Twin Pregnancy Complicated by Gestational Diabetes Mellitus: Maternal and Neonatal Outcomes.

Context: The risk of gestational diabetes mellitus (GDM) in twin pregnancies is more than double that of singleton pregnancies. Although twin pregnancies present unique challenges for fetal growth and prenatal management, the approach to GDM diagnosis and treatment is the same regardless of plurality. Data on pregnancy outcomes for individuals with GDM and a twin pregnancy are limited and conflicting. Objective: To describe the maternal characteristics associated with GDM in twin pregnancies and to assess the associated pregnancy outcomes compared to twin pregnancies unaffected by GDM. Methods: A retrospective cohort study was conducted at Mayo Clinic, Rochester, Minnesota, USA, and included predominantly Causasian women aged 18 to 45 years who received prenatal care for a twin pregnancy from 2017-2022. Maternal characteristics and a broad spectrum of pregnancy outcomes were evaluated. Universal GDM screening involved a 50 g oral glucose challenge test +/- a 100 g oral glucose tolerance test. Results: GDM was diagnosed in 23% pregnancies (n = 104/452). Compared to those without, women with GDM had known risk factors including a higher prepregnancy body mass index (31.1vs 26.3 kg/m2; P < .01) and a prior history of GDM (21.7 vs 5.9%; P < .01). There were no differences in maternal pregnancy complications or neonatal outcomes between groups. Attendance at postpartum glucose testing among women with GDM was poor at 27.9% (29/104). Conclusion: These data suggest that women with twin pregnancies share a similar GDM risk profile to those with singleton pregnancies and provide reassuring evidence that current management for GDM twin pregnancies produces similar outcomes to twin pregnancies without GDM.

In T2DM, periconceptional, noninsulin, second-line antidiabetes medications were not linked to major congenital malformations vs. insulin.

SOURCE CITATION: Cesta CE, Rotem R, Bateman BT, et al. Safety of GLP-1 receptor agonists and other second-line antidiabetics in early pregnancy. JAMA Intern Med. 2024;184:144-152. 38079178.

Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

Glucagon-like peptide-1 receptor blockade impairs islet secretion and glucose metabolism in humans.

BACKGROUNDProglucagon can be processed to glucagon-like peptide1 (GLP-1) within the islet, but its contribution to islet function in humans remains unknown. We sought to understand whether pancreatic GLP-1 alters islet function in humans and whether this is affected by type 2 diabetes.METHODSWe therefore studied individuals with and without type 2 diabetes on two occasions in random order. On one occasion, exendin 9-39, a competitive antagonist of the GLP-1 Receptor (GLP1R), was infused, while on the other, saline was infused. The tracer dilution technique ([3-3H] glucose) was used to measure glucose turnover during fasting and during a hyperglycemic clamp.RESULTSExendin 9-39 increased fasting glucose concentrations; fasting islet hormone concentrations were unchanged, but inappropriate for the higher fasting glucose observed. In people with type 2 diabetes, fasting glucagon concentrations were markedly elevated and persisted despite hyperglycemia. This impaired suppression of endogenous glucose production by hyperglycemia.CONCLUSIONThese data show that GLP1R blockade impairs islet function, implying that intra-islet GLP1R activation alters islet responses to glucose and does so to a greater degree in people with type 2 diabetes.TRIAL REGISTRATIONThis study was registered at ClinicalTrials.gov NCT04466618.FUNDINGThe study was primarily funded by NIH NIDDK DK126206. AV is supported by DK78646, DK116231 and DK126206. CDM was supported by MIUR (Italian Minister for Education) under the initiative "Departments of Excellence" (Law 232/2016).

Effects of acute changes in fasting glucose and free fatty acid concentrations on indices of ß-cell function and glucose metabolism in subjects without diabetes.

Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased ß-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose alter islet function. We studied 10 subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT) on two occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG/IGT. In addition, we studied seven subjects with IFG/IGT on two occasions. On one occasion, insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG/NGT. The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and ß-cell function. Elevation of overnight fasting FFA and glucose in NFG/NGT did not alter peak or integrated glucose concentrations (2.0 ± 0.1 vs. 2.0 ± 0.1 Mol per 5 h, Saline vs. Intralipid/glucose, P = 0.55). Although overall ß-cell function quantified by the Disposition Index was unchanged, the dynamic component of ß-cell responsivity (ϕd) was decreased by Intralipid and glucose infusion (9 ± 1 vs. 16 ± 3 10-9, P = 0.02). In people with IFG/IGT, insulin did not alter postprandial glucose concentrations or indices of ß-cell function. Endogenous glucose production and glucose disappearance were also unchanged in both groups. We conclude that acute, overnight changes in FFA, and glucose concentrations do not alter islet function or glucose metabolism in prediabetes.NEW & NOTEWORTHY This experiment studied the effect of changes in overnight concentrations of free fatty acids (FFAs) and glucose on ß-cell function and glucose metabolism. In response to elevation of these metabolites, the dynamic component of the ß-cell response to glucose was impaired. This suggests that in health overnight hyperglycemia and FFA elevation can deplete preformed insulin granules in the ß-cell.

The Effect of Glucagon-Like Peptide 1 Receptor Blockade on Glucagon-Induced Stimulation of Insulin Secretion.

Data from transgenic rodent models suggest that glucagon acts as an insulin secretagogue by signaling through the glucagon-like peptide 1 receptor (GLP-1R) present on ß-cells. However, its net contribution to physiologic insulin secretion in humans is unknown. To address this question, we studied individuals without diabetes in two separate experiments. Each subject was studied on two occasions in random order. In the first experiment, during a hyperglycemic clamp, glucagon was infused at 0.4 ng/kg/min, increasing by 0.2 ng/kg/min every hour for 5 h. On one day, exendin-9,39 (300 pmol/kg/min) was infused to block GLP-1R, while on the other, saline was infused. The insulin secretion rate (ISR) was calculated by nonparametric deconvolution from plasma concentrations of C-peptide. Endogenous glucose production and glucose disappearance were measured using the tracer-dilution technique. Glucagon concentrations, by design, did not differ between study days. Integrated ISR was lower during exendin-9,39 infusion (213 ± 26 vs. 191 ± 22 nmol/5 h, saline vs. exendin-9,39, respectively; P = 0.02). In the separate experiment, exendin-9,39 infusion, compared with saline infusion, also decreased the ß-cell secretory response to a 1-mg glucagon bolus. These data show that, in humans without diabetes, glucagon partially stimulates the ß-cell through GLP-1R.

Utility of screening for silent myocardial ischaemia in diabetes with an annual electrocardiogram.

BACKGROUND AND METHODS: Asymptomatic coronary artery disease (CAD) is common in people with diabetes mellitus, but there is a lack of consensus regarding appropriate screening for the condition. We performed a 12-lead electrocardiogram (ECG) on 312 consecutive participants with diabetes mellitus attending for routine annual outpatient review in order to determine the effectiveness of a yearly ECG in screening people with diabetes for asymptomatic CAD. RESULTS: Three of 312 participants (0.96%, 95% CI 0.2%-2.78%) had a newly identified ECG abnormality. One person had newly discovered atrial fibrillation. Two people had abnormalities which prompted further investigation for asymptomatic CAD. One of these participants underwent percutaneous coronary intervention. Seventeen further participants had abnormalities on ECG which had been previously documented, the majority having been present since their diagnosis of diabetes. CONCLUSION: A low positive yield of routine annual ECG in our study does not support its use as a screening tool for asymptomatic CAD in diabetes. Our findings support advice to perform an ECG at diagnosis of diabetes and to repeat only if a person develops relevant symptoms.

Attendance at pre-pregnancy care clinics for women with type 1 diabetes: A scoping review.

