351 results on '"Colhoun H."'
Search Results
52. Hypertension management in primary prevention Type 2 diabetic patients in the Collaborative Atorvastatin Diabetes Study (CARDS)
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Thomason, M. J., Livingstone, S. J., Betteridge, D. J., Colhoun, H. M., Durrington, P. N., Hitman, G. A., Neil, H. A. W., and Fuller, J. H.
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- 2003
53. Design of the Collaborative AtoRvastatin Diabetes Study (CARDS) in patients with Type 2 diabetes
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Colhoun, H. M., Thomason, M. J., Mackness, M. I., Maton, S. M., Betteridge, D. J., Durrington, P. N., Hitman, G. A., Neil, H. A. W., and Fuller, J. H.
- Published
- 2002
54. vWF activity, endothelial nitric oxide production and atherosclerosis in type 1 diabetes
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CHAN, N N, VALLANCE, P, FULLER, J H, and COLHOUN, H M
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- 2001
55. ALTERED CENTRAL HAEMODYNAMIC PARAMETERS DERIVED FROM RESERVOIR PRESSURE ANALYSIS
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Aizawa, K., Casanova, F., Mawson, D. M., Gooding, K. M., Strain, W. D., Gates, P. E., Östling, G., Khan, F., Colhoun, H. M., Palombo, C., Parker, K. H., Nilsson, J., Shore, A. C., and Hughes, A. D.
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- 2019
56. The effect of DAFNE education, continuous subcutaneous insulin infusion, or both in a population with type 1 diabetes in Scotland
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McKnight, J. A., primary, Ochs, A., additional, Mair, C., additional, McKnight, O., additional, Wright, R., additional, Gibb, F. W., additional, Cunningham, S. G., additional, Strachan, M., additional, Ritchie, S., additional, McGurnaghan, S. J., additional, and Colhoun, H. M., additional
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- 2020
- Full Text
- View/download PDF
57. Risk stratification for diabetic eye screening. Reply to Stratton I. M. and Aldington S. J. [letter]
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Looker, H. C., Nyangoma, S. O., Cromie, D. T., Olson, J. A., Leese, G. P., Philip, S., Black, M. W., Doig, J., Lee, N., Briggs, A., Hothersall, E. J., Morris, A. D., Lindsay, R. S., McKnight, J. A., Pearson, D. W. M., Sattar, N. A., Wild, S. H., McKeigue, P., Colhoun, H. M., and on behalf of the Scottish Diabetes Research Network Epidemiology Group and the Scottish Diabetic Retinopathy Collaborative
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- 2014
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58. Blood lead concentrations in United Kingdom have fallen substantially since 1984
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Delves, H. T., Diaper, S. J., Oppert, S., Prescott-Clarke, P., Periam, J., Dong, W., Colhoun, H., and Gompertz, D.
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- 1996
59. A genome-wide association study suggested that the mitogen-activated protein kinase 14 gene (MAPK14) is associated with diabetic foot ulcer
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Meng, W, Veluchamy, A, Hébert, H L, Campbell, A, Colhoun, H M, and Palmer, C N A
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Journal Article - Abstract
BACKGROUND: Diabetic foot ulcer (DFU) is a devastating complication of diabetes.OBJECTIVES: We aimed to identify genetic contributors of DFU based on a genome-wide association study approach using a Scottish diabetic cohort.METHODS: A genome-wide association approach was applied. A case was defined as a diabetic patient (type 1 or type 2) who had ever been recorded in the linked e-health records as having a foot ulcer (current or previous) in at least one foot as well as a positive result of the monofilament test in the longitudinal e-health records. A control in this study was defined as a diabetic individual (type 1 or type 2) who has never been recorded as having a foot ulcer in either foot in the linked e-health records and the monofilament test results of any foot was once recorded to be positive in the longitudinal e-health records.RESULTS: We have 699 DFU cases and 2,695 controls in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) dataset. The lowest P value of rs80028505 (Chr6p21.31) in the MAPK14 gene was 2.45x10(-8) . The narrow-sense heritability of this phenotype is 0.06.CONCLUSIONS: We suggest that the MAPK14 gene is associated with DFU. This article is protected by copyright. All rights reserved.
