of T1DM.

Table 1

Immune/inflammatory molecules implicated in endometriosis (ENDO) and type 1 diabetes mellitus (T1DM).

MoleculesENDOT1DM
IFN-γMier-Cabrera et al. (2011), Gueuvoghlanian-Silva et al. (2018)Driver et al. (2017), Osum et al. (2018)
TNFαBirt et al. (2013), Kocbek et al. (2016)Lee et al. (2005), Qiao et al. (2017)
MIFRakhila et al. (2014), Zhang & Mu (2015), Nothnick et al. (2018)Sánchez-Zamora et al. (2016)
NF-κβVeillat et al. (2009), Kaponis et al. (2012), Gou et al. (2019)Liuwantara et al. (2006), Kim et al. (2007)
IL-8Jørgensen et al. (2017), Burns et al. (2018)Devaraj et al. (2011), Purohit etal. (2015)
IL-6Burns et al. (2018), Woo et al. (2017)Hundhausen et al. (2016)
MCP-1Grandi et al. (2016), Younis et al. (2014)Waugh et al. (2017)

IFN-γ, interferon gamma; IL-6, interleukin 6; IL-8, interleukin 8; MCP-1, monocyte chemotactic protein-1; MIF, macrophage migration inhibitory factor; NF-κβ, nuclear factor- kappa β; TNFα, tumor necrosis factor α.

Potential therapeutic complications in co-morbid T1DM and ENDO

To date, no systematic studies have addressed the question of whether treatments administered to singly manage ENDO or T1DM in women with either condition might influence the efficacy of agents in patients with both conditions. Nevertheless, published studies provide support for this possibility. Gonadotropin-releasing hormone (GnRH) agonists and progestins are standard treatments for ENDO. In women with ENDO (but without T1DM), intake of the GnRH agonist leuprorelin or use of subdermal progestin implant for symptoms of pelvic endometriosis decreased insulin sensitivity and glucose utilization (Cagnacci et al. 2005). A causal effect of progestin intake on disruption of glucoregulatory function was confirmed in adult rhesus macaques undergoing treatment for ENDO with medroxy-progesterone acetate (MPA) (Cruzen et al. 2011). Further, in a retrospective study of rhesus macaques with ENDO, treatment with depot MPA increased the risk of incident T1DM (Connolly et al. 2016). In a randomized trial of non-ENDO women with uncomplicated (i.e., managed) T1DM, the use of progestin levonorgestrel for contraception showed no adverse effect on glucose metabolism as measured by glycosylated hemoglobin, fasting serum-glucose levels and daily insulin dose requirements (Rogovskaya et al. 2005). However, in a case report, progestin administration to prevent preterm delivery and miscarriage in a pregnant woman with T1DM, elicited a decline in glycemic control, which necessitated the adjustment of the patient’s basal insulin rate (Sasaki et al. 2013). Danazol is an androgen antagonist used to treat ENDO since it normalizes aromatase cytochrome P450 expression in EU from women with ENDO (Ishihara et al. 2003). In a comparison of non-T1DM women with and without ENDO, danazol decreased the response of glucose to insulin in women with ENDO, indicating its promotion of insulin resistance (Bruce et al. 1992, Matalliotakis et al. 1997). Collectively, the results suggest that current clinical management of ENDO may compromise women with accompanying T1DM and thus, advocate for physicians to recognize patients with ENDO and T1DM co-morbidities for provision of appropriate and optimal care.

Given increasing support for the role of specific diets in the promotion of a pro-inflammatory state that is associated with T1DM (Vaarala 2011, Knip et al. 2012, van Bussel et al. 2013) and ENDO (Saguyod et al. 2018, Simmen & Kelley 2018), it is prudent to consider dietary changes, which can significantly impact the intestinal microbiota, for management of co-morbid ENDO and T1DM (Henschel et al. 2018). Similarly, the use of metformin for targeting co-morbid T1DM and ENDO may have value, given recent evidence for its efficacy in reducing T1DM (Bjornstad et al. 2018, Cree-Green et al. 2019) and hindering the progression of ENDO lesions and associated signaling pathways (Takemura et al. 2007, Yilmaz et al. 2010). Additionally, therapies that reduce inflammation could prove beneficial, given the pro-inflammatory status of T1DM and ENDO. Further investigations into these possibilities are warranted.

Concluding remarks

ENDO and of T1DM are complex conditions due to their polygenic nature and their susceptibility to environmental triggers. Figure 1 is a schematic summary of how immune dysfunction and enhanced inflammatory status may promote ENDO and T1DM in high-risk women and the overlaps in the association of each condition to many clinical disorders. Reproductive-age women with co-morbid ENDO and T1DM may suffer from infertility at a higher rate than those with either condition yet pre-conception counseling for this cohort of women is likely non-existent, given their asymptomatic nature at early stages. Moreover, current therapies addressing ENDO to mitigate infertility can exacerbate T1DM via their negative effects on glucose control. Thus, there is a current unmet need to identify and develop novel therapeutic strategies that are safe and effective to address these co-morbid conditions. Relevant and convenient animal models that concomitantly recapitulate T1DM and ENDO are crucial for the design of mechanistic studies to address how T1DM can promote ENDO and conversely, how ENDO may complicate T1DM. The provision of these animal models will advance current understanding of biomarkers for predicting disease development and therapeutically targetable pathways to ameliorate disease pathogenesis. Finally, ENDO and T1DM should continue to be at the forefront of future research since there remains a large gap in knowledge on how genetic, endocrine and immunological factors contribute to their onset and progression.

Figure 1
Figure 1

A schematic summary of immune system components potentially involved in co-morbid endometriosis and type 1 diabetes. Also shown are the substantial overlaps in clinical disorders associated with each condition.

Citation: Journal of Endocrinology 243, 3; 10.1530/JOE-19-0248

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review.

Funding

Work described in this review from our laboratory was supported in part by the National Institutes of Health (HD21961), the Sturgis Foundation and the Development Enhancement Awards for Proposals Grant Program of the University of Arkansas for Medical Sciences.

References

  • AbeKKuklinaEVHooperWCCallaghanWM 2019 Venous thromboembolism as a cause of severe maternal morbidity and mortality in the United States. Seminars in Perinatology 200204. (https://doi.org/10.1053/j.semperi.2019.03.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • AhnSHKhalajKYoungSLLesseyBAKotiMTayadeC 2016 Immune-inflammation gene signatures in endometriosis patients. Fertility and Sterility 1420.e71431.e7. (https://doi.org/10.1016/j.fertnstert.2016.07.005)

    • Search Google Scholar
    • Export Citation
  • AlfadhliEKohAAlbakerWBhargavaRAckermanTMcDonaldCRyanEAShapiroAMSeniorPA 2009 High prevalence of ovarian cysts in premenopausal women receiving sirolimus and tacrolimus after clinical islet transplantation. Transplant International 622625. (https://doi.org/10.1111/j.1432-2277.2009.00839.x)

    • Search Google Scholar
    • Export Citation
  • AlkananiAKRewersMDongFWaughKGottliebPAZiprisD 2012 Dysregulated toll-like receptor-induced interleukin-1β and interleukin-6 responses in subjects at risk for the development of type 1 diabetes. Diabetes 25252533. (https://doi.org/10.2337/db12-0099)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • AllhornSBöingCKochAAKimmigRGashawI 2008 TLR3 and TLR4 expression in healthy and diseased human endometrium. Reproductive Biology and Endocrinology 40. (https://doi.org/10.1186/1477-7827-6-40)

    • Search Google Scholar
    • Export Citation
  • AmatoMCGuarnottaVCiresiAModicaRPantòFGiordanoC 2014 No phenotypic differences for polycystic ovary syndrome (PCOS) between women with and without type 1 diabetes mellitus. Journal of Clinical Endocrinology and Metabolism 203211. (https://doi.org/10.1210/jc.2013-2669)

    • Search Google Scholar
    • Export Citation
  • AndersenCLBoisenMMSikoraMJMaTTsengGSuryawanshiSVladAElishaevEEdwardsRPOesterreichS 2018 The evolution of estrogen receptor signaling in the progression of endometriosis to endometriosis-associated ovarian cancer. Hormones and Cancer 399407. (https://doi.org/10.1007/s12672-018-0350-9)

    • Search Google Scholar
    • Export Citation
  • AnglesioMSPapadopoulosNAyhanANazeranTMNoëMHorlingsHMLumAJonesSSenzJSeckinTet al. 2017 Cancer-associated mutations in endometriosis without cancer. New England Journal of Medicine 18351848. (https://doi.org/10.1056/NEJMoa1614814)

    • Search Google Scholar
    • Export Citation
  • BackonjaUHedigerMLChenZLauverDRSunLPetersonCMBuck LouisGM 2017 Beyond body mass index: using anthropometric measures and body composition indicators to assess odds of an endometriosis diagnosis. Journal of Women’s Health 941950. (https://doi.org/10.1089/jwh.2016.6128)

