Publications
198 results found
Lagou V, Jiang L, Ulrich A, et al., 2023, GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification., Nat Genet, Vol: 55, Pages: 1448-1461
Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.
Izzi-Engbeaya C, Patel B, Mills E, et al., 2023, The effects of kisspeptin on food intake in women with overweight or obesity, Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 25, Pages: 2393-2397, ISSN: 1462-8902
Wewer Albrechtsen NJ, Holst JJ, Cherrington AD, et al., 2023, 100 years of glucagon and 100 more., Diabetologia, Vol: 66, Pages: 1378-1394
The peptide hormone glucagon, discovered in late 1922, is secreted from pancreatic alpha cells and is an essential regulator of metabolic homeostasis. This review summarises experiences since the discovery of glucagon regarding basic and clinical aspects of this hormone and speculations on the future directions for glucagon biology and glucagon-based therapies. The review was based on the international glucagon conference, entitled 'A hundred years with glucagon and a hundred more', held in Copenhagen, Denmark, in November 2022. The scientific and therapeutic focus of glucagon biology has mainly been related to its role in diabetes. In type 1 diabetes, the glucose-raising properties of glucagon have been leveraged to therapeutically restore hypoglycaemia. The hyperglucagonaemia evident in type 2 diabetes has been proposed to contribute to hyperglycaemia, raising questions regarding underlying mechanism and the importance of this in the pathogenesis of diabetes. Mimicry experiments of glucagon signalling have fuelled the development of several pharmacological compounds including glucagon receptor (GCGR) antagonists, GCGR agonists and, more recently, dual and triple receptor agonists combining glucagon and incretin hormone receptor agonism. From these studies and from earlier observations in extreme cases of either glucagon deficiency or excess secretion, the physiological role of glucagon has expanded to also involve hepatic protein and lipid metabolism. The interplay between the pancreas and the liver, known as the liver-alpha cell axis, reflects the importance of glucagon for glucose, amino acid and lipid metabolism. In individuals with diabetes and fatty liver diseases, glucagon's hepatic actions may be partly impaired resulting in elevated levels of glucagonotropic amino acids, dyslipidaemia and hyperglucagonaemia, reflecting a new, so far largely unexplored pathophysiological phenomenon termed 'glucagon resistance'. Importantly, the hyperglucagonaemia as part of
Avari P, Tang W, Jugnee N, et al., 2023, The Accuracy of Continuous Glucose Sensors in People with Diabetes Undergoing Hemodialysis (ALPHA Study)., Diabetes Technol Ther, Vol: 25, Pages: 447-456
Objectives: Real-time and intermittently scanned continuous glucose monitoring are increasingly used for glucose monitoring in people with diabetes requiring renal replacement therapy, with limited data reporting their accuracy in this cohort. We evaluated the accuracy of Dexcom G6 and Abbott Freestyle Libre 1 glucose monitoring systems in people with diabetes undergoing hemodialysis. Methods: Participants on hemodialysis with diabetes (on insulin or sulfonylureas) were recruited. Paired sensor glucose from Dexcom G6 and Freestyle Libre 1 were recorded with plasma glucose analyzed using the Yellow Springs Instrument (YSI) method at frequent intervals during hemodialysis. Analysis of accuracy metrics included mean absolute relative difference (MARD), Clarke error grid (CEG) analysis and proportion of CGM values within 15% and 20% or 15 and 20 mg/dL of YSI reference values for blood glucose >100 or ≤100 mg/dL, respectively (% 15/15, % 20/20). Results: Forty adults (median age 64.7 [60.2-74.4] years) were recruited. Overall MARD for Dexcom G6 was 22.7% (2656 matched glucose pairs), and 11.3% for Libre 1 (n = 2785). The proportions of readings meeting %15/15 and %20/20 were 29.1% and 45.4% for Dexcom G6, respectively, and 73.5% and 85.6% for Libre 1. CEG analysis showed 98.9% of all values in zones A and B for Dexcom G6 and 99.8% for Libre 1. Conclusions: Our results indicate Freestyle Libre 1 is a reliable tool for glucose monitoring in adults on hemodialysis. Further studies are required to evaluate Dexcom G6 accuracy in people on hemodialysis.
