About

Clare Flannery, MD, is an endocrinologist and Associate Professor with dual appointments in the Department of Obstetrics, Gynecology, and Reproductive Sciences (Reproductive Endocrinology) and the Department of Internal Medicine (Endocrinology) at Yale School of Medicine. Her educational background includes an undergraduate degree in Chemistry from Wellesley College and an M.D. from Trinity College, Dublin. She completed her internship at St. James’s Hospital in Dublin and her residency in Internal Medicine at Jacobi Hospital, Albert Einstein College of Medicine, where she also served as Chief Resident. Dr. Flannery pursued her fellowship in Endocrinology & Metabolism at Yale, where she also conducted research fellowships in labs focusing on endometrial physiology and the pathophysiology of Type-2 diabetes mellitus. Her translational research lab studies mechanisms for endometrial cancer development and the effects of weight and diabetes on women's reproductive health. She sees patients with diabetes and endocrine disorders, with a specialty interest in diabetes prevention, weight management, Polycystic Ovary Syndrome, perimenopause, and gender-affirming hormone therapy.

Research topics

• Endocrinology
• Internal medicine
• Medicine
• Biology
• Biochemistry

Selected publications

• <p>GROW Questionnaire Measures.</p>

  Figshare · 2026-03-02

  dataset

  <div> Background Gestational diabetes mellitus (GDM) is linked with adverse health outcomes for both mother and infant and increases the risk of type 2 diabetes mellitus (T2DM) and long-term metabolic dysfunction postpartum. American Samoa experiences among the highest prevalence of GDM globally, with estimates suggesting 26–42% of women develop the condition. To date, no studies have attempted to understand the underlying etiology of GDM in Pacific Islanders or examine population-specific progression from GDM to T2DM. The GROW study will characterize glucose homeostasis, diabetes progression, and the impact of a Pacific-specific variant (rs373863828) in the <i>CREBRF</i> gene, which is known to protect against T2DM, on glucose metabolism during and after pregnancy. Methods We will establish a prospective cohort study of 350 pregnant women in American Samoa, enrolled in their first trimester and followed through 18 months postpartum. Participants will be genotyped for <i>CREBRF</i> rs373863828 and undergo frequently-sampled oral glucose tolerance test (fs-OGTTs), glycated hemoglobin (HbA1c), and continuous glucose monitoring (CGM) measurements to identify glycemic patterns across the perinatal period. Participants will complete questionnaires assessing reproductive health history, diet, physical activity, sleep, and psychosocial health. We will examine associations between <i>CREBRF</i> genotype and glucose homeostasis across pregnancy and postpartum and evaluate risk of GDM and subsequent T2DM. We will also explore associations between <i>CREBRF</i> genotype, changes in insulin secretion in pregnancy, and risk of adverse birth outcomes. Discussion Findings from this study are expected to inform precision medicine approaches to diabetes prevention, refine public health policies and clinical guidelines, and support community-based interventions aimed at reducing GDM and T2DM among Pacific Islander women and more broadly. </div>

  DOI

• <p>Overview of GROW study procedures.</p>

  Figshare · 2026-03-02

  dataset

  <div> Background Gestational diabetes mellitus (GDM) is linked with adverse health outcomes for both mother and infant and increases the risk of type 2 diabetes mellitus (T2DM) and long-term metabolic dysfunction postpartum. American Samoa experiences among the highest prevalence of GDM globally, with estimates suggesting 26–42% of women develop the condition. To date, no studies have attempted to understand the underlying etiology of GDM in Pacific Islanders or examine population-specific progression from GDM to T2DM. The GROW study will characterize glucose homeostasis, diabetes progression, and the impact of a Pacific-specific variant (rs373863828) in the <i>CREBRF</i> gene, which is known to protect against T2DM, on glucose metabolism during and after pregnancy. Methods We will establish a prospective cohort study of 350 pregnant women in American Samoa, enrolled in their first trimester and followed through 18 months postpartum. Participants will be genotyped for <i>CREBRF</i> rs373863828 and undergo frequently-sampled oral glucose tolerance test (fs-OGTTs), glycated hemoglobin (HbA1c), and continuous glucose monitoring (CGM) measurements to identify glycemic patterns across the perinatal period. Participants will complete questionnaires assessing reproductive health history, diet, physical activity, sleep, and psychosocial health. We will examine associations between <i>CREBRF</i> genotype and glucose homeostasis across pregnancy and postpartum and evaluate risk of GDM and subsequent T2DM. We will also explore associations between <i>CREBRF</i> genotype, changes in insulin secretion in pregnancy, and risk of adverse birth outcomes. Discussion Findings from this study are expected to inform precision medicine approaches to diabetes prevention, refine public health policies and clinical guidelines, and support community-based interventions aimed at reducing GDM and T2DM among Pacific Islander women and more broadly. </div>

