Publications

Publication: Nature Genetics

Yajie Zhao, Maria Chukanova, Katherine A. Kentistou, Zammy Fairhurst-Hunter, Anna Maria Siegert, Raina Y. Jia, Georgina K. C. Dowsett, Eugene J. Gardner, Katherine Lawler, Felix R. Day, Lena R. Kaisinger, Yi-Chun Loraine Tung, Brian Yee Hong Lam, Hsiao-Jou Cortina Chen, Quanli Wang, Jaime Berumen-Campos, Pablo Kuri-Morales, Roberto Tapia-Conyer, Jesus Alegre-Diaz, Inês Barroso, Jonathan Emberson, Jason M. Torres, Rory Collins, Danish Saleheen, Katherine R. Smith, Dirk S. Paul, Florian Merkle, I. Sadaf Farooqi, Nick J. Wareham, Slavé Petrovski, Stephen O’Rahilly, Ken K. Ong, Giles S. H. Yeo & John R. B. Perry

4 April 2024

Summary

A study has identified genetic variants in two genes that have some of the largest impacts on obesity risk discovered to date.

The discovery of rare variants in the genes BSN and APBA1 are some of the first obesity-related genes identified for which the increased risk of obesity is not observed until adulthood.

Publication: Nature

M. Fejzo, N. Rocha, I. Cimino, S. M. Lockhart, C. J. Petry, R. G. Kay, K. Burling, P. Barker, A. L. George, N. Yasara, A. Premawardhena, S. Gong, E. Cook, D. Rimmington, K. Rainbow, D. J. Withers, V. Cortessis, P. M. Mullin, K. W. MacGibbon, E. Jin, A. Kam, A. Campbell, O. Polasek, G. Tzoneva, F. M. Gribble, G. S. H. Yeo, B. Y. H. Lam, V. Saudek, I. A. Hughes, K. K. Ong, J. R. B. Perry, A. Sutton Cole, M. Baumgarten, P. Welsh, N. Sattar, G. C. S. Smith, D. S. Charnock-Jones, A. P. Coll, C. L. Meek, S. Mettananda, C. Hayward, N. Mancuso & S. O’Rahilly

Summary

13 December 2023

A Cambridge-led study supported by the NIHR Cambridge BRC has shown why many women experience nausea and vomiting during pregnancy – and why some women become so sick they need to be admitted to hospital. The culprit is a hormone produced by the fetus – a protein known as GDF15. But how sick the mother feels depends on a combination of how much of the hormone is produced by the fetus and how much exposure the mother had to this hormone before becoming pregnant. Read the full news story.

Publication: Journal of Internal Medicine

Youngwon Kim, Haeyoon Jang, Mengyao Wang, Qiaoxin Shi, Tessa Strain, Stephen J Sharp, Shiu Lun Au Yeung, Shan Luo, Simon Griffin, Nicholas J. Wareham, Katrien Wijndaele, Soren Brage

23 August 2023

Summary

Excess sedentary time (ST) is recognized as an important modifiable risk factor for coronary heart disease (CHD). However, whether the associations of genetic susceptibility with CHD incidence can be modified by replacing wearable-device-measured ST with physical activity (PA) is unknown.

Publication: Cell Reports Medicine

Ruth Hanssen, Chiara Auwerx, Maarja Jõeloo, Sadaf Farooqi, Alexandre Reymond, Katherine Lawler

15 August 2023

New approaches are needed to treat people whose obesity and type 2 diabetes (T2D) are driven by specific mechanisms. We investigate a deletion on chromosome 16p11.2 (breakpoint 2–3 [BP2–3]) encompassing SH2B1, a mediator of leptin and insulin signaling. Phenome-wide association scans in the UK (N = 502,399) and Estonian (N = 208,360) biobanks show that deletion carriers have increased body mass index (BMI; p = 1.3 × 10−10) and increased rates of T2D. Compared with BMI-matched controls, deletion carriers have an earlier onset of T2D, with poorer glycemic control despite higher medication usage. Cystatin C, a biomarker of kidney function, is significantly elevated in deletion carriers, suggesting increased risk of renal impairment. In a Mendelian randomization study, decreased SH2B1 expression increases T2D risk (p = 8.1 × 10−6). We conclude that people with 16p11.2 BP2–3 deletions have early, complex obesity and T2D and may benefit from therapies that enhance leptin and insulin signaling.

