Serum bile acid measurements in women of European and South Asian ethnicity with or without gestational diabetes mellitus: A cohort study.

OBJECTIVE: Investigation of serum bile acid profiles in pregnancies complicated by gestational diabetes mellitus (GDM) in a multi-ethnic cohort of women who are lean or obese. DESIGN: Prospective cohort study. SETTING: UK multicentre study. POPULATION: Fasting serum from participants of European or South Asian self-reported ethnicity from the PRiDE study, between 23 and 31 weeks of gestation. METHODS: Bile acids were measured using ultra-performance liquid chromatography-tandem mass spectrometry. Log-transformed data were analysed using linear regression in STATA/IC 15.0. MAIN OUTCOME MEASURES: Total bile acids (TBAs), C4, fasting glucose and insulin. RESULTS: The TBAs were 1.327-fold (1.105-1.594) increased with GDM in European women (P = 0.003). Women with GDM had 1.162-fold (1.002-1.347) increased levels of the BA synthesis marker C4 (P = 0.047). In South Asian women, obesity (but not GDM) increased TBAs 1.522-fold (1.193-1.942, P = 0.001). Obesity was associated with 1.420-fold (1.185-1.702) increased primary/secondary BA ratio (P < 0.001) related to 1.355-fold (1.140-1.611) increased primary BA concentrations (P = 0.001). TBAs were positively correlated with fasting glucose (P = 0.039) in all women, and with insulin (P = 0.001) and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (P = 0.001) in women with GDM. CONCLUSIONS: Serum BA homeostasis in late gestation depends on body mass index and GDM in ethnicity-specific ways. This suggests ethnicity-specific aetiologies may contribute to metabolic risk in European and South Asian women, with the relationship between BAs and insulin resistance of greater importance in European women. Further studies into ethnicity-specific precision medicine for GDM are required.

Kinbank: A global database of kinship terminology.

For a single species, human kinship organization is both remarkably diverse and strikingly organized. Kinship terminology is the structured vocabulary used to classify, refer to, and address relatives and family. Diversity in kinship terminology has been analyzed by anthropologists for over 150 years, although recurrent patterning across cultures remains incompletely explained. Despite the wealth of kinship data in the anthropological record, comparative studies of kinship terminology are hindered by data accessibility. Here we present Kinbank, a new database of 210,903 kinterms from a global sample of 1,229 spoken languages. Using open-access and transparent data provenance, Kinbank offers an extensible resource for kinship terminology, enabling researchers to explore the rich diversity of human family organization and to test longstanding hypotheses about the origins and drivers of recurrent patterns. We illustrate our contribution with two examples. We demonstrate strong gender bias in the phonological structure of parent terms across 1,022 languages, and we show that there is no evidence for a coevolutionary relationship between cross-cousin marriage and bifurcate-merging terminology in Bantu languages. Analysing kinship data is notoriously challenging; Kinbank aims to eliminate data accessibility issues from that challenge and provide a platform to build an interdisciplinary understanding of kinship.

Implementation of a compulsory clinical pharmacist-led medication deprescribing intervention in high-risk seniors in the emergency department.

OBJECTIVES: The objective of this study was to assess the impact of an emergency department (ED) deprescribing intervention for geriatric adults. We hypothesized that pharmacist-led medication reconciliation for at-risk aging patients would increase the 60-day case rate of primary care provider (PCP) deprescribing of potentially inappropriate medications (PIMs). METHODS: This was a retrospective, before-and-after intervention pilot study conducted at an urban Veterans Affairs ED. In November 2020, a protocol utilizing pharmacists to perform medication reconciliations for patients 75 years or older who screened positive using an Identification of Seniors at Risk tool at triage was implemented. Reconciliations focused on identifying PIMs and providing deprescribing recommendations to patients' PCPs. A preintervention group was collected between October 2019 and October 2020, and a postintervention group was collected between February 2021 to February 2022. The primary outcome compared case rates of PIM deprescribing in the preintervention group to the postintervention group. Secondary outcomes include per-medication PIM deprescribing rate, 30-day PCP follow-up visits, 7- and 30-day ED visits, 7- and 30-day hospitalizations, and 60-day mortality. RESULTS: A total of 149 patients were analyzed in each group. Both groups were similar in age and sex, with an average age of 82 years and 98% male. The case rate of PIM deprescribing at 60 days was 11.1% preintervention compared to 57.1% postintervention (p < 0.001). Preintervention, 91% of PIMs remained unchanged at 60 days compared to 49% (p < 0.05) postintervention. Regardless of PIM identification, the 30-day primary care follow-up rate increased postintervention: 31.5% and 55.7% (p < 0.0001), respectively. There was no improvement in 7- or 30-day subsequent ED visits, hospitalization, or mortality. CONCLUSIONS: Pharmacist-led medication reconciliation in high-risk geriatric patients was associated with an increase both in the rate of PIM deprescribing and in post-ED primary care engagement.