  DOI

• Gestational diabetes–Risk factors and outcomes among American Samoan Women (GROW): A longitudinal cohort study protocol

  PLoS ONE · 2026-03-02

  articleOpen access

  BACKGROUND: Gestational diabetes mellitus (GDM) is linked with adverse health outcomes for both mother and infant and increases the risk of type 2 diabetes mellitus (T2DM) and long-term metabolic dysfunction postpartum. American Samoa experiences among the highest prevalence of GDM globally, with estimates suggesting 26-42% of women develop the condition. To date, no studies have attempted to understand the underlying etiology of GDM in Pacific Islanders or examine population-specific progression from GDM to T2DM. The GROW study will characterize glucose homeostasis, diabetes progression, and the impact of a Pacific-specific variant (rs373863828) in the CREBRF gene, which is known to protect against T2DM, on glucose metabolism during and after pregnancy. METHODS: We will establish a prospective cohort study of 350 pregnant women in American Samoa, enrolled in their first trimester and followed through 18 months postpartum. Participants will be genotyped for CREBRF rs373863828 and undergo frequently-sampled oral glucose tolerance test (fs-OGTTs), glycated hemoglobin (HbA1c), and continuous glucose monitoring (CGM) measurements to identify glycemic patterns across the perinatal period. Participants will complete questionnaires assessing reproductive health history, diet, physical activity, sleep, and psychosocial health. We will examine associations between CREBRF genotype and glucose homeostasis across pregnancy and postpartum and evaluate risk of GDM and subsequent T2DM. We will also explore associations between CREBRF genotype, changes in insulin secretion in pregnancy, and risk of adverse birth outcomes. DISCUSSION: Findings from this study are expected to inform precision medicine approaches to diabetes prevention, refine public health policies and clinical guidelines, and support community-based interventions aimed at reducing GDM and T2DM among Pacific Islander women and more broadly.

  PublisherDOI

• Gestational Diabetes - Risk Factors and Outcomes among American Samoan Women (GROW): A Longitudinal Cohort Study Protocol

  medRxiv · 2025-10-27

  preprintOpen access

  Abstract Background Gestational diabetes mellitus (GDM) is linked with adverse health outcomes for both mother and infant and increases the risk of type 2 diabetes mellitus (T2DM) and long-term metabolic dysfunction postpartum. American Samoa experiences among the highest prevalence of GDM globally, with estimates suggesting 26-42% of women develop the condition. To date, no studies have attempted to understand the underlying etiology of GDM in Pacific Islanders or examine population-specific progression from GDM to T2DM. The GROW study will characterize glucose homeostasis, diabetes progression, and the impact of a Pacific-specific variant (rs373863828) in the CREBRF gene, which is known to protect against T2DM, on glucose metabolism during and after pregnancy. Methods We will establish a prospective cohort study of 350 pregnant women in American Samoa, enrolled in their first trimester and followed through 18 months postpartum. Participants will be genotyped for CREBRF rs373863828 and undergo frequently-sampled oral glucose tolerance test (fs-OGTTs), glycated hemoglobin (HbA1c), and continuous glucose monitoring (CGM) measurements to identify glycemic patterns across the perinatal period. Participants will complete questionnaires assessing reproductive health history, diet, physical activity, sleep, and psychosocial health. We will examine associations between CREBRF genotype and glucose homeostasis across pregnancy and postpartum and evaluate risk of GDM and subsequent T2DM. We will also explore associations between CREBRF genotype, changes in insulin secretion in pregnancy, and risk of adverse birth outcomes. Discussion Findings from this study are expected to inform precision medicine approaches to diabetes prevention, refine public health policies and clinical guidelines, and support community-based interventions aimed at reducing GDM and T2DM among Pacific Islander women and more broadly.