Publication: Nature Medicine

Agatha A. van der Klaauw, Emily C. Horner, Pehuén Pereyra-Gerber, Utkarsh Agrawal, William S. Foster, Sarah Spencer, Bensi Vergese, Miriam Smith, Elana Henning, Isobel D. Ramsay, Jack A. Smith, Stephane M. Guillaume, Hayley J. Sharpe, Iain M. Hay, Sam Thompson, Silvia Innocentin, Lucy H. Booth, Chris Robertson, Colin McCowan, Steven Kerr, Thomas E. Mulroney, Martin J. O’Reilly, Thevinya P. Gurugama, Lihinya P. Gurugama, Maria A. Rust, Alex Ferreira, Soraya Ebrahimi, Lourdes Ceron-Gutierrez, Jacopo Scotucci, Barbara Kronsteiner, Susanna J. Dunachie, Paul Klenerman, PITCH Consortium, Adrian J. Park, Francesco Rubino, Abigail A. Lamikanra, Hannah Stark, Nathalie Kingston, Lise Estcourt, Heli Harvala, David J. Roberts, Rainer Doffinger, Michelle A. Linterman, Nicholas J. Matheson, Aziz Sheikh, I. Sadaf Farooqi & James E. D. Thaventhiran

11 May 2023

Summary

Clinical trials have shown that COVID-19 vaccines are highly effective at reducing symptoms, hospitalisation and deaths caused by the virus, including for people with obesity. Previous studies have suggested that antibody levels may be lower in vaccinated people who have obesity and that they may remain at higher risk of severe disease than vaccinated people with normal weight. The reasons for this have, however, remained unclear. Read the news story.

Publication: Nature Medicine

Aideen B. Daly, Charlotte K. Boughton, Munachiso Nwokolo, Sara Hartnell, Malgorzata E. Wilinska, Alina Cezar, Mark L. Evans & Roman Hovorka

12 January 2023

Summary

Cambridge scientists have successfully trialled an artificial pancreas for use by patients living with type 2 diabetes. The device – powered by an algorithm developed at the University of Cambridge – doubled the amount of time patients were in the target range for glucose and halved the time spent experiencing high glucose levels. Read the full news story.

Publication: Nutrients

Dimitra Zannidi, Pinal S. Patel, Eleni Leventea, Jessica Paciepnik,  Frances Dobson,  Caroline Heyes, Robert J. B. Goudie,  Linda M. Oude Griep,  Jacobus Preller, and Lynsey N. Spillman, 

8 October 2022

Summary

Previous research has shown that people hospitalised with COVID-19 are at risk of weight loss and malnutrition. This study looked at patients who experienced weight loss of 10% or more during their hospital admission to Cambridge University Hospitals NHS with COVID-19 during the first wave of the pandemic. Weight loss of 10% or more is considered a large amount to lose as it increases the chance of someone becoming more poorly and not surviving. Therefore, preventing weight loss may help patients to survive and recover. The study looked at risk factors for weight loss to help better recognise the patients that need more support to prevent weight loss. 

Publication: The Lancet Diabetes and Endocrinology

Nick Wareham, Nita Forouhi

27 October 2021

Summary

Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. Researcgers aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks.

Publication: Elife

Brogan Ashley, Claire Simner, Antigoni Manousopoulou, Carl Jenkinson, Felicity Hey, Jennifer M Frost, Faisal I Rezwan, Cory H White, Emma M Lofthouse, Emily Hyde, Laura DF Cooke, Sheila Barton, Pamela Mahon, Elizabeth M Curtis, Rebecca J Moon, Sarah R Crozier, Hazel M Inskip, Keith M Godfrey, John W Holloway, Cyrus Cooper, Kerry S Jones, Rohan M Lewis, Martin Hewison, Spiros DD Garbis, Miguel R Branco, Nicholas C Harvey, Jane K Cleal

8 March 2022

Summary

This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself.

Publication: Clinical Nutrition

Inge A.L.P. van Beijsterveldt, Pernille Neve Myers, Stuart G. Snowden, Ken K. Ong, Susanne Brix, Anita C.S. Hokken-Koelega, Albert Koulman 

21 April 2022

Summary

Early life is a critical window for adiposity programming and metabolic profile may affect this programming. Researchers investigated if plasma metabolites at age 3 months were associated with fat mass, fat free mass and abdominal subcutaneous and visceral fat outcomes at age 2 years in a cohort of healthy infants and if these associations were different between infants receiving exclusive breastfeeding and those with exclusive formula feeding.