    • Search Google Scholar
    • Export Citation
  • BirtJANabliHStilleyJAWindhamEAFrazierSRSharpe-TimmsKL 2013 Elevated peritoneal fluid TNF-α incites ovarian early growth response factor 1 expression and downstream protease mediators: a correlation with ovulatory dysfunction in endometriosis. Reproductive Sciences 514523. (https://doi.org/10.1177/1933719113477479)

    • Search Google Scholar
    • Export Citation
  • BjornstadPSchäferMTruongUCree-GreenMPyleLBaumgartnerAGarcia ReyesYManiatisANayakSWadwaRPet al. 2018 Metformin improves insulin sensitivity and vascular health in youth with type 1 diabetes mellitus. Circulation 28952907. (https://doi.org/10.1161/CIRCULATIONAHA.118.035525)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • BoveGM 2016 A model for radiating leg pain of endometriosis. Journal of Bodywork and Movement Therapies 931936. (https://doi.org/10.1016/j.jbmt.2016.04.013)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • BruceRGodslandIStevensonJDevenportMBorthFCrookDGhateiMWhiteheadMWynnV 1992 Danazol induces resistance to both insulin and glucagon in young women. Clinical Science 211217. (https://doi.org/10.1042/cs0820211)

    • Search Google Scholar
    • Export Citation
  • BulunSEWanYMateiD 2019 Epithelial mutations in endometriosis: link to ovarian cancer. Endocrinology 626638. (https://doi.org/10.1210/en.2018-00794)

  • BurkeSDDongHHazanADCroyBA 2007 Aberrant endometrial features of pregnancy in diabetic NOD mice. Diabetes 29192926. (https://doi.org/10.2337/db07-0773)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • BurneyROGiudiceLC 2012 Pathogenesis and pathophysiology of endometriosis. Fertility and Sterility 511519. (https://doi.org/10.1016/j.fertnstert.2012.06.029)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • BurnsKARodriguezKFHewittSCJanardhanKSYoungSLKorachKS 2012 Role of estrogen receptor signaling required for endometriosis-like lesion establishment in a mouse model. Endocrinology 39603971. (https://doi.org/10.1210/en.2012-1294)

    • Search Google Scholar
    • Export Citation
  • BurnsKAThomasSYHamiltonKJYoungSLCookDNKorachKS 2018 Early endometriosis in females is directed by immune-mediated estrogen receptor α and IL-6 cross-talk. Endocrinology 159 103118 (https://doi.org/10.1210/en.2017-00562)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • BusiahKColmenaresABidetMTubiana-RufiNLevy-MarchalCDelcroixCJacquinPMartinDBenadjaoudLJacqz-AigrainEet al. 2017 High prevalence of polycystic ovary syndrome in type 1 diabetes mellitus adolescents: is there a difference depending on the NIH and Rotterdam criteria? Hormone Research in Paediatrics 333341. (https://doi.org/10.1159/000471805)

    • Search Google Scholar
    • Export Citation
  • CabreraSMHenschelAMHessnerMJ 2016 Innate inflammation in type 1 diabetes. Translational Research 214227. (https://doi.org/10.1016/j.trsl.2015.04.011)

    • Search Google Scholar
    • Export Citation
  • CagnacciATirelliACannolettaMPirilloDVolpeA 2005 Effect on insulin sensitivity of Implanon vs. GnRH agonist in women with endometriosis. Contraception 443446. (https://doi.org/10.1016/j.contraception.2005.05.021)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • CapobiancoAMonnoACottoneLVenneriMABiziatoDDi PuppoFFerrariSDe PalmaMManfrediAARovere-QueriniP 2011 Proangiogenic Tie2(+) macrophages infiltrate human and murine endometriotic lesions and dictate their growth in a mouse model of the disease. American Journal of Pathology 26512659. (https://doi.org/10.1016/j.ajpath.2011.07.029)

    • Search Google Scholar
    • Export Citation
  • CardinezNLovblomLEBaiJWLewisEAbrahamAScarrDLovshinJALytvynYBouletGFarooqiMAet al. 2018 Sex differences in neuropathic pain in longstanding diabetes: results from the Canadian Study of Longevity in Type 1 Diabetes. Journal of Diabetes and its Complications 660664. (https://doi.org/10.1016/j.jdiacomp.2018.05.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • CarstensenBReadSHFriisSSundRKeskimäkiISvenssonAMLjungRWildSHKerssensJJHardingJLet al. 2016 Cancer incidence in persons with type 1 diabetes: a five-country study of 9,000 cancers in type 1 diabetic individuals. Diabetologia 980988. (https://doi.org/10.1007/s00125-016-3884-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • CastellanoJMNavarroVMRoaJPinedaRSánchez-GarridoMAGarcía-GalianoDVigoEDieguezCAguilarEPinillaLet al. 2009 Alterations in hypothalamic KiSS-1 system in experimental diabetes: early changes and functional consequences. Endocrinology 784794. (https://doi.org/10.1210/en.2008-0849)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • ChuangPCLinYJWuMHWingLYShojiYTsaiSJ 2010 Inhibition of CD36-dependent phagocytosis by prostaglandin E2 contributes to the development of endometriosis. American Journal of Pathology 850860. (https://doi.org/10.2353/ajpath.2010.090551)

    • Search Google Scholar
    • Export Citation
  • CodnerEIñíguezGVillarroelCLopezPSotoNSir-PetermannTCassorlaFReyRA 2007 Hormonal profile in women with polycystic ovarian syndrome with or without type 1 diabetes mellitus. Journal of Clinical Endocrinology and Metabolism 47424746. (https://doi.org/10.1210/jc.2007-1252)

    • Search Google Scholar
    • Export Citation
  • CodnerEMerinoPMTena-SempereM 2012 Female reproduction and type 1 diabetes: from mechanisms to clinical findings. Human Reproduction Update 568585. (https://doi.org/10.1093/humupd/dms024)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • CollierAConnellyPJHairMCameronLGhoshSWaughN 2018 Mortality risk remains higher in individuals with type 1 diabetes: a population-based cohort study (the Ayrshire diabetes follow-up cohort [ADOC]). Diabetes Obesity and Metabolism 19651971. (https://doi.org/10.1111/dom.13334)

    • Search Google Scholar
    • Export Citation
  • ConnollyMATrentalangeMZeissCJ 2016 Long-term clinical outcomes in diabetic rhesus macaques (Macaca mulatta) treated with medroxyprogesterone acetate for endometriosis. Comparative Medicine 343348.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cree-GreenMStuppyJJThurstonJBergmanBCCoeGVBaumgartnerADBaconSScherzingerAPyleLNadeauKJ 2018 Youth with type 1 diabetes have adipose, hepatic, and peripheral insulin resistance. Journal of Clinical Endocrinology and Metabolism 36473657. (https://doi.org/10.1210/jc.2018-00433)

    • Search Google Scholar
    • Export Citation
  • Cree-GreenMBergmanBCCengizEFoxLAHannonTSMillerKNathanBPyleLKahnDTanseyMet al. 2019 Metformin improves peripheral insulin sensitivity in youth with type 1 diabetes. Journal of Clinical Endocrinology and Metabolism 32653278. (https://doi.org/10.1210/jc.2019-00129)

    • Search Google Scholar
    • Export Citation
  • CruzenCLBaumSTColmanRJ 2011 Glucoregulatory function in adult rhesus macaques (Macaca mulatta) undergoing treatment with medroxyprogesterone acetate for endometriosis. Journal of the American Association for Laboratory Animal Science 921925.