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- 2017
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60. Socio‐economic status and mortality in people with type 1 diabetes in Scotland 2006–2015: a retrospective cohort study.
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Campbell, R. A. S., Colhoun, H. M., Kennon, B., McCrimmon, R. J., Sattar, N., McKnight, J., and Wild, S. H
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TYPE 1 diabetes , *LONGITUDINAL method , *MEDICAL records , *SEX distribution , *SOCIOECONOMIC factors , *RETROSPECTIVE studies , *ACQUISITION of data methodology - Abstract
Aims: To describe the association between socio‐economic status and mortality in a nation‐wide cohort of people with type 1 diabetes in Scotland and to compare patterns over time and with the general population. Methods: A retrospective cohort study was performed using data for people with type 1 diabetes from a population‐based register linked to mortality records. Socio‐economic status was derived from quintiles of an area‐based measure: the Scottish Index of Multiple Deprivation. Sex‐specific directly age‐standardized mortality rates for each Scottish Index of Multiple Deprivation quintile and rate ratios comparing the most vs least deprived quintile were calculated for two time periods: 2006–2010 and 2011–2015. Data for the population without type 1 diabetes between 2011 and 2015 were available for comparison. Results: Data for 3802 deaths among 33 547 people with type 1 diabetes were available. The age‐standardized mortality rate per 1000 person‐years decreased over time (from 2006–2010 to 2011–2015) for men and women with type 1 diabetes: 24.8 to 20.2 and 22.5 to 17.6, respectively. Mortality in populations with and without type 1 diabetes was generally higher for men than women and was inversely associated with socio‐economic status. Rate ratios for the most vs least deprived groups increased over time among people with type 1 diabetes (men: 2.49 to 2.81; women: 1.92 to 2.86) and were higher than among populations without type 1 diabetes in 2011–2015 (men: 2.06; women: 1.66). Conclusions: Socio‐economic deprivation was associated with a steeper mortality gradient in people with type 1 diabetes than in the population without type 1 diabetes in Scotland. Age‐standardized mortality has decreased over time but socio‐economic inequalities may be increasing. What's new?: The socio‐economic gradient in mortality within the general population and in type 2 diabetes is established. Scandinavian population‐based cohort studies of people with type 1 diabetes have reported an inverse association between socio‐economic status and mortality but there are no contemporary data for the UK.This study found that socio‐economic deprivation was associated with higher mortality in people with type 1 diabetes in Scotland, that the effect of deprivation was larger than in the general population and that inequalities appear to be widening over time.Effective interventions to reduce socio‐economic inequalities in outcomes of type 1 diabetes are required. [ABSTRACT FROM AUTHOR]
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- 2020
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61. The cost of prevalent and incident cardiovascular disease in people with type 2 diabetes in Scotland: data from the Scottish Care Information–Diabetes Collaboration.
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McMeekin, P., Geue, C., Mocevic, E., Hoxer, C. S., Ochs, A., McGurnaghan, S., Colhoun, H. M., Wild, S. H., and Wu, O.