Publication: Journal of the American Heart Association

Paddy C. Dempsey, Tessa Strain, Elisabeth A. H. Winkler, Kate Westgate, Kirsten L. Rennie, Nicholas J. Wareham, Soren Brage, Katrien Wijndaele

26 April 2022

Summary

Emerging evidence suggests accruing sedentary behavior in relatively more prolonged periods may convey additional cardiometabolic risks, but few studies have examined prospective outcomes. Researchers examined the association of sedentary behavior accumulation patterns with incident cardiovascular disease, cancer, and all‐cause mortality.

Publication: International Journal of Epidemiology

Michelle Venables, Caireen Roberts, Kerry Jones, Anila Farooq, Albert Koulman, Nick Wareham, Polly Page

28 May 2022

Since 2008, the Government in the United Kingdom has funded a large, annual survey called the National Diet and Nutrition Survey Rolling Programme (NDNS RP) to collect detailed information from people on the foods they are eating and their nutritional health.

The survey is used to monitor how well the UK population is doing in terms of dietary guidelines and inform the development of new nutrition policies. It is also used to monitor chemical exposure risk to protect food safety. In this NIHR Cambridge BRC paper, the authors have provided easy access to comprehensive information about the NDNS for the academic and wider public health community.

The paper describes the data collected in the first 11 years of the NDNS RP, how it has been used, and demonstrates the scope of publicly available data. The authors present an overview of survey methods to collect and analyse the data.

Between 2008 and 2019, 7999 adults and 7656 children completed food diaries; 4181 adults and 2014 children had a blood sample taken; 3246 adults and 2318 children gave a urine sample and 419 adults and 352 children had their energy expenditure measured. The authors explain how NDNS survey reports and data provide information on the foods, calories and nutrients such as fat, sugar and vitamins consumed by the UK population, and how Government use these data in public health campaigns such as the Change4Life, 5 A DAY and sugar reduction and folate fortification policies.

They also highlight that many other institutions and individuals use the survey including international organisations like the World Health Organisation. Reports are published regularly by Government: https://www.gov.uk/government/collections/national-diet-and-nutrition-survey. Anonymised individual data can be accessed from the Data Service and stored blood and urine samples are available for further research via the NDNS Bioresource.

The NDNS RP provides a unique and valuable publicly available resource for the UK Government, researchers, health professionals and others looking to understand and improve population health and nutrition.

Publication: JAMA Pediatrics

Soren Brage

23 May 2022

This was a randomised controlled trial examining the effect of restricting screen use in 89 families living in Denmark. Children in intervention families reduced their objectively measured sedentary time by 45 min/day, which was significantly more than the 1 min/day increase observed in children from control families.

Publication: Nature

V. Pellegrinelli, S. Rodriguez-Cuenca, C. Rouault, E. Figueroa-Juarez, H. Schilbert, S. Virtue, J. M. Moreno-Navarrete, G. Bidault, M. C. Vázquez-Borrego, A. R. Dias, B. Pucker, M. Dale, M. Campbell, S. Carobbio, Y. H. Lin, M. Vacca, J. Aron-Wisnewsky, S. Mora, M. M. Masiero, A. Emmanouilidou, S. Mukhopadhyay, G. Dougan, M. den Hoed, R. J. F. Loos, J. M. Fernández-Real, D. Chiarugi, K. Clément & A. Vidal-Puig

25 April 2022

Summary

New research shows that an enzyme produced by macrophages (immune system cells) in fat tissue plays an essential role in the loss of metabolic health in people with obesity and might serve as a biomarker to help us identify those at the highest risk of fibrosis, inflammation and insulin resistance or type 2 diabetes associated with obesity. It also identifies a potential target for drugs that might prevent or reverse metabolic disease and could throw light on a long-unexplained paradox. Read more.

Publication: JAMA Psychiatry

Soren Brage

13 April 2022

Depression is a disorder characterised by persistent sadness and a lack of interest or pleasure in previously enjoyable activities. It is the leading cause of mental health-related disease burden, affecting approximately 1 in 20 adults worldwide. Reviews of the scientific evidence have shown that depression may be prevented by physical activity, but the benefits at different levels of activity are unclear.