    • Search Google Scholar
    • Export Citation
  • CurePPileggiAFroudTNorrisPMBaidalDACornejoAHafizMMPonteGPoggioliRYuJet al. 2004 Alterations of the female reproductive system in recipients of islet grafts. Transplantation 15761581. (https://doi.org/10.1097/01.tp.0000147301.41864.c0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • DevarajSTobiasPJialalI 2011 Knockout of toll-like receptor-4 attenuates the pro-inflammatory state of diabetes. Cytokine 441445. (https://doi.org/10.1016/j.cyto.2011.03.023)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • DriverJPRacineJJYeCLamontDJNewbyBNLeethCMChapmanHDBruskoTMChenYGMathewsCEet al. 2017 Interferon-γ limits diabetogenic CD8+ T-cell effector responses in type 1 diabetes. Diabetes 710721. (https://doi.org/10.2337/db16-0846)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • ErTKSuYFWuCCChenCCWangJHsiehTHHerreros-VillanuevaMChenWTChenYTLiuTCet al. 2016 Targeted next-generation sequencing for molecular diagnosis of endometriosis-associated ovarian cancer. Journal of Molecular Medicine 835847. (https://doi.org/10.1007/s00109-016-1395-2)

    • Search Google Scholar
    • Export Citation
  • Escobar-MorrealeHF 2018 Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nature Reviews: Endocrinology 270284. (https://doi.org/10.1038/nrendo.2018.24)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Escobar-MorrealeHFRoldán-MartínMB 2016 Type 1 diabetes and polycystic ovary syndrome: systematic review and meta-analysis. Diabetes Care 639648. (https://doi.org/10.2337/dc15-2577)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • FarlandLVMissmerSABijonAGustoGGelotAClavel-ChapelonFMesrineSBoutron-RuaultMCKvaskoffM 2017 Associations among body size across the life course, adult height and endometriosis. Human Reproduction 17321742. (https://doi.org/10.1093/humrep/dex207)

    • Search Google Scholar
    • Export Citation
  • FerraraCTGeyerSMEvans-MolinaCLibmanIMBeckerDJWentworthJMMoranAGitelmanSERedondoMJ & Type 1 Diabetes TrialNet Study Group 2017 The role of age and excess body mass index in progression to type 1 diabetes in at-risk adults. Journal of Clinical Endocrinology and Metabolism 45964603. (https://doi.org/10.1210/jc.2017-01490)

    • Search Google Scholar
    • Export Citation
  • GalettisACampbellSMorrisJMJacksonCJTwiggSMGalleryED 2004 Monocyte adhesion to decidual endothelial cells is increased in pregnancies complicated by type 1 diabetes but not by gestational diabetes. Diabetes Care 25142515. (https://doi.org/10.2337/diacare.27.10.2514)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • GoetzLGMamillapalliRTaylorHS 2016 Low body mass index in endometriosis is promoted by hepatic metabolic gene dysregulation in mice. Biology of Reproduction 115 (https://doi.org/10.1095/biolreprod.116.142877)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • GouYLiXLiPZhangHXuTWangHWangBMaXJiangXZhangZ 2019 Estrogen receptor β upregulates CCL2 via NF-κB signaling in endometriotic stromal cells and recruits macrophages to promote the pathogenesis of endometriosis. Human Reproduction 646658. (https://doi.org/10.1093/humrep/dez019)

    • Search Google Scholar
    • Export Citation
  • GrandiGMuellerMBersingerNPapadiaANirgianakisKCagnacciAMcKinnonB 2016 Progestin suppressed inflammation and cell viability of tumor necrosis factor-α-stimulated endometriotic stromal cells. American Journal of Reproductive Immunology 292298. (https://doi.org/10.1111/aji.12552)

    • Search Google Scholar
    • Export Citation
  • GreavesECousinsFLMurrayAEsnal-ZufiaurreAFassbenderAHorneAWSaundersPT 2014 A novel mouse model of endometriosis mimics human phenotype and reveals insights into the inflammatory contribution of shed endometrium. American Journal of Pathology 19301939. (https://doi.org/10.1016/j.ajpath.2014.03.011)

    • Search Google Scholar
    • Export Citation
  • Gueuvoghlanian-SilvaBYBellelisPBarbeiroDFHernandesCPodgaecS 2018 Treg and NK cells related cytokines are associated with deep rectosigmoid endometriosis and clinical symptoms related to the disease. Journal of Reproductive Immunology 3238. (https://doi.org/10.1016/j.jri.2018.02.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • GüldenEIhiraMOhashiAReinbeckALFreudenbergMAKolbHBurkartV 2013 Toll-like receptor 4 deficiency accelerates the development of insulin-deficient diabetes in non-obese diabetic mice. PLoS ONE e75385. (https://doi.org/10.1371/journal.pone.0075385)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • GurrSKobsKSteindelE 1986 Ultrasonic measurements of the uterus in adolescents. Zentralblatt für Gynakologie 14201424.

  • HanSJJungSYWuSPHawkinsSMParkMJKyoSQinJLydonJPTsaiSYTsaiMJet al. 2015 Estrogen receptor β modulates apoptosis complexes and the inflammasome to drive the pathogenesis of endometriosis. Cell 960974. (https://doi.org/10.1016/j.cell.2015.10.034)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • HayashiCChishimaFSugitaniMIchikawaGNakazawa-WatanabeTSugitaKSuzukiMNemotoNYamamotoT 2013 Relationship between Toll-like receptor-4 and mPGES-1 gene expression in local lesions of endometriosis patients. American Journal of Reproductive Immunology 231239. (https://doi.org/10.1111/aji.12056)

    • Search Google Scholar
    • Export Citation
  • HeardMEMelnykSBSimmenFAYangYPabonaJMSimmenRC 2016 High-fat diet promotion of endometriosis in an immunocompetent mouse model is associated with altered peripheral and ectopic lesion redox and inflammatory status. Endocrinology 28702882. (https://doi.org/10.1210/en.2016-1092)

    • Search Google Scholar
    • Export Citation
  • HenschelAMCabreraSMKaldunskiMLJiaSGeoffreyRRoethleMFLamVChenYGWangXSalzmanNHet al. 2018 Modulation of the diet and gastrointestinal microbiota normalizes systemic inflammation and β-cell chemokine expression associated with autoimmune diabetes susceptibility. PLoS ONE e0190351. (https://doi.org/10.1371/journal.pone.0190351)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hotta-IwamuraCTarbellKV 2016 Type 1 diabetes genetic susceptibility and dendritic cell function: potential targets for treatment. Journal of Leukocyte Biology 6580. (https://doi.org/10.1189/jlb.3MR1115-500R)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • HsuPCLinWHKuoTHLeeHMKuoCLiCY 2015 A population-based cohort study of all-cause and site-specific cancer incidence among patients with type 1 diabetes mellitus in Taiwan. Journal of Epidemiology 567573. (https://doi.org/10.2188/jea.JE20140197)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • HundhausenCRothAWhalenEChenJSchneiderALongSAWeiSRawlingsRKinsmanMEvankoSPet al. 2016 Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Science Translational Medicine 356ra119. (https://doi.org/10.1126/scitranslmed.aad9943)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • HuxleyRRPetersSAMishraGDWoodwardM 2015 Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis. Lancet: Diabetes and Endocrinology 198206. (https://doi.org/10.1016/S2213-8587(14)70248-7)

    • Search Google Scholar
    • Export Citation
  • IshiharaHKitawakiJKadoNKoshibaHFushikiSHonjoH 2003 Gonadotropin-releasing hormone agonist and danazol normalize aromatase cytochrome P450 expression in eutopic endometrium from women with endometriosis, adenomyosis, or leiomyomas. Fertility and Sterility (Supplement 1) 735742. (https://doi.org/10.1016/s0015-0282(02)04813-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • JørgensenHHillASBesteMTKumarMPChiswickEFedorcsakPIsaacsonKBLauffenburgerDAGriffithLGQvigstadE 2017 Peritoneal fluid cytokines related to endometriosis in patients evaluated for infertility. Fertility and Sterility 1191.e21199.e2. (https://doi.org/10.1016/j.fertnstert.2017.03.013)

    • Search Google Scholar
    • Export Citation
  • KaponisAIwabeTTaniguchiFItoMDeuraIDecavalasGTerakawaNHaradaT 2012 The role of NF-kappaB in endometriosis. Frontiers in Bioscience 12131234.

    • Search Google Scholar
    • Export Citation
  • KellenbergerLDPetrikJ 2018 Hyperglycemia promotes insulin-independent ovarian tumor growth. Gynecologic Oncology 361370. (https://doi.org/10.1016/j.ygyno.2018.02.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • KimSMilletIKimHSKimJYHanMSLeeMKKimKWSherwinRSKarinMLeeMS 2007 NF-kappa B prevents beta cell death and autoimmune diabetes in NOD mice. PNAS 19131918. (https://doi.org/10.1073/pnas.0610690104)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • KimCMillerRSBraffettBHPanYArendsVLSaengerAKBarnieASarmaAV & EDIC Research Group 2018 Ovarian markers and irregular menses among women with type 1 diabetes in the Epidemiology of Diabetes Interventions and Complications study. Clinical Endocrinology 453459. (https://doi.org/10.1111/cen.13546)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • KnipMSimellO 2012 Environmental triggers of type 1 diabetes. Cold Spring Harbor Perspectives in Medicine a007690. (https://doi.org/10.1101/cshperspect.a007690)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • KnipMLuopajärviKHärkönenT 2017 Early life origin of type 1 diabetes. Seminars in Immunopathology 653667. (https://doi.org/10.1007/s00281-017-0665-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • KocbekVGrandiGBlankFWotzkowCBersingerNAMuellerMDKyoSMcKinnonBD 2016 TNFα-induced IKKβ complex activation influences epithelial, but not stromal cell survival in endometriosis. Molecular Human Reproduction 768777. (https://doi.org/10.1093/molehr/gaw054)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LambeletMTerraLFFukayaMMeyerovichKLabriolaLCardozoAKAllagnatF 2018 Dysfunctional autophagy following exposure to pro-inflammatory cytokines contributes to pancreatic β-cell apoptosis. Cell Death and Disease 96. (https://doi.org/10.1038/s41419-017-0121-5)