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.

A multi-centered trial investigating gestational treatment with ursodeoxycholic acid compared to metformin to reduce effects of diabetes mellitus (GUARD): a randomized controlled trial protocol.

BACKGROUND: Each year in the UK, approximately 35,000 women develop gestational diabetes mellitus (GDM). The condition increases the risk of obstetric and neonatal complications for mother and child, including preeclampsia, preterm birth, and large for gestational age babies. Biochemical consequences include maternal hyperglycemia, neonatal hypoglycemia, and dyslipidemia. Metformin is the most commonly used firstline pharmacological treatment. However, there are concerns about its widespread use during pregnancy, due to its limited efficacy and potential safety concerns. Therefore, there is a need for additional therapies that improve both maternal-fetal glucose and lipid metabolism. Ursodeoxycholic acid (UDCA) is not currently used for treatment for GDM. However, it can improve glucose control in type 2 diabetes, and it improves fetal lipid profiles in gestational cholestasis. Consequentially, it is hypothesized that treatment with UDCA for women with GDM may improve both maternal metabolism and neonatal outcomes. The primary outcome of this trial is to assess the efficacy of UDCA compared with metformin to improve glucose levels in women with GDM. METHODS: The trial is a two-armed, open-label, multi-center, randomized controlled trial. Women are eligible if they have been diagnosed with GDM by an oral glucose tolerance test between 24 + 0 and 30 + 6 weeks' gestation, and if they require pharmacological intervention. In total, 158 pregnant women will be recruited across seven NHS Trusts in England and Wales. Women who consent will be recruited and randomized to either metformin or UDCA, which will be taken daily until the birth of their baby. Maternal and neonatal blood samples will be taken to evaluate the impact of the treatments on maternal glucose control, and maternal and neonatal lipid metabolism. Maternal and fetal outcomes will be evaluated, and acceptability of UDCA compared with metformin will be assessed. DISCUSSION: This trial has the potential to identify a potential new treatment for women with GDM. If successful, a future large multi-center trial will be designed to investigate where decisions can be personalized to identify which women will respond more effectively to UDCA than alternatives to improve maternal and baby outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04407650.

"The world is so white": improving cultural safety in healthcare systems for Australian Indigenous people with rheumatic heart disease.

OBJECTIVE: To examine the views of senior health system knowledge holders, including Aboriginal experts, regarding the spaces where elimination strategies for rheumatic heart disease take place: Aboriginal and Torres Strait Islander ways of knowing, being and doing; and biomedical healthcare models. We aimed to support the implementation of the RHD Endgame Strategy by providing some of the 'how'. METHODS: In-depth interviews were undertaken with 23 participants. The design of the interview questions and analysis of the data used strengths-based approaches as directed by Aboriginal researchers. RESULTS: Given the dominance of the biomedical worldview, and the complex trajectory of RHD, there is significant tension in the intersection of worldviews. Tensions that limit productive dialogue are juxtaposed with suggestions on how to reduce tension through reflexivity, power shifting and endorsing Aboriginal leadership and governance. Evidence supported cultural safety for RHD care, prevention and elimination as the key action. CONCLUSIONS: Recommendations include addressing power imbalances between dominant and minority populations throughout the health system; reform that both supports and is supported by Non-Indigenous and Aboriginal and Torres Strait Islander leadership. IMPLICATIONS FOR PUBLIC HEALTH: Increased understanding of and support for Indigenous leadership and cultural safety will enable implementation of the new RHD strategy.