The aim of this study was to combine results from previously published studies to estimate the association between different levels of physical activity and depression. We searched medical databases for studies including at least 3000 adults published up until 12th November 2020. The studies had to report the risk of developing depression for at least three different levels of physical activity.

We included studies irrespective of how they measured physical activity. We standardised these measures to a common format so that the published results could be analysed together and make sense on the same physical activity scale. We estimated what proportion of depression cases would have been avoided if all adults in the studies met the current physical activity recommendations. We included 15 studies with 191,130 participants and found that even small doses of physical activity appeared to substantially lower risks of depression. Adults meeting physical activity recommendations (equivalent to 2.5 hrs/week of brisk walking) had 25% lower risk of depression compared with adults reporting no physical activity.

Our findings suggested that most benefits occurred when moving from no activity to at least some, and that only minor additional benefits were achieved by further increasing activity levels. Approximately 1 in 9 cases of depression might have been prevented if everybody in the population was active at the level of current health recommendations.

Publication: European Journal of Preventive Cardiology

Nita Forouhi, Soren Brage, Nick Wareham

11 April 2022

This study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors. In people with CHD risk factors, moderate physical activity, equivalent to 40 mins of walking per day, attenuates but does not completely offset CHD risk.

Publication: Nutrients

Marleen A. H. Lentjes, Linda M. Oude Griep, Angela A. Mulligan, Scott Montgomery, Nick J. Wareham and Kay-Tee Khaw

6 January 2022

Summary

Researchers studied how associations between meal patterns and non-fasting triglyceride and glucose concentrations were influenced by the hour of day at which the blood sample was collected to ascertain face validity of reported meal patterns, as well as the influence of reporting bias (assessed using formula of energy expenditure) on this association.

Meal size (i.e., reported energy content), mealtime and meal frequency were reported using pre-structured 7-day diet diaries. Associations between meal patterns and concentration biomarkers can be observed when accounting for diurnal variation and underreporting. These findings support the use of 7-day diet diaries for studying associations between meal patterns and health.

Publication: Nutrients

Camille M. Mba, Albert Koulman, Nita G. Forouhi, Fumiaki Imamura, Felix Assah, Jean Claude Mbanya, and Nick J. Wareham

30 December 2021

Summary

A low intake of fruit and vegetables and a high intake of meat are associated with higher cardiometabolic disease risk; however much prior research has relied on subjective methods for dietary assessment and focused on Western populations.

Researchers aimed to investigate the association of blood folate as an objective marker of fruit and vegetable intake and holotranscobalamin (holoTC) as a marker of animal-sourced food intake with cardiometabolic risk factors. In conclusion, serum folate and holoTC were associated with the metabolic syndrome score in opposite directions. The positive association between serum holoTC and the metabolic syndrome score was partly dependent on sociodemographic characteristics. These findings suggest that, based on these biomarkers reflecting dietary intakes, public health approaches promoting a higher intake of fruit and vegetables may lower cardiometabolic risk factors in this population

Publication: New England Journal of Medicine

Julia Ware,  Janet M. Allen, Charlotte K. Boughton, Malgorzata E. Wilinska, Sara Hartnell, Ajay Thankamony, Carine de Beaufort, Ulrike Schierloh, Elke Fröhlich-Reiterer, Julia K. Mader, Thomas M. Kapellen, Birgit Rami-Merhar, Martin Tauschmann, Katrin Nagl, Sabine E. Hofer, Fiona M. Campbell, James Yong, Korey K. Hood, Julia Lawton, Stephane Roze, Judy Sibayan, Laura E. Bocchino, Craig Kollman, and Roman Hovorka

20 January 2022

Summary

In this multicenter, randomized, crossover trial, researchers recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). Read the full press release.

Publication: International Journal of Obesity

Tim Lindsay, Katrien Wijndaele, Kate Westgate, Paddy Dempsey, Tessa Strain, Emanuella De Lucia Rolfe, Nita G. Forouhi, Simon Griffin, Nick J. Wareham & Søren Brage

30 September 2021

Summary

Physical activity energy expenditure (PAEE) represents the total volume of all physical activity. This can be accumulated as different underlying intensity profiles. Although volume and intensity have been studied in isolation, less is known about their joint association with health. Researchers examined this association with body fatness in a population-based sample of middle-aged British adults.