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CONFIDENCE intervals ,MEDICAL care costs ,CARDIOVASCULAR diseases ,DISEASE incidence ,TYPE 2 diabetes ,COST analysis ,SCOTS ,DESCRIPTIVE statistics ,DATA analysis software - Abstract
Aim: To compare costs for three groups of people with type 2 diabetes, those at high risk of future cardiovascular disease, those without cardiovascular disease and those with established cardiovascular disease, and to also compare costs incurred by people with type 2 diabetes with an incident cardiovascular disease event with those who remain incident event‐free over a 3‐year period. Methods: Data about people with type 2 diabetes in Scotland were obtained from the Scottish Care Information Diabetes registry. Data linkage was used to retrieve information on healthcare utilization, care home use and deaths. Productivity effects were estimated for those of non‐pensionable age. We estimated costs over 12 months (prevalent cardiovascular disease) and 3 years from incident cardiovascular disease event. Results: Mean annual cost per person with established cardiovascular disease was £6900, £3300 for a person at high risk of future cardiovascular disease, and £2500 for a person without cardiovascular disease and not at high risk. In year 1, the cost of an incident cardiovascular disease event was £16 700 compared with £2100 for people without an incident event. Over 2 years, the cumulative costs were £21 500 and £4200, and by year 3, £25 000 and £5900, respectively. Conclusions: Cardiovascular disease in people with type 2 diabetes places a significant financial burden on healthcare and the wider economy. Our results emphasize the financial consequences of cardiovascular disease prevention strategies. What's new?: People with type 2 diabetes are at an elevated risk of being affected by cardiovascular disease.Cardiovascular disease is the leading cause of co‐morbidity and death among people with type 2 diabetes.Cost comparisons are usually between two groups of people with type 2 diabetes, those with and without cardiovascular disease.The majority of studies take a cardiovascular disease prevalence‐based approach to estimating the cost of illness. [ABSTRACT FROM AUTHOR]
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- 2020
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62. Socio‐economic differences in cardiovascular disease risk factor prevalence in people with type 2 diabetes in Scotland: a cross‐sectional study.
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Whittaker, E., Read, S. H., Colhoun, H. M., Lindsay, R. S., McGurnaghan, S., McKnight, J. A., Sattar, N., and Wild, S. H.
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BLOOD pressure ,CARDIOVASCULAR diseases risk factors ,CHOLESTEROL ,CONFIDENCE intervals ,PEOPLE with diabetes ,GLYCOSYLATED hemoglobin ,HEALTH services accessibility ,HEALTH status indicators ,TYPE 2 diabetes ,SMOKING ,LOGISTIC regression analysis ,PSYCHOSOCIAL factors ,SOCIOECONOMIC factors ,BODY mass index ,DISEASE prevalence ,CROSS-sectional method ,DESCRIPTIVE statistics ,ODDS ratio - Abstract