Living with Rheumatic Heart Disease at the Intersection of Biomedical and Aboriginal Worldviews.

Rheumatic heart disease (RHD) significantly impacts the lives of First Nations Australians. Failure to eliminate RHD is in part attributed to healthcare strategies that fail to understand the lived experience of RHD. To rectify this, a PhD study was undertaken in the Northern Territory (NT) of Australia, combining Aboriginal ways of knowing, being and doing with interviews (24 participants from clinical and community settings) and participant observation to privilege Aboriginal voices, including the interpretations and experiences of Aboriginal co-researchers (described in the adjunct article). During analysis, Aboriginal co-researchers identified three interwoven themes: maintaining good feelings; creating clear understanding (from good information); and choosing a good djalkiri (path). These affirm a worldview that prioritises relationships, positive emotions and the wellbeing of family/community. The findings demonstrate the inter-connectedness of knowledge, choice and behaviour that become increasingly complex in stressful and traumatic health, socioeconomic, political, historical and cultural contexts. Not previously heard in the RHD domain, the findings reveal fundamental differences between Aboriginal and biomedical worldviews contributing to the failure of current approaches to communicating health messages. Mitigating this, Aboriginal co-researchers provided targeted recommendations for culturally responsive health encounters, including: communicating to create positive emotions; building trust; and providing family and community data and health messages (rather than individualistic).

"Weaving a Mat That We Can All Sit On": Qualitative Research Approaches for Productive Dialogue in the Intercultural Space.

Research remains a site of struggle for First Nations peoples globally. Biomedical research often reinforces existing power structures, perpetuating ongoing colonisation by dominating research priorities, resource allocation, policies, and services. Addressing systemic health inequities requires decolonising methodologies to facilitate new understandings and approaches. These methodologies promote a creative tension and productive intercultural dialogue between First Nations and Western epistemologies. Concurrently, the potential of critical theory, social science, and community participatory action research approaches to effectively prioritise First Nations peoples' lived experience within the biomedical worldview is increasingly recognised. This article describes learnings regarding research methods that enable a better understanding of the lived experience of rheumatic heart disease-an intractable, potent marker of health inequity for First Nations Australians, requiring long-term engagement in the troubled intersection between Indigenist and biomedical worldviews. Working with Yolŋu (Aboriginal) co-researchers from remote Northern Territory (Australia), the concept of ganma (turbulent co-mingling of salt and fresh water) was foundational for understanding and applying relationality (gurrutu), deep listening (nhina, nhäma ga ŋäma), and the use of metaphors-approaches that strengthen productive dialogue, described by Yolŋu co-researchers as weaving a 'mat we can all sit on'. The research results are reported in a subsequent article.

Sulfated Progesterone Metabolites That Enhance Insulin Secretion via TRPM3 Are Reduced in Serum From Women With Gestational Diabetes Mellitus.

Serum progesterone sulfates were evaluated in the etiology of gestational diabetes mellitus (GDM). Serum progesterone sulfates were measured using ultra-performance liquid chromatography-tandem mass spectrometry in four patient cohorts: 1) the Hyperglycemia and Adverse Pregnancy Outcomes study; 2) London-based women of mixed ancestry and 3) U.K.-based women of European ancestry with or without GDM; and 4) 11-13 weeks pregnant women with BMI ≤25 or BMI ≥35 kg/m2 with subsequent uncomplicated pregnancies or GDM. Glucose-stimulated insulin secretion (GSIS) was evaluated in response to progesterone sulfates in mouse islets and human islets. Calcium fluorescence was measured in HEK293 cells expressing transient receptor potential cation channel subfamily M member 3 (TRPM3). Computer modeling using Molecular Operating Environment generated three-dimensional structures of TRPM3. Epiallopregnanolone sulfate (PM5S) concentrations were reduced in GDM (P < 0.05), in women with higher fasting plasma glucose (P < 0.010), and in early pregnancy samples from women who subsequently developed GDM with BMI ≥35 kg/m2 (P < 0.05). In islets, 50 µmol/L PM5S increased GSIS by at least twofold (P < 0.001); isosakuranetin (TRPM3 inhibitor) abolished this effect. PM5S increased calcium influx in TRPM3-expressing HEK293 cells. Computer modeling and docking showed identical positioning of PM5S to the natural ligand in TRPM3. PM5S increases GSIS and is reduced in GDM serum. The activation of GSIS by PM5S is mediated by TRPM3 in both mouse and human islets.