  PublisherOA PDFDOI

• Management of Severe Hypertriglyceridemia in Pregnancy With Niacin: Reevaluating Safety and Therapeutic Benefits

  Case Reports in Endocrinology · 2025-01-01 · 1 citations

  articleOpen access

  Background: Severe hypertriglyceridemia (triglycerides (TGs) &gt;1000 mg/dL, &gt;11.3 mmol/L) is a rare but potentially morbid condition in pregnancy. Physiological changes in pregnancy may unmask or exacerbate an underlying defect in TG metabolism. When conventional therapies are ineffective in controlling TG levels, a personalized management approach is needed. We present a case of severe hypertriglyceridemic pancreatitis successfully managed with niacin, a treatment that has seen limited use in pregnancy due to the paucity of available data. Case Presentation: A 29‐year‐old pregnant woman with a history of cholecystectomy and a prepregnancy BMI of 30.6 kg/m 2 presented at 12 weeks’ gestation with acute pancreatitis and severe hypertriglyceridemia (6900 mg/dL, 77.9 mmol/L). After initial management with intravenous (IV) fluids, insulin infusion, and a low‐fat diet, her TG levels improved. However, she was readmitted at 23 weeks’ gestation with recurrent hypertriglyceridemia (2872 mg/dL, 32.4 mmol/L), requiring a more aggressive insulin regimen. Despite various interventions, including omega‐3 fatty acids (O3FAs), fenofibrate, and central venous catheter insulin infusion, her TG levels remained elevated, necessitating early delivery at 34 weeks’ gestation. Her postpartum recovery included continued TG management with fenofibrate and O3FAs. Four years later, during a second pregnancy, she presented with similar hypertriglyceridemia, managed with diet, metformin, fenofibrate, and insulin. Due to persistent hypertriglyceridemia (&gt;3000 mg/dL, 33.9 mmol/L), niacin was added as an additional therapy and titrated to 2000 mg/day, which successfully sustained TG levels below 1000 mg/dL (11.3 mmol/L) through the remainder of her pregnancy. She delivered her second child via cesarean section at 35 weeks’ gestation due to preeclampsia. Both children had developmental issues, with her first child diagnosed with attention‐deficient hyperactivity disorder (ADHD) and her second child with autism spectrum disorder and motor delays. The patient was encouraged to remain on long‐term management for her metabolic condition. Conclusions: Managing severe hypertriglyceridemia during pregnancy is challenging due to uncertainties about treatment efficacy and safety. Timely reduction of maternal TGs is essential to prevent complications and requires adjustments throughout pregnancy. This case demonstrates the effectiveness and safety of niacin, often underutilized due to perceived side effects, in managing severe hypertriglyceridemia in pregnancy when other treatments were inadequate.

  PublisherOA PDFDOI

• 183P Frequency of actionable fusions in 7,735 patients with solid tumors

  Annals of Oncology · 2023-10-01

  articleOpen access
  PublisherOA PDFDOI

• Estradiol cycling drives female obesogenic adipocyte hyperplasia

  Cell Reports · 2023 · 25 citations

  • Internal medicine
  • Endocrinology
  • Biology

  White adipose tissue (WAT) distribution is sex dependent. Adipocyte hyperplasia contributes to WAT distribution in mice driven by cues in the tissue microenvironment, with females displaying hyperplasia in subcutaneous and visceral WAT, while males and ovariectomized females have visceral WAT (VWAT)-specific hyperplasia. However, the mechanism underlying sex-specific hyperplasia remains elusive. Here, transcriptome analysis in female mice shows that high-fat diet (HFD) induces estrogen signaling in adipocyte precursor cells (APCs). Analysis of APCs throughout the estrous cycle demonstrates increased proliferation only when proestrus (high estrogen) coincides with the onset of HFD feeding. We further show that estrogen receptor α (ERα) is required for this proliferation and that estradiol treatment at the onset of HFD feeding is sufficient to drive it. This estrous influence on APC proliferation leads to increased obesity driven by adipocyte hyperplasia. These data indicate that estrogen drives ERα-dependent obesogenic adipocyte hyperplasia in females, exacerbating obesity and contributing to the differential fat distribution between the sexes.