    • Search Google Scholar
    • Export Citation
  • ŁebkowskaAAdamskaAJacewiczMTołwińskaJKrentowskaAHryniewickaJLeśniewskaMBossowskiAGórskaMKowalskaI 2017 Association between polycystic ovary syndrome and the risk of subclinical vascular disease in normal‑weight women with type 1 diabetes. Polish Archives of Internal Medicine 741748. (https://doi.org/10.20452/pamw.4116)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LeeLFXuBMichieSABeilhackGFWarganichTTurleySMcDevittHO 2005 The role of TNF-alpha in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse: analysis of dendritic cell maturation. PNAS 1599516000. (https://doi.org/10.1073/pnas.0508122102)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LeeAWTemplemanCStramDABeesleyJTyrerJBerchuckAPharoahPPChenevix-TrenchGPearceCL & Ovarian Cancer Association Consortium 2016 Evidence of a genetic link between endometriosis and ovarian cancer. Fertility and Sterility 35.e143.e1. (https://doi.org/10.1016/j.fertnstert.2015.09.023)

    • Search Google Scholar
    • Export Citation
  • LiawYPKoPCJanSRHuangJYNforONLungCCChiangYCYehLTChouMCTsaiHDet al. 2015 Implications of type1/2 diabetes mellitus in breast cancer development: a general female population-based cohort study. Journal of Cancer 734739. (https://doi.org/10.7150/jca.12197)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LienEZiprisD 2009 The role of toll-like receptor pathways in the mechanism of type 1 diabetes. Current Molecular Medicine 5268. (https://doi.org/10.2174/156652409787314453)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LinYHChenKJPengYSChenPCYangYH 2018 Type 1 diabetes impairs female fertility even before it is diagnosed. Diabetes Research and Clinical Practice 151158. (https://doi.org/10.1016/j.diabres.2018.07.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LiuwantaraDElliotMSmithMWYamAOWaltersSNMarinoEMcSheaAGreyST 2006 Nuclear factor-kappa B regulates beta-cell death: a critical role for A20 in beta-cell protection. Diabetes 24912501. (https://doi.org/10.2337/db06-0142)

    • Search Google Scholar
    • Export Citation
  • LjunggrenPMaahsDMJohanssonPLudvigssonJPyleLSipplRWadwaRPSnell-BergeonJ 2016 Reduced brachial artery distensibility in patients with type 1 diabetes. Journal of Diabetes and its Complications 893897. (https://doi.org/10.1016/j.jdiacomp.2016.03.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LudvigssonJFNeoviusMSöderlingJGudbjörnsdottirSSvenssonAMFranzénSStephanssonOPasternakB 2019 Maternal glycemic control in type 1 diabetes and the risk for preterm birth: a population-based cohort study. Annals of Internal Medicine 691701. (https://doi.org/10.7326/M18-1974)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LuoXZZhouWJTaoYWangXQLiDJ 2015 TLR4 activation promotes the secretion of IL-8 which enhances the invasion and proliferation of endometrial stromal cells in an autocrine manner via the FAK signal pathway. American Journal of Reproductive Immunology 467479. (https://doi.org/10.1111/aji.12425)

    • Search Google Scholar
    • Export Citation
  • MaahsDMWestNALawrenceJMMayer-DavisEJ 2010 Epidemiology of type 1 diabetes. Endocrinology and Metabolism Clinics of North America 481497. (https://doi.org/10.1016/j.ecl.2010.05.011)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • MaffeisCBirkebaekNHKonstantinovaMSchwandtAVazeouACasteelsKJaliSLimbertCPundziute-LyckaAToth-HeynPet al. 2018 Prevalence of underweight, overweight, and obesity in children and adolescents with type 1 diabetes: data from the international SWEET registry. Pediatric Diabetes 12111220. (https://doi.org/10.1111/pedi.12730)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • MahalingaiahSSunFChengJJChowETLunettaKLMurabitoJM 2017 Cardiovascular risk factors among women with self-reported infertility. Fertility Research and Practice 7. (https://doi.org/10.1186/s40738-017-0034-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • MatalliotakisIPanidisDVlassisGNeonakiMKoumantakisE 1997 Decreased sensitivity to insulin during treatment with danazol in women with endometriosis. Clinical and Experimental Obstetrics and Gynecology 160162.

    • Search Google Scholar
    • Export Citation
  • Mier-CabreraJJiménez-ZamudioLGarcía-LatorreECruz-OrozcoOHernández-GuerreroCQ 2011 Quantitative and qualitative peritoneal immune profiles, T-cell apoptosis and oxidative stress-associated characteristics in women with minimal and mild endometriosis. BJOG 616. (https://doi.org/10.1111/j.1471-0528.2010.02777.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • MorottiMVincentKBrawnJZondervanKTBeckerCM 2014 Peripheral changes in endometriosis-associated pain. Human Reproduction Update 717736. (https://doi.org/10.1093/humupd/dmu021)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • NeedellJCZiprisD 2017 Targeting innate immunity for type 1 diabetes prevention. Current Diabetes Reports 113. (https://doi.org/10.1007/s11892-017-0930-z)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • NothnickWBFalconeTOlsonMRFazleabasATTawfikOWGrahamA 2018 Macrophage migration inhibitory factor receptor, CD74, is overexpressed in human and baboon (Papio Anubis) endometriotic lesions and modulates endometriotic epithelial cell survival and interleukin 8 expression. Reproductive Sciences 15571566. (https://doi.org/10.1177/1933719118766262)

    • Search Google Scholar
    • Export Citation
  • OsumKCBurrackALMartinovTSahliNLMitchellJSTuckerCGPaukenKEPapasKAppakalaiBSpanierJAet al. 2018 Interferon-gamma drives programmed death ligand 1 expression on islet β cells to limit T cell function during autoimmune diabetes. Scientific Reports 8295. (https://doi.org/10.1038/s41598-018-26471-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • PabonaJMSimmenFANikiforovMAZhuangDShankarKVelardeMCZelenkoZGiudiceLCSimmenRC 2012 Krüppel-like factor 9 and progesterone receptor coregulation of decidualizing endometrial stromal cells: implications for the pathogenesis of endometriosis. Journal of Clinical Endocrinology and Metabolism E376E392. (https://doi.org/10.1210/jc.2011-2562)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • PencovichNLukJHantisteanuSHornsteinMDFainaruO 2014 The development of endometriosis in a murine model is dependent on the presence of dendritic cells. Reproductive Biomedicine Online 515521. (https://doi.org/10.1016/j.rbmo.2013.12.011)

    • Search Google Scholar
    • Export Citation
  • PurohitSSharmaAHopkinsDSteedLBodeBAndersenSWReedJCSteedRDYangTSheJX 2015 Large-scale discovery and validation studnies demonstrate significant reductions in circulating levels of IL-8, IL1Ra, MCP-1, and MIP-1B in patients with type 1 diabetes. MIP-1β in patients with type 1 diabetes. Journal of Clinical Endocrinology and Metabolism 100 E1179E1187. (https://doi.org/10.1210/JC.2015-1388)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • QiaoYCChenYLPanYHTianFXuYZhangXXZhaoHL 2017 The change of serum tumor necrosis factor alpha in patients with type 1 diabetes mellitus: a systematic review and meta-analysis. PLoS ONE e0176157. (https://doi.org/10.1371/journal.pone.0176157) .

    • PubMed
    • Search Google Scholar
    • Export Citation
  • RahmiogluNMacgregorSDrongAWHedmanÅKHarrisHRRandallJCProkopenkoINyholtDRMorrisAPet al. 2015 Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci. Human Molecular Genetics 11851199. (https://doi.org/10.1093/hmg/ddu516)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • RakhilaHGirardKLeboeufMLemyreMAkoumA 2014 Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development. PLoS ONE e110434. (https://doi.org/10.1371/journal.pone.0110434)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • RogovskayaSRiveraRGrimesDAChenPLPierre-LouisBPrilepskayaVKulakovV 2005 Effect of a levonorgestrel intrauterine system on women with type 1 diabetes: a randomized trial. Obstetrics and Gynecology 811815. (https://doi.org/10.1097/01.AOG.0000156301.11939.56)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • SaguyodSJUKelleyASVelardeMCSimmenRC 2018 Diet and endometriosis-revisiting the linkages to inflammation. Journal of Endometriosis and Pelvic Pain Disorders 5158. (https://doi.org/10.1177/2284026518769022)

    • Search Google Scholar
    • Export Citation
  • Sánchez-ZamoraYIJuarez-AvelarIVazquez-MendozaAHiriartMRodriguez-SosaM 2016 Altered macrophage and dendritic cell response in Mif-/- mice reveals a role of Mif for inflammatory-Th1 response in type 1 diabetes. Journal of Diabetes Research 7053963.