Behary P, Alessimii H, Miras AD, et al., 2023, Tripeptide gut hormone infusion does not alter food preferences or sweet taste function in volunteers with obesity and prediabetes/diabetes but promotes restraint eating: a secondary analysis of a randomized single-blind placebo-controlled study, Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 25, Pages: 1731-1739, ISSN: 1462-8902
AimsTo investigate whether the elevation in postprandial concentrations of the gut hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM) and peptide YY (PYY) accounts for the beneficial changes in food preferences, sweet taste function and eating behaviour after Roux-en-Y gastric bypass (RYGB).Materials and methodsThis was a secondary analysis of a randomized single-blind study in which we infused GLP-1, OXM, PYY (GOP) or 0.9% saline subcutaneously for 4 weeks in 24 subjects with obesity and prediabetes/diabetes, to replicate their peak postprandial concentrations, as measured at 1 month in a matched RYGB cohort (ClinicalTrials.gov NCT01945840). A 4-day food diary and validated eating behaviour questionnaires were completed. Sweet taste detection was measured using the method of constant stimuli. Correct sucrose identification (corrected hit rates) was recorded, and sweet taste detection thresholds (EC50s: half maximum effective concencration values) were derived from concentration curves. The intensity and consummatory reward value of sweet taste were assessed using the generalized Labelled Magnitude Scale.ResultsMean daily energy intake was reduced by 27% with GOP but no significant changes in food preferences were observed, whereas a reduction in fat and increase in protein intake were seen post-RYGB. There was no change in corrected hit rates or detection thresholds for sucrose detection following GOP infusion. Additionally, GOP did not alter the intensity or consummatory reward value of sweet taste. A significant reduction in restraint eating, comparable to the RYGB group was observed with GOP.ConclusionThe elevation in plasma GOP concentrations after RYGB is unlikely to mediate changes in food preferences and sweet taste function after surgery but may promote restraint eating.
Davies I, Tan TMM, 2023, Design of novel therapeutics targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) to aid weight loss., Expert Opin Drug Discov, Vol: 18, Pages: 659-669
INTRODUCTION: With obesity rates growing globally, there is a paramount need for new obesity pharmacotherapies to tackle this pandemic. AREAS COVERED: This review focuses on the design of therapeutics that target the glucose-dependent insulinotropic polypeptide receptor (GIPR) to aid weight loss. The authors highlight the paradoxical observation that both GIPR agonism and antagonism appear to provide metabolic benefits when combined with glucagon-like peptide-1 receptor (GLP-1 R) agonism. The therapeutic potential of compounds that target the GIPR alongside the GLP-1 R and the glucagon receptor are discussed, and the impressive clinical findings of such compounds are reviewed. EXPERT OPINION: In this area, the translation of pre-clinical findings to clinical studies appears to be particularly difficult. Well-designed physiological studies in man are required to answer the paradox highlighted above, and to support the safe future development of a combination of GLP-1 R/GIPR targeting therapies.
Phylactou M, Comninos A, salih A, et al., 2023, Derivation and comparison of formulae for the adjustment of total calcium, Frontiers in Endocrinology, Vol: 14, Pages: 1-10, ISSN: 1664-2392
Background: Free ionized calcium (Ca2+) is the biologically active component of total calcium (TCa) and hence responsible for its biological action. TCa is routinely adjusted for albumin using several formulae (e.g. James, Orell, Payne and Berry) to more closely reflect Ca2+. Here, we derive a novel formula to estimate Ca2+ and compare its performance to established formulae.Methods: Cohort for prediction of Ca2+: 2806 serum samples (TCa) taken contemporaneously with blood gas samples (Ca2+) at Imperial College Healthcare NHS Trust were used to derive formulae to estimate Ca2+ using multivariable linear regression. Cohort for prediction of PTH: Performance of novel and existing formulae to predict PTH in 5510 patients was determined by Spearman correlation.Results: Ca2+ prediction Cohort: Adjusted calcium (r2 = 0.269) was less strongly associated with Ca2+, than TCa (r2 = 0.314). Prediction of Ca2+ from a newly derived formula incorporating TCa, potassium, albumin, and hematocrit had an improved r2 of 0.327, whereas inclusion of all available parameters increased the r2 further to 0.364. Of the established formulae, James performed best in predicting Ca2+ (r2 = 0.27). PTH prediction cohort: Berry resulted in higher whereas Orell in lower adjusted calcium levels. Prediction of PTH was strongest in the setting of hypercalcemia, with James having the highest Spearman correlation coefficient (+0.496) similar to including all parameters (+0.499).Conclusion: Adjustment of calcium for albumin using established formulae does not always outperform unadjusted TCa in the reflection of Ca2+. Further prospective studies are needed to optimise adjustment of TCa and to establish bounds for validity.
