Publications

Publication: Journal of Clinical Endocrinology & Metabolism

Katherine Lawler, Isabel Huang-Doran, Takuhiro Sonoyama, Tinh-Hai Collet, Julia M Keogh, Elana Henning, Stephen O’Rahilly, Leonardo Bottolo, I Sadaf Farooqi

11 May 2020


Summary:

The hormone leptin is a key regulator of weight. Children who lack leptin (due to changes in the leptin gene) have a very large appetite and rapidly gain weight. After treatment with leptin injections, they can lose weight.

The researchers know that leptin works by reducing their appetite, but they wanted to find out if leptin can affect other metabolic processes around the body too.

They used a cutting-edge technique called metabolomics to simultaneously measure more than 600 metabolic reactions in a single blood sample taken from children and young adults before and after a short period of leptin treatment.

They found that leptin not only caused big shifts in how the body processes fats, but it affected amino acids (which make proteins), bile acids (which can act as cell signals) and steroids (involved in making hormones). These changes overlapped with the changes discovered previously in healthy adults after a period of fasting.

The research findings show that as well as affecting how much food we eat, leptin affects other aspects of our metabolism. This research paves the way for further research into leptin’s action on different cells in the human body.

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Publication: Scientific Reports

T. D. Turmezei, G. M. Treece, A. H. Gee, S. Sigurdsson, H. Jonsson, T. Aspelund, V. Gudnason & K. E. S. Poole

March 2020


Summary

Hip osteoarthritis is a very common condition that will affect up to 25% of the population in their lifetime. There is no cure for this painful and debilitating disease, with the mainstay of treatment currently being surgical replacement of the joint once it has become too stiff or painful to use. Research trials trying to find effective therapies for osteoarthritis currently rely on x-ray radiograph imaging to test if there have been any meaningful changes in the structure of the joint for a new therapy, but this method suffers from being unable to detect small changes reliably and from only being able to see the joint in 2D.

We developed the joint space mapping (JSM) technique in a collaboration between the Departments of Medicine and Engineering at the University of Cambridge and have since taken it to test on patient data from the widely regarded AGES-Reykjavik patient cohort of healthy older Icelandic adults.

Our research showed that JSM can identify structurally relevant disease features related to the important outcome of joint replacement in hip osteoarthritis better than the current clinical trial 2D imaging gold standards. This means that JSM could be a significantly better way of identifying who might be at high risk from getting hip osteoarthritis, those in whom the disease might be progressing rapidly, and whether any new therapy is effective at stopping the joint destruction that ultimately leads to joint failure. These results have been achieved by using an existing and readily available clinical imaging technique to look at the hip joint in 3D.

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Publication: Nature

Anthony P. Coll, Michael Chen, Stephen O’Rahilly et al

25 December 2019


Cambridge scientists have discovered that metformin causes the cells of the intestine to make large amounts of a hormone, called GDF15, and secrete it into the bloodstream.

The high blood levels of GDF15 are sensed by a highly specific area of the brain where they suppress hunger and reduce food intake. When GDF15 is blocked, metformin has no effect on body weight.

The work was undertaken in the MRC Metabolic Diseases Unit at the University of Cambridge with collaborators at NGM Biopharmaceuticals, the University of Glasgow and elsewhere.

Dr Tony Coll, a lead author, said “We usually think that drugs have to pass through the intestine to have their effects in the body. In this case, though, the cells of the intestine themselves respond to the drug to create a hormonal signal which does the work.”

Metformin has been used to treat Type 2 diabetes for over 60 years and is the world’s most commonly prescribed anti-diabetic drug. It can also prevent the onset of diabetes in those at risk, doing so by helping people to lose and keep off weight. However, how metformin reduces body weight has been a mystery.

Professor Stephen O’Rahilly said: “How metformin keeps body weight down has been a mystery. This work shows that all of this effect is down to GDF15 acting on a tiny number of cells in the brain.”

These findings are supported  by an independent study from McMaster University published in Nature Metabolism  and should stimulate research into the use of GDF15 itself as an anti-obesity agent.

 

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Publication: J Clin Endocrinol Metab.

David Church, Luís Cardoso, Richard G Kay, Claire L Williams, Bernard Freudenthal, Catriona Clarke, Julie Harris, Myuri Moorthy, Efthmia Karra, Fiona M Gribble, Frank Reimann, Keith Burling, Alistair J K Williams, Alia Munir, T Hugh Jones, Dagmar Führer, Lars C Moeller, Mark Cohen, Bernard Khoo, David Halsall, Robert K Semple

31 July 2018


Insulin and c-peptide levels are routinely measured to monitor glucose-competence in patients, however, ocassionally the standard assays give readings well ouside the normal range. Very high readings could indicate an insulin producing tumor or exogenous insulin overdosing or in rare patients can be a result of insulin-auto antibodies.

