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1. Estimating natural history of a treatment-eligible type 2 diabetes mellitus population in Scotland using linked primary and secondary care data: Scottish Diabetes Research Network - National Diabetes Dataset

Author: Lili Wei, Elaine Butterly, Peter Hanlon, Houra Haghpanahan, Robert Lindsay, Amanda I Adler, Luke A K Blackbourn, Sofia Dias, Katherine Hughes, Stuart McGurnaghan, John Petrie, Naveed Sattar, Laurie A Tomlinson, Nicky Welton, Sarah Wild, Jim Lewsey, and David McAllister
Subjects: Demography. Population. Vital events, HB848-3697
Abstract: Healthcare commissioners and those making reimbursement decisions require data on the “natural history” of diseases to estimate quantities such as life expectancy and quality of life. However, such data are commonly acquired from unrepresentative sources like trial placebo arms or case series. We used Scottish Diabetes Research Network-National Diabetes Dataset to characterise life expectancy for people with type 2 diabetes mellitus (T2DM). Data from >99% of people with diabetes in Scotland are available from primary and secondary care (including from clinical investigations) and can be linked to hospital admission and death records for research purposes. As part of an MRC-funded (MR/T017112/1) systematic review and modelling study (PROSPERO registration CRD42020184174) building on work funded by the Chief Scientific Office for Scotland (CSO HIPS_17_26), we used these linked data to define a treatment-eligible population for three drug classes — SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors. Fitting a Gompertz model, we estimated life expectancy for this ‘treatment-eligible’ group. The treatment-eligible population, compared to the entire Scottish T2DM population, was younger (63.8 (12.1) vs. 66.7 (12.7) year-old), with larger proportions of men (60.6% vs. 56.2%), higher HbA1c levels (67.4 (13.1) vs. 60.2 (15.1) mmol/L), larger proportions prescribed metformin (69.2% vs 55.2%) and higher life expectancy at age 65 (in women 21 vs 19 years and in men 20 vs 18 years). Using linked data to define and characterise treatment-eligible populations is feasible and may impact decision models. These findings will be useful to those making resourcing decisions and future economic analyses.
Published: 2024
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2. Variation in colorectal cancer treatment and outcomes in Scotland: real world evidence from national linked administrative health data

Author: Elizabeth Lemmon, Catherine Hanna, Katharina Diernberger, Hugh Paterson, Sarah Wild, Holly Ennis, and Peter Hall
Subjects: colorectal cancer, survivorship, Administrative data, Geographic variation, cancer registry, Demography. Population. Vital events, HB848-3697
Abstract: Background Colorectal cancer (CRC) is the fourth most common type of cancer in the United Kingdom and the second leading cause of cancer death. Despite improvements in CRC survival over time, Scotland lags behind its UK and European counterparts. In this study, we carry out an exploratory analysis which aims to provide contemporary, population level evidence on CRC treatment and survival in Scotland. Methods We conducted a retrospective population-based analysis of adults with incident CRC registered on the Scottish Cancer Registry (Scottish Morbidity Record 06 (SMR06)) between January 2006 and December 2018. The CRC cohort was linked to hospital inpatient (SMR01) and National Records of Scotland (NRS) deaths records allowing a description of their demographic, diagnostic and treatment characteristics. Cox proportional hazards regression models were used to explore the demographic and clinical factors associated with all-cause mortality and CRC specific mortality after adjusting for patient and tumour characteristics among people identified as early-stage and treated with surgery. Results Overall, 32,691 (73%) and 12,184 (27%) patients had a diagnosis of colon and rectal cancer respectively, of whom 55% and 53% were early-stage and treated with surgery. Five year overall survival (CRC specific survival) within this cohort was 72% (82%) and 76% (84%) for patients with colon and rectal cancer respectively. Cox proportional hazards models revealed significant variation in mortality by sex, area-based deprivation and geographic location. Conclusions In a Scottish population of patients with early-stage CRC treated with surgery, there was significant variation in risk of death, even after accounting for clinical factors and patient characteristics.
Published: 2024
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3. Cohort profile: the Scottish Diabetes Research Network national diabetes cohort – a population-based cohort of people with diabetes in Scotland

Author: Naveed Sattar, Sarah Wild, David McAllister, Katherine Hughes, Ewan R Pearson, Helen M Colhoun, Paul M McKeigue, Sam Philip, John Petrie, John McKnight, Robert Lindsay, Graham P Leese, Anna Barnett, Stuart J. McGurnaghan, Luke A. K. Blackbourn, Thomas M. Caparrotta, Joseph Mellor, and Andy Collier
Subjects: Medicine
Abstract: Purpose The Scottish Diabetes Research Network (SDRN)-diabetes research platform was established to combine disparate electronic health record data into research-ready linked datasets for diabetes research in Scotland. The resultant cohort, ‘The SDRN-National Diabetes Dataset (SDRN-NDS)’, has many uses, for example, understanding healthcare burden and socioeconomic trends in disease incidence and prevalence, observational pharmacoepidemiology studies and building prediction tools to support clinical decision making.Participants We estimate that >99% of those diagnosed with diabetes nationwide are captured into the research platform. Between 2006 and mid-2020, the cohort comprised 472 648 people alive with diabetes at any point in whom there were 4 million person-years of follow-up. Of the cohort, 88.1% had type 2 diabetes, 8.8% type 1 diabetes and 3.1% had other types (eg, secondary diabetes). Data are captured from all key clinical encounters for diabetes-related care, including diabetes clinic, primary care and podiatry and comprise clinical history and measurements with linkage to blood results, microbiology, prescribed and dispensed drug and devices, retinopathy screening, outpatient, day case and inpatient episodes, birth outcomes, cancer registry, renal registry and causes of death.Findings to date There have been >50 publications using the SDRN-NDS. Examples of recent key findings include analysis of the incidence and relative risks for COVID-19 infection, drug safety of insulin glargine and SGLT2 inhibitors, life expectancy estimates, evaluation of the impact of flash monitors on glycaemic control and diabetic ketoacidosis and time trend analysis showing that diabetic ketoacidosis (DKA) remains a major cause of death under age 50 years. The findings have been used to guide national diabetes strategy and influence national and international guidelines.Future plans The comprehensive SDRN-NDS will continue to be used in future studies of diabetes epidemiology in the Scottish population. It will continue to be updated at least annually, with new data sources linked as they become available.
Published: 2022
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4. Calibrating a network meta-analysis of diabetes trials of sodium glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor analogues and dipeptidyl peptidase-4 inhibitors to a representative routine population: a systematic review protocol

Author: Naveed Sattar, Sofia Dias, Sarah Wild, Laurie A Tomlinson, David McAllister, Amanda I Adler, Nicky Welton, Lili Wei, Katherine Hughes, Peter Hanlon, Elaine Butterly, Jim Lewsey, John Petrie, Robert Lindsay, Saleh A M Almazam, Khalid Alsallumi, Luke A K Blackbourn, Stuart McGurnaghan, and David Phillippo
Subjects: Medicine
Abstract: Introduction Participants in randomised controlled trials (trials) are generally younger and healthier than many individuals encountered in clinical practice. Consequently, the applicability of trial findings is often uncertain. To address this, results from trials can be calibrated to more representative data sources. In a network meta-analysis, using a novel approach which allows the inclusion of trials whether or not individual-level participant data (IPD) is available, we will calibrate trials for three drug classes (sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) receptor analogues and dipeptidyl peptidase-4 (DPP4) inhibitors) to the Scottish diabetes register.Methods and analysis Medline and EMBASE databases, the US clinical trials registry (clinicaltrials.gov) and the Chinese Clinical Trial Registry (chictr.org.cn) will be searched from 1 January 2002. Two independent reviewers will apply eligibility criteria to identify trials for inclusion. Included trials will be phase 3 or 4 trials of SGLT2 inhibitors, GLP1 receptor analogues or DPP4 inhibitors, with placebo or active comparators, in participants with type 2 diabetes, with at least one of glycaemic control, change in body weight or major adverse cardiovascular event as outcomes. Unregistered trials will be excluded.We have identified a target population from the population-based Scottish diabetes register. The chosen cohort comprises people in Scotland with type 2 diabetes who either (1) require further treatment due to poor glycaemic control where any of the three drug classes may be suitable, or (2) who have adequate glycaemic control but are already on one of the three drug classes of interest or insulin.Ethics and dissemination Ethical approval for IPD use was obtained from the University of Glasgow MVLS College Ethics Committee (Project: 200160070). The Scottish diabetes register has approval from the Scottish A Research Ethics Committee (11/AL/0225) and operates with Public Benefit and Privacy Panel for Health and Social Care approval (1617-0147).PROSPERO registration number CRD42020184174.
Published: 2022
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5. Severe mental illness and quality of diabetes care: a retrospective national linked cohort study.

Author: Stine Scheuer, Kelly Fleetwood, Kirsty Licence, Stewart Mercer, Daniel Smith, Sarah Wild, and Caroline Jackson
Subjects: Type 2 Diabetes, Diabetes care, Severe mental illness, Retrospective cohort, Demography. Population. Vital events, HB848-3697
Abstract: Objective To use a Scottish national linked diabetes care dataset to determine whether annual monitoring of clinical guideline-recommended diabetes care indicators differ by severe mental illness (SMI) status among people with type 2 diabetes (T2D) during the first year following diabetes diagnosis and thereafter. Approach We examined receipt of 9 diabetes care indicators (HbA1c; cholesterol; urinary albumin; serum creatinine; blood pressure; retinopathy screening; foot examination; body mass index; and smoking status) in people with T2D diagnosed 2009-2018, comparing people with a prior hospital record of schizophrenia, bipolar disorder and depression versus no hospital record for any mental illness. We analysed receipt of care in the first year using logistic regression and for the entire follow-up period (until death or 31 December 2018) using generalized linear mixed effects models, adjusting for calendar year, sociodemographic and lifestyle factors and comorbidities (and in the latter, diabetes duration). Results We included 119,508 people with T2D (mean age 59.7 [±13.2 SD]), of which 1701 (1%), 768 (0.5%) and 5211 (3%) had schizophrenia, bipolar disorder and depression, respectively. During the first year, compared to people without mental illness those with each SMI were more likely to receive cholesterol and serum creatinine measurement and, for schizophrenia only, HbA1c measurement, after adjustment for confounding factors. People with depression had higher odds of receiving a smoking review, but lower odds of receiving urinary albumin measurement. Receipt of all other indicators were similar across comparison groups. In the longitudinal analyses, people with schizophrenia had persistently higher odds of receiving HbA1c and people with a SMI had lower odds of receiving retinopathy screening. Conclusion Receipt of care delivered in the primary care setting was generally similar in people with versus without SMI in the short and long term. However, people with SMI were less likely to receive retinopathy screening, highlighting a need for better monitoring of care indicators delivered outside primary care settings.
Published: 2022
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6. Large socioeconomic gap in period life expectancy and life years spent with complications of diabetes in the Scottish population with type 1 diabetes, 2013-2018.