  PublisherDOI

• Hyperinsulinemia induces early and dyssynchronous puberty in lean female mice

  Journal of Endocrinology · 2022 · 8 citations

  Senior authorCorresponding
  • Internal medicine
  • Endocrinology
  • Medicine

  Girls with obesity are at increased risk of early puberty. Obesity is associated with insulin resistance and hyperinsulinemia. We hypothesized that insulin plays a physiological role in pubertal transition, and super-imposed hyperinsulinemia due to childhood obesity promotes early initiation of puberty in girls. To isolate the effect of hyperinsulinemia from adiposity, we compared pre-pubertal and pubertal states in hyperinsulinemic, lean muscle (M)-insulin-like growth factor 1 receptor (IGF-1R)-lysine (K)-arginine (R) (MKR) mice to normoinsulinemic WT, with puberty onset defined by vaginal opening (VO). Our results show MKR had greater insulin resistance and higher insulin levels (P < 0.05) than WT despite lower body weight (P < 0.0001) and similar IGF-1 levels (P = NS). Serum luteinizing hormone (LH) levels were higher in hyperinsulinemic MKR (P = 0.005), and insulin stimulation induced an increase in LH levels in WT. VO was earlier in hyperinsulinemic MKR vs WT (P < 0.0001). When compared on the day of VO, kisspeptin expression was higher in hyperinsulinemic MKR vs WT (P < 0.05), and gonadotropin-releasing hormone and insulin receptor isoform expression was similar (P = NS). Despite accelerated VO, MKR had delayed, disordered ovarian follicle and mammary gland development. In conclusion, we found that hyperinsulinemia alone without adiposity triggers earlier puberty. In our study, hyperinsulinemia also promoted dyssynchrony between pubertal initiation and progression, urging future studies in girls with obesity to assess alterations in transition to adulthood.

  PublisherOA PDFDOI

• Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity

  Molecular Metabolism · 2022 · 18 citations

  Senior authorCorresponding
  • Endocrinology
  • Internal medicine
  • Biology

  OBJECTIVE: Maternal obesity increases the incidence of excess adiposity in newborns, resulting in lifelong diabetes risk. Elevated intrauterine fetal adiposity has been attributed to maternal hyperglycemia; however, this hypothesis does not account for the increased adiposity seen in newborns of mothers with obesity who have euglycemia. We aimed to explore the placental response to maternal hyperinsulinemia and the effect of insulin-like growth factor 2 (IGF-2) in promoting fetal adiposity by increasing storage and availability of nutrients to the fetus. METHODS: We used placental villous explants and isolated trophoblasts from normal weight and obese women to assess the effect of insulin and IGF-2 on triglyceride content and insulin receptor signaling. Stable isotope tracer methods were used ex vivo to determine effect of hormone treatment on de novo lipogenesis (DNL), fatty acid uptake, fatty acid oxidation, and esterification in the placenta. RESULTS: Here we show that placentae from euglycemic women with normal weight and obesity both have abundant insulin receptor. Placental depth and triglyceride were greater in women with obesity compared with normal weight women. In syncytialized placental trophoblasts and villous explants, insulin and IGF-2 activate insulin receptor, induce expression of lipogenic transcription factor SREBP-1 (sterol regulatory element-binding protein 1), and stimulate triglyceride accumulation. We demonstrate elevated triglyceride is attributable to increased esterification of fatty acids, without contribution from DNL and without an acceleration of fatty acid uptake. CONCLUSIONS: Our work reveals that obesity-driven aberrations in maternal metabolism, such as hyperinsulinemia, alter placental metabolism in euglycemic conditions, and may explain the higher prevalence of excess adiposity in the newborns of obese women.