A clinical decision framework to guide the outpatient treatment of emergency department patients diagnosed with acute pulmonary embolism or deep vein thrombosis: Results from a multidisciplinary consensus panel.

The outpatient treatment of select emergency department patients with acute pulmonary embolism (PE) or deep vein thrombosis (DVT) has been shown to be safe, cost effective and associated with high patient satisfaction. Despite this, outpatient PE and DVT treatment remains uncommon. To address this, the American College of Emergency Physicians assembled a multidisciplinary team of content experts to provide evidence-based recommendations and practical advice to help clinicians safely treat patients with low-risk PE and DVT without hospitalization. The emergency clinician must stratify the patient's risk of clinical decompensation due to their PE or DVT as well as their risk of bleeding due to anticoagulation. The clinician must also select and start an anticoagulant and ensure that the patient has access to the medication in a timely manner. Reliable follow-up is critical, and the patient must also be educated about signs or symptoms that should prompt a return to the emergency department. To facilitate access to these recommendations, the consensus panel also created 2 web-based "point-of-care tools."

A community-based program to reduce acute rheumatic fever and rheumatic heart disease in northern Australia.

BACKGROUND: In Australia's north, Aboriginal peoples live with world-high rates of rheumatic heart disease (RHD) and its precursor, acute rheumatic fever (ARF); driven by social and environmental determinants of health. We undertook a program of work to strengthen RHD primordial and primary prevention using a model addressing six domains: housing and environmental support, community awareness and empowerment, health literacy, health and education service integration, health navigation and health provider education. Our aim is to determine how the model was experienced by study participants. METHODS: This is a two-year, outreach-to-household, pragmatic intervention implemented by Aboriginal Community Workers in three remote communities. The qualitative component was shaped by Participatory Action Research. Yarning sessions and semi-structured interviews were conducted with 14 individuals affected by, or working with, ARF/RHD. 31 project field reports were collated. We conducted a hybrid inductive-deductive thematic analysis guided by critical theory. RESULTS: Aboriginal Community Workers were best placed to support two of the six domains: housing and environmental health support and health navigation. This was due to trusting relationships between ACWs and families and the authority attributed to ACWs through the project. ACWs improved health literacy and supported awareness and empowerment; but this was limited by disease complexities. Consequently, ACWs requested more training to address knowledge gaps and improve knowledge transfer to families. ACWs did not have skills to provide health professionals with education or ensure health and education services participated in ARF/RHD. Where knowledge gain among participant family members was apparent, motivation or structural capability to implement behaviour change was lacking in some domains, even though the model was intended to support structural changes through care navigation and housing fixes. CONCLUSIONS: This is the first multi-site effort in northern Australia to strengthen primordial and primary prevention of RHD. Community-led programs are central to the overarching strategy to eliminate RHD. Future implementation should support culturally safe relationships which build the social capital required to address social determinants of health and enable holistic ways to support sustainable individual and community-level actions. Government and services must collaborate with communities to address systemic, structural issues limiting the capacity of Aboriginal peoples to eliminate RHD.

Single-View Echocardiography by Nonexpert Practitioners to Detect Rheumatic Heart Disease: A Prospective Study of Diagnostic Accuracy.