Hope DCD, Tan TM-M, 2023, Glucagon and energy expenditure; Revisiting amino acid metabolism and implications for weight loss therapy., Peptides, Vol: 162
Glucagon receptor (GCGR)-targeted multi-agonists are being developed for the treatment of obesity and metabolic disease. GCGR activity is utilised for its favourable weight loss and metabolic properties, including increased energy expenditure (EE) and hepatic lipid metabolism. GLP1R and GIPR activities are increasingly present in a multi-agonist strategy. Due to the compound effect of increased satiety, reduced food intake and increased energy expenditure, the striking weight loss effects of these multi-agonists has been demonstrated in pre-clinical models of obesity. The precise contribution and mechanism of GCGR activity to enhanced energy expenditure and weight loss in both rodents and humans is not fully understood. In this review, our understanding of glucagon-mediated EE is explored, and an amino acid-centric paradigm contributing to this phenomenon is presented. The current progress of GCGR-targeted multi-agonists in development is also highlighted with a focus on the implications of glucagon-stimulated hypoaminoacidemia.
Kowalka AMM, Alexiadou K, Cuenco J, et al., 2023, Commentary on "The road to reliable peptide assays is paved with good guidelines", CLINICAL ENDOCRINOLOGY, ISSN: 0300-0664
Clarke SA, Phylactou M, Patel B, et al., 2023, Letter to the Editor of Clinical Endocrinology: Assessment of adrenal function in patients who survive COVID‐19, Clinical Endocrinology, Vol: 98, Pages: 270-272, ISSN: 0300-0664
It is widely recognised that the effects of COVID-19 extend beyond the respiratory system. Moreover, there are an estimated 1.3 million people living with Long COVID (symptoms persisting beyond 12 weeks after infection) in the UK alone.
Tan TM-M, 2022, Co-agonist therapeutics come of age for obesity, NATURE REVIEWS ENDOCRINOLOGY, Vol: 19, Pages: 66-67, ISSN: 1759-5029
Kowalka AM, Alexiadou K, Cuenco J, et al., 2022, The postprandial secretion of peptide YY1-36 and (3-36) in obesity is differentially increased after gastric bypass versus sleeve gastrectomy, CLINICAL ENDOCRINOLOGY, ISSN: 0300-0664
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Hope D, Hinds C, Lopes T, et al., 2022, Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss, Cell Reports Medicine, Vol: 3, ISSN: 2666-3791
Glucagon analogues show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analogue, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a prerequisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics.
Frampton J, Izzi-Engbeaya C, Salem V, et al., 2022, The acute effect of glucagon on components of energy balance and glucose homoeostasis in adults without diabetes: a systematic review and meta-analysis, International Journal of Obesity, Vol: 46, Pages: 1948-1959, ISSN: 0307-0565
ObjectiveUsing a systematic review and meta-analysis, we aimed to estimate the mean effect of acute glucagon administration on components of energy balance and glucose homoeostasis in adults without diabetes.MethodsCENTRAL, CINAHL, Embase, MEDLINE, PubMed, and Scopus databases were searched from inception to May 2021. To be included, papers had to be a randomised, crossover, single- or double-blind study, measuring ad libitum meal energy intake, energy expenditure, subjective appetite, glucose, and/or insulin following acute administration of glucagon and an appropriate comparator in adults without diabetes. Risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Randomized trials with additional considerations for cross-over trials. Certainty of evidence was assessed using the GRADE approach. Random-effect meta-analyses were performed for outcomes with at least five studies. This study is registered on PROSPERO (CRD42021269623).ResultsIn total, 13 papers (15 studies) were considered eligible: energy intake (5 studies, 77 participants); energy expenditure (5 studies, 59 participants); subjective appetite (3 studies, 39 participants); glucose (13 studies, 159 participants); insulin (12 studies, 147 participants). All studies had some concerns with regards to risk of bias. Mean intervention effect of acute glucagon administration on energy intake was small (standardised mean difference [SMD]: –0.19; 95% CI, –0.59 to 0.21; P = 0.345). Mean intervention effect of acute glucagon administration on energy expenditure (SMD: 0.72; 95% CI, 0.37–1.08; P < 0.001), glucose (SMD: 1.11; 95% CI, 0.60–1.62; P < 0.001), and insulin (SMD: 1.33; 95% CI, 0.88–1.77; P < 0.001) was moderate to large.ConclusionsAcute glucagon administration produces substantial increases in energy expenditure, and in circulating insulin and glucose concentrations. However, the effect of acute g
Takis PG, Vuckovic I, Tan T, et al., 2022, NMRpQuant: an automated software for large scale urinary total protein quantification by one-dimensional 1H NMR profiles, Bioinformatics, Vol: 38, Pages: 4437-4439, ISSN: 1367-4803
Summary1H nuclear magnetic resonance (NMR) spectroscopy is an established bioanalytical technology for metabolic profiling of biofluids in both clinical and large-scale population screening applications. Recently, urinary protein quantification has been demonstrated using the same 1D 1H NMR experimental data captured for metabolic profiling. Here, we introduce NMRpQuant, a freely available platform that builds on these findings with both novel and further optimized computational NMR approaches for rigorous, automated protein urine quantification. The results are validated by interlaboratory comparisons, demonstrating agreement with clinical/biochemical methodologies, pointing at a ready-to-use tool for routine protein urinalyses.Availability and implementationNMRpQuant was developed on MATLAB programming environment. Source code and Windows/macOS compiled applications are available at https://github.com/pantakis/NMRpQuant, and working examples are available at https://doi.org/10.6084/m9.figshare.18737189.v1.
McGlone ER, Dunsterville C, Carling D, et al., 2022, Hepatocyte cholesterol content modulates glucagon receptor signalling, Molecular Metabolism, Vol: 63, ISSN: 2212-8778
ObjectiveTo determine whether glucagon receptor (GCGR) actions are modulated by cellular cholesterol levels.MethodsWe determined the effects of experimental cholesterol depletion and loading on glucagon-mediated cAMP production, ligand internalisation and glucose production in human hepatoma cells, mouse and human hepatocytes. GCGR interactions with lipid bilayers were explored using coarse-grained molecular dynamic simulations. Glucagon responsiveness was measured in mice fed a high cholesterol diet with or without simvastatin to modulate hepatocyte cholesterol content.ResultsGCGR cAMP signalling was reduced by higher cholesterol levels across different cellular models. Ex vivo glucagon-induced glucose output from mouse hepatocytes was enhanced by simvastatin treatment. Mice fed a high cholesterol diet had increased hepatic cholesterol and a blunted hyperglycaemic response to glucagon, both of which were partially reversed by simvastatin. Simulations identified likely membrane-exposed cholesterol binding sites on the GCGR, including a site where cholesterol is a putative negative allosteric modulator.ConclusionsOur results indicate that cellular cholesterol content influences glucagon sensitivity and indicate a potential molecular basis for this phenomenon. This could be relevant to the pathogenesis of non-alcoholic fatty liver disease, which is associated with both hepatic cholesterol accumulation and glucagon resistance.