LC-MS/MS can be a highly selective method to detect insulin and distinguishes between natural insulin and insulin drugs, making it valuable add-on to “standard” immunoassays when these give unexpected readings. It can also measure multiple analytes in a single extraction, reducing the volume of blood needed for analysis.

The superior performance of LC-MS/MS in analysing blood from insulin autoimmune syndrome patients should enable clearer diagnosis and the initiation of immunomodulatory therapy.

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Publication: Kidney International

Lia Bally, Philipp Gubler, Hood Thabit, Sara Hartnell, Yue Ruan, Malgorzata E. Wilinska, Mark L. Evans, Mariam Semmo, Bruno Vogt, Anthony P. Coll, Christoph Stettler, Roman Hovorka
20 March 2019

Summary:
In a post hoc analysis of a randomised controlled clinical trial, researchers compared the efficacy of fully automated closed-loop insulin delivery vs. usual care in patients undergoing hemodialysis while in hospital.
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Publication: Human Molecular Genetics

Pavlova EV, Shatunov A, Wartosch L, Moskvina AI, Nikolaeva LE, Bright NA, Tylee KL, Church HJ, Ballabio A, Luzio JP, Cox TM.

10 April 2019

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Publication: Cell

Lotta LA, Mokrosiński J, Mendes de Oliveira E, Li C, Sharp SJ, Luan J, Brouwers B, Ayinampudi V, Bowker N, Kerrison N, Kaimakis V, Hoult D, Stewart ID,  Wheeler E, Day FR, Perry JRB, Langenberg C, Wareham NJ, Farooqi IS.

18 April 2019

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Publication: Nature Genetics

Lotta LA, Gulati P, Day FR, Payne F, Ongen H, van de Bunt M, Gaulton KJ, Eicher JD, Sharp SJ, Luan J, De Lucia Rolfe E, Stewart ID, Wheeler E, Willems SM, Adams C, Yaghootkar H; EPIC-InterAct Consortium; Cambridge FPLD1 Consortium, Forouhi NG, Khaw KT, Johnson AD, Semple RK, Frayling T, Perry JR, Dermitzakis E,  McCarthy MI, Barroso I, Wareham NJ, Savage DB, Langenberg C, O’Rahilly S, Scott RA.

14 November 2016

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Publication: Cell

van der Klaauw AA, Croizier S, Mendes de Oliveira E, Stadler LKJ, Park S, Kong Y, Banton MC, Tandon P, Hendricks AE, Keogh JM, Riley SE, Papadia S, Henning E, Bounds R, Bochukova EG, Mistry V, O’Rahilly S, Simerly RB; INTERVAL; UK10K Consortium, Minchin JEN, Barroso I, Jones EY, Bouret SG, Farooqi IS.

17 January 2019

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Publication: JCI Insight

Cangul H, Liao XH, Schoenmakers E, Kero J, Barone S, Srichomkwun P, Iwayama H,Serra EG, Saglam H, Eren E, Tarim O, Nicholas AK, Zvetkova I, Anderson CA, FranklFEK, Boelaert K, Ojaniemi M, Jääskeläinen J, Patyra K, Löf C, Williams ED; UK10K Consortium, Soleimani M, Barrett T, Maher ER, Chatterjee VK, Refetoff S,Schoenmakers N

18 October 2018

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Publication: The New England Journal of Medicine

Marcovecchio ML, Chiesa ST, Bond S, Daneman D, Dawson S, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dalton RN, Deanfield J, Dunger DB; AdDIT Study Group

2 November 2017

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Publication: The Lancet

Tauschmann M, Thabit H, Bally L, Allen JM, Hartnell S, Wilinska ME, Ruan Y, Sibayan J, Kollman C, Cheng P, Beck RW, Acerini CL, Evans ML, Dunger DB, Elleri D, Campbell F, Bergenstal RM, Criego A, Shah VN, Leelarathna L, Hovorka R; APCam11 Consortium.

3 October 2018

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Publication: Bone

Poole KE, Skingle L, Gee AH, Turmezei TD, Johannesdottir F, Blesic K, Rose C, Vindlacheruvu M, Donell S, Vaculik J, Dungl P, Horak M, Stepan JJ, Reeve J, Treece GM.

21 October 2016

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Publication: Appetite

Joost Overduin, Tinh-Hai Collet, Nenad Medic, Elana Henning , Julia M. Keogh, Faye Forsyth, Cheryl Stephenson, Marja W. Kanning, Rianne M.A.J. Ruijschop, I. Sadaf Farooqi, Agatha A. van der Klaauw.

1 December 2016

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Publication: Nat Comms

Agatha A. van der Klaauw, Julia M. Keogh, Elana Henning, Cheryl Stephenson, Sarah Kelway, Victoria M. Trowse, Naresh Subramanian, Stephen O’Rahilly, Paul C. Fletcher, I. Sadaf Farooqi.

4 October 2016

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