    • Search Google Scholar
    • Export Citation
  • SaraswatLAyansinaDTCooperKGBhattacharyaSMiligkosDHorneAWBhattacharyaS 2017 Pregnancy outcomes in women with endometriosis: a national record linkage study. BJOG 444452. (https://doi.org/10.1111/1471-0528.13920)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • SasakiSYasudaTKanetoHKurodaAFujitaYFujisawaKTabuchiYKasamiRMatsuokaTAMatsuhisaMet al. 2013 Basal insulin requirements after progesterone treatment in a type 1 diabetic pregnant woman. Internal Medicine 259262. (https://doi.org/10.2169/internalmedicine.52.8675)

    • Search Google Scholar
    • Export Citation
  • SchreiberAKNonesCFReisRCChichorroJGCunhaJM 2015 Diabetic neuropathic pain: physiopathology and treatment. World Journal of Diabetes 432444. (https://doi.org/10.4239/wjd.v6.i3.432)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • SeyfarthJFörtschKAhlertHLawsHJKargesBDeenenRKöhrerKMayatepekEMeissnerTJacobsenM 2017 Dominant TNFα and impaired IL-2 cytokine profiles of CD4+ T cells from children with type-1 diabetes. Immunology and Cell Biology 630639. (https://doi.org/10.1038/icb.2017.24)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • ShigiyamaFKumashiroNRikitakeTUsuiSSaegusaMKitamuraMUchinoHHiroseT 2016 A case of lean polycystic ovary syndrome with early stage of type 1 diabetes successfully treated with metformin. Endocrine Journal 193198. (https://doi.org/10.1507/endocrj.EJ15-0548)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • ShuXJiJLiXSundquistJSundquistKHemminkiK 2010 Cancer risk among patients hospitalized for type 1 diabetes mellitus: a population-based cohort study in Sweden. Diabetic Medicine 791797. (https://doi.org/10.1111/j.1464-5491.2010.03011.x)

    • Search Google Scholar
    • Export Citation
  • SimmenRCMKelleyAS 2018 Seeing red: diet and endometriosis risk. Annals of Translational Medicine (Supplement 2) S119. (https://doi.org/10.21037/atm.2018.12.14)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • SjöbergLKaajaRGisslerMTuomilehtoJTiitinenAPitkäniemiJ 2017 Termination of pregnancy and sterilisation in women with childhood-onset type 1 diabetes. Diabetologia 23772383. (https://doi.org/10.1007/s00125-017-4428-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • StanicAKKimMStyerAKRuedaBR 2014 Dendritic cells attenuate the early establishment of endometriosis-like lesions in a murine model. Reproductive Sciences 12281236. (https://doi.org/10.1177/1933719114525267)

    • Search Google Scholar
    • Export Citation
  • SudaKNakaokaHYoshiharaKIshiguroTTamuraRMoriYYamawakiKAdachiSTakahashiTKaseHet al. 2018 Clonal expansion and diversification of cancer-associated mutations in endometriosis and normal endometrium. Cell Reports 17771789. (https://doi.org/10.1016/j.celrep.2018.07.037)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sugiura-OgasawaraMEbaraTMatsukiTYamadaYOmoriTMatsumotoYKatoSKanoHKuriharaTSaitohSet al. 2019 Endometriosis and recurrent pregnancy loss as new risk factors for venous thromboembolism during pregnancy and post-partum: the JECS Birth Cohort. Thrombosis and Haemostasis 606617. (https://doi.org/10.1055/s-0039-1677733)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • SwerdlowAJLaingSPQiaoZSlaterSDBurdenACBothaJLWaughNRMorrisADGatlingWGaleEAet al. 2005 Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study. British Journal of Cancer 20702075. (https://doi.org/10.1038/sj.bjc.6602611)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • SymonsLKMillerJEKayVRMarksRMLiblikKKotiMTayadeC 2018 The immunopathophysiology of endometriosis. Trends in Molecular Medicine 748762. (https://doi.org/10.1016/j.molmed.2018.07.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • TaiNWongFSWenL 2013 TLR9 deficiency promotes CD73 expression in T cells and diabetes protection in nonobese diabetic mice. Journal of Immunology 29262937. (https://doi.org/10.4049/jimmunol.1300547)

    • Search Google Scholar
    • Export Citation
  • TakemuraYOsugaYYoshinoOHasegawaAHirataTHirotaYNoseEMorimotoCHaradaMKogaKet al. 2007 Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. Journal of Clinical Endocrinology and Metabolism 32133218. (https://doi.org/10.1210/jc.2006-2486)

    • Search Google Scholar
    • Export Citation
  • ThomasNJJonesSEWeedonMNShieldsBMOramRAHattersleyAT 2018 Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank. Lancet: Diabetes and Endocrinology 122129. (https://doi.org/10.1016/S2213-8587(17)30362-5)

    • Search Google Scholar
    • Export Citation
  • ThomasNJLynamALHillAVWeedonMNShieldsBMOramRAMcDonaldTJHattersleyATJonesAG 2019 Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes. Diabetologia 11671172. (https://doi.org/10.1007/s00125-019-4863-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • UlukusMAriciA 2005 Immunology of endometriosis. Minerva Ginecologica 237248.

  • VaaralaO 2011 The gut as a regulator of early inflammation in type 1 diabetes. Current Opinion in Endocrinology Diabetes and Obesity 241247. (https://doi.org/10.1097/MED.0b013e3283488218)

    • Search Google Scholar
    • Export Citation
  • van BusselBCSoedamah-MuthuSSHenryRMSchalkwijkCGFerreiraIChaturvediNToellerMFullerJHStehouwerCD & EURODIAB Prospective Complications Study Group 2013 Unhealthy dietary patterns associated with inflammation and endothelial dysfunction in type 1 diabetes: the EURODIAB study. Nutrition Metabolism and Cardiovascular Diseases 758764. (https://doi.org/10.1016/j.numecd.2012.04.005)

    • Search Google Scholar
    • Export Citation
  • VeillatVLavoieCHMetzCNRogerTLabelleYAkoumA 2009 Involvement of nuclear factor-kappaB in macrophage migration inhibitory factor gene transcription up-regulation induced by interleukin- 1 beta in ectopic endometrial cells. Fertility and Sterility (Supplement) 21482156. (https://doi.org/10.1016/j.fertnstert.2008.05.017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • VeillatVSengersVMetzCNRogerTLeboeufMMaillouxJAkoumA 2012 Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis. American Journal of Pathology 917927. (https://doi.org/10.1016/j.ajpath.2012.05.018)

    • Search Google Scholar
    • Export Citation
  • WangYSosinowskiTNovikovACrawfordFWhiteJJinNLiuZZouJNeauDDavidsonHWet al. 2019 How C-terminal additions to insulin B-chain fragments create superagonists for T cells in mouse and human type 1 diabetes. Science Immunology eaav7517. (https://doi.org/10.1126/sciimmunol.aav7517)

    • Search Google Scholar
    • Export Citation
  • WaughKSnell-BergeonJMichelsADongFSteckAKFrohnertBINorrisJMRewersM 2017 Increased inflammation is associated with islet autoimmunity and type 1 diabetes in the Diabetes Autoimmunity Study in the Young (DAISY). PLoS ONE e0174840. (https://doi.org/10.1371/journal.pone.0174840)

    • Search Google Scholar
    • Export Citation
  • WiseJ 2016 Type 1 diabetes is associated with increased risk of several cancers. BMJ i1210. (https://doi.org/10.1136/bmj.i1210)

  • WooJHYangYIAhnJHChoiYSChoiJH 2017 Interleukin 6 secretion from alternatively activated macrophages promotes the migration of endometriotic epithelial cells. Biology of Reproduction 660670. (https://doi.org/10.1093/biolre/iox118)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • WorleyMJJrLiuSHuaYKwokJSSamuelAHouLShoniMLuSSandbergEMKeryanAet al. 2015 Molecular changes in endometriosis-associated ovarian clear cell carcinoma. European Journal of Cancer 18311842. (https://doi.org/10.1016/j.ejca.2015.05.011)

    • Search Google Scholar
    • Export Citation
  • YilmazBSucakAKilicSAksakalOAksoyYLortlarNSutNGungorT 2010 Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9. American Journal of Obstetrics and Gynecology 368.e1368.e8. (https://doi.org/10.1016/j.ajog.2009.10.873)

    • Search Google Scholar
    • Export Citation
  • YounisAHawkinsKMahiniHButlerWGarelnabiM 2014 Serum tumor necrosis factor-α, interleukin-6, monocyte chemotactic protein-1 and paraoxonase-1 profiles in women with endometriosis, PCOS, or unexplained infertility. Journal of Assisted Reproduction and Genetics 14451451. (https://doi.org/10.1007/s10815-014-0237-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • ZhangXMuL 2015 Association between macrophage migration inhibitory factor in the endometrium and estrogen in endometriosis. Experimental and Therapeutic Medicine 787791. (https://doi.org/10.3892/etm.2015.2516)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • ZulloFSpagnoloESacconeGAcunzoMXodoSCeccaroniMBerghellaV 2017 Endometriosis and obstetrics complications: a systematic review and meta-analysis. Fertility and Sterility 667.e5672.e5. (https://doi.org/10.1016/j.fertnstert.2017.07.019)

    • Search Google Scholar
    • Export Citation

If the inline PDF is not rendering correctly, you can download the PDF file here.