BACKGROUND: Echocardiographic screening can detect asymptomatic cases of rheumatic heart disease (RHD), facilitating access to treatment. Barriers to implementation of echocardiographic screening include the requirement for expensive equipment and expert practitioners. We aimed to evaluate the diagnostic accuracy of an abbreviated echocardiographic screening protocol (single parasternal-long-axis view with a sweep of the heart) performed by briefly trained, nonexpert practitioners using handheld ultrasound devices. METHODS: Participants aged 5 to 20 years in Timor-Leste and the Northern Territory of Australia had 2 echocardiograms: one performed by an expert echocardiographer using a GE Vivid I or Vivid Q portable ultrasound device (reference test), and one performed by a nonexpert practitioner using a GE Vscan handheld ultrasound device (index test). The accuracy of the index test, compared with the reference test, for identifying cases with definite or borderline RHD was determined. RESULTS: There were 3111 enrolled participants; 2573 had both an index test and reference test. Median age was 12 years (interquartile range, 10-15); 58.2% were female. Proportion with definite or borderline RHD was 5.52% (95% CI, 4.70-6.47); proportion with definite RHD was 3.23% (95% CI, 2.61-3.98). Compared with the reference test, sensitivity of the index test for definite or borderline RHD was 70.4% (95% CI, 62.2-77.8), specificity was 78.1% (95% CI, 76.4-79.8). CONCLUSIONS: Nonexpert practitioners can be trained to perform single parasternal-long-axis view with a sweep of the heart echocardiography. However, the specificity and sensitivity are inadequate for echocardiographic screening. Improved training for nonexpert practitioners should be investigated.

Health seeking behaviours and treatments received by Australian women with vulvodynia: A cross-sectional survey.

BACKGROUND: Vulvodynia is a condition characterised by pain in the vulva lasting more than three months and for which no obvious aetiology can be found. It affects around 8% of women and has significant negative impacts on quality of life. There is a paucity of research on healthcare management pathways and the use of evidence-based treatments in an Australian community setting. AIMS: To explore which healthcare professionals Australian women with vulvodynia seek treatment from, and which treatments are recommended, provided, or prescribed by these healthcare professionals. MATERIALS AND METHODS: A cross-sectional online survey was conducted from May 2019 to August 2019. Women were eligible to participate if they had been diagnosed with vulvodynia by a healthcare professional, were currently living in Australia, and were over 18 years old. RESULTS: Fifty respondents meet the inclusion criteria, with a mean age of 30.5 years. On average, respondents reported seeing four different types of healthcare professionals in the management of their vulvodynia, with general practitioners (GPs) (98%), medical specialists (96%), and physiotherapists (80%) being the three most commonly consulted. Most respondents reported seeing multiple GPs (>87%), multiple medical specialists (>77%), and multiple physiotherapists (50%). The most commonly prescribed interventions were pelvic floor down-training exercises (76%), topical (70%) and oral (70%) medication, and vulvodynia information (56%). CONCLUSIONS: Australian women with vulvodynia seek help from several professionals and receive a variety of treatments for their pain. Of concern is many treatments that are being offered clinically have very little peer-reviewed evidence of effectiveness in vulvodynia.

Using community-led development to build health communication about rheumatic heart disease in Aboriginal children: a developmental evaluation.

OBJECTIVE: A high prevalence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) among Aboriginal children in northern Australia is coupled with low understanding among families. This has negative impacts on children's health, limits opportunities for prevention and suggests that better health communication is needed. METHODS: During an RHD echocardiography screening project, Aboriginal teachers in a remote community school created lessons to teach children about RHD in their home languages, drawing on principles of community-led development. Access to community-level RHD data, previously unknown to teachers and families, was a catalyst for this innovative work. Careful, iterative discussions among speakers of four Aboriginal languages ensured a culturally coherent narrative and accompanying teaching resources. RESULTS: The evaluation demonstrated the importance of collective work, local Indigenous Knowledge and metaphors. As a result of the lessons, some children showed new responses and attitudes to skin infections and their RHD treatment. Language teachers used natural social networks to disseminate new information. A community interagency collaboration working to prevent RHD commenced. Conclusions and implications for public health: Action to address high rates of RHD must include effective health communication strategies that value Indigenous Knowledge, language and culture, collaborative leadership and respect for Indigenous data sovereignty.

Decolonizing Indigenous health: Generating a productive dialogue to eliminate Rheumatic Heart Disease in Australia.