Author: Andreas Höhn, Stuart J McGurnaghan, Thomas M Caparrotta, Anita Jeyam, Joseph E O'Reilly, Luke A K Blackbourn, Sara Hatam, Christian Dudel, Rosie J Seaman, Joseph Mellor, Naveed Sattar, Rory J McCrimmon, Brian Kennon, John R Petrie, Sarah Wild, Paul M McKeigue, Helen M Colhoun, and SDRN-Epi Group
Subjects: Medicine, Science
Abstract: BackgroundWe report the first study to estimate the socioeconomic gap in period life expectancy (LE) and life years spent with and without complications in a national cohort of individuals with type 1 diabetes.MethodsThis retrospective cohort study used linked healthcare records from SCI-Diabetes, the population-based diabetes register of Scotland. We studied all individuals aged 50 and older with a diagnosis of type 1 diabetes who were alive and residing in Scotland on 1 January 2013 (N = 8591). We used the Scottish Index of Multiple Deprivation (SIMD) 2016 as an area-based measure of socioeconomic deprivation. For each individual, we constructed a history of transitions by capturing whether individuals developed retinopathy/maculopathy, cardiovascular disease, chronic kidney disease, and diabetic foot, or died throughout the study period, which lasted until 31 December 2018. Using parametric multistate survival models, we estimated total and state-specific LE at an attained age of 50.ResultsAt age 50, remaining LE was 22.2 years (95% confidence interval (95% CI): 21.6 - 22.8) for males and 25.1 years (95% CI: 24.4 - 25.9) for females. Remaining LE at age 50 was around 8 years lower among the most deprived SIMD quintile when compared with the least deprived SIMD quintile: 18.7 years (95% CI: 17.5 - 19.9) vs. 26.3 years (95% CI: 24.5 - 28.1) among males, and 21.2 years (95% CI: 19.7 - 22.7) vs. 29.3 years (95% CI: 27.5 - 31.1) among females. The gap in life years spent without complications was around 5 years between the most and the least deprived SIMD quintile: 4.9 years (95% CI: 3.6 - 6.1) vs. 9.3 years (95% CI: 7.5 - 11.1) among males, and 5.3 years (95% CI: 3.7 - 6.9) vs. 10.3 years (95% CI: 8.3 - 12.3) among females. SIMD differences in transition rates decreased marginally when controlling for time-updated information on risk factors such as HbA1c, blood pressure, BMI, or smoking.ConclusionsIn addition to societal interventions, tailored support to reduce the impact of diabetes is needed for individuals from low socioeconomic backgrounds, including access to innovations in management of diabetes and the prevention of complications.
Published: 2022
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7. Representation of people with comorbidity and multimorbidity in clinical trials of novel drug therapies: an individual-level participant data analysis

Author: Peter Hanlon, Laurie Hannigan, Jesus Rodriguez-Perez, Colin Fischbacher, Nicky J. Welton, Sofia Dias, Frances S. Mair, Bruce Guthrie, Sarah Wild, and David A. McAllister
Subjects: Randomised controlled trials, Comorbidity, Multimorbidity, Medicine
Abstract: Abstract Background Clinicians are less likely to prescribe guideline-recommended treatments to people with multimorbidity than to people with a single condition. Doubts as to the applicability of clinical trials of drug treatments (the gold standard for evidence-based medicine) when people have co-existing diseases (comorbidity) may underlie this apparent reluctance. Therefore, for a range of index conditions, we measured the comorbidity among participants in clinical trials of novel drug therapies and compared this to the comorbidity among patients in the community. Methods Data from industry-sponsored phase 3/4 multicentre trials of novel drug therapies for chronic medical conditions were identified from two repositories: Clinical Study Data Request and the Yale University Open Data Access project. We identified 116 trials (n = 122,969 participants) for 22 index conditions. Community patients were identified from a nationally representative sample of 2.3 million patients in Wales, UK. Twenty-one comorbidities were identified from medication use based on pre-specified definitions. We assessed the prevalence of each comorbidity and the total number of comorbidities (level of multimorbidity), for each trial and in community patients. Results In the trials, the commonest comorbidities in order of declining prevalence were chronic pain, cardiovascular disease, arthritis, affective disorders, acid-related disorders, asthma/COPD and diabetes. These conditions were also common in community-based patients. Mean comorbidity count for trial participants was approximately half that seen in community-based patients. Nonetheless, a substantial proportion of trial participants had a high degree of multimorbidity. For example, in asthma and psoriasis trials, 10–15% of participants had ≥ 3 conditions overall, while in osteoporosis and chronic obstructive pulmonary disease trials 40–60% of participants had ≥ 3 conditions overall. Conclusions Comorbidity and multimorbidity are less common in trials than in community populations with the same index condition. Comorbidity and multimorbidity are, nevertheless, common in trials. This suggests that standard, industry-funded clinical trials are an underused resource for investigating treatment effects in people with comorbidity and multimorbidity.
Published: 2019
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8. Associations of autozygosity with a broad range of human phenotypes

Author: David W Clark, Yukinori Okada, Kristjan H S Moore, Dan Mason, Nicola Pirastu, Ilaria Gandin, Hannele Mattsson, Catriona L K Barnes, Kuang Lin, Jing Hua Zhao, Patrick Deelen, Rebecca Rohde, Claudia Schurmann, Xiuqing Guo, Franco Giulianini, Weihua Zhang, Carolina Medina-Gomez, Robert Karlsson, Yanchun Bao, Traci M Bartz, Clemens Baumbach, Ginevra Biino, Matthew J Bixley, Marco Brumat, Jin-Fang Chai, Tanguy Corre, Diana L Cousminer, Annelot M Dekker, David A Eccles, Kristel R van Eijk, Christian Fuchsberger, He Gao, Marine Germain, Scott D Gordon, Hugoline G de Haan, Sarah E Harris, Edith Hofer, Alicia Huerta-Chagoya, Catherine Igartua, Iris E Jansen, Yucheng Jia, Tim Kacprowski, Torgny Karlsson, Marcus E Kleber, Shengchao Alfred Li, Ruifang Li-Gao, Anubha Mahajan, Koichi Matsuda, Karina Meidtner, Weihua Meng, May E Montasser, Peter J van der Most, Matthias Munz, Teresa Nutile, Teemu Palviainen, Gauri Prasad, Rashmi B Prasad, Tallapragada Divya Sri Priyanka, Federica Rizzi, Erika Salvi, Bishwa R Sapkota, Daniel Shriner, Line Skotte, Melissa C Smart, Albert Vernon Smith, Ashley van der Spek, Cassandra N Spracklen, Rona J Strawbridge, Salman M Tajuddin, Stella Trompet, Constance Turman, Niek Verweij, Clara Viberti, Lihua Wang, Helen R Warren, Robyn E Wootton, Lisa R Yanek, Jie Yao, Noha A Yousri, Wei Zhao, Adebowale A Adeyemo, Saima Afaq, Carlos Alberto Aguilar-Salinas, Masato Akiyama, Matthew L Albert, Matthew A Allison, Maris Alver, Tin Aung, Fereidoun Azizi, Amy R Bentley, Heiner Boeing, Eric Boerwinkle, Judith B Borja, Gert J de Borst, Erwin P Bottinger, Linda Broer, Harry Campbell, Stephen Chanock, Miao-Li Chee, Guanjie Chen, Yii-Der I Chen, Zhengming Chen, Yen-Feng Chiu, Massimiliano Cocca, Francis S Collins, Maria Pina Concas, Janie Corley, Giovanni Cugliari, Rob M van Dam, Anna Damulina, Maryam S Daneshpour, Felix R Day, Graciela E Delgado, Klodian Dhana, Alexander S F Doney, Marcus Dörr, Ayo P Doumatey, Nduna Dzimiri, S Sunna Ebenesersdóttir, Joshua Elliott, Paul Elliott, Ralf Ewert, Janine F Felix, Krista Fischer, Barry I Freedman, Giorgia Girotto, Anuj Goel, Martin Gögele, Mark O Goodarzi, Mariaelisa Graff, Einat Granot-Hershkovitz, Francine Grodstein, Simonetta Guarrera, Daniel F Gudbjartsson, Kamran Guity, Bjarni Gunnarsson, Yu Guo, Saskia P Hagenaars, Christopher A Haiman, Avner Halevy, Tamara B Harris, Mehdi Hedayati, David A van Heel, Makoto Hirata, Imo Höfer, Chao Agnes Hsiung, Jinyan Huang, Yi-Jen Hung, M Arfan Ikram, Anuradha Jagadeesan, Pekka Jousilahti, Yoichiro Kamatani, Masahiro Kanai, Nicola D Kerrison, Thorsten Kessler, Kay-Tee Khaw, Chiea Chuen Khor, Dominique P V de Kleijn, Woon-Puay Koh, Ivana Kolcic, Peter Kraft, Bernhard K Krämer, Zoltán Kutalik, Johanna Kuusisto, Claudia Langenberg, Lenore J Launer, Deborah A Lawlor, I-Te Lee, Wen-Jane Lee, Markus M Lerch, Liming Li, Jianjun Liu, Marie Loh, Stephanie J London, Stephanie Loomis, Yingchang Lu, Jian’an Luan, Reedik Mägi, Ani W Manichaikul, Paolo Manunta, Gísli Másson, Nana Matoba, Xue W Mei, Christa Meisinger, Thomas Meitinger, Massimo Mezzavilla, Lili Milani, Iona Y Millwood, Yukihide Momozawa, Amy Moore, Pierre-Emmanuel Morange, Hortensia Moreno-Macías, Trevor A Mori, Alanna C Morrison, Taulant Muka, Yoshinori Murakami, Alison D Murray, Renée de Mutsert, Josyf C Mychaleckyj, Mike A Nalls, Matthias Nauck, Matt J Neville, Ilja M Nolte, Ken K Ong, Lorena Orozco, Sandosh Padmanabhan, Gunnar Pálsson, James S Pankow, Cristian Pattaro, Alison Pattie, Ozren Polasek, Neil Poulter, Peter P Pramstaller, Lluis Quintana-Murci, Katri Räikkönen, Sarju Ralhan, Dabeeru C Rao, Wouter van Rheenen, Stephen S Rich, Paul M Ridker, Cornelius A Rietveld, Antonietta Robino, Frank J A van Rooij, Daniela Ruggiero, Yasaman Saba, Charumathi Sabanayagam, Maria Sabater-Lleal, Cinzia Felicita Sala, Veikko Salomaa, Kevin Sandow, Helena Schmidt, Laura J Scott, William R Scott, Bahareh Sedaghati-Khayat, Bengt Sennblad, Jessica van Setten, Peter J Sever, Wayne H-H Sheu, Yuan Shi, Smeeta Shrestha, Sharvari Rahul Shukla, Jon K Sigurdsson, Timo Tonis Sikka, Jai Rup Singh, Blair H Smith, Alena Stančáková, Alice Stanton, John M Starr, Lilja Stefansdottir, Leon Straker, Patrick Sulem, Gardar Sveinbjornsson, Morris A Swertz, Adele M Taylor, Kent D Taylor, Natalie Terzikhan, Yih-Chung Tham, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Annika Tillander, Russell P Tracy, Teresa Tusié-Luna, Ioanna Tzoulaki, Simona Vaccargiu, Jagadish Vangipurapu, Jan H Veldink, Veronique Vitart, Uwe Völker, Eero Vuoksimaa, Salma M Wakil, Melanie Waldenberger, Gurpreet S Wander, Ya Xing Wang, Nicholas J Wareham, Sarah Wild, Chittaranjan S Yajnik, Jian-Min Yuan, Lingyao Zeng, Liang Zhang, Jie Zhou, Najaf Amin, Folkert W Asselbergs, Stephan J L Bakker, Diane M Becker, Benjamin Lehne, David A Bennett, Leonard H van den Berg, Sonja I Berndt, Dwaipayan Bharadwaj, Lawrence F Bielak, Murielle Bochud, Mike Boehnke, Claude Bouchard, Jonathan P Bradfield, Jennifer A Brody, Archie Campbell, Shai Carmi, Mark J Caulfield, David Cesarini, John C Chambers, Giriraj Ratan Chandak, Ching-Yu Cheng, Marina Ciullo, Marilyn Cornelis, Daniele Cusi, George Davey Smith, Ian J Deary, Rajkumar Dorajoo, Cornelia M van Duijn, David Ellinghaus, Jeanette Erdmann, Johan G Eriksson, Evangelos Evangelou, Michele K Evans, Jessica D Faul, Bjarke Feenstra, Mary Feitosa, Sylvain Foisy, Andre Franke, Yechiel Friedlander, Paolo Gasparini, Christian Gieger, Clicerio Gonzalez, Philippe Goyette, Struan F A Grant, Lyn R Griffiths, Leif Groop, Vilmundur Gudnason, Ulf Gyllensten, Hakon Hakonarson, Anders Hamsten, Pim van der Harst, Chew-Kiat Heng, Andrew A Hicks, Hagit Hochner, Heikki Huikuri, Steven C Hunt, Vincent W V Jaddoe, Philip L De Jager, Magnus Johannesson, Åsa Johansson, Jost B Jonas, J Wouter Jukema, Juhani Junttila, Jaakko Kaprio, Sharon L. R. Kardia, Fredrik Karpe, Meena Kumari, Markku Laakso, Sander W van der Laan, Jari Lahti, Matthias Laudes, Rodney A Lea, Wolfgang Lieb, Thomas Lumley, Nicholas G Martin, Winfried März, Giuseppe Matullo, Mark I McCarthy, Sarah E Medland, Tony R Merriman, Andres Metspalu, Brian F Meyer, Karen L Mohlke, Grant W Montgomery, Dennis Mook-Kanamori, Patricia B Munroe, Kari E North, Dale R Nyholt, Jeffery R O’connell, Carole Ober, Albertine J Oldehinkel, Walter Palmas, Colin Palmer, Gerard G Pasterkamp, Etienne Patin, Craig E Pennell, Louis Perusse, Patricia A Peyser, Mario Pirastu, Tinca J. C. Polderman, David J Porteous, Danielle Posthuma, Bruce M Psaty, John D Rioux, Fernando Rivadeneira, Charles Rotimi, Jerome I Rotter, Igor Rudan, Hester M Den Ruijter, Dharambir K Sanghera, Naveed Sattar, Reinhold Schmidt, Matthias B Schulze, Heribert Schunkert, Robert A Scott, Alan R Shuldiner, Xueling Sim, Neil Small, Jennifer A Smith, Nona Sotoodehnia, E-Shyong Tai, Alexander Teumer, Nicholas J Timpson, Daniela Toniolo, David-Alexandre Tregouet, Tiinamaija Tuomi, Peter Vollenweider, Carol A Wang, David R Weir, John B Whitfield, Cisca Wijmenga, Tien-Yin Wong, John Wright, Jingyun Yang, Lei Yu, Babette S Zemel, Alan B Zonderman, Markus Perola, Patrik K. E. Magnusson, André G Uitterlinden, Jaspal S Kooner, Daniel I Chasman, Ruth J. F. Loos, Nora Franceschini, Lude Franke, Chris S Haley, Caroline Hayward, Robin G Walters, John R. B. Perry, Tōnu Esko, Agnar Helgason, Kari Stefansson, Peter K Joshi, Michiaki Kubo, and James F Wilson
Subjects: Science
Abstract: Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.
Published: 2019
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9. Associations of statin adherence and lipid targets with adverse outcomes in myocardial infarction survivors: a retrospective cohort study