INTRODUCTION: Type 1 diabetes mellitus occurs in one in every 275 pregnancies and can result in increased morbidity and mortality for both mother and baby. Several pregnancy complications can be reduced or prevented by attendance at pre-pregnancy care (PPC). Despite this, less than 40% of pregnant women with pre-gestational diabetes receive formal PPC. The aim of this scoping review is to identify the barriers to PPC attendance among women with type 1 diabetes. METHODS: We conducted a scoping review by searching five databases (Ebsco, Embase, Ovid and PubMed for literature and the ProQuest for any grey/unpublished literature) for studies in English between 2000 and 2022. Studies that evaluated attendance at PPC for women with type 1 diabetes were included. RESULTS: There are multiple barriers to PPC attendance, and many of these barriers have been unchanged since the 1990s. Identified barriers can be grouped under patient-centered and clinician-centered headings. Patient factors include knowledge and awareness, unplanned pregnancies, negative perceptions of healthcare and communication issues, unclear attendance pathways and logistical issues including time off work and childcare. Clinician factors include physician knowledge, time constraints and lack of comfort discussing pregnancy/contraception. CONCLUSION: This review highlights the ongoing problem of poor attendance at PPC and identifies key barriers to be addressed when developing and implementing PPC programs for women with type 1 diabetes.

Differential contribution of alpha and beta cell dysfunction to impaired fasting glucose and impaired glucose tolerance.

AIMS/HYPOTHESIS: People with isolated impaired fasting glucose (IFG) have normal beta cell function. We hypothesised that an increased glucose threshold for beta cell secretion explains IFG. METHODS: We used graded glucose infusion to examine the relationship of insulin secretion rate (ISR) and glucagon secretion rate (GSR) with rising glucose. We studied 39 non-diabetic individuals (53 ± 2 years, BMI 30 ± 1 kg/m2), categorised by fasting glucose and glucose tolerance status. After an overnight fast, a variable insulin infusion was used to maintain glucose at ~4.44 mmol/l (07:00 to 08:30 hours). At 09:00 hours, graded glucose infusion commenced at 1 mg kg-1 min-1 and doubled every 60 min until 13:00 hours. GSR and ISR were calculated by nonparametric deconvolution from concentrations of glucagon and C-peptide, respectively. RESULTS: The relationship of ISR with glucose was linear and the threshold for insulin secretion in isolated IFG did not differ from that in people with normal fasting glucose and normal glucose tolerance. GSR exhibited a single-exponential relationship with glucose that could be characterised by G50, the change in glucose necessary to suppress GSR by 50%. G50 was increased in IFG compared with normal fasting glucose regardless of the presence of impaired or normal glucose tolerance. CONCLUSIONS/INTERPRETATION: These data show that, in non-diabetic humans, alpha cell dysfunction contributes to the pathogenesis of IFG independently of defects in insulin secretion. We also describe a new index that quantifies the suppression of glucagon secretion by glucose.

Observations on the interaction between plant growth-promoting bacteria and the root-knot nematode Meloidogyne javanica.

Pseudomonas fluorescens, strains L124, L228, L321, and the positive control strain F113 used in this study, produce compounds associated with plant growth promotion, biocontrol, antimicrobial and antiviral activity, and adaptation to stresses. These bacterial strains were tested in vitro and in vivo in tomato plants, to determine their potential role in Meloidogyne javanica suppression. In laboratory experiments, only 2% of M. javanica eggs hatched when exposed to the metabolites of each bacterial strain. Additionally, 100% M. javanica J2 mortality was recorded when nematodes were exposed to the metabolites of F113 and L228. In greenhouse experiments, M. javanica infected tomato plants, which were also inoculated with the bacterial strains F113 and L124, displayed the highest biomass (height, number of leaves, fresh and dry weight) of all bacterial treatments tested. Results from the development and induced systemic resistance experiments indicated that the bacterial strains F113 and L321 had the most effective biocontrol capacity over nematode infection, delayed nematode development (J3/J4, adults and galls), and reduced nematode fecundity. In addition, these results indicated that the bacterial strain L124 is an effective plant growth promoter of tomato plants. Furthermore, it was determined that the bacterial strain L321 was capable of M. javanica biocontrol. P. fluorescens F113 was effective at both increasing tomato plant biomass and M. javanica biocontrol. In an agricultural context, applying successional drenches with these beneficial plant growth promoting rhizobacteria would ensure bacteria viability in the rhizosphere of the plants, encourage positive plant bacterial interactions and increase biocontrol against M. javanica.