Aim: To describe the association between socio‐economic status and prevalence of key cardiovascular risk factors in people with type 2 diabetes in Scotland. Methods: A cross‐sectional study of 264 011 people with type 2 diabetes in Scotland in 2016 identified from the population‐based diabetes register. Socio‐economic status was defined using quintiles of the area‐based Scottish Index of Multiple Deprivation (SIMD) with quintile (Q)1 and Q5 used to identify the most‐ and least‐deprived fifths of the population, respectively. Logistic regression models adjusted for age, sex, health board, history of cardiovascular disease and duration of diabetes were used to estimate odds ratios (ORs) for Q1 compared with Q5 for each risk factor. Results: The mean (sd) age of the study population was 66.7 (12.8) years, 56% were men, 24% were in Q1 and 15% were in Q5. Crude prevalence in Q1/Q5 was 24%/8.8% for smoking, 62%/49% for BMI ≥ 30 kg/m2, 44%/40% for HbA1c ≥ 58 mmol/mol (7.5%), 31%/31% for systolic blood pressure (SBP) ≥ 140 mmHg, and 24%/25% for total cholesterol ≥ 5 mmol/l, respectively. ORs [95% confidence intervals (CI)] were 3.08 (2.95–3.21) for current smoking, 1.48 (1.44–1.52) for BMI ≥ 30 kg/m2, 1.11 (1.08–1.15) for HbA1c ≥ 58 mmol/mol (7.5%), 1.03 (1.00–1.06) for SBP ≥ 140 mmHg and 0.87 (0.84–0.90) for total cholesterol ≥ 5 mmol/l. Conclusions: Socio‐economic deprivation is associated with higher prevalence of smoking, BMI ≥ 30 kg/m2 and HbA1c ≥ 58 mmol/mol (7.5%), and lower prevalence of total cholesterol ≥ 5 mmol/l among people with type 2 diabetes in Scotland. Effective approaches to reducing inequalities are required as well as reducing risk factor prevalence across the whole population. What's new?: Socio‐economic deprivation is associated with increased risk of cardiovascular disease in people with diabetes.This study, using a national database of quarter of a million people, found that socio‐economic deprivation is strongly positively associated with smoking and obesity, modestly positively associated with above‐target HbA1c, and modestly negatively associated with above‐target cholesterol, with no evidence of an association with above‐target blood pressure.Inequalities appear to have widened over time.Our findings may enable more effective interventions to reduce these inequalities by targeted approaches in subgroups of the population. [ABSTRACT FROM AUTHOR]
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- 2020
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63. Cardiovascular disease prevalence and risk factor prevalence in Type 2 diabetes: a contemporary analysis
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McGurnaghan, S., primary, Blackbourn, L. A. K., additional, Mocevic, E., additional, Haagen Panton, U., additional, McCrimmon, R. J., additional, Sattar, N., additional, Wild, S., additional, and Colhoun, H. M., additional
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- 2018
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64. Body weight variability and cardiovascular outcomes in patients with type 2 diabetes
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Waters, D., primary, Fayyad, R., additional, Colhoun, H., additional, Demicco, D., additional, and Bangalore, S., additional
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- 2018
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65. New genetic loci link adipose and insulin biology to body fat distribution
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Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, Cooper, R, Dedoussis, G, Ferrucci, L, Froguel, P, Grabe, H, Hamsten, A, Hui, J, Hveem, K, Jöckel, K, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, März, W, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Pe'Russe, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sinisalo, J, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Van Der