 

      Society for Endocrinology

Related Articles

Article Information

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 125 125 125
PDF Downloads 29 29 29

Altmetrics

Figures

  • View in gallery

    A schematic summary of immune system components potentially involved in co-morbid endometriosis and type 1 diabetes. Also shown are the substantial overlaps in clinical disorders associated with each condition.

References

  • AbeKKuklinaEVHooperWCCallaghanWM 2019 Venous thromboembolism as a cause of severe maternal morbidity and mortality in the United States. Seminars in Perinatology 200204. (https://doi.org/10.1053/j.semperi.2019.03.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • AhnSHKhalajKYoungSLLesseyBAKotiMTayadeC 2016 Immune-inflammation gene signatures in endometriosis patients. Fertility and Sterility 1420.e71431.e7. (https://doi.org/10.1016/j.fertnstert.2016.07.005)

    • Search Google Scholar
    • Export Citation
  • AlfadhliEKohAAlbakerWBhargavaRAckermanTMcDonaldCRyanEAShapiroAMSeniorPA 2009 High prevalence of ovarian cysts in premenopausal women receiving sirolimus and tacrolimus after clinical islet transplantation. Transplant International 622625. (https://doi.org/10.1111/j.1432-2277.2009.00839.x)

    • Search Google Scholar
    • Export Citation
  • AlkananiAKRewersMDongFWaughKGottliebPAZiprisD 2012 Dysregulated toll-like receptor-induced interleukin-1β and interleukin-6 responses in subjects at risk for the development of type 1 diabetes. Diabetes 25252533. (https://doi.org/10.2337/db12-0099)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • AllhornSBöingCKochAAKimmigRGashawI 2008 TLR3 and TLR4 expression in healthy and diseased human endometrium. Reproductive Biology and Endocrinology 40. (https://doi.org/10.1186/1477-7827-6-40)

    • Search Google Scholar
    • Export Citation
  • AmatoMCGuarnottaVCiresiAModicaRPantòFGiordanoC 2014 No phenotypic differences for polycystic ovary syndrome (PCOS) between women with and without type 1 diabetes mellitus. Journal of Clinical Endocrinology and Metabolism 203211. (https://doi.org/10.1210/jc.2013-2669)

    • Search Google Scholar
    • Export Citation
  • AndersenCLBoisenMMSikoraMJMaTTsengGSuryawanshiSVladAElishaevEEdwardsRPOesterreichS 2018 The evolution of estrogen receptor signaling in the progression of endometriosis to endometriosis-associated ovarian cancer. Hormones and Cancer 399407. (https://doi.org/10.1007/s12672-018-0350-9)

    • Search Google Scholar
    • Export Citation
  • AnglesioMSPapadopoulosNAyhanANazeranTMNoëMHorlingsHMLumAJonesSSenzJSeckinTet al. 2017 Cancer-associated mutations in endometriosis without cancer. New England Journal of Medicine 18351848. (https://doi.org/10.1056/NEJMoa1614814)

    • Search Google Scholar
    • Export Citation
  • BackonjaUHedigerMLChenZLauverDRSunLPetersonCMBuck LouisGM 2017 Beyond body mass index: using anthropometric measures and body composition indicators to assess odds of an endometriosis diagnosis. Journal of Women’s Health 941950. (https://doi.org/10.1089/jwh.2016.6128)

    • Search Google Scholar
    • Export Citation
  • BirtJANabliHStilleyJAWindhamEAFrazierSRSharpe-TimmsKL 2013 Elevated peritoneal fluid TNF-α incites ovarian early growth response factor 1 expression and downstream protease mediators: a correlation with ovulatory dysfunction in endometriosis. Reproductive Sciences 514523. (https://doi.org/10.1177/1933719113477479)

    • Search Google Scholar
    • Export Citation
  • BjornstadPSchäferMTruongUCree-GreenMPyleLBaumgartnerAGarcia ReyesYManiatisANayakSWadwaRPet al. 2018 Metformin improves insulin sensitivity and vascular health in youth with type 1 diabetes mellitus. Circulation 28952907. (https://doi.org/10.1161/CIRCULATIONAHA.118.035525)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • BoveGM 2016 A model for radiating leg pain of endometriosis. Journal of Bodywork and Movement Therapies 931936. (https://doi.org/10.1016/j.jbmt.2016.04.013)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • BruceRGodslandIStevensonJDevenportMBorthFCrookDGhateiMWhiteheadMWynnV 1992 Danazol induces resistance to both insulin and glucagon in young women. Clinical Science 211217. (https://doi.org/10.1042/cs0820211)

    • Search Google Scholar
    • Export Citation
  • BulunSEWanYMateiD 2019 Epithelial mutations in endometriosis: link to ovarian cancer. Endocrinology 626638. (https://doi.org/10.1210/en.2018-00794)

  • BurkeSDDongHHazanADCroyBA 2007 Aberrant endometrial features of pregnancy in diabetic NOD mice. Diabetes 29192926. (https://doi.org/10.2337/db07-0773)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • BurneyROGiudiceLC 2012 Pathogenesis and pathophysiology of endometriosis. Fertility and Sterility 511519. (https://doi.org/10.1016/j.fertnstert.2012.06.029)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • BurnsKARodriguezKFHewittSCJanardhanKSYoungSLKorachKS 2012 Role of estrogen receptor signaling required for endometriosis-like lesion establishment in a mouse model. Endocrinology 39603971. (https://doi.org/10.1210/en.2012-1294)

    • Search Google Scholar
    • Export Citation
  • BurnsKAThomasSYHamiltonKJYoungSLCookDNKorachKS 2018 Early endometriosis in females is directed by immune-mediated estrogen receptor α and IL-6 cross-talk. Endocrinology 159 103118 (https://doi.org/10.1210/en.2017-00562)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • BusiahKColmenaresABidetMTubiana-RufiNLevy-MarchalCDelcroixCJacquinPMartinDBenadjaoudLJacqz-AigrainEet al. 2017 High prevalence of polycystic ovary syndrome in type 1 diabetes mellitus adolescents: is there a difference depending on the NIH and Rotterdam criteria? Hormone Research in Paediatrics 333341. (https://doi.org/10.1159/000471805)

    • Search Google Scholar
    • Export Citation
  • CabreraSMHenschelAMHessnerMJ 2016 Innate inflammation in type 1 diabetes. Translational Research 214227. (https://doi.org/10.1016/j.trsl.2015.04.011)

    • Search Google Scholar
    • Export Citation
  • CagnacciATirelliACannolettaMPirilloDVolpeA 2005 Effect on insulin sensitivity of Implanon vs. GnRH agonist in women with endometriosis. Contraception 443446. (https://doi.org/10.1016/j.contraception.2005.05.021)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • CapobiancoAMonnoACottoneLVenneriMABiziatoDDi PuppoFFerrariSDe PalmaMManfrediAARovere-QueriniP 2011 Proangiogenic Tie2(+) macrophages infiltrate human and murine endometriotic lesions and dictate their growth in a mouse model of the disease. American Journal of Pathology 26512659. (https://doi.org/10.1016/j.ajpath.2011.07.029)

    • Search Google Scholar
    • Export Citation
  • CardinezNLovblomLEBaiJWLewisEAbrahamAScarrDLovshinJALytvynYBouletGFarooqiMAet al. 2018 Sex differences in neuropathic pain in longstanding diabetes: results from the Canadian Study of Longevity in Type 1 Diabetes. Journal of Diabetes and its Complications 660664. (https://doi.org/10.1016/j.jdiacomp.2018.05.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • CarstensenBReadSHFriisSSundRKeskimäkiISvenssonAMLjungRWildSHKerssensJJHardingJLet al. 2016 Cancer incidence in persons with type 1 diabetes: a five-country study of 9,000 cancers in type 1 diabetic individuals. Diabetologia 980988. (https://doi.org/10.1007/s00125-016-3884-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • CastellanoJMNavarroVMRoaJPinedaRSánchez-GarridoMAGarcía-GalianoDVigoEDieguezCAguilarEPinillaLet al. 2009 Alterations in hypothalamic KiSS-1 system in experimental diabetes: early changes and functional consequences. Endocrinology 784794. (https://doi.org/10.1210/en.2008-0849)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • ChuangPCLinYJWuMHWingLYShojiYTsaiSJ 2010 Inhibition of CD36-dependent phagocytosis by prostaglandin E2 contributes to the development of endometriosis. American Journal of Pathology 850860. (https://doi.org/10.2353/ajpath.2010.090551)