Author: Sarah Wild, Paul Welsh, Jennifer Logue, Rosemary Brown, and Jim Lewsey
Subjects: Medicine
Published: 2021
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10. What factors explain the much higher diabetes prevalence in Russia compared with Norway? Major sex differences in the contribution of adiposity

Author: Sarah Wild, Anne Elise Eggen, Alexander V Kudryavtsev, and David A Leon
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Introduction Compared with many other countries Russia has a high prevalence of diabetes in men and women. However, contrary to what is found in most other populations, the risk is greater among women than men. The reasons for this are unclear.Research design and methods Prevalence and risk factors for diabetes at ages 40–69 years were compared in two population-based studies: Know Your Heart (KYH) (Russia, 2015–2018, n=4121) and the seventh wave of the Tromsø Study (Tromsø 7) (Norway, 2015–2016, n=17 649). Diabetes was defined by the level of glycated hemoglobin and/or self-reported diabetes and/or diabetes medication use. Marginal structural models were used to estimate the role of key risk factors for diabetes in differences between the studies.Results Age-standardized prevalence of diabetes was higher in KYH compared with Tromsø 7 in men (11.6% vs 6.2%) and in women (13.2% vs 4.3%). Age-adjusted ORs for diabetes in KYH compared with Tromsø 7 were 2.01 (95% CI 1.68 to 2.40) for men and 3.66 (95% CI 3.13 to 4.26) for women. Adiposity (body mass index and waist circumference) explained none of this effect for men but explained 46.0% (39.6, 53.8) for women. Addition of smoking and C reactive protein, as further mediators, slightly increased the percentage explained of the difference between studies to 55.5% (46.5, 66.0) for women but only to 9.9% (−0.6, 20.8) for men.Conclusions Adiposity is a key modifiable risk factor that appears to explain half of the almost threefold higher female prevalence of diabetes in Russia compared with Norway, but none of the twofold male difference.
Published: 2021
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11. Defining remission of type 2 diabetes in research studies: A systematic scoping review.

Author: Mireille Captieux, Regina Prigge, Sarah Wild, and Bruce Guthrie
Subjects: Medicine
Abstract: BackgroundRemission has been identified as a top priority by people with type 2 diabetes. Remission is commonly used as an outcome in research studies; however, a widely accepted definition of remission of type 2 diabetes is lacking. A report on defining remission was published (but not formally endorsed) in Diabetes Care, an American Diabetes Association (ADA) journal. This Diabetes Care report remains widely used. It was the first to suggest 3 components necessary to define the presence of remission: (1) absence of glucose-lowering therapy (GLT); (2) normoglycaemia; and (3) for duration ≥1 year. Our aim is to systematically review how remission of type 2 diabetes has been defined by observational and interventional studies since publication of the 2009 report.Methods and findingsFour databases (MEDLINE, EMBASE, Cochrane Library, and CINAHL) were searched for studies published from 1 September 2009 to 18 July 2020 involving at least 100 participants with type 2 diabetes in their remission analysis, which examined an outcome of type 2 diabetes remission in adults ≥18 years and which had been published in English since 2009. Remission definitions were extracted and categorised by glucose-lowering therapy, glycaemic thresholds, and duration. A total of 8,966 titles/abstracts were screened, and 178 studies (165 observational and 13 interventional) from 33 countries were included. These contributed 266 definitions, of which 96 were unique. The 2009 report was referenced in 121 (45%) definitions. In total, 247 (93%) definitions required the absence of GLT, and 232 (87%) definitions specified numeric glycaemic thresholds. The most frequently used threshold was HbA1cConclusionsWe found that there is substantial heterogeneity in the definition of type 2 diabetes remission in research studies published since 2009, at least partly reflecting ambiguity in the 2009 report. This complicates interpretation of previous research on remission of type 2 diabetes and the implications for people with type 2 diabetes. Any new consensus definition of remission should include unambiguous glycaemic thresholds and emphasise duration. Until an international consensus is reached, studies describing remission should clearly define all 3 components of remission.Systematic review registrationPROSPERO CRD42019144619.
Published: 2020
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12. Risk of acute kidney injury and survival in patients treated with Metformin: an observational cohort study