Harst, P, Veronesi, G, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Abecasis, G, Assimes, T, Berndt, S, Boehnke, M, Borecki, I, Deloukas, P, Franke, L, Frayling, T, Groop, L, Hunter, D, Kaplan, R, O'Connell, J, Qi, L, Schlessinger, D, Strachan, D, Stefansson, K, Van Duijn, C, Willer, C, Visscher, P, Yang, J, Hirschhorn, J, Zillikens, M, Mccarthy, M, Speliotes, E, North, K, Fox, C, Barroso, I, Franks, P, Ingelsson, E, Heid, I, Loos, R, Cupples, L, Lindgren, C, Mohlke, K, Dastani, Z, Timpson, N, Yuan, X, Henneman, P, Kizer, J, Lyytikainen, L, Fuchsberger, C, Small, K, Coassin, S, Lohman, K, Pankow, J, Uh, H, Wu, Y, Bidulescu, A, Rasmussen Torvik, L, Greenwood, C, Ladouceur, M, Grimsby, J, Manning, A, Mooser, V, Kapur, K, Frants, R, Willemsvan vanDijk, K, Willems, S, Psaty, B, Tracy, R, Brody, J, Chen, I, Viikari, J, Kähönen, M, Evans, D, St Pourcain, B, Sattar, N, Carlson, O, Egan, J, van Heemst, D, Kedenko, L, Nuotio, M, Loo, B, Kanaya, A, Haun, M, Klopp, N, Katsareli, E, Couper, D, Duncan, B, Kloppenburg, M, Borja, J, Musani, S, Guo, X, Semple, R, Teslovich, T, Allison, M, Redline, S, Buxbaum, S, Meulenbelt, I, Ballantyne, C, Hu, F, Paulweber, B, Florez, J, Smith, G, Siscovick, D, Kronenberg, F, van Duijn, C, Waterworth, D, Meigs, J, Dupuis, J, Richards, J, Willenborg, C, Thompson, J, Erdmann, J, Goldstein, B, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikäinen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Cox, D, Dimitriou, M, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Peden, J, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Basart, H, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Goodall, A, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kim, H, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Hovingh, G, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Kathiresan, S, Roberts, R, Schunkert, H, Pattaro, C, Köttgen, A, Garnaas, M, Böger, C, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Döring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Wright, A, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Völzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Krämer, B, Portas, L, Ford, I, Buckley, B, Adam, M, Thun, G, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Gasparini, P, 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- Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
- Published
- 2015
66. Genetic studies of body mass index yield new insights for obesity biology
- Author
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S., El Mokhtari N., Fontanillas P., Hager J., Han B. G., Hunt S. E., Kang H. M., Kessler T., Knowles J. W., Kolovou G., Langford C., Lokki M. L., Lundmark A., Meisinger C., Melander O., Maouche S., Nikus K., Rasheed A., Rosinger S., Rubin D., Rumpf M. P., Schafer A., Sivananthan M., Song C., Stewart A. F., Thorgeirsson G., van der Schoot C. E., Wagner P. J., Wells G. A., Wild P. S., Tsun-Po Y., Basart H. V., Brambilla P., Cambien F., Cupples A. L., Dehghan A., Diemert P., Epstein S. E., Evans A., Ferrario M., Gauguier D., Hazen S. L., Holm H., Iribarren C., Jang Y., Kahonen M., Kee F., Kim H. S., Klopp N., Kuulasmaa K., Laaksonen R., Ouwehand W. H., Parish S., Park J. E., Rader D. J., Shah S. H., Stark K., Wallentin L., Zimmermann M. E., Nieminen M. S., Sandhu M. S., Pastinen T., Zalloua P. A., Siegbahn A., Schreiber S., Ripatti S., Blankenberg S. S., O'donnell C. J., Reilly M., Collins R., Roberts R., Pattaro C., Kottgen A., Garnaas M., Boger C. A., Fuchsberger C., Olden M., Chen M. H., Tin A., Taliun D., Li M., Gao X., Yang Q., Hundertmark C., Foster M. C., O'seaghdha C. M., Glazer