    • Search Google Scholar
    • Export Citation
  • CodnerEIñíguezGVillarroelCLopezPSotoNSir-PetermannTCassorlaFReyRA 2007 Hormonal profile in women with polycystic ovarian syndrome with or without type 1 diabetes mellitus. Journal of Clinical Endocrinology and Metabolism 47424746. (https://doi.org/10.1210/jc.2007-1252)

    • Search Google Scholar
    • Export Citation
  • CodnerEMerinoPMTena-SempereM 2012 Female reproduction and type 1 diabetes: from mechanisms to clinical findings. Human Reproduction Update 568585. (https://doi.org/10.1093/humupd/dms024)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • CollierAConnellyPJHairMCameronLGhoshSWaughN 2018 Mortality risk remains higher in individuals with type 1 diabetes: a population-based cohort study (the Ayrshire diabetes follow-up cohort [ADOC]). Diabetes Obesity and Metabolism 19651971. (https://doi.org/10.1111/dom.13334)

    • Search Google Scholar
    • Export Citation
  • ConnollyMATrentalangeMZeissCJ 2016 Long-term clinical outcomes in diabetic rhesus macaques (Macaca mulatta) treated with medroxyprogesterone acetate for endometriosis. Comparative Medicine 343348.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cree-GreenMStuppyJJThurstonJBergmanBCCoeGVBaumgartnerADBaconSScherzingerAPyleLNadeauKJ 2018 Youth with type 1 diabetes have adipose, hepatic, and peripheral insulin resistance. Journal of Clinical Endocrinology and Metabolism 36473657. (https://doi.org/10.1210/jc.2018-00433)

    • Search Google Scholar
    • Export Citation
  • Cree-GreenMBergmanBCCengizEFoxLAHannonTSMillerKNathanBPyleLKahnDTanseyMet al. 2019 Metformin improves peripheral insulin sensitivity in youth with type 1 diabetes. Journal of Clinical Endocrinology and Metabolism 32653278. (https://doi.org/10.1210/jc.2019-00129)

    • Search Google Scholar
    • Export Citation
  • CruzenCLBaumSTColmanRJ 2011 Glucoregulatory function in adult rhesus macaques (Macaca mulatta) undergoing treatment with medroxyprogesterone acetate for endometriosis. Journal of the American Association for Laboratory Animal Science 921925.

    • Search Google Scholar
    • Export Citation
  • CurePPileggiAFroudTNorrisPMBaidalDACornejoAHafizMMPonteGPoggioliRYuJet al. 2004 Alterations of the female reproductive system in recipients of islet grafts. Transplantation 15761581. (https://doi.org/10.1097/01.tp.0000147301.41864.c0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • DevarajSTobiasPJialalI 2011 Knockout of toll-like receptor-4 attenuates the pro-inflammatory state of diabetes. Cytokine 441445. (https://doi.org/10.1016/j.cyto.2011.03.023)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • DriverJPRacineJJYeCLamontDJNewbyBNLeethCMChapmanHDBruskoTMChenYGMathewsCEet al. 2017 Interferon-γ limits diabetogenic CD8+ T-cell effector responses in type 1 diabetes. Diabetes 710721. (https://doi.org/10.2337/db16-0846)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • ErTKSuYFWuCCChenCCWangJHsiehTHHerreros-VillanuevaMChenWTChenYTLiuTCet al. 2016 Targeted next-generation sequencing for molecular diagnosis of endometriosis-associated ovarian cancer. Journal of Molecular Medicine 835847. (https://doi.org/10.1007/s00109-016-1395-2)

    • Search Google Scholar
    • Export Citation
  • Escobar-MorrealeHF 2018 Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nature Reviews: Endocrinology 270284. (https://doi.org/10.1038/nrendo.2018.24)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Escobar-MorrealeHFRoldán-MartínMB 2016 Type 1 diabetes and polycystic ovary syndrome: systematic review and meta-analysis. Diabetes Care 639648. (https://doi.org/10.2337/dc15-2577)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • FarlandLVMissmerSABijonAGustoGGelotAClavel-ChapelonFMesrineSBoutron-RuaultMCKvaskoffM 2017 Associations among body size across the life course, adult height and endometriosis. Human Reproduction 17321742. (https://doi.org/10.1093/humrep/dex207)

    • Search Google Scholar
    • Export Citation
  • FerraraCTGeyerSMEvans-MolinaCLibmanIMBeckerDJWentworthJMMoranAGitelmanSERedondoMJ & Type 1 Diabetes TrialNet Study Group 2017 The role of age and excess body mass index in progression to type 1 diabetes in at-risk adults. Journal of Clinical Endocrinology and Metabolism 45964603. (https://doi.org/10.1210/jc.2017-01490)

    • Search Google Scholar
    • Export Citation
  • GalettisACampbellSMorrisJMJacksonCJTwiggSMGalleryED 2004 Monocyte adhesion to decidual endothelial cells is increased in pregnancies complicated by type 1 diabetes but not by gestational diabetes. Diabetes Care 25142515. (https://doi.org/10.2337/diacare.27.10.2514)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • GoetzLGMamillapalliRTaylorHS 2016 Low body mass index in endometriosis is promoted by hepatic metabolic gene dysregulation in mice. Biology of Reproduction 115 (https://doi.org/10.1095/biolreprod.116.142877)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • GouYLiXLiPZhangHXuTWangHWangBMaXJiangXZhangZ 2019 Estrogen receptor β upregulates CCL2 via NF-κB signaling in endometriotic stromal cells and recruits macrophages to promote the pathogenesis of endometriosis. Human Reproduction 646658. (https://doi.org/10.1093/humrep/dez019)

    • Search Google Scholar
    • Export Citation
  • GrandiGMuellerMBersingerNPapadiaANirgianakisKCagnacciAMcKinnonB 2016 Progestin suppressed inflammation and cell viability of tumor necrosis factor-α-stimulated endometriotic stromal cells. American Journal of Reproductive Immunology 292298. (https://doi.org/10.1111/aji.12552)

    • Search Google Scholar
    • Export Citation
  • GreavesECousinsFLMurrayAEsnal-ZufiaurreAFassbenderAHorneAWSaundersPT 2014 A novel mouse model of endometriosis mimics human phenotype and reveals insights into the inflammatory contribution of shed endometrium. American Journal of Pathology 19301939. (https://doi.org/10.1016/j.ajpath.2014.03.011)

    • Search Google Scholar
    • Export Citation
  • Gueuvoghlanian-SilvaBYBellelisPBarbeiroDFHernandesCPodgaecS 2018 Treg and NK cells related cytokines are associated with deep rectosigmoid endometriosis and clinical symptoms related to the disease. Journal of Reproductive Immunology 3238. (https://doi.org/10.1016/j.jri.2018.02.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • GüldenEIhiraMOhashiAReinbeckALFreudenbergMAKolbHBurkartV 2013 Toll-like receptor 4 deficiency accelerates the development of insulin-deficient diabetes in non-obese diabetic mice. PLoS ONE e75385. (https://doi.org/10.1371/journal.pone.0075385)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • GurrSKobsKSteindelE 1986 Ultrasonic measurements of the uterus in adolescents. Zentralblatt für Gynakologie 14201424.

  • HanSJJungSYWuSPHawkinsSMParkMJKyoSQinJLydonJPTsaiSYTsaiMJet al. 2015 Estrogen receptor β modulates apoptosis complexes and the inflammasome to drive the pathogenesis of endometriosis. Cell 960974. (https://doi.org/10.1016/j.cell.2015.10.034)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • HayashiCChishimaFSugitaniMIchikawaGNakazawa-WatanabeTSugitaKSuzukiMNemotoNYamamotoT 2013 Relationship between Toll-like receptor-4 and mPGES-1 gene expression in local lesions of endometriosis patients. American Journal of Reproductive Immunology 231239. (https://doi.org/10.1111/aji.12056)

    • Search Google Scholar
    • Export Citation
  • HeardMEMelnykSBSimmenFAYangYPabonaJMSimmenRC 2016 High-fat diet promotion of endometriosis in an immunocompetent mouse model is associated with altered peripheral and ectopic lesion redox and inflammatory status. Endocrinology 28702882. (https://doi.org/10.1210/en.2016-1092)