Author: Samira Bell, Bassam Farran, Stuart McGurnaghan, Rory J. McCrimmon, Graham P Leese, John R Petrie, Paul McKeigue, Naveed Sattar, Sarah Wild, John McKnight, Robert Lindsay, Helen M. Colhoun, and Helen Looker
Subjects: Acute kidney injury, Diabetes, Epidemiology, Metformin, Survival, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Abstract Background Whether metformin precipitates lactic acidosis in patients with chronic kidney disease (CKD) remains under debate. We examined whether metformin use was associated with an increased risk of acute kidney injury (AKI) as a proxy for lactic acidosis and whether survival among those with AKI varied by metformin exposure. Methods All individuals with type 2 diabetes and available prescribing data between 2004 and 2013 in Tayside, Scotland were included. The electronic health record for diabetes which includes issued prescriptions was linked to laboratory biochemistry, hospital admission, death register and Scottish Renal Registry data. AKI events were defined using the Kidney Disease Improving Global Outcomes criteria with a rise in serum creatinine of at least 26.5 μmol/l or a rise of greater than 150% from baseline for all hospital admissions. Cox Regression Analyses were used to examine whether person-time periods in which current metformin exposure occurred were associated with an increased rate of first AKI compared to unexposed periods. Cox regression was also used to compare 28 day survival rates following first AKI events in those exposed to metformin versus those not exposed. Results Twenty-five thousand one-hundred fourty-eight patients were included with a total person-time of 126,904 person years. 4944 (19.7%) people had at least one episode of AKI during the study period. There were 32.4 cases of first AKI/1000pyrs in current metformin exposed person-time periods compared to 44.9 cases/1000pyrs in unexposed periods. After adjustment for age, sex, diabetes duration, calendar time, number of diabetes drugs and baseline renal function, current metformin use was not associated with AKI incidence, HR 0.94 (95% CI 0.87, 1.02, p = 0.15). Among those with incident AKI, being on metformin at admission was associated with a higher rate of survival at 28 days (HR 0.81, 95% CI 0.69, 0.94, p = 0.006) even after adjustment for age, sex, pre-admission eGFR, HbA1c and diabetes duration. Conclusions Contrary to common perceptions, we found no evidence that metformin increases incidence of AKI and was associated with higher 28 day survival following incident AKI.
Published: 2017
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13. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Anne E. Justice, Thomas W. Winkler, Mary F. Feitosa, Misa Graff, Virginia A. Fisher, Kristin Young, Llilda Barata, Xuan Deng, Jacek Czajkowski, David Hadley, Julius S. Ngwa, Tarunveer S. Ahluwalia, Audrey Y. Chu, Nancy L. Heard-Costa, Elise Lim, Jeremiah Perez, John D. Eicher, Zoltán Kutalik, Luting Xue, Anubha Mahajan, Frida Renström, Joseph Wu, Qibin Qi, Shafqat Ahmad, Tamuno Alfred, Najaf Amin, Lawrence F. Bielak, Amelie Bonnefond, Jennifer Bragg, Gemma Cadby, Martina Chittani, Scott Coggeshall, Tanguy Corre, Nese Direk, Joel Eriksson, Krista Fischer, Mathias Gorski, Marie Neergaard Harder, Momoko Horikoshi, Tao Huang, Jennifer E. Huffman, Anne U. Jackson, Johanne Marie Justesen, Stavroula Kanoni, Leena Kinnunen, Marcus E. Kleber, Pirjo Komulainen, Meena Kumari, Unhee Lim, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Ani Manichaikul, Jonathan Marten, Rita P. S. Middelberg, Martina Müller-Nurasyid, Pau Navarro, Louis Pérusse, Natalia Pervjakova, Cinzia Sarti, Albert Vernon Smith, Jennifer A. Smith, Alena Stančáková, Rona J. Strawbridge, Heather M. Stringham, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W. van der Laan, Peter J. van der Most, Jana V. Van Vliet-Ostaptchouk, Sailaja L. Vedantam, Niek Verweij, Jacqueline M. Vink, Veronique Vitart, Ying Wu, Loic Yengo, Weihua Zhang, Jing Hua Zhao, Martina E. Zimmermann, Niha Zubair, Gonçalo R. Abecasis, Linda S. Adair, Saima Afaq, Uzma Afzal, Stephan J. L. Bakker, Traci M. Bartz, John Beilby, Richard N. Bergman, Sven Bergmann, Reiner Biffar, John Blangero, Eric Boerwinkle, Lori L. Bonnycastle, Erwin Bottinger, Daniele Braga, Brendan M. Buckley, Steve Buyske, Harry Campbell, John C. Chambers, Francis S. Collins, Joanne E. Curran, Gert J. de Borst, Anton J. M. de Craen, Eco J. C. de Geus, George Dedoussis, Graciela E. Delgado, Hester M. den Ruijter, Gudny Eiriksdottir, Anna L. Eriksson, Tõnu Esko, Jessica D. Faul, Ian Ford, Terrence Forrester, Karl Gertow, Bruna Gigante, Nicola Glorioso, Jian Gong, Harald Grallert, Tanja B. Grammer, Niels Grarup, Saskia Haitjema, Göran Hallmans, Anders Hamsten, Torben Hansen, Tamara B. Harris, Catharina A. Hartman, Maija Hassinen, Nicholas D. Hastie, Andrew C. Heath, Dena Hernandez, Lucia Hindorff, Lynne J. Hocking, Mette Hollensted, Oddgeir L. Holmen, Georg Homuth, Jouke Jan Hottenga, Jie Huang, Joseph Hung, Nina Hutri-Kähönen, Erik Ingelsson, Alan L. James, John-Olov Jansson, Marjo-Riitta Jarvelin, Min A. Jhun, Marit E. Jørgensen, Markus Juonala, Mika Kähönen, Magnus Karlsson, Heikki A. Koistinen, Ivana Kolcic, Genovefa Kolovou, Charles Kooperberg, Bernhard K. Krämer, Johanna Kuusisto, Kirsti Kvaløy, Timo A. Lakka, Claudia Langenberg, Lenore J. Launer, Karin Leander, Nanette R. Lee, Lars Lind, Cecilia M. Lindgren, Allan Linneberg, Stephane Lobbens, Marie Loh, Mattias Lorentzon, Robert Luben, Gitta Lubke, Anja Ludolph-Donislawski, Sara Lupoli, Pamela A. F. Madden, Reija Männikkö, Pedro Marques-Vidal, Nicholas G. Martin, Colin A. McKenzie, Barbara McKnight, Dan Mellström, Cristina Menni, Grant W. Montgomery, AW (Bill) Musk, Narisu Narisu, Matthias Nauck, Ilja M. Nolte, Albertine J. Oldehinkel, Matthias Olden, Ken K. Ong, Sandosh Padmanabhan, Patricia A. Peyser, Charlotta Pisinger, David J. Porteous, Olli T. Raitakari, Tuomo Rankinen, D. C. Rao, Laura J. Rasmussen-Torvik, Rajesh Rawal, Treva Rice, Paul M. Ridker, Lynda M. Rose, Stephanie A. Bien, Igor Rudan, Serena Sanna, Mark A. Sarzynski, Naveed Sattar, Kai Savonen, David Schlessinger, Salome Scholtens, Claudia Schurmann, Robert A. Scott, Bengt Sennblad, Marten A. Siemelink, Günther Silbernagel, P Eline Slagboom, Harold Snieder, Jan A. Staessen, David J. Stott, Morris A. Swertz, Amy J. Swift, Kent D. Taylor, Bamidele O. Tayo, Barbara Thorand, Dorothee Thuillier, Jaakko Tuomilehto, Andre G. Uitterlinden, Liesbeth Vandenput, Marie-Claude Vohl, Henry Völzke, Judith M. Vonk, Gérard Waeber, Melanie Waldenberger, R. G. J. Westendorp, Sarah Wild, Gonneke Willemsen, Bruce H. R. Wolffenbuttel, Andrew Wong, Alan F. Wright, Wei Zhao, M Carola Zillikens, Damiano Baldassarre, Beverley Balkau, Stefania Bandinelli, Carsten A. Böger, Dorret I. Boomsma, Claude Bouchard, Marcel Bruinenberg, Daniel I. Chasman, Yii-DerIda Chen, Peter S. Chines, Richard S. Cooper, Francesco Cucca, Daniele Cusi, Ulf de Faire, Luigi Ferrucci, Paul W. Franks, Philippe Froguel, Penny Gordon-Larsen, Hans- Jörgen Grabe, Vilmundur Gudnason, Christopher A. Haiman, Caroline Hayward, Kristian Hveem, Andrew D. Johnson, J Wouter Jukema, Sharon L. R. Kardia, Mika Kivimaki, Jaspal S. Kooner, Diana Kuh, Markku Laakso, Terho Lehtimäki, Loic Le Marchand, Winfried März, Mark I. McCarthy, Andres Metspalu, Andrew P. Morris, Claes Ohlsson, Lyle J. Palmer, Gerard Pasterkamp, Oluf Pedersen, Annette Peters, Ulrike Peters, Ozren Polasek, Bruce M. Psaty, Lu Qi, Rainer Rauramaa, Blair H. Smith, Thorkild I. A. Sørensen, Konstantin Strauch, Henning Tiemeier, Elena Tremoli, Pim van der Harst, Henrik Vestergaard, Peter Vollenweider, Nicholas J. Wareham, David R. Weir, John B. Whitfield, James F. Wilson, Jessica Tyrrell, Timothy M. Frayling, Inês Barroso, Michael Boehnke, Panagiotis Deloukas, Caroline S. Fox, Joel N. Hirschhorn, David J. Hunter, Tim D. Spector, David P. Strachan, Cornelia M. van Duijn, Iris M. Heid, Karen L. Mohlke, Jonathan Marchini, Ruth J. F. Loos, Tuomas O. Kilpeläinen, Ching-Ti Liu, Ingrid B. Borecki, Kari E. North, and L Adrienne Cupples
Subjects: Science
Abstract: Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.
Published: 2017
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14. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author: Yingchang Lu, Felix R. Day, Stefan Gustafsson, Martin L. Buchkovich, Jianbo Na, Veronique Bataille, Diana L. Cousminer, Zari Dastani, Alexander W. Drong, Tõnu Esko, David M. Evans, Mario Falchi, Mary F. Feitosa, Teresa Ferreira, Åsa K. Hedman, Robin Haring, Pirro G. Hysi, Mark M. Iles, Anne E. Justice, Stavroula Kanoni, Vasiliki Lagou, Rui Li, Xin Li, Adam Locke, Chen Lu, Reedik Mägi, John R. B. Perry, Tune H. Pers, Qibin Qi, Marianna Sanna, Ellen M. Schmidt, William R. Scott, Dmitry Shungin, Alexander Teumer, Anna A. E. Vinkhuyzen, Ryan W. Walker, Harm-Jan Westra, Mingfeng Zhang, Weihua Zhang, Jing Hua Zhao, Zhihong Zhu, Uzma Afzal, Tarunveer Singh Ahluwalia, Stephan J. L. Bakker, Claire Bellis, Amélie Bonnefond, Katja Borodulin, Aron S. Buchman, Tommy Cederholm, Audrey C. Choh, Hyung Jin Choi, Joanne E. Curran, Lisette C. P. G. M. de Groot, Philip L. De Jager, Rosalie A. M. Dhonukshe-Rutten, Anke W. Enneman, Elodie Eury, Daniel S. Evans, Tom Forsen, Nele Friedrich, Frédéric Fumeron, Melissa E. Garcia, Simone Gärtner, Bok-Ghee Han, Aki S. Havulinna, Caroline Hayward, Dena Hernandez, Hans Hillege, Till Ittermann, Jack W. Kent, Ivana Kolcic, Tiina Laatikainen, Jari Lahti, Irene Mateo Leach, Christine G. Lee, Jong-Young Lee, Tian Liu, Youfang Liu, Stéphane Lobbens, Marie Loh, Leo-Pekka Lyytikäinen, Carolina Medina-Gomez, Karl Michaëlsson, Mike A. Nalls, Carrie M. Nielson, Laticia Oozageer, Laura Pascoe, Lavinia Paternoster, Ozren Polašek, Samuli Ripatti, Mark A. Sarzynski, Chan Soo Shin, Nina Smolej Narančić, Dominik Spira, Priya Srikanth, Elisabeth Steinhagen-Thiessen, Yun Ju Sung, Karin M. A. Swart, Leena Taittonen, Toshiko Tanaka, Emmi Tikkanen, Nathalie van der Velde, Natasja M. van Schoor, Niek Verweij, Alan F. Wright, Lei Yu, Joseph M. Zmuda, Niina Eklund, Terrence Forrester, Niels Grarup, Anne U. Jackson, Kati Kristiansson, Teemu Kuulasmaa, Johanna Kuusisto, Peter Lichtner, Jian'an Luan, Anubha Mahajan, Satu Männistö, Cameron D. Palmer, Janina S. Ried, Robert A. Scott, Alena Stancáková, Peter J. Wagner, Ayse Demirkan, Angela Döring, Vilmundur Gudnason, Douglas P. Kiel, Brigitte Kühnel, Massimo Mangino, Barbara Mcknight, Cristina Menni, Jeffrey R. O'Connell, Ben A. Oostra, Alan R. Shuldiner, Kijoung Song, Liesbeth Vandenput, Cornelia M. van Duijn, Peter Vollenweider, Charles C. White, Michael Boehnke, Yvonne Boettcher, Richard S. Cooper, Nita G. Forouhi, Christian Gieger, Harald Grallert, Aroon Hingorani, Torben Jørgensen, Pekka Jousilahti, Mika Kivimaki, Meena Kumari, Markku Laakso, Claudia Langenberg, Allan Linneberg, Amy Luke, Colin A. Mckenzie, Aarno Palotie, Oluf Pedersen, Annette Peters, Konstantin Strauch, Bamidele O. Tayo, Nicholas J. Wareham, David A. Bennett, Lars Bertram, John Blangero, Matthias Blüher, Claude Bouchard, Harry Campbell, Nam H. Cho, Steven R. Cummings, Stefan A. Czerwinski, Ilja Demuth, Rahel Eckardt, Johan G. Eriksson, Luigi Ferrucci, Oscar H. Franco, Philippe Froguel, Ron T. Gansevoort, Torben Hansen, Tamara B. Harris, Nicholas Hastie, Markku Heliövaara, Albert Hofman, Joanne M. Jordan, Antti Jula, Mika Kähönen, Eero Kajantie, Paul B. Knekt, Seppo Koskinen, Peter Kovacs, Terho Lehtimäki, Lars Lind, Yongmei Liu, Eric S. Orwoll, Clive Osmond, Markus Perola, Louis Pérusse, Olli T. Raitakari, Tuomo Rankinen, D. C. Rao, Treva K. Rice, Fernando Rivadeneira, Igor Rudan, Veikko Salomaa, Thorkild I. A. Sørensen, Michael Stumvoll, Anke Tönjes, Bradford Towne, Gregory J. Tranah, Angelo Tremblay, André G. Uitterlinden, Pim van der Harst, Erkki Vartiainen, Jorma S. Viikari, Veronique Vitart, Marie-Claude Vohl, Henry Völzke, Mark Walker, Henri Wallaschofski, Sarah Wild, James F. Wilson, Loïc Yengo, D. Timothy Bishop, Ingrid B. Borecki, John C. Chambers, L. Adrienne Cupples, Abbas Dehghan, Panos Deloukas, Ghazaleh Fatemifar, Caroline Fox, Terrence S. Furey, Lude Franke, Jiali Han, David J. Hunter, Juha Karjalainen, Fredrik Karpe, Robert C. Kaplan, Jaspal S. Kooner, Mark I. McCarthy, Joanne M. Murabito, Andrew P. Morris, Julia A. N. Bishop, Kari E. North, Claes Ohlsson, Ken K. Ong, Inga Prokopenko, J. Brent Richards, Eric E. Schadt, Tim D. Spector, Elisabeth Widén, Cristen J. Willer, Jian Yang, Erik Ingelsson, Karen L. Mohlke, Joel N. Hirschhorn, John Andrew Pospisilik, M. Carola Zillikens, Cecilia Lindgren, Tuomas Oskari Kilpeläinen, and Ruth J. F. Loos
Subjects: Science
Abstract: A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.
Published: 2016
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15. Correction: Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

Author: Mariaelisa Graff, Robert A Scott, Anne E Justice, Kristin L Young, Mary F Feitosa, Llilda Barata, Thomas W Winkler, Audrey Y Chu, Anubha Mahajan, David Hadley, Luting Xue, Tsegaselassie Workalemahu, Nancy L Heard-Costa, Marcel den Hoed, Tarunveer S Ahluwalia, Qibin Qi, Julius S Ngwa, Frida Renström, Lydia Quaye, John D Eicher, James E Hayes, Marilyn Cornelis, Zoltan Kutalik, Elise Lim, Jian'an Luan, Jennifer E Huffman, Weihua Zhang, Wei Zhao, Paula J Griffin, Toomas Haller, Shafqat Ahmad, Pedro M Marques-Vidal, Stephanie Bien, Loic Yengo, Alexander Teumer, Albert Vernon Smith, Meena Kumari, Marie Neergaard Harder, Johanne Marie Justesen, Marcus E Kleber, Mette Hollensted, Kurt Lohman, Natalia V Rivera, John B Whitfield, Jing Hua Zhao, Heather M Stringham, Leo-Pekka Lyytikäinen, Charlotte Huppertz, Gonneke Willemsen, Wouter J Peyrot, Ying Wu, Kati Kristiansson, Ayse Demirkan, Myriam Fornage, Maija Hassinen, Lawrence F Bielak, Gemma Cadby, Toshiko Tanaka, Reedik Mägi, Peter J van der Most, Anne U Jackson, Jennifer L Bragg-Gresham, Veronique Vitart, Jonathan Marten, Pau Navarro, Claire Bellis, Dorota Pasko, Åsa Johansson, Søren Snitker, Yu-Ching Cheng, Joel Eriksson, Unhee Lim, Mette Aadahl, Linda S Adair, Najaf Amin, Beverley Balkau, Juha Auvinen, John Beilby, Richard N Bergman, Sven Bergmann, Alain G Bertoni, John Blangero, Amélie Bonnefond, Lori L Bonnycastle, Judith B Borja, Søren Brage, Fabio Busonero, Steve Buyske, Harry Campbell, Peter S Chines, Francis S Collins, Tanguy Corre, George Davey Smith, Graciela E Delgado, Nicole Dueker, Marcus Dörr, Tapani Ebeling, Gudny Eiriksdottir, Tõnu Esko, Jessica D Faul, Mao Fu, Kristine Færch, Christian Gieger, Sven Gläser, Jian Gong, Penny Gordon-Larsen, Harald Grallert, Tanja B Grammer, Niels Grarup, Gerard van Grootheest, Kennet Harald, Nicholas D Hastie, Aki S Havulinna, Dena Hernandez, Lucia Hindorff, Lynne J Hocking, Oddgeir L Holmens, Christina Holzapfel, Jouke Jan Hottenga, Jie Huang, Tao Huang, Jennie Hui, Cornelia Huth, Nina Hutri-Kähönen, Alan L James, John-Olov Jansson, Min A Jhun, Markus Juonala, Leena Kinnunen, Heikki A Koistinen, Ivana Kolcic, Pirjo Komulainen, Johanna Kuusisto, Kirsti Kvaløy, Mika Kähönen, Timo A Lakka, Lenore J Launer, Benjamin Lehne, Cecilia M Lindgren, Mattias Lorentzon, Robert Luben, Michel Marre, Yuri Milaneschi, Keri L Monda, Grant W Montgomery, Marleen H M De Moor, Antonella Mulas, Martina Müller-Nurasyid, A W Musk, Reija Männikkö, Satu Männistö, Narisu Narisu, Matthias Nauck, Jennifer A Nettleton, Ilja M Nolte, Albertine J Oldehinkel, Matthias Olden, Ken K Ong, Sandosh Padmanabhan, Lavinia Paternoster, Jeremiah Perez, Markus Perola, Annette Peters, Ulrike Peters, Patricia A Peyser, Inga Prokopenko, Hannu Puolijoki, Olli T Raitakari, Tuomo Rankinen, Laura J Rasmussen-Torvik, Rajesh Rawal, Paul M Ridker, Lynda M Rose, Igor Rudan, Cinzia Sarti, Mark A Sarzynski, Kai Savonen, William R Scott, Serena Sanna, Alan R Shuldiner, Steve Sidney, Günther Silbernagel, Blair H Smith, Jennifer A Smith, Harold Snieder, Alena Stančáková, Barbara Sternfeld, Amy J Swift, Tuija Tammelin, Sian-Tsung Tan, Barbara Thorand, Dorothée Thuillier, Liesbeth Vandenput, Henrik Vestergaard, Jana V van Vliet-Ostaptchouk, Marie-Claude Vohl, Uwe Völker, Gérard Waeber, Mark Walker, Sarah Wild, Andrew Wong, Alan F Wright, M Carola Zillikens, Niha Zubair, Christopher A Haiman, Loic Lemarchand, Ulf Gyllensten, Claes Ohlsson, Albert Hofman, Fernando Rivadeneira, André G Uitterlinden, Louis Pérusse, James F Wilson, Caroline Hayward, Ozren Polasek, Francesco Cucca, Kristian Hveem, Catharina A Hartman, Anke Tönjes, Stefania Bandinelli, Lyle J Palmer, Sharon L R Kardia, Rainer Rauramaa, Thorkild I A Sørensen, Jaakko Tuomilehto, Veikko Salomaa, Brenda W J H Penninx, Eco J C de Geus, Dorret I Boomsma, Terho Lehtimäki, Massimo Mangino, Markku Laakso, Claude Bouchard, Nicholas G Martin, Diana Kuh, Yongmei Liu, Allan Linneberg, Winfried März, Konstantin Strauch, Mika Kivimäki, Tamara B Harris, Vilmundur Gudnason, Henry Völzke, Lu Qi, Marjo-Riitta Järvelin, John C Chambers, Jaspal S Kooner, Philippe Froguel, Charles Kooperberg, Peter Vollenweider, Göran Hallmans, Torben Hansen, Oluf Pedersen, Andres Metspalu, Nicholas J Wareham, Claudia Langenberg, David R Weir, David J Porteous, Eric Boerwinkle, Daniel I Chasman, CHARGE Consortium, EPIC-InterAct Consortium, PAGE Consortium, Gonçalo R Abecasis, Inês Barroso, Mark I McCarthy, Timothy M Frayling, Jeffrey R O'Connell, Cornelia M van Duijn, Michael Boehnke, Iris M Heid, Karen L Mohlke, David P Strachan, Caroline S Fox, Ching-Ti Liu, Joel N Hirschhorn, Robert J Klein, Andrew D Johnson, Ingrid B Borecki, Paul W Franks, Kari E North, L Adrienne Cupples, Ruth J F Loos, and Tuomas O Kilpeläinen
Subjects: Genetics, QH426-470
Abstract: [This corrects the article DOI: 10.1371/journal.pgen.1006528.].
Published: 2017
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16. Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

Author: Mariaelisa Graff, Robert A Scott, Anne E Justice, Kristin L Young, Mary F Feitosa, Llilda Barata, Thomas W Winkler, Audrey Y Chu, Anubha Mahajan, David Hadley, Luting Xue, Tsegaselassie Workalemahu, Nancy L Heard-Costa, Marcel den Hoed, Tarunveer S Ahluwalia, Qibin Qi, Julius S Ngwa, Frida Renström, Lydia Quaye, John D Eicher, James E Hayes, Marilyn Cornelis, Zoltan Kutalik, Elise Lim, Jian'an Luan, Jennifer E Huffman, Weihua Zhang, Wei Zhao, Paula J Griffin, Toomas Haller, Shafqat Ahmad, Pedro M Marques-Vidal, Stephanie Bien, Loic Yengo, Alexander Teumer, Albert Vernon Smith, Meena Kumari, Marie Neergaard Harder, Johanne Marie Justesen, Marcus E Kleber, Mette Hollensted, Kurt Lohman, Natalia V Rivera, John B Whitfield, Jing Hua Zhao, Heather M Stringham, Leo-Pekka Lyytikäinen, Charlotte Huppertz, Gonneke Willemsen, Wouter J Peyrot, Ying Wu, Kati Kristiansson, Ayse Demirkan, Myriam Fornage, Maija Hassinen, Lawrence F Bielak, Gemma Cadby, Toshiko Tanaka, Reedik Mägi, Peter J van der Most, Anne U Jackson, Jennifer L Bragg-Gresham, Veronique Vitart, Jonathan Marten, Pau Navarro, Claire Bellis, Dorota Pasko, Åsa Johansson, Søren Snitker, Yu-Ching Cheng, Joel Eriksson, Unhee Lim, Mette Aadahl, Linda S Adair, Najaf Amin, Beverley Balkau, Juha Auvinen, John Beilby, Richard N Bergman, Sven Bergmann, Alain G Bertoni, John Blangero, Amélie Bonnefond, Lori L Bonnycastle, Judith B Borja, Søren Brage, Fabio Busonero, Steve Buyske, Harry Campbell, Peter S Chines, Francis S Collins, Tanguy Corre, George Davey Smith, Graciela E Delgado, Nicole Dueker, Marcus Dörr, Tapani Ebeling, Gudny Eiriksdottir, Tõnu Esko, Jessica D Faul, Mao Fu, Kristine Færch, Christian Gieger, Sven Gläser, Jian Gong, Penny Gordon-Larsen, Harald Grallert, Tanja B Grammer, Niels Grarup, Gerard van Grootheest, Kennet Harald, Nicholas D Hastie, Aki S Havulinna, Dena Hernandez, Lucia Hindorff, Lynne J Hocking, Oddgeir L Holmens, Christina Holzapfel, Jouke Jan Hottenga, Jie Huang, Tao Huang, Jennie Hui, Cornelia Huth, Nina Hutri-Kähönen, Alan L James, John-Olov Jansson, Min A Jhun, Markus Juonala, Leena Kinnunen, Heikki A Koistinen, Ivana Kolcic, Pirjo Komulainen, Johanna Kuusisto, Kirsti Kvaløy, Mika Kähönen, Timo A Lakka, Lenore J Launer, Benjamin Lehne, Cecilia M Lindgren, Mattias Lorentzon, Robert Luben, Michel Marre, Yuri Milaneschi, Keri L Monda, Grant W Montgomery, Marleen H M De Moor, Antonella Mulas, Martina Müller-Nurasyid, A W Musk, Reija Männikkö, Satu Männistö, Narisu Narisu, Matthias Nauck, Jennifer A Nettleton, Ilja M Nolte, Albertine J Oldehinkel, Matthias Olden, Ken K Ong, Sandosh Padmanabhan, Lavinia Paternoster, Jeremiah Perez, Markus Perola, Annette Peters, Ulrike Peters, Patricia A Peyser, Inga Prokopenko, Hannu Puolijoki, Olli T Raitakari, Tuomo Rankinen, Laura J Rasmussen-Torvik, Rajesh Rawal, Paul M Ridker, Lynda M Rose, Igor Rudan, Cinzia Sarti, Mark A Sarzynski, Kai Savonen, William R Scott, Serena Sanna, Alan R Shuldiner, Steve Sidney, Günther Silbernagel, Blair H Smith, Jennifer A Smith, Harold Snieder, Alena Stančáková, Barbara Sternfeld, Amy J Swift, Tuija Tammelin, Sian-Tsung Tan, Barbara Thorand, Dorothée Thuillier, Liesbeth Vandenput, Henrik Vestergaard, Jana V van Vliet-Ostaptchouk, Marie-Claude Vohl, Uwe Völker, Gérard Waeber, Mark Walker, Sarah Wild, Andrew Wong, Alan F Wright, M Carola Zillikens, Niha Zubair, Christopher A Haiman, Loic Lemarchand, Ulf Gyllensten, Claes Ohlsson, Albert Hofman, Fernando Rivadeneira, André G Uitterlinden, Louis Pérusse, James F Wilson, Caroline Hayward, Ozren Polasek, Francesco Cucca, Kristian Hveem, Catharina A Hartman, Anke Tönjes, Stefania Bandinelli, Lyle J Palmer, Sharon L R Kardia, Rainer Rauramaa, Thorkild I A Sørensen, Jaakko Tuomilehto, Veikko Salomaa, Brenda W J H Penninx, Eco J C de Geus, Dorret I Boomsma, Terho Lehtimäki, Massimo Mangino, Markku Laakso, Claude Bouchard, Nicholas G Martin, Diana Kuh, Yongmei Liu, Allan Linneberg, Winfried März, Konstantin Strauch, Mika Kivimäki, Tamara B Harris, Vilmundur Gudnason, Henry Völzke, Lu Qi, Marjo-Riitta Järvelin, John C Chambers, Jaspal S Kooner, Philippe Froguel, Charles Kooperberg, Peter Vollenweider, Göran Hallmans, Torben Hansen, Oluf Pedersen, Andres Metspalu, Nicholas J Wareham, Claudia Langenberg, David R Weir, David J Porteous, Eric Boerwinkle, Daniel I Chasman, CHARGE Consortium, EPIC-InterAct Consortium, PAGE Consortium, Gonçalo R Abecasis, Inês Barroso, Mark I McCarthy, Timothy M Frayling, Jeffrey R O'Connell, Cornelia M van Duijn, Michael Boehnke, Iris M Heid, Karen L Mohlke, David P Strachan, Caroline S Fox, Ching-Ti Liu, Joel N Hirschhorn, Robert J Klein, Andrew D Johnson, Ingrid B Borecki, Paul W Franks, Kari E North, L Adrienne Cupples, Ruth J F Loos, and Tuomas O Kilpeläinen
Subjects: Genetics, QH426-470
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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17. Farming, Foreign Holidays, and Vitamin D in Orkney.