  PublisherDOI

• Identification of Cellular Damage in Uteri From Hyperinsulinemic Mice Treated With Unopposed Estradiol

  Journal of the Endocrine Society · 2021-05-01

  articleOpen accessSenior author

  Abstract Unopposed estradiol and obesity are known risk factors for endometrial adenocarcinoma (EC). Endometrium from women with obesity was found to have an increase in mutations relative to tissue from normal weight women, indicating DNA damage may be accelerated in the setting of obesity. Since obesity is associated with high levels of insulin and anovulatory cycles, we sought to mimic these conditions in a mouse model. We previously found that hyperinsulinemic MKR mice, without the confounder of obesity, have an increased incidence of nuclear atypia in endometrial glands. We hypothesized that hyperinsulinemia and unopposed estradiol have a synergistic effect on inducing abnormal architecture and DNA damage in the endometrium, than either alone. At 8-10 weeks old, cohorts of MKR (n=20) and WT (n=20) mice underwent ovariectomy and placement of either an estradiol (E2) or placebo (P) pellet. Metabolic profiling included insulin tolerance testing and MR for body composition. At 3 months post-implantation, mice received a partial hysterectomy and second pellet replacement. At 6 months, the remaining uterus was bisected into pieces. A blinded histological analysis was conducted by a gynecology pathologist. A marker of DNA damage due to oxidative stress, 8-oxoguanine-DNA-glycosylase (8-OHdG), was quantified by ELISA. Data was analyzed using Kruskal-Wallis test with multiple test correction, or Fischer’s exact test. By 6 months, MKR-E2 treated mice had a 27% lower body weight than MKR-P mice (p&amp;lt;0.05), and 31% lower than WT-E2 mice (p&amp;lt;0.01). WT-E2 and WT-P had similar weight, and were similar to MKR-P (p=ns). Percent body fat was similar across all 4 cohorts of mice (p=ns). Since placebo-treated mice had small, atrophied uteri with minimal gland formation, E2 pellet failure was determined by the presence of small, atrophied uteri and occurred in 4 MKR and 3 WT mice at either 3 or 6 months. All other MKR and WT E2 treated mice had enlarged uteri. The frequency of endometrial gland dilation was similar in MKR-E2 and WT-E2 uteri (p=ns), but all MKR mice had moderate-severe dilation, whereas WT mice had 50% mild and 50% moderate-severe dilation (p=0.07). Focal hyperplasia was present in one MKR-E2 mouse, and nuclear atypia was present in one WT-E2 mouse. MKR-P uteri had a 7-fold higher mean 8-OHdG relative to MKR-E2 uteri (5.0±3.7 vs 0.7±1.6, p&amp;lt;0.002). WT-E2 and WT-P uteri had similar 8-OHdG (1.6±0.8 vs 1.8±0.6, p=ns), as did MKR-E2 and WT-E2 uteri (p=ns). Our findings show that hyperinsulinemia exacerbates the cystic dilation induced by chronic unopposed estradiol, indicating a synergy of insulin and estradiol in promoting abnormal glandular growth in the endometrium. Surprisingly, uterine DNA damage was highest in the setting of hyperinsulinemia alone, in a hormonal state mimicking post-menopause. Further work is needed to understand the effect of estradiol on intrauterine oxidative stress-induced damage.

  PublisherOA PDFDOI

Recent grants

• Effect of Insulin on Estrogen Receptor Alpha Activity in Human Endometrial Cells

  NIH · $658k · 2012–2017

• Obesity-driven endometrial hyperplasia in postmenopausal women: Synergistic role for insulin and estrone

  NIH · $2.3M · 2019–2026

Frequent coauthors

• Hugh S. Taylor

  Yale University

  13 shared

• Gerald I. Shulman

  Howard Hughes Medical Institute

  12 shared

• Jichun Zhou

  11 shared

• Martin Mueller

  University of Bern

  8 shared

• Lihua Yang

  Zhujiang Hospital

  8 shared

• Lei Yan

  8 shared

• Yuan Gao

  Heilongjiang Academy of Forestry

  6 shared

• Gina Choe

  6 shared

Labs

• Flannery LabPI

Education

• M.B., B.Ch., B.A.O.

  Trinity College, Dublin

  2001

• BA

  Wellesley College

  1995

Awards & honors

• NIH K08 mentored career award
• NIH R01 funding