    • Search Google Scholar
    • Export Citation
  • HenschelAMCabreraSMKaldunskiMLJiaSGeoffreyRRoethleMFLamVChenYGWangXSalzmanNHet al. 2018 Modulation of the diet and gastrointestinal microbiota normalizes systemic inflammation and β-cell chemokine expression associated with autoimmune diabetes susceptibility. PLoS ONE e0190351. (https://doi.org/10.1371/journal.pone.0190351)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hotta-IwamuraCTarbellKV 2016 Type 1 diabetes genetic susceptibility and dendritic cell function: potential targets for treatment. Journal of Leukocyte Biology 6580. (https://doi.org/10.1189/jlb.3MR1115-500R)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • HsuPCLinWHKuoTHLeeHMKuoCLiCY 2015 A population-based cohort study of all-cause and site-specific cancer incidence among patients with type 1 diabetes mellitus in Taiwan. Journal of Epidemiology 567573. (https://doi.org/10.2188/jea.JE20140197)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • HundhausenCRothAWhalenEChenJSchneiderALongSAWeiSRawlingsRKinsmanMEvankoSPet al. 2016 Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Science Translational Medicine 356ra119. (https://doi.org/10.1126/scitranslmed.aad9943)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • HuxleyRRPetersSAMishraGDWoodwardM 2015 Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis. Lancet: Diabetes and Endocrinology 198206. (https://doi.org/10.1016/S2213-8587(14)70248-7)

    • Search Google Scholar
    • Export Citation
  • IshiharaHKitawakiJKadoNKoshibaHFushikiSHonjoH 2003 Gonadotropin-releasing hormone agonist and danazol normalize aromatase cytochrome P450 expression in eutopic endometrium from women with endometriosis, adenomyosis, or leiomyomas. Fertility and Sterility (Supplement 1) 735742. (https://doi.org/10.1016/s0015-0282(02)04813-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • JørgensenHHillASBesteMTKumarMPChiswickEFedorcsakPIsaacsonKBLauffenburgerDAGriffithLGQvigstadE 2017 Peritoneal fluid cytokines related to endometriosis in patients evaluated for infertility. Fertility and Sterility 1191.e21199.e2. (https://doi.org/10.1016/j.fertnstert.2017.03.013)

    • Search Google Scholar
    • Export Citation
  • KaponisAIwabeTTaniguchiFItoMDeuraIDecavalasGTerakawaNHaradaT 2012 The role of NF-kappaB in endometriosis. Frontiers in Bioscience 12131234.

    • Search Google Scholar
    • Export Citation
  • KellenbergerLDPetrikJ 2018 Hyperglycemia promotes insulin-independent ovarian tumor growth. Gynecologic Oncology 361370. (https://doi.org/10.1016/j.ygyno.2018.02.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • KimSMilletIKimHSKimJYHanMSLeeMKKimKWSherwinRSKarinMLeeMS 2007 NF-kappa B prevents beta cell death and autoimmune diabetes in NOD mice. PNAS 19131918. (https://doi.org/10.1073/pnas.0610690104)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • KimCMillerRSBraffettBHPanYArendsVLSaengerAKBarnieASarmaAV & EDIC Research Group 2018 Ovarian markers and irregular menses among women with type 1 diabetes in the Epidemiology of Diabetes Interventions and Complications study. Clinical Endocrinology 453459. (https://doi.org/10.1111/cen.13546)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • KnipMSimellO 2012 Environmental triggers of type 1 diabetes. Cold Spring Harbor Perspectives in Medicine a007690. (https://doi.org/10.1101/cshperspect.a007690)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • KnipMLuopajärviKHärkönenT 2017 Early life origin of type 1 diabetes. Seminars in Immunopathology 653667. (https://doi.org/10.1007/s00281-017-0665-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • KocbekVGrandiGBlankFWotzkowCBersingerNAMuellerMDKyoSMcKinnonBD 2016 TNFα-induced IKKβ complex activation influences epithelial, but not stromal cell survival in endometriosis. Molecular Human Reproduction 768777. (https://doi.org/10.1093/molehr/gaw054)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LambeletMTerraLFFukayaMMeyerovichKLabriolaLCardozoAKAllagnatF 2018 Dysfunctional autophagy following exposure to pro-inflammatory cytokines contributes to pancreatic β-cell apoptosis. Cell Death and Disease 96. (https://doi.org/10.1038/s41419-017-0121-5)

    • Search Google Scholar
    • Export Citation
  • ŁebkowskaAAdamskaAJacewiczMTołwińskaJKrentowskaAHryniewickaJLeśniewskaMBossowskiAGórskaMKowalskaI 2017 Association between polycystic ovary syndrome and the risk of subclinical vascular disease in normal‑weight women with type 1 diabetes. Polish Archives of Internal Medicine 741748. (https://doi.org/10.20452/pamw.4116)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LeeLFXuBMichieSABeilhackGFWarganichTTurleySMcDevittHO 2005 The role of TNF-alpha in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse: analysis of dendritic cell maturation. PNAS 1599516000. (https://doi.org/10.1073/pnas.0508122102)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LeeAWTemplemanCStramDABeesleyJTyrerJBerchuckAPharoahPPChenevix-TrenchGPearceCL & Ovarian Cancer Association Consortium 2016 Evidence of a genetic link between endometriosis and ovarian cancer. Fertility and Sterility 35.e143.e1. (https://doi.org/10.1016/j.fertnstert.2015.09.023)

    • Search Google Scholar
    • Export Citation
  • LiawYPKoPCJanSRHuangJYNforONLungCCChiangYCYehLTChouMCTsaiHDet al. 2015 Implications of type1/2 diabetes mellitus in breast cancer development: a general female population-based cohort study. Journal of Cancer 734739. (https://doi.org/10.7150/jca.12197)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LienEZiprisD 2009 The role of toll-like receptor pathways in the mechanism of type 1 diabetes. Current Molecular Medicine 5268. (https://doi.org/10.2174/156652409787314453)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LinYHChenKJPengYSChenPCYangYH 2018 Type 1 diabetes impairs female fertility even before it is diagnosed. Diabetes Research and Clinical Practice 151158. (https://doi.org/10.1016/j.diabres.2018.07.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LiuwantaraDElliotMSmithMWYamAOWaltersSNMarinoEMcSheaAGreyST 2006 Nuclear factor-kappa B regulates beta-cell death: a critical role for A20 in beta-cell protection. Diabetes 24912501. (https://doi.org/10.2337/db06-0142)

    • Search Google Scholar
    • Export Citation
  • LjunggrenPMaahsDMJohanssonPLudvigssonJPyleLSipplRWadwaRPSnell-BergeonJ 2016 Reduced brachial artery distensibility in patients with type 1 diabetes. Journal of Diabetes and its Complications 893897. (https://doi.org/10.1016/j.jdiacomp.2016.03.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LudvigssonJFNeoviusMSöderlingJGudbjörnsdottirSSvenssonAMFranzénSStephanssonOPasternakB 2019 Maternal glycemic control in type 1 diabetes and the risk for preterm birth: a population-based cohort study. Annals of Internal Medicine 691701. (https://doi.org/10.7326/M18-1974)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • LuoXZZhouWJTaoYWangXQLiDJ 2015 TLR4 activation promotes the secretion of IL-8 which enhances the invasion and proliferation of endometrial stromal cells in an autocrine manner via the FAK signal pathway. American Journal of Reproductive Immunology 467479. (https://doi.org/10.1111/aji.12425)

    • Search Google Scholar
    • Export Citation
  • MaahsDMWestNALawrenceJMMayer-DavisEJ 2010 Epidemiology of type 1 diabetes. Endocrinology and Metabolism Clinics of North America 481497. (https://doi.org/10.1016/j.ecl.2010.05.011)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • MaffeisCBirkebaekNHKonstantinovaMSchwandtAVazeouACasteelsKJaliSLimbertCPundziute-LyckaAToth-HeynPet al. 2018 Prevalence of underweight, overweight, and obesity in children and adolescents with type 1 diabetes: data from the international SWEET registry. Pediatric Diabetes 12111220. (https://doi.org/10.1111/pedi.12730)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • MahalingaiahSSunFChengJJChowETLunettaKLMurabitoJM 2017 Cardiovascular risk factors among women with self-reported infertility. Fertility Research and Practice 7. (https://doi.org/10.1186/s40738-017-0034-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • MatalliotakisIPanidisDVlassisGNeonakiMKoumantakisE 1997 Decreased sensitivity to insulin during treatment with danazol in women with endometriosis. Clinical and Experimental Obstetrics and Gynecology 160162.

    • Search Google Scholar
    • Export Citation
  • Mier-CabreraJJiménez-ZamudioLGarcía-LatorreECruz-OrozcoOHernández-GuerreroCQ 2011 Quantitative and qualitative peritoneal immune profiles, T-cell apoptosis and oxidative stress-associated characteristics in women with minimal and mild endometriosis. BJOG 616. (https://doi.org/10.1111/j.1471-0528.2010.02777.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • MorottiMVincentKBrawnJZondervanKTBeckerCM 2014 Peripheral changes in endometriosis-associated pain. Human Reproduction Update 717736. (https://doi.org/10.1093/humupd/dmu021)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • NeedellJCZiprisD 2017 Targeting innate immunity for type 1 diabetes prevention. Current Diabetes Reports 113. (https://doi.org/10.1007/s11892-017-0930-z)