Author: Emily Weiss, Lina Zgaga, Stephanie Read, Sarah Wild, Malcolm G Dunlop, Harry Campbell, Ruth McQuillan, and James F Wilson
Subjects: Medicine, Science
Abstract: Orkney, north of mainland Scotland, has the world's highest prevalence of multiple sclerosis (MS); vitamin D deficiency, a marker of low UV exposure, is also common in Scotland. Strong associations have been identified between vitamin D deficiency and MS, and between UV exposure and MS independent of vitamin D, although causal relationships remain to be confirmed. We aimed to compare plasma 25-hydroxyvitamin D levels in Orkney and mainland Scotland, and establish the determinants of vitamin D status in Orkney. We compared mean vitamin D and prevalence of deficiency in cross-sectional study data from participants in the Orkney Complex Disease Study (ORCADES) and controls in the Scottish Colorectal Cancer Study (SOCCS). We used multivariable regression to identify factors associated with vitamin D levels in Orkney. Mean (standard deviation) vitamin D was significantly higher among ORCADES than SOCCS participants (35.3 (18.0) and 31.7 (21.2), respectively). Prevalence of severe vitamin D deficiency was lower in ORCADES than SOCCS participants (6.6% to 16.2% p = 1.1 x 10(-15)). Older age, farming occupations and foreign holidays were significantly associated with higher vitamin D in Orkney. Although mean vitamin D levels are higher in Orkney than mainland Scotland, this masks variation within the Orkney population which may influence MS risk.
Published: 2016
Full Text: View/download PDF

18. Impact of telemetry supported home blood pressure monitoring: experiences of patients and professionals participating in the HITS randomised controlled trial of telemetry enabled home blood pressure (BP)

Author: Janet Hanley, Jenny Ure, Mary Paterson, Sarah Wild, Paul Padfield, Claudia Pagliari, and Brian McKinstry
Subjects: blood pressure monitoring, primary care, Medicine (General), R5-920
Published: 2012

19. Localising loci underlying complex trait variation using Regional Genomic Relationship Mapping.

Author: Yoshitaka Nagamine, Ricardo Pong-Wong, Pau Navarro, Veronique Vitart, Caroline Hayward, Igor Rudan, Harry Campbell, James Wilson, Sarah Wild, Andrew A Hicks, Peter P Pramstaller, Nicholas Hastie, Alan F Wright, and Chris S Haley
Subjects: Medicine, Science
Abstract: The limited proportion of complex trait variance identified in genome-wide association studies may reflect the limited power of single SNP analyses to detect either rare causative alleles or those of small effect. Motivated by studies that demonstrate that loci contributing to trait variation may contain a number of different alleles, we have developed an analytical approach termed Regional Genomic Relationship Mapping that, like linkage-based family methods, integrates variance contributed by founder gametes within a pedigree. This approach takes advantage of very distant (and unrecorded) relationships, and this greatly increases the power of the method, compared with traditional pedigree-based linkage analyses. By integrating variance contributed by founder gametes in the population, our approach provides an estimate of the Regional Heritability attributable to a small genomic region (e.g. 100 SNP window covering ca. 1 Mb of DNA in a 300000 SNP GWAS) and has the power to detect regions containing multiple alleles that individually contribute too little variance to be detectable by GWAS as well as regions with single common GWAS-detectable SNPs. We use genome-wide SNP array data to obtain both a genome-wide relationship matrix and regional relationship ("identity by state" or IBS) matrices for sequential regions across the genome. We then estimate a heritability for each region sequentially in our genome-wide scan. We demonstrate by simulation and with real data that, when compared to traditional ("individual SNP") GWAS, our method uncovers new loci that explain additional trait variation. We analysed data from three Southern European populations and from Orkney for exemplar traits - serum uric acid concentration and height. We show that regional heritability estimates are correlated with results from genome-wide association analysis but can capture more of the genetic variance segregating in the population and identify additional trait loci.
Published: 2012
Full Text: View/download PDF

20. Quantifying Health Inequalities Induced by Data and AI Models.

Author: Honghan Wu, Aneeta Sylolypavan, Minhong Wang 0002, and Sarah Wild
Published: 2022
Full Text: View/download PDF

21. Zivilrecht und Token-Ökonomie in Liechtenstein: Eine Analyse der zivilrechtlichen Bestimmungen des TVTG unter Berücksichtigung des Wertrechts

Author: Sarah Wild and Sarah Wild
Published: 2020

22. Leaving academia for industry? Here’s how to handle salary negotiations

Author: Sarah Wild
Subjects: Multidisciplinary
Published: 2023

23. Depression, diabetes, comorbid depression and diabetes and risk of all-cause and cause-specific mortality: a prospective cohort study

Author: Sarah Wild, Regina Prigge, and Caroline Jackson
Subjects: Diabetes Mellitus, Type 2, Cardiovascular Diseases, Depression, Risk Factors, Cause of Death, Neoplasms, Endocrinology, Diabetes and Metabolism, Internal Medicine, Humans, Prospective Studies, Proportional Hazards Models
Abstract: Aims/hypothesis The aim of this study was to investigate the risks of all-cause and cause-specific mortality among participants with neither, one or both of diabetes and depression in a large prospective cohort study in the UK. Methods Our study population included 499,830 UK Biobank participants without schizophrenia and bipolar disorder at baseline. Type 1 and type 2 diabetes and depression were identified using self-reported diagnoses, prescribed medication and hospital records. Mortality was identified from death records using the primary cause of death to define cause-specific mortality. We performed Cox proportional hazards models to estimate the risk of all-cause mortality and mortality from cancer, circulatory disease and causes of death other than circulatory disease or cancer among participants with either depression (n=41,791) or diabetes (n=22,677) alone and with comorbid diabetes and depression (n=3597) compared with the group with neither condition (n=431,765), adjusting for sociodemographic and lifestyle factors, comorbidities and history of CVD or cancer. We also investigated the interaction between diabetes and depression. Results During a median of 6.8 (IQR 6.1–7.5) years of follow-up, there were 13,724 deaths (cancer, n=7976; circulatory disease, n=2827; other causes, n=2921). Adjusted HRs of all-cause mortality and mortality from cancer, circulatory disease and other causes were highest among people with comorbid depression and diabetes (HRs 2.16 [95% CI 1.94, 2.42]; 1.62 [95% CI 1.35, 1.93]; 2.22 [95% CI 1.80, 2.73]; and 3.60 [95% CI 2.93, 4.42], respectively). The risks of all-cause, cancer and other mortality among those with comorbid depression and diabetes exceeded the sum of the risks due to diabetes and depression alone. Conclusions/interpretation We confirmed that depression and diabetes individually are associated with an increased mortality risk and also identified that comorbid depression and diabetes have synergistic effects on the risk of all-cause mortality that are largely driven by deaths from cancer and causes other than circulatory disease and cancer. Graphical abstract
Published: 2022

24. A plan to improve global type 1 diabetes epidemiology data

Author: David Beran, Kurt Højlund, Stéphane Besançon, Mads Loftager Mundt, Graham D Ogle, Kaushik Ramaiya, Tom Robinson, Jannet Svensson, Jaakko Tuomilehto, Sarah Wild, and Anders Green
Subjects: Endocrinology, Diabetes Mellitus, Type 2/epidemiology, Endocrinology, Diabetes and Metabolism, Diabetes Mellitus, Type 1/epidemiology, Internal Medicine, Humans
Published: 2023

25. Conservation setbacks? The secrets to lifting morale

Author: Sarah Wild
Subjects: Multidisciplinary
Published: 2023

26. Assessing Representativeness of Randomised Controlled Trials using Serious Adverse Events

Author: Peter Hanlon, Sofia Dias, David McAllister, Sarah Wild, Frances Mair, Bruce Guthrie, Elaine Butterly, Nicky Welton, and Laurie Hannigan
Published: 2023

27. ‘Great scientific step forward’: Construction of world’s largest radio observatory is finally under way

Author: Sarah Wild
Subjects: Multidisciplinary
Published: 2022

28. Calibrating a network meta-analysis of diabetes trials of sodium glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor analogues and dipeptidyl peptidase-4 inhibitors to a representative routine population: a systematic review protocol