Pitfalls in Diagnosing Hypoglycemia Due to Exogenous Insulin: Validation and Utility of an Insulin Analog Assay.

OBJECTIVE: To overcome the limitations of commercially available insulin immunoassays which have variable detection of analog insulin and can lead to clinically discordant results and misdiagnosis in the workup of factitious hypoglycemia. PATIENTS AND METHODS: We performed analytical validation of a liquid chromatography high resolution accurate mass (LC-HRAM) immunoassay to detect insulin analogs. We completed clinical assessment using a large cohort of human serum samples from 78 unique individuals, and subsequently used the assay in the evaluation of eight individuals with high diagnostic suspicion for factitious hypoglycemia. RESULTS: The performance characteristics show that the LC-HRAM immunoassay can be applied to detect five commonly used synthetic insulin analogs (lispro, glulisine, aspart, glargine metabolite, and detemir) in human serum. Our clinical cases show that this assay could be used in the diagnosis of factitious hypoglycemia by identifying the analog insulin(s) in question. CONCLUSION: The LC-HRAM immunoassay reported here overcomes a gap in our diagnostic pathway for hypoglycemia. The results obtained from our studies suggest that this method is appropriate for use in clinical laboratories when factitious hypoglycemia is considered as a differential diagnosis.

Diabetic Ketoacidosis in Pregnancy: Clinical Risk Factors, Presentation, and Outcomes.

CONTEXT: Diabetic ketoacidosis (DKA) in pregnancy is an obstetric emergency with risk of maternofetal death. OBJECTIVE: This work aimed to evaluate DKA events in pregnant women admitted to our inpatient obstetric service, and to examine associated clinical risk factors, presentation, and pregnancy outcomes. METHODS: A retrospective cohort study was conducted at the Mayo Clinic, Rochester, Minnesota, USA, and included women aged 17 to 45 years who were treated for DKA during pregnancy between January 1, 2004 and December 31, 2021. Main outcome measures included maternal and fetal death along with a broad spectrum of maternal and fetal pregnancy outcomes. RESULTS: A total of 71 DKA events were identified in 58 pregnancies among 51 women, 48 (82.8%) of whom had type 1 diabetes. There were no maternal deaths, but fetal demise occurred in 10 (17.2%) pregnancies (6 miscarriages and 4 stillbirths). Maternal social stressors were frequently present (n = 30, 51.0%), and glycemic control was suboptimal (median first trimester glycated hemoglobin A1c = 9.0%). Preeclampsia was diagnosed in 17 (29.3%) pregnancies. Infants born to women with DKA were large for gestational age (n = 16, 33.3%), suffered from neonatal hypoglycemia (n = 29, 60.4%) and required intensive care unit admission (n = 25, 52.1%). CONCLUSION: DKA is associated with a high rate of maternofetal morbidity and fetal loss. Prenatal education strategies for women with diabetes mellitus should include a strong focus on DKA prevention, and clinicians and patients should have a high index of suspicion for DKA in all pregnant women who present with symptoms that could be attributed to this condition.

Retrospective national cohort study of pregnancy outcomes for women with type 1 and type 2 diabetes mellitus in Republic of Ireland.

AIM: Report the outcomes of pregnant women with type 1 and type 2 diabetes and to identify modifiable and non-modifiable factors associated with poor outcomes. METHODS: Retrospective analysis of pregnancy preparedness, pregnancy care and outcomes in the Republic of Ireland from 2015 to 2020 and subsequent multivariate analysis. RESULTS: In total 1104 pregnancies were included. Less than one third attended pre-pregnancy care (PPC), mean first trimester haemoglobin A1c was 7.2 ± 3.6% (55.5 ± 15.7 mmol/mol) and 52% received pre-conceptual folic acid. Poor preparation translated into poorer pregnancy outcomes. Livebirth rates (80%) were comparable to the background population however stillbirth rates were 8.7/1000 (four times the national rate). Congenital anomalies occurred in 42.5/1000 births (1.5 times the background rate). More than half of infants were large for gestational age and 47% were admitted to critical care. Multivariate analyses showed strong associations between non-attendance at PPC, poor glycaemic control and critical care admission (adjusted odds ratio of 1.68 (1.48-1.96) and 1.61 (1.43-1.86), p < 0.05 respectively) for women with type 1 diabetes. Smoking and teratogenic medications were also associated with critical care admission and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy outcomes in women with diabetes are suboptimal. Significant effort is needed to optimize the modifiable factors identified in this study.

The Effect of Diabetes-Associated Variation in TCF7L2 on Postprandial Glucose Metabolism When Glucagon and Insulin Concentrations Are Matched.

Background: The rs7903146 variant in the TCF7L2 gene is associated with defects in postprandial insulin and glucagon secretion and increased risk of type 2 diabetes. However, it is unclear if this variant has effects on glucose metabolism that are independent of islet function. Methods: We studied 54 nondiabetic subjects on two occasions where endogenous hormone secretion was inhibited by somatostatin. Twenty-nine subjects were homozygous for the diabetes-associated allele (TT) and 25 for the diabetes-protective allele (CC) at rs7903146, but otherwise matched for anthropometric characteristics. On 1 day, glucagon infused at a rate of 0.65 ng/kg/min, and at 0 min prevented a fall in glucagon (nonsuppressed day). On the contrary, infusion commenced at 120 min to create a transient fall in glucagon (suppressed day). Subjects received glucose (labeled with [3-3H]-glucose) infused to mimic the systemic appearance of oral glucose. Insulin was infused to mimic a prandial insulin response. Endogenous glucose production (EGP) was measured using the tracer dilution technique. Results: Lack of glucagon suppression increased postchallenge glucose concentrations and impaired EGP suppression. However, in the presence of matched insulin and glucagon concentrations, genetic variation in TCF7L2 did not alter glucose metabolism. Conclusion: These data suggest that genetic variation in TCF7L2 alters glucose metabolism through changes in islet hormone secretion.

Dynamic changes in energy expenditure in response to underfeeding: a review.

The observation that 64% of English adults are overweight or obese despite a rising prevalence in weight-loss attempts suggests our understanding of energy balance is fundamentally flawed. Weight-loss is induced through a negative energy balance; however, we typically view weight change as a static function, in that energy intake and energy expenditure are independent variables, resulting in a fixed rate of weight-loss assuming a constant energy deficit. Such static modelling provides the basis for the clinical assumption that a 14644 kJ (3500 kcal) deficit translates to a 1 lb weight-loss. However, this '3500 kcal (14644 kJ) rule' is consistently shown to significantly overestimate weight-loss. Static modelling disregards obligatory changes in energy expenditure associated with the loss of metabolically active tissue, i.e. skeletal muscle. Additionally, it disregards the presence of adaptive thermogenesis, the underfeeding-associated fall in resting energy expenditure beyond that caused by loss of fat-free mass. This metabolic manipulation of energy expenditure is observed from the onset of energy restriction to maintain weight at a genetically pre-determined set point. As a result, the observed magnitude of weight-loss is disproportionally less, followed by earlier weight plateau, despite strict compliance to a dietary intervention. By simulating dynamic changes in energy expenditure associated with underfeeding, mathematical modelling may provide a more accurate method of weight-loss prediction. However, accuracy at an individual level is limited due to difficulty estimating energy requirements, physical activity and dietary intake in free-living individuals. In the present paper, we aim to outline the contribution of dynamic changes in energy expenditure to weight-loss resistance and weight plateau.