Publication: British Journal of Nutrition

L.E.T. Vissers, I. Sluijs, S. Burgess, N.G. Forouhi,H. Freisling, F. Imamura, T.K. Nilsson, F. Renström, E. Weiderpass, K. Aleksandrova, C.C. Dahm, A. Perez-Cornago, M.B. Schulze, T.Y.N. Tong, D. Aune, C. Bonet, J.M.A. Boer, H. Boeing, M.D. Chirlaque, M.I. Conchi, L. Imaz, S. Jäger, V. Krogh, C. Kyrø, G. Masala,O. Melander, K. Overvad, S. Panico, M.J. Sánches, E. Sonestedt, A. Tjønneland, I. Tzoulaki, W.M.M. Verschuren, E. Riboli, N.J. Wareham, J. Danesh, A.S. Butterworth, Y.T. van der Schouw

21 October 2021

Higher milk intake has been associated with a lower stroke risk, but not with risk of coronary heart disease (CHD). Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses.

Publication: Journal of the American Heart Association

Marinka Steur, Laura Johnson, Stephen J. Sharp, Fumiaki Imamura, Ivonne Sluijs, Timothy J. Key, Angela Wood, Rajiv Chowdhury, Marcela Guevara, Marianne U. Jakobsen, Ingegerd Johansson, Albert Koulman, Kim Overvad, Maria‐José Sánchez, Yvonne T. van der Schouw, Antonia Trichopoulou, Elisabete Weiderpass, Maria Wennberg, Ju‐Sheng Zheng, Heiner Boeing, Jolanda M. A. Boer, Marie‐Christine Boutron‐Ruault, Ulrika Ericson, Alicia K. Heath, Inge Huybrechts, Liher Imaz, Rudolf Kaaks, Vittorio Krogh, Tilman Kühn, Cecilie Kyrø, Giovanna Masala, Olle Melander, Conchi Moreno‐Iribas, Salvatore Panico, José R. Quirós, Miguel Rodríguez‐Barranco, Carlotta Sacerdote, Carmen Santiuste, Guri Skeie, Anne Tjønneland, Rosario Tumino, W. M. Monique Verschuren, Raul Zamora‐Ros, Christina C. Dahm, Aurora Perez‐Cornago, Matthias B. Schulze, Tammy Y. N. Tong, Elio Riboli, Nicholas J.Wareham, John Danesh, Adam S. Butterworth, and Nita G. Forouhi

7 December 2021

Summary

Once thought to be the best dietary advice for the prevention of heart attacks, reducing saturated fat in the diet is increasingly questioned as a strategy for improving heart health. This change, which is evident in the increasing popularity of low carbohydrate, not low fat diets, is happening for a variety of reasons.

Researchers conducted research across nine countries of Europe testing the link between different types of dietary fats and the future risk of developing heart disease. This study involved 10,529 people who developed heart disease over time and compared them with 16,730 people who did not develop heart disease, who were randomly selected from 385,747 European Prospective Investigation into Cancer (EPIC) study volunteers in the EPIC-CVD Study.

Publication: Journal of the Academy of Nutrition and Dietetics

Ghadeer S. Aljuraiban, Rachel Gibson, Leenah Al-Freeh, Sara Al-Musharaf, Nitin Shivappa, James R. Hébert, Linda M. Oude Griep, Queenie Chan,

1 September 2021

Summary

Saudi Arabian diets are transitioning to more Western dietary patterns that have been associated with higher levels of inflammation. Emerging evidence suggests plant-based diets are related to lower levels of inflammation; however, the definition of plant-based diets varies.

Researchers aimed to identify the extent to which an overall Plant-Based Diet Index (PDI), Healthy-PDI (hPDI), and Unhealthy-PDI (uPDI) vs Energy-Adjusted Dietary Inflammatory Index correlate with high-sensitivity C-reactive protein (hs-CRP) level.

Although all indexes had a small or moderate correlation with hs-CRP, only E-DII score was positively associated with hs-CRP level. Future research can examine PDI-based interventions for lowering inflammation.