Author: Elaine Butterly, Lili Wei, Amanda I Adler, Saleh A M Almazam, Khalid Alsallumi, Luke A K Blackbourn, Sofia Dias, Peter Hanlon, Katherine Hughes, Jim Lewsey, Robert Lindsay, Stuart McGurnaghan, John Petrie, David Phillippo, Naveed Sattar, Laurie A Tomlinson, Nicky Welton, Sarah Wild, and David McAllister
Subjects: Dipeptidyl-Peptidase IV Inhibitors, Diabetes Mellitus, Type 2/drug therapy, Sodium-Glucose Transporter 2 Inhibitors/therapeutic use, Network Meta-Analysis, Hypoglycemic Agents/therapeutic use, General Medicine, Glucagon-Like Peptide-1 Receptor, Diabetes Mellitus, Type 2, Meta-Analysis as Topic, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/therapeutic use, Humans, Hypoglycemic Agents, Dipeptidyl-Peptidase IV Inhibitors/therapeutic use, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Sodium-Glucose Transporter 2 Inhibitors, Systematic Reviews as Topic
Abstract: IntroductionParticipants in randomised controlled trials (trials) are generally younger and healthier than many individuals encountered in clinical practice. Consequently, the applicability of trial findings is often uncertain. To address this, results from trials can be calibrated to more representative data sources. In a network meta-analysis, using a novel approach which allows the inclusion of trials whether or not individual-level participant data (IPD) is available, we will calibrate trials for three drug classes (sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) receptor analogues and dipeptidyl peptidase-4 (DPP4) inhibitors) to the Scottish diabetes register.Methods and analysisMedline and EMBASE databases, the US clinical trials registry (clinicaltrials.gov) and the Chinese Clinical Trial Registry (chictr.org.cn) will be searched from 1 January 2002. Two independent reviewers will apply eligibility criteria to identify trials for inclusion. Included trials will be phase 3 or 4 trials of SGLT2 inhibitors, GLP1 receptor analogues or DPP4 inhibitors, with placebo or active comparators, in participants with type 2 diabetes, with at least one of glycaemic control, change in body weight or major adverse cardiovascular event as outcomes. Unregistered trials will be excluded.We have identified a target population from the population-based Scottish diabetes register. The chosen cohort comprises people in Scotland with type 2 diabetes who either (1) require further treatment due to poor glycaemic control where any of the three drug classes may be suitable, or (2) who have adequate glycaemic control but are already on one of the three drug classes of interest or insulin.Ethics and disseminationEthical approval for IPD use was obtained from the University of Glasgow MVLS College Ethics Committee (Project: 200160070). The Scottish diabetes register has approval from the Scottish A Research Ethics Committee (11/AL/0225) and operates with Public Benefit and Privacy Panel for Health and Social Care approval (1617-0147).PROSPERO registration numberCRD42020184174.
Published: 2022

29. Cohort profile:the Scottish Diabetes Research Network national diabetes cohort – a population-based cohort of people with diabetes in Scotland

Author: Stuart J. McGurnaghan, Luke A. K. Blackbourn, Thomas M. Caparrotta, Joseph Mellor, Anna Barnett, Andy Collier, Naveed Sattar, John McKnight, John Petrie, Sam Philip, Robert Lindsay, Katherine Hughes, David McAllister, Graham P Leese, Ewan R Pearson, Sarah Wild, Paul M McKeigue, and Helen M Colhoun
Subjects: Scotland/epidemiology, Diabetes Mellitus, Type 2, Scotland, Naphthalenesulfonates, Diabetes Mellitus, Type 2/complications, COVID-19, Humans, Insulin Glargine, General Medicine, Middle Aged, Sodium-Glucose Transporter 2 Inhibitors, Diabetic Ketoacidosis
Abstract: PurposeThe Scottish Diabetes Research Network (SDRN)-diabetes research platform was established to combine disparate electronic health record data into research-ready linked datasets for diabetes research in Scotland. The resultant cohort, ‘The SDRN-National Diabetes Dataset (SDRN-NDS)’, has many uses, for example, understanding healthcare burden and socioeconomic trends in disease incidence and prevalence, observational pharmacoepidemiology studies and building prediction tools to support clinical decision making.ParticipantsWe estimate that >99% of those diagnosed with diabetes nationwide are captured into the research platform. Between 2006 and mid-2020, the cohort comprised 472 648 people alive with diabetes at any point in whom there were 4 million person-years of follow-up. Of the cohort, 88.1% had type 2 diabetes, 8.8% type 1 diabetes and 3.1% had other types (eg, secondary diabetes). Data are captured from all key clinical encounters for diabetes-related care, including diabetes clinic, primary care and podiatry and comprise clinical history and measurements with linkage to blood results, microbiology, prescribed and dispensed drug and devices, retinopathy screening, outpatient, day case and inpatient episodes, birth outcomes, cancer registry, renal registry and causes of death.Findings to dateThere have been >50 publications using the SDRN-NDS. Examples of recent key findings include analysis of the incidence and relative risks for COVID-19 infection, drug safety of insulin glargine and SGLT2 inhibitors, life expectancy estimates, evaluation of the impact of flash monitors on glycaemic control and diabetic ketoacidosis and time trend analysis showing that diabetic ketoacidosis (DKA) remains a major cause of death under age 50 years. The findings have been used to guide national diabetes strategy and influence national and international guidelines.Future plansThe comprehensive SDRN-NDS will continue to be used in future studies of diabetes epidemiology in the Scottish population. It will continue to be updated at least annually, with new data sources linked as they become available.
Published: 2022

30. Where is the UK science minister? Government’s plans worry researchers

Author: Sarah Wild
Subjects: Multidisciplinary
Published: 2022

31. Estimating individual lifetime risk of incident cardiovascular events in adults with type 2 diabetes: an update and geographical calibration of the DIAbetes Lifetime perspective model (DIAL2)

Author: Helena Bleken Østergaard, Steven H J Hageman, Stephanie H Read, Owen Taylor, Lisa Pennells, Stephen Kaptoge, Carmen Petitjean, Zhe Xu, Fanchao Shi, John William McEvoy, William Herrington, Frank L J Visseren, Angela Wood, Björn Eliasson, Naveed Sattar, Sarah Wild, Emanuele Di Angelantonio, and Jannick A N Dorresteijn
Subjects: cardiovascular disease, Epidemiology, Type 2 diabetes, prediction, Cardiology and Cardiovascular Medicine
Abstract: Aims The 2021 European Society of Cardiology cardiovascular disease (CVD) prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding intensified preventive treatment options in adults with Type 2 diabetes, e.g. the DIAbetes Lifetime perspective model (DIAL model). The aim of this study was to update the DIAL model using contemporary and representative registry data (DIAL2) and to systematically calibrate the model for use in other European countries. Methods and results The DIAL2 model was derived in 467 856 people with Type 2 diabetes without a history of CVD from the Swedish National Diabetes Register, with a median follow-up of 7.3 years (interquartile range: 4.0–10.6 years) and comprising 63 824 CVD (including fatal CVD, non-fatal stroke and non-fatal myocardial infarction) events and 66 048 non-CVD mortality events. The model was systematically recalibrated to Europe’s low- and moderate-risk regions using contemporary incidence data and mean risk factor distributions. The recalibrated DIAL2 model was externally validated in 218 267 individuals with Type 2 diabetes from the Scottish Care Information—Diabetes (SCID) and Clinical Practice Research Datalink (CPRD). In these individuals, 43 074 CVD events and 27 115 non-CVD fatal events were observed. The DIAL2 model discriminated well, with C-indices of 0.732 [95% confidence interval (CI) 0.726–0.739] in CPRD and 0.700 (95% CI 0.691–0.709) in SCID. Conclusion The recalibrated DIAL2 model provides a useful tool for the prediction of CVD-free life expectancy and lifetime CVD risk for people with Type 2 diabetes without previous CVD in the European low- and moderate-risk regions. These long-term individualized measures of CVD risk are well suited for shared decision-making in clinical practice as recommended by the 2021 CVD ESC prevention guidelines.
Published: 2022

32. P32 Quality of diabetes care in people with and without prior hospitalisation for serious mental illness: a retrospective national cohort study

Author: Caroline Jackson, Stine Scheuer, Kelly Fleetwood, Kirsty Licence, Stewart Mercer, Daniel Smith, Cathie Sudlow, Gregers Anderson, and Sarah Wild
Published: 2022

33. Lifestyle interventions for type 2 diabetes prevention in children and adolescents of African descent in OECD countries:a systematic review protocol

Author: Damilola, Iduye, Sarah, Wild, Kayla, Ostrishko, Marilyn, Macdonald, Melissa, Helwig, Steve, Iduye, and Keisha, Jefferies
Subjects: Adolescent, pediatrics, Black People, diabetes prevention, prediabetes, Review Literature as Topic, Diabetes Mellitus, Type 2, Meta-Analysis as Topic, Behavior Therapy, OECD, Humans, African/Black/Afro-Caribbean people, Child, Life Style, Organisation for Economic Co-Operation and Development, General Nursing
Abstract: OBJECTIVES: The objectives of this review are to investigate the effectiveness of lifestyle interventions for type 2 diabetes prevention in children and adolescents of African descent in the Organization for Economic Co-operation and Development (OECD) member countries and to attempt to ascertain what aspects of these interventions are most effective in this population.INTRODUCTION: Lifestyle interventions have been shown to prevent or delay the onset of type 2 diabetes; however, the extent to which these interventions are effective for children and adolescents of African descent is not well established. The increasing type 2 diabetes incidence and prevalence in children and adolescents of African descent in some OECD member countries underscores the need to pool available evidence to ascertain the effectiveness of lifestyle interventions for type 2 diabetes prevention in this population.INCLUSION CRITERIA: Lifestyle interventions to be considered include individual- or group-based lifestyle or behavioral modification interventions aimed at preventing or delaying the onset of type 2 diabetes in children and adolescents of African descent aged 19 years and under in OECD countries. Randomized controlled trials and non-randomized studies that assess the effectiveness of lifestyle interventions for type 2 diabetes prevention will be considered.METHODS: The databases to be searched include MEDLINE (Ovid), Embase (Elsevier), CINAHL (EBSCO), PsycINFO (EBSCO), Social Services Abstracts, Cochrane Central Register of Controlled Trials (CENTRAL; Wiley), and ProQuest Dissertations and Theses Global databases. Two independent reviewers will conduct the titles, abstracts, and full-text screening, then followed by critical appraisal and data extraction. Data will undergo meta-analysis where appropriate, and otherwise narrative synthesis.SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO registration number CRD42021247267.
Published: 2022

34. David Beckitt

Author: Sarah Wild
Subjects: General Medicine
Published: 2023

35. Depression, diabetes, their comorbidity and all-cause and cause-specific mortality: a prospective cohort study

Author: Sarah Wild, Regina Prigge, and Caroline Jackson
Abstract: Aims/hypothesisTo investigate the risk of all-cause and cause-specific mortality among participants with neither, one, or both of diabetes and depression in a large prospective cohort study in the United Kingdom.MethodsOur study population included 499,830 UK Biobank participants without schizophrenia and bipolar disorder at baseline. Type 1 or type 2 diabetes and depression were identified using self-reported diagnoses, prescribed medication and hospital records. Mortality was identified from death records using the primary cause of death to define cause-specific mortality. We performed Cox proportional hazards models to estimate the risk of all-cause mortality and mortality due to cancer, circulatory disease and causes of death other than circulatory disease or cancer among participants with either depression (n=41,791) or diabetes alone (n=22,677) and with comorbid diabetes and depression (n=3,597), compared to the group with neither condition (n=431,765) adjusting for sociodemographic and lifestyle factors, comorbidities, and history of CVD or cancer. We investigated for interaction between diabetes and depression.ResultsDuring a median of 6.8 (IQR: 6.1 – 7.5) years of follow-up, there were 13,724 deaths (cancer (n=7,976), circulatory disease (n=2,827), and other causes (n=2,921)). Adjusted hazard ratios of all-cause mortality and mortality due to cancer, circulatory disease and other causes were highest among people with comorbid depression and diabetes (HRs 2.16, 95% CI 1.94 – 2.42; 1.62, 95% CI 1.35 – 1.93; 2.22 95% CI 1.80 – 2.73 and 3.60, 95% CI 2.93 – 4.42, respectively). Among those with comorbid diabetes and depression, the risks of all-cause, cancer and other mortality exceeded the sum of the risks due to diabetes and depression alone.Conclusions/interpretationWe confirmed the negative impact of depression and diabetes on mortality outcomes, and also identified that comorbid depression and diabetes had synergistic effects on all-cause mortality which was largely driven by deaths due to cancer and causes other than circulatory disease and cancer.RESEARCH IN CONTEXTWhat is already known about this subject?-Comorbid depression is common in individuals with diabetes and associated with increased risks of all-cause and cardiovascular mortality-The mortality risk among people with comorbid diabetes and depression might exceed the sum of the risks associated with each disorder alone-There is limited knowledge about the individual and joint effects of depression and diabetes on risk of death from specific causes.What is the key question?-What is the risk of all-cause and cause-specific mortality associated with neither, one, or both of diabetes (of any type) and depression?What are the new findings?-In a large prospective cohort study in the United Kingdom, comorbid depression and diabetes had synergistic effects on all-cause mortality which was largely driven by deaths due to cancer and causes other than circulatory disease and cancerHow might this impact on clinical practice in the foreseeable future?-These findings help identify individuals at high risk of adverse events, and suggest a need for cost-effective interventions to support psychological well-being and risk reduction in people with diabetes
Published: 2022