N. L., Liu C. T., Struchalin M., Li G., Johnson A. D., Gierman H. J., Hwang S. J., Atkinson E. J., Lohman K. K., Cornelis M. C., Chouraki V., Holliday E. G., Sorice R., Deshmukh H., Ulivi S., Chu A. Y., Murgia F., Imboden M., Kollerits B., Pistis G., Launer L. J., Aspelund T., Eiriksdottir G., Mitchell B. D., Schmidt H., Cavalieri M., Rao M., Hu F. B., de Andrade M., Turner S. T., Ding J., Andrews J. S., Freedman B. I., Doring A., Kolcic I., Zemunik T., Boban M., Minelli C., Wheeler H. E., Igl W., Zaboli G., Wild S. H., Ellinghaus D., Nothlings U., Jacobs G., Biffar R., Endlich K., Ernst F., Kroemer H. K., Nauck M., Stracke S., Volzke H., Aulchenko Y., Polasek O., Hastie N. D., Vitart V., Helmer C., Wang J. J., Ruggiero D., Bergmann S., Viikari J., Nikopensius T., Province M. A., Ketkar S., Colhoun H. M., Doney A., Robino A., Giulianini F., Kramer B. K., Portas L., Buckley B. M., Adam M., Thun G. A., Paulweber B., Haun M., Sala C., Metzger M., Mitchell P., Ciullo M., Kim S. K., Vollenweider P., Palmer C., Gasparini P., Pirastu M., Probst-Hensch N. M., Kronenberg F., Toniolo D., Coresh J., Schmidt R., Siscovick D. S., Kardia S. L., Curhan G., Franke A., Parsa A., Goessling W., Kao W. H., de Boer I. H., Peralta C. A., Akylbekova E., Kramer H., Arking D. E., Franceschini N., Egan J., Hernandez D. G., Townsend R. R., Lumley T., Psaty B. M., Kestenbaum B., Haritunians T., Mooser V., Florez J. C., Meigs J. B., Lu X., Leak T. S., Aasarod K., Skorpen F., Baumert J., Devuyst O., Mychaleckyj J. C., Kedenko L., Coassin S., Hallan S., Navis G., Shlipak M. G., Bull S. B., Paterson A. D., Rotter J. I., Dreisbach A. W., Anderson C. A., Guo Q., Henders A., Lambert A., Lee S. H., Kraft P., Kennedy S. H., Macgregor S., Missmer S. A., Painter J. N., Roseman F., Treloar S. A., Wallace L., Forsblom C., Isakova T., McKay G. J., Williams W. W., Sadlier D. M., Makinen V. P., Swan E. J., Boright A. P., Ahlqvist E., Keller B. J., Huang H., Ahola A., Fagerholm E., Gordin D., Harjutsalo V., He B., Heikkila O., Hietala K., Kyto J., Lahermo P., Lehto M., Osterholm A. M., Parkkonen M., Pitkaniemi J., Rosengard-Barlund M., Saraheimo M., Sarti C., Soderlund J., Soro-Paavonen A., Syreeni A., Thorn L. M., Tikkanen H., Tolonen N., Tryggvason K., Waden J., Gill G. V., Prior S., Guiducci C., Mirel D. B., Taylor A., Hosseini M., Parving H. H., Rossing P., Tarnow L., Ladenvall C., Alhenc-Gelas F., Lefebvre P., Rigalleau V., Roussel R., Maestroni A., Maestroni S., Falhammar H., Gu T., Mollsten A., Cimponeriu D., Mihai I., Mota M., Mota E., Serafinceanu C., Stavarachi M., Hanson R. L., Nelson R. G., Kretzler M., Panduru N. M., Gu H. F., Brismar K., Zerbini G., Hadjadj S., Marre M., Lajer M., Waggott D., Savage D. A., Bain S. C., Martin F., Godson C., Groop P. H., Maxwell A. P., Sengupta S., Peloso G. M., Ganna A., Mora S., Chang H. Y., Den Hertog H. M., Donnelly L. A., Freitag D. F., Gurdasani D., Heikkila K., Johnson T., Kaakinen M., Kettunen J., Li X., Montasser M. E., Petersen A. K., Saxena R., Service S. K., Sidore C., Surakka I., Teslovich T. M., Van den Herik E. G., Volcik K. A., Wu Y., Asiki G., Been L. F., Burnett M. S., Elliott P., Eyjolfsson G. I., Goodarzi M. O., Gravito M. L., Hartikainen A. L., Hung Y. J., Jones M. R., Kaleebu P., Khaw K. T., Kim E., Komulainen P., Lin S. Y., Narisu N., Nieminen T. V., Nsubuga R. N., Olafsson I., Palotie A., Papamarkou T., Pomilla C., Pouta A., Ruokonen A., Seeley J., Silander K., Tiret L., van Pelt L., Wainwright N., Wijmenga C., Young E. H., Bennett F., Boomsma D. I., Burnier M., Chen Y. D., Feranil