Tabbakh Y, Malallah K, Alexiadou K, et al., 2022, TRENDS IN ENERGY EXPENDITURE IN PATIENTS UNDERGOING ROUX-EN-Y GASTRIC BYPASS SURGERY, Publisher: SPRINGER, Pages: 580-581, ISSN: 0960-8923
Patel P, Thomas R, Hamady M, et al., 2022, O102 We know about left gastric artery embolisation and will embio provide the next solution to treat obesity?, Annual Scientific Meeting of the Surgical-Research-Society, Publisher: OXFORD UNIV PRESS, ISSN: 0007-1323
Patel P, Thomas R, Hamady M, et al., 2022, Simulation training to create the gold standard framework to run the EMBIO trial (left gastric artery embolisation vs placebo), a double blinded, multi-centre, randomised controlled trial., 13th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: 27-27, ISSN: 0960-8923
Patel P, Thomas R, Hamady M, et al., 2022, What we know about left gastric artery embolisation and will EMBIO provide the next solution to treat obesity?, Publisher: SPRINGER, Pages: 26-27, ISSN: 0960-8923
Mohamed RS, Abuelgasim B, Barker S, et al., 2022, Late night salivary cortisol and cortisone should be the initial screening test for Cushing’s syndrome, Endocrine Connections, Vol: 11, ISSN: 2049-3614
Endogenous Cushing’s syndrome (CS) poses considerable diagnostic challenges. Although late night salivary cortisol (LNSC) is recommended as a first line screening investigation, it remains the least widely used test in many countries. The combined measurement of LNSC and late-night salivary cortisone (LNS cortisone) has shown to further improve diagnostic accuracy1. We present a retrospective study in a tertiary referral centre comparing LNSC, LNS cortisone, overnight dexamethasone suppression test, low dose dexamethasone suppression test and 24-hour urinary free cortisol results of patients investigated for CS. Patients were categorised into those who had CS (21 patients) and those who did not (33 patients).LNSC had a sensitivity of 95% and a specificity of 91%. LNS cortisone had a specificity of 100% and a sensitivity of 86%. With an optimal cut-off for LNS cortisone of >14.5 nmol/l the sensitivity was 95.2%, and the specificity was 100% with an area under the curve of 0.997, for diagnosing CS. Saliva collection is non-invasive and can be carried out at home.We therefore advocate simultaneous measurement of LNSC and LNS cortisone as the first-line screening test to evaluate patients with suspected CS.
Correia GDS, Takis PG, Sands CJ, et al., 2022, 1H NMR Signals from urine excreted protein are a source of bias in probabilistic quotient normalization, Analytical Chemistry, Vol: 94, Pages: 6919-6923, ISSN: 0003-2700
Normalization to account for variation in urinary dilution is crucial for interpretation of urine metabolic profiles. Probabilistic quotient normalization (PQN) is used routinely in metabolomics but is sensitive to systematic variation shared across a large proportion of the spectral profile (>50%). Where 1H nuclear magnetic resonance (NMR) spectroscopy is employed, the presence of urinary protein can elevate the spectral baseline and substantially impact the resulting profile. Using 1H NMR profile measurements of spot urine samples collected from hospitalized COVID-19 patients in the ISARIC 4C study, we determined that PQN coefficients are significantly correlated with observed protein levels (r2 = 0.423, p < 2.2 × 10–16). This correlation was significantly reduced (r2 = 0.163, p < 2.2 × 10–16) when using a computational method for suppression of macromolecular signals known as small molecule enhancement spectroscopy (SMolESY) for proteinic baseline removal prior to PQN. These results highlight proteinuria as a common yet overlooked source of bias in 1H NMR metabolic profiling studies which can be effectively mitigated using SMolESY or other macromolecular signal suppression methods before estimation of normalization coefficients.
Eng PC, Distaso W, Durreshahwar H, et al., 2022, The benefit of dexamethasone in patients with COVID-19 infection is preserved in patients with diabetes., Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 24, Pages: 1385-1389, ISSN: 1462-8902
Dexamethasone significantly reduces mortality1 and is now standard treatment for patients with COVID-19 who require supplemental oxygen and/or mechanical ventilation. However, supraphysiological doses of glucocorticoids may exacerbate dysglycaemia and precipitate hyperglycaemic complications, particularly in those with or at risk of Type 2 diabetes2. The RECOVERY trial1 reported a low incidence of hyperglycaemic complications (2/1996, 0.1%), although the real-world incidence is likely to be much higher3. Type 2 diabetes itself increases the risk of severe COVID-194, and hyperglycaemia independently predicts poor outcomes5. We investigated the possibility that patients with diabetes may derive less survival benefit from steroid therapy in the setting of severe COVID-19 infection
Hanson H, Durkie M, Lalloo F, et al., 2022, UK recommendations for SDHA germline genetic testing and surveillance in clinical practice, JOURNAL OF MEDICAL GENETICS, ISSN: 0022-2593
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Comninos AN, Hansen MS, Courtney A, et al., 2022, Acute effects of kisspeptin administration on bone metabolism in healthy men, Journal of Clinical Endocrinology and Metabolism, Vol: 107, ISSN: 0021-972X
CONTEXT: Osteoporosis results from disturbances in bone formation and resorption. Recent non-human data suggests that the reproductive hormone, kisspeptin, directly stimulates osteoblast differentiation in vitro and thus could have clinical therapeutic potential. However, the effects of kisspeptin on human bone metabolism are currently unknown. OBJECTIVE: To assess the effects of kisspeptin on human bone metabolism in vitro and in vivo. DESIGN: In vitro study: Mono- and co-cultures of human osteoblasts and osteoclasts treated with kisspeptin. Clinical study: Randomized, placebo-controlled, double-blind, two-way crossover clinical study in twenty-six men investigating the effects of acute kisspeptin administration (90 minutes) on human bone metabolism, with blood sampling every 30 minutes to +90 minutes. PARTICIPANTS: In vitro study: Twelve male blood donors and eight patients undergoing hip replacement surgery. Clinical Study: Twenty-six healthy eugonadal men (age 26.8±5.8 years). INTERVENTION: Kisspeptin (versus placebo). MAIN OUTCOME MEASURES: Changes in bone parameters and turnover markers. RESULTS: Incubation with kisspeptin in vitro increased alkaline phosphatase levels in human bone marrow mesenchymal stem cells by 41.1% (P=0.0022), and robustly inhibited osteoclastic resorptive activity by up to 53.4% (P<0.0001), in a dose-dependent manner. Kisspeptin administration to healthy men increased osteoblast activity, as evidenced by a 20.3% maximal increase in total osteocalcin (P=0.021) and 24.3% maximal increase in carboxylated osteocalcin levels (P=0.014). CONCLUSIONS: Collectively, these data provide the first human evidence that kisspeptin promotes osteogenic differentiation of osteoblast progenitors and inhibits bone resorption in vitro. Furthermore, kisspeptin acutely increases the bone formation marker osteocalcin but not resorption markers in healthy men, independent of downstream sex-steroid levels. Kisspeptin could therefore have clinical thera
Kenkre JS, Malallah K, Davies I, et al., 2022, Patients with liver fibrosis may be less likely to remit from type 2 diabetes following bariatric surgery, Publisher: WILEY, ISSN: 0742-3071
Alexiadou K, Choudhury S, Malallah K, et al., 2022, The effect of PYY (3-36) on bone turnover markers in obese patient with type 2 diabetes, Diabetes UK Professional Conference 2022, Publisher: Wiley, Pages: 1-1, ISSN: 0742-3071
Background: Gut hormones have emerged as new promising therapies for the treatment of obesity and type 2 diabetes as well as viable alternatives to bariatric surgery. PYY has mainly been studied for its effect on appetite suppression and lately for its role in diabetes remission post-bariatric surgery. Animal data have suggested that PYY may act on the bone remodelling process by increasing bone resorption.Aims: The aim of our study was to assess the effect of PYY infusion on bone turn over markers in obese patients with type 2 diabetes.Methods: Ten obese patients with type 2 diabetes on diet or one hypoglycaemic agent were enrolled in the study. An infusion of PYY (3-36) was administered daily for up to 16 hours for a duration of 4 weeks. Metabolic profiling at fasting state and during a Mixed Meal Test (MMT) was performed prior to the initiation of the infusion and at the end of 4 weeks. Bone markers (plasma P1NP, CTX, OC) were measured at the beginning and the end of the 4 weeks both at fasting state and during the MMT. Urinary NTX was measured at fasting state only.Results: There was no significant difference in bone markers before and after the intervention. P1NP and CTX reduced significantly during the MMT compared to the fasting state both prior and 4 weeks after the infusion of PYY (3-36).Conclusions: Infusion of PYY (3-36) for 4 weeks does not affect the bone turnover markers in obese patients with type 2 diabetes. P1NP and CTX reduce significantly as a response to nutrient intake. PYY (3-36) could be developed as treatment for obesity with type 2 diabetes without negative implications for bone health.
Davies I, Dong J, Hope D, et al., 2022, Chronic glucagon administration does not induce inguinal white adipose tissue browning in rats, Publisher: WILEY, ISSN: 0742-3071
Clarke S, Phylactou M, Patel B, et al., 2022, Preserved C-peptide in survivors of COVID-19: post-hoc analysis, Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 24, Pages: 570-574, ISSN: 1462-8902
Tan TM-M, Khoo B, 2022, Steps to redressing an imbalance: GLP-1 analogues for obesity in east Asia, LANCET DIABETES & ENDOCRINOLOGY, Vol: 10, Pages: 153-+, ISSN: 2213-8587
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