36. The individual and combined associations of depression and socioeconomic status with risk of major cardiovascular events: a prospective cohort study

Author: Sarah Wild, Regina Prigge, and Caroline Jackson
Abstract: ObjectiveWe aimed to investigate the individual and combined associations of depression and low socioeconomic status (SES) with risk of major cardiovascular events (MCVE), defined as first-ever fatal or non-fatal stroke or myocardial infarction, in a large prospective cohort study.MethodsWe used data from 466,238 UK Biobank participants, aged 40 – 69 years without cardiovascular disease, bipolar disorder or schizophrenia at baseline. We performed Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) of the individual and combined associations of depression and each of educational attainment, area-based deprivation and income with risk of MCVE. We assessed effect modification and explored interaction on the additive and multiplicative scale.ResultsDepression, low education, high area-based deprivation and low income were individually associated with increased risks of MCVE (adjusted HR, 95% CI: 1.28, 1.19 – 1.38; 1.20, 1.14 – 1.27; 1.17, 1.11 – 1.23; and 1.22, 1.16 – 1.29, respectively). Depression was associated with increased risks of MCVE among individuals with high and low SES. Individuals with depression and each of low education, high area-based deprivation and low income were at particularly high risk of MCVE (HR, 95% CI: 1.50, 1.38 – 1.63; 1.63, 1.46 – 1.82; 1.31, 1.23 – 1.40, respectively). There was interaction between depression and area-based deprivation on multiplicative and additive scales but no interaction with education or income.ConclusionDepression was associated with increased risks of MCVE among individuals with high and low SES, with particularly high risks among those living in areas of high deprivation.
Published: 2022

37. TP5.2.9 Mortality following major lower extremity amputation in people with and without diabetes in Scotland 2004-2013

Author: Ellen Murgitroyd, Xuehan Yao, Jan Kerssens, Jeremy Walker, and Sarah Wild
Subjects: Surgery
Abstract: Aim To describe short and longer-term mortality following major lower extremity amputation (LEA) by diabetes status over two time periods. Methods A retrospective cohort study of patients who underwent major LEA between 2004 and 2013 was conducted based on linkage of national population-based hospital records and a register of people with diagnosed diabetes. Post-operative mortality was estimated at 30 days, one year and where available, five years. Using logistic regression models, we estimated the odds of death associated with diabetes adjusted for age, sex and socio-economic status within these time points compared to the non-diabetic population stratified by type of diabetes and five-year calendar periods. Results There were a total of 5436 people who received an amputation during the study period of whom approximately 40% had diabetes. Overall mortality for the 2004-8 and 2009-13 cohorts respectively was not significantly different at 7.9% and 7.3% at 30 days and 31% and 27% at one year. Almost 64% of the 2004-8 cohort were dead within five years. The only statistically significantly associations between diabetes and mortality were observed within five year follow-up of the 2004-8 cohort with odds ratios (95% CI) compared to the non-diabetic population of 1.62 (1.17, 2.26) for type 1 diabetes and 1.38 (1.14, 1.66) for type 2 diabetes. Conclusions An adverse association between diabetes and mortality after LEA only became apparent in longer term follow-up.
Published: 2021

38. Epidemiology and Public Health

Author: Sarah Wild and Jackie Price
Abstract: Epidemiological studies provide valuable information about the definition, incidence, and prevalence of diabetes and its complications and their risk factors. Prevalence of diabetes is increasing globally as a consequence of ageing populations and increasing urbanization and obesity. Incidence of type 2 diabetes is falling in some developed countries, but prevalence continues to increase as a consequence of increasing survival. Differences between populations in prevalence of diabetes have provided important information in understanding the aetiology of diabetes and in developing approaches to prevention and treatment. However, there are still considerable gaps in our knowledge of the epidemiology of diabetes and in how we apply existing knowledge about effective approaches to the prevention of diabetes and its complications at a population level. Complications of diabetes results in major costs to individuals, health systems, and societies.
Published: 2021

39. Wellcome says it has perpetuated ‘systemic racism’ in science

Author: Sarah Wild
Subjects: Multidisciplinary
Published: 2022

40. No link between depression and serotonin, finds major analysis

Author: Sarah Wild
Subjects: Multidisciplinary
Published: 2022

41. Physics in South Africa

Author: Sarah Wild
Subjects: Library science
Published: 2020

42. How to Decolonize South African Physics

Author: Sarah Wild
Subjects: Anthropology, Decolonization
Published: 2020

43. 207 Taking practice to the peripheries on Neuro-ICU

Author: James Sira, Sidra A Awan, and Sarah Wild
Subjects: Inotrope, medicine.medical_specialty, business.industry, medicine.medical_treatment, Pharmacy, Intensive care unit, Discontinuation, law.invention, law, Shock (circulatory), Emergency medicine, Cohort, medicine, medicine.symptom, Adverse effect, business, Central venous catheter
Abstract: Introduction Vasopressors are integral for the management of shock and haemodynamic augmentation. The early initiation of vasoactive treatment is associated with improved survival; however, the placement of a central venous catheter is identified as a barrier to the implementation of early goal-directed therapy. Considerations of initiating Noradrenaline peripherally raised concerns around complications including tissue necrosis as well as the potential for prescribing and administration errors. This caused persistent resistance for the change of management on critical care. Aim Introduce peripheral administration of Noradrenaline on ICU (different dose, concentration, diluent and site). Strategy of Improvement and Measurement: The project took seven months with approvals from the Drugs and Therapeutics committee. Each risk reduction strategy created had ideas incorporated from medicines safety champions within the nursing, pharmacy and medical cohort. Feedback was taken on board, and processes adapted with staff being recognised for their contribution. Results Type of shock Hypovolaemic/haemorrhagic: 40/50 Cardiogenic: 3/50 Septic: 7/50 Duration of infusion of Noradrenaline, Median (IQR) • 30 hours (14,52) Reason for discontinuation: Infusion changed to a central venous catheter: 9 (18%) Vasopressor no longer required: 38 (76%) Patient deceased: 2 (4%) Adverse effect (extravasation): 1(2%) Prescribing errors (diluents, dose, rate): 0% Administration errors (diluents, dose, site, rate): 0% Conclusion The initial challenge was resolved with the outcome being the nurses feeling empowered through knowledge of evidence-based medicine. This, in turn, resulted in a working force with excellent knowledge and approach towards pharmacological management, which further developed self-confidence in their capabilities and roles. The overall safety culture surrounding peripheral inotropes on the critical care unit has been enhanced.
Published: 2020

44. Major African radio telescope will help to image black holes

Author: Sarah Wild
Subjects: Multidisciplinary
Published: 2022

45. South Africa slashes science budget, funds for giant radio telescope

Author: Sarah Wild
Subjects: Radio telescope, Multidisciplinary, Geography, Astronomy
Published: 2020

46. Acoustic Diode Hits the Perfect Note

Author: Sarah Wild
Subjects: Physics, Optics, business.industry, business, Diode
Published: 2020

47. This powerful observatory studying the formation of galaxies is getting a massive, $54 million expansion

Author: Sarah Wild
Subjects: Multidisciplinary, Observatory, Galaxy formation and evolution, Astronomy, Geology
Published: 2020

48. Green Light for Terahertz Movies

Author: Sarah Wild
Subjects: Physics, business.industry, Terahertz radiation, Optoelectronics, Green-light, business
Published: 2020

49. COVID-19 Disease in People with Diabetes in Scotland: Incidence, Severity and Risk Stratification Using Matched Case-Control and Prospective Cohort Studies

Author: Stuart J McGurnaghan, Amanda Weir, Jen Bishop, Sharon Kennedy, Luke AK Blackbourn, Sharon Hutchinson, Thomas M Caparrotta, Joseph Mellor, Anita Jeyam, Joseph E O’Reilly, Sarah Wild, Sara Hatam, Andreas Höhn, Marco Colombo, Chris Robertson, Nazir I. Lone, Janet Murray, Elaine Butterly, John Petrie, Brian Kennon, Rory McCrimmon, Robert Lindsay, Ewan Pearson, Naveed Sattar, John McKnight, Ashirwad Philip Samuel, Andrew Collier, Jim McMenamin, Alison Smith-Palmer, David Goldberg, Paul M McKeigue, Helen M Colhoun, and Scottish Diabetes Research Network Group
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Incidence (epidemiology), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Disease, medicine.disease, Internal medicine, Diabetes mellitus, Risk stratification, Medicine, Prospective cohort study, business
Abstract: Background: The risks of, and risk factors for, COVID-19 disease associated with diabetes are poorly quantified brbrMethods: We identified as cases all th
Published: 2020

50. REPRINT OF: CLASSIFICATION OF DIABETES MELLITUS

Author: Amanda Adler, Peter Bennett, Stephen Colagiuri Chair, Edward Gregg, KM Venkat Narayan, Maria Inês Schmidt, Eugene Sobngwi, Naoko Tajima, Nikhil Tandon, Nigel Unwin, Sarah Wild, John Yudkin, Naomi Levitt, Viswanathan Mohan, Sarah Montgomery, Moffat J Nyirenda, Jaakko Tuomilehto, Saskia Den Boon, and Samantha Hocking
Subjects: Type 1 diabetes, medicine.medical_specialty, Executive summary, business.industry, Endocrinology, Diabetes and Metabolism, MEDLINE, General Medicine, Type 2 diabetes, medicine.disease, World health, Endocrinology, Categorization, Family medicine, Diabetes mellitus, Internal Medicine, Etiology, Medicine, business
Abstract: Executive Summary This document updates the 1999 World Health Organization (WHO) classification of diabetes. It prioritizes clinical care and guides health professionals in choosing appropriate treatments at the time of diabetes diagnosis, and provides practical guidance to clinicians in assigning a type of diabetes to individuals at the time of diagnosis. It is a compromise between clinical and aetiological classification because there remain gaps in knowledge of the aetiology and pathophysiology of diabetes. While acknowledging the progress that is being made towards a more precise categorization of diabetes subtypes, the aim of this document is to recommend a classification that is feasible to implement in different settings throughout the world. The revised classification is presented in Table 1. Unlike the previous classification, this classification does not recognize subtypes of type 1 diabetes and type 2 diabetes and includes new types of diabetes ("hybrid types of diabetes" and "unclassified diabetes").
Published: 2021

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