Use of core outcome sets was low in clinical trials published in major medical journals.

OBJECTIVES: To examine current practices in late-phase trials published in major medical journals and examine trialists' views about core outcome set (COS) use. STUDY DESIGN AND SETTING: A sequential multi-methods study was conducted. We examined late-phase trials published between October 2019 and March 2020 in JAMA, NEJM, The Lancet, BMJ, and Annals of Internal Medicine. The COMET database was searched for COS potentially relevant to trials not reporting using a COS; overlap of trial and COS outcomes was examined. An online survey examined awareness of, and decisions to search for and use a COS. RESULTS: Ninety-five trials were examined; 93 (98%) did not report using a COS. Relevant COS were identified for 31 trials (33%). Core outcomes were measured in 9 (23%) studies; all trials measured at least one core outcome. Thirty-one trialists (33%) completed our survey. The most common barrier to COS use was trialist's own outcome preferences and choice (68%). The most common perceived facilitator was awareness and knowledge about COS (90%). CONCLUSION: COS use in this cohort of trials was low, even when relevant COS were available. Increased use of COS in clinical trials can improve evaluation of intervention effects and evidence synthesis and reduce research waste.

Plant Parasitic Nematodes: A Review on Their Behaviour, Host Interaction, Management Approaches and Their Occurrence in Two Sites in the Republic of Ireland.

Plant parasitic nematodes are a major problem for growers worldwide, causing severe crop losses. Several conventional strategies, such as chemical nematicides and biofumigation, have been employed in the past to manage their infection in plants and spread in soils. However, the search for the most sustainable and environmentally safe practices is still ongoing. This review summarises information on plant parasitic nematodes, their distribution, and their interaction with their host plants, along with various approaches to manage their infestations. It also focuses on the application of microbial and fermentation-based bionematicides that have not only been successful in controlling nematode infection but have also led to plant growth promotion and proven to be environmentally safe. Studies with new information on the relative abundance of plant parasitic nematodes in two agricultural sites in the Republic of Ireland are also reported. This review, with the information it provides, will help to generate an up-to-date knowledge base on plant parasitic nematodes and their management practices.

Patient-reported outcomes (PROs) in randomised controlled trials in diabetes and pregnancy: protocol for a systematic review.

INTRODUCTION: Diabetes mellitus is the most common metabolic complication of pregnancy and its prevalence worldwide is rising. The number of randomised controlled trials (RCTs) being conducted in people with diabetes is also increasing. Many studies preferentially publish findings on clinical endpoints and do not report patient-reported outcomes (PROs). In studies that do include PROs, PRO reporting is often of poor quality. METHODS: We will conduct this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using a combination of medical subject headings and keywords (combined using Boolean operators), we will search web-based databases (PubMed, Cochrane and EMBASE) for RCTs published in English between 2013 and 2021. Two reviewers will review titles and abstracts. We will review the full texts of any relevant abstracts and extract the following data: date of publication or recruitment period, journal of publication, country of study, multicentre or single centre, population and number of participants, type of intervention, frequency of PRO assessment and type of PRO (or PRO measurement) used. We will also record if the PRO was a primary, secondary or exploratory outcome. We will exclude reviews, observational studies, unpublished data for example, conference abstracts and trial protocols. Any published RCT that includes data on a PRO as a primary or secondary outcome will then be compared against the Consolidated Standards of Reporting Trials-Patient-Reported Outcome extension checklist, a structured and approved framework for the publication of results of PROs. ETHICS AND DISSEMINATION: Ethical approval to conduct this study was obtained from the ethics committee at Galway University Hospitals on 24 March 2021 (CA 2592). We aim to publish our findings in a peer-reviewed journal and present our findings at national and international conferences. SYSTEMATIC REVIEW REGISTRATION: This systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO). Registration number CRD42021234917.