Publication: Nature Medicine

Charlotte K. Boughton, Afroditi Tripyla, Sara Hartnell, Aideen Daly, David Herzig, Malgorzata E. Wilinska, Cecilia Czerlau, Andrew Fry, Lia Bally & Roman Hovorka 

04 August 2021

Summary

An artificial pancreas could soon help people living with type 2 diabetes and who also require kidney dialysis. Tests led by the University of Cambridge and Inselspital, University Hospital of Bern, Switzerland show that the device can help patients safely and effectively manage their blood sugar levels and reduce the risk of low blood sugar levels. Read the full press release.

Publication: Proceedings of the National Academy of Sciences (PNAS)

Irene Cimino, Hanna Kim, Y. C. Loraine Tung, Kent Pedersen, Debra Rimmington, John A. Tadross,  Sara N. Kohnke, Ana Neves-Costa, André Barros, Stephanie Joaquim, Don Bennett, Audrey Melvin, Samuel M. Lockhart,  Anthony J. Rostron, Jonathan Scott, Hui Liu,  Keith Burling, Peter Barker, Menna R. Clatworthy, E-Chiang Lee,A. John Simpson, Giles S. H. Yeo, Luís F. Moita, Kendra K. Bence, Sebastian Beck Jørgensen, Anthony P. Coll, Danna M. Breen, and Stephen O’Rahilly

30 June 2021

Summary

Researchers have described a new way that the body senses damage and activates hormones in response to stressful situations – involving the protein GDF15

Publication: Nature Medicine

Kaitlin H. Wade, Brian Y. H. Lam, Audrey Melvin, Warren Pan, Laura J. Corbin, David A. Hughes, Kara Rainbow, Jian-Hua Chen, Katie Duckett, Xiaoming Liu, Jacek Mokrosiński, Alexander Mörseburg, Sam Neaves, Alice Williamson, Chen Zhang, I. Sadaf Farooqi, Giles S. H. Yeo, Nicholas J. Timpson & Stephen O’Rahilly 

27 May 2021

Summary

Could a gene be the key why some of us carry extra fat? New research has found that one in every 340 people might carry a mutation in a single gene that makes them more likely to have a greater weight from early childhood and, by 18 years of age, they could be up to 30 pounds heavier with the excess weight likely to be mostly fat. Read the full story

Publication: The Lancet

Kathryn Beardsall, Lynn Thomson, Catherine Guy, Isabel Iglesias-Platas, Prof Mirjam M van Weissenbruch, Simon Bond, et al

9 February 2021

Hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants.

Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care.

This international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6–10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life.

Between July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis.

Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6–10 mmol/L glucose concentration target range. More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group. There were no serious adverse events related to the use of the device or episodes of infection.

Real-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes.

Publication: The Lancet: Diabetes and Endocrinology

Prof Karine Clément, MD, Prof Erica van den Akker, MD, Prof Jesús Argente, MD, Allison Bahm, MD, Prof Wendy K Chung, MD, Hillori Connors, MS, Kathleen De Waele, MD, Prof I Sadaf Farooqi, PhD, Julie Gonneau-Lejeune, MD, Gregory Gordon, MD, Katja Kohlsdorf, MD, Prof Christine Poitou, MD, Lia Puder, MD, James Swain, MD, Murray Stewart, DM, Guojun Yuan, PhD, Prof Martin Wabitsch, MD, Prof Peter Kühnen, MD

30 October 2020

Summary:

In this international phase 3 study, researchers wanted to see if the drug Setmelanotide could help people whose severe obesity is caused by pro-opiomelanocortin (POMC) or leptin (LEPR) deficiency.

Melanocortin 4 Receptor (MC4R), plays a critical part in bodyweight regulation and Setmelanotide is an MC4R agonist. This trial was conducted in several countries with participants with severe obesity due to either POMC deficiency LEPR deficiency.

After approximately 1 year, eight (80%) participants in the POMC trial and five (45%) participants in the LEPR trial achieved at least 10% weight loss. Researchers found Setmelanotide to be a safe and effective treatment for people with POMC or LEPR deficiency.

This research could benefit people who find it hard to lose weight. There are ongoing trials to test whether Setmelanotide is effective in other genetic obesity syndromes.

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.

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.

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.

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

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

Publication: Kidney International

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

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

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

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.

Publication: Surgery for obesity and related diseases

Roberts GP, Kay RG, Howard J, Hardwick RH, Reimann F, Gribble FM.

2 February 2018

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

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

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

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

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