In common with colonized Indigenous people worldwide, many Australian Aboriginal people experience inequitable health outcomes. While the commitment and advocacy of researchers and health practitioners has resulted in many notable improvements in policy and practice, systemic and structural impediments continue to restrain widespread gains in addressing Indigenous health injustices. We take Rheumatic Heart Disease (RHD), a potent marker of extreme health inequity, as a case study, and critically examine RHD practitioners' perspectives regarding the factors that need to be addressed to improve RHD prevention and care. This study is an important explanatory component of a broader study to inform new clinical practices, and health system strategies and policies to reduce RHD. A decolonising, critical medical anthropology (CMA) analysis of findings from 22 RHD practitioner in-depth interviews conducted in May 2016 revealed both practitioners' perceptions of health system shortcomings and a sense of hopelessness and powerlessness to transform existing health system inequities, the negative impacts of which were subsequently confirmed in a separate study of RHD patients' lived realities. We reveal how biomedical dominance, normalized deficit discourses and systemic racism influence the current policy and practice landscape, narrowing the intercultural space for productive dialogue and reinforcing the conditions that cause disease. To counter biomedical approaches that contribute to existing health inequities in health care, we recommend localized, strength-based, community-led research projects focused on actions that use critical decolonizing social science approaches to achieve system change. We demonstrate the importance of integrating biological and social sciences approaches in research, education/training, and practice to: 1) be guided by Indigenous strengths, knowledges and worldview, and 2) adopt a critical reflexive stance to examine systems, structures and practices. Such an approach facilitates productive cross-cultural dialogue and social transformation; providing direction and hope to practitioners, enhancing their knowledge, skills and capacity and improving Aboriginal health outcomes.

Uniparental isodisomy of chromosome 2 causing MRPL44-related multisystem mitochondrial disease.

Mutations in nuclear-encoded protein subunits of the mitochondrial ribosome are an increasingly recognised cause of oxidative phosphorylation system (OXPHOS) disorders. Among them, mutations in the MRPL44 gene, encoding a structural protein of the large subunit of the mitochondrial ribosome, have been identified in four patients with OXPHOS defects and early-onset hypertrophic cardiomyopathy with or without additional clinical features. A 23-year-old individual with cardiac and skeletal myopathy, neurological involvement, and combined deficiency of OXPHOS complexes in skeletal muscle was clinically and genetically investigated. Analysis of whole-exome sequencing data revealed a homozygous mutation in MRPL44 (c.467 T > G), which was not present in the biological father, and a region of homozygosity involving most of chromosome 2, raising the possibility of uniparental disomy. Short-tandem repeat and genome-wide SNP microarray analyses of the family trio confirmed complete maternal uniparental isodisomy of chromosome 2. Mitochondrial ribosome assembly and mitochondrial translation were assessed in patient derived-fibroblasts. These studies confirmed that c.467 T > G affects the stability or assembly of the large subunit of the mitochondrial ribosome, leading to impaired mitochondrial protein synthesis and decreased levels of multiple OXPHOS components. This study provides evidence of complete maternal uniparental isodisomy of chromosome 2 in a patient with MRPL44-related disease, and confirms that MRLP44 mutations cause a mitochondrial translation defect that may present as a multisystem disorder with neurological involvement.

ENDOCRINOLOGY IN PREGNANCY: Metabolic impact of bile acids in gestation.

Bile acids are lipid-solubilising molecules that also regulate metabolic processes. Farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR5) are two bile acid receptors with key metabolic roles. FXR regulates bile acid synthesis in the liver and influences bile acid uptake in the intestine. TGR5 is mainly involved in regulation of signalling pathways in response to bile acid uptake in the gut and therefore prandial response. Both FXR and TGR5 have potential as therapeutic targets for disorders of glucose and/or lipid homeostasis. Gestation is also known to cause small increases in bile acid concentrations, but physiological hypercholanaemia of pregnancy is usually not sufficient to cause any clinically relevant effects. This review focuses on how gestation alters bile acid homeostasis, which can become pathological if the elevation of maternal serum bile acids is more marked than physiological hypercholanaemia, and on the influence of FXR and TGR5 function in pregnancy on glucose and lipid metabolism. This will be discussed with reference to two gestational disorders: intrahepatic cholestasis of pregnancy (ICP), a disease where bile acids are pathologically elevated, and gestational diabetes mellitus (GDM), characterised by hyperglycaemia during pregnancy.