A. B., Freimer N. B., Hsiung C. A., Kesaniemi A., Koudstaal P. J., Krauss R. M., Kyvik K. O., Meneton P., Moilanen L., Sanghera D. K., Sheu W. H., Whitfield J. B., Wolffenbuttel B. H., Ordovas J. M., Rich S. S., Johnson A., Johnson L., Larson M., Levy D., Newton-Cheh C., O'reilly P., Palmas W., Rice K., Smith A., Snider H., Tobin M., Verwoert G., Rice K. M., Verwoert G. C., Pihur V., Heath S., Sober S., Arora P., Zhang F., Lucas G., Milaneschi Y., Parker A. N., Fava C., Fox E. R., Go M. J., Sjogren M., Vinay D., Alexander M., Tabara Y., Shaw-Hawkins S., Whincup P. H., Shi G., Seielstad M., Sim X., Nguyen K. D., Matullo G., Gaunt T. R., Onland-Moret N. C., Cooper M. N., Platou C. G., Org E., Hardy R., Dahgam S., Palmen J., Kuznetsova T., Uiterwaal C. S., Adeyemo A., Ludwig B., Tomaszewski M., Tzoulaki I., Palmer N. D., Chang Y. P., Steinle N. I., Grobbee D. E., Morrison A. C., Najjar S., Hadley D., Brown M. J., Connell J. M., Day I. N., Lawlor D. A., Lawrence R. W., Ongen H., Li Y., Young J. H., Bis J. C., Bolton J. A., Chaturvedi N., Islam M., Jafar T. H., Kulkarni S. R., Howard P., Guarrera S., Ricceri F., Emilsson V., Plump A., Weder A. B., Sun Y. V., Scott L. J., Peltonen L., Vartiainen E., Brand S. M., Staessen J. A., Wang T. J., Burton P. R., Artigas M. S., Dong Y., Wang X., Zhu H., Rudock M. E., Heckbert S. R., Smith N. L., Wiggins K. L., Doumatey A., Shriner D., Veldre G., Viigimaa M., Kinra S., Prabhakaran D., Tripathy V., Langefeld C. D., Rosengren A., Thelle D. S., Corsi A. M., Singleton A., Hilton G., Salako T., Iwai N., Kita Y., Ogihara T., Ohkubo T., Okamura T., Ueshima H., Umemura S., Eyheramendy S., Meitinger T., Cho Y. S., Kim H. L., Scott J., Sehmi J. S., Hedblad B., Nilsson P., Smith G. D., Raffel L. J., Yao J., Schwartz S. M., Ikram M., W L., Mosley T. H., Seshadri S., Shrine N. R., Wain L. V., Zitting P., Cooper J. A., van Gilst W. H., Janipalli C. S., Mani K., Yajnik C. S., Mattace-Raso F. U., Lakatta E. G., Orru M., Scuteri A., Ala-Korpela M., Kangas A. J., Soininen P., Tukiainen T., Wurtz P., Ong R. T., Dorr M., Galan P., Hercberg S., Lathrop M., Zelenika D., Zhai G., Meschia J. F., Sharma P., Terzic J., Kumar M., Denniff M., Zukowska-Szczechowska E., Wagenknecht L. E., Fowkes F., Charchar F. J., Guo X., Rotimi C., Bots M. L., Brand E., Talmud P. J., Nyberg F., Laan M., Palmer L. J., van der Schouw Y. T., Casas J. P., Vineis P., Ganesh S. K., Wong T. Y., Tai E. S., Morris R. W., Marmot M. G., Miki T., Chandak G. R., Zhu X., Elosua R., Soranzo N., Sijbrands E. J., Uda M., Vasan R. S., Alizadeh B. Z., de Boer R. A., Boezen H. M., Hillege H. L., van der Klauw M. M., Ormel J., Rosmalen J. G., Slaets J. P., Lagou V., Welch R. P., Wheeler E., Rehnberg E., Rasmussen-Torvik L. J., Lecoeur C., Johnson P. C., Sennblad B., Salo P., Timpson N. J., Evans D. M., St Pourcain B., Bielak L. F., Horikoshi M., Navarro P., Raychaudhuri S., Chen H., Rybin D., Willems S. M., Song K., An P., Marullo L., Jansen H., Pankow J. S., Edkins S., Varga T. V., Oksa H., Antonella M., Kong A., Herder C., Antti J., Small K., Miljkovic I., Atalay M., Kiess W., Smit J. H., Campbell S., Fowkes G. R., Rathmann W., Maerz W., Watanabe R. M., de Geus E. J., Penninx B. W., Toenjes A., Peyser P. A., Korner A., Dupuis J., Cucca F., Balkau B., Bouatia-Naji N., Purcell S., Musunuru K., Ardissino D., Mannucci P. M., Anand S., Engert J. C., Morgan T., Spertus J. A., Stoll M., Girelli D., McKeown P. P., Patterson C. C., Merlini P. A., Berzuini C., Bernardinelli L., Peyvandi F., Tubaro M., Celli P., Fetiveau R., Marziliano N., Casari G., Galli M., Ribichini F., Rossi M., Bernardi F., Zonzin P., Piazza A., Yee J., Friedlander Y., Marrugat J., Subirana I., Sala J., Ramos R., Williams G., Nathan D. M., Macrae C. A., Berglund G., Asselta R., Duga S., Spreafico M., Daly M. J., Nemesh J., Korn J. M., Surti A., Gianniny L., Parkin M., Burtt N., Gabriel S. B., Wright B. J., Ball S. G., Schunkert I., Linsel-Nitschke P., Lieb W., Fischer M., Grosshennig A., Preuss M., Scholz M., Chen Z., Wilensky R., Matthai W., Qasim A., Hakonarson H. H., Devaney J., Pichard A. D., Kent K. M., Satler L., Lindsay J. M., Waksman R., Knouff C. W., Scheffold T., Berger K., Huge A., Martinelli N., Olivieri O., Corrocher R., Xie C., Ahmadi K. R., Ainali C., Bataille V., Bell J. T., Buil A., Dermitzakis E. T., Dimas A. S., Durbin R., Glass D., Hassanali N., Ingle C., Knowles D., Krestyaninova M., Lowe C. E., Meduri E., Di Meglio P., Montgomery S. B., Nestle F. O., Nica A. C., Nisbet J., O'rahilly S., Parts L., Potter S., Sekowska M., Shin S. Y., Surdulescu G., Travers M. E., Tsaprouni L., Tsoka S., Wilk A., Yang T. P., Higashio J., Williams R., Nato A., Ambite J. L., Deelman E., Manolio T., Heiss G., Taylor K., Avery C., Graff M., Lin D., Quibrera M., Cochran B., Kao L., Umans J., Cole S., Maccluer J., Person S., Gross M., Fornage M., Durda P., Jenny N., Patsy B., Arnold A., Buzkova P., Haines J., Murdock D., Glenn K., Brown-Gentry K., Thornton-Wells T., Dumitrescu L., Bush W. S., Mitchell S. L., Goodloe R., Wilson S., Boston J., Malinowski J., Restrepo N., Oetjens M., Fowke J., Spencer K., Pendergrass S., Le Marchand L., Park L., Tiirikainen M., Kolonel L., Cheng I., Wang H., Shohet R., Stram D., Henderson B., Monroe K., Anderson G., Carlson C., Prentice R., Lacroix A., Wu C., Carty C., Rosse S., Young A., Kocarnik J., Lin Y., Jackson R., Duggan D., Kuller L., He C., Sulem P., Barbalic M., Broer L., Byrne E. M., Gudbjartsson D. F., McArdle P. F., Porcu E., van Wingerden S. W., Zhuang W. V., Lauc L. B., Broekmans F. J., Burri A., Chen C., Corre T., Coviello A. D., D'adamo P., Davies G., Deary I. J., Ebrahim S., Fauser B. C., Ferreli L., Folsom A. R., Hankinson S. E., Hass M., Janssens A. C., Karasik D., Keyzer J., Kiel D. P., Lahti J., Lai S., Laisk T., Laven J. S., Liu J., Lopez L. M., Louwers Y. V., Marongiu M., Klaric I. M., Masciullo C., Melzer D., Newman A. B., Pare G., Peeters P. H., Pop V. J., Raikkonen K., Salumets A., Stacey S. N., Starr J. M., Stathopoulou M. G., Styrkarsdottir U., Tenesa A., Tryggvadottir L., Tsui K., van Dam R. M., van Gils C. H., van Nierop P., Vink J. M., Voorhuis M., Widen E., Wijnands-Van Gent C. J., Yerges-Armstrong L. M., Zgaga L., Zygmunt M., Buring J. E., Crisponi L., Demerath E. W., Streeten E. A., Murray A., Visser J. A., Lunetta K. L., Elks C. E., Cousminer D. L., Koller D. L., Lin P., Smith E. N., Warrington N. M., Alavere H., Berenson G. S., Blackburn H., Busonero F., Chen W., Couper D., Easton D. F., Eriksson J., Foroud T., Kilpelainen T. O., Li S., Murray S. S., Ness A. R., Northstone K., Peacock M., Pennell C. E., Pharoah P., Rafnar T., Rice J. P., Ring S. M., Schork N. J., Segre A. V., Sovio U., Srinivasan S. R., Tammesoo M. L., van Meurs J. B., Young L., Bierut L. J., and Econs M. J.
- Abstract
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 % of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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- 2015
67. Heritability of variation in glycaemic response to metformin: A genome-wide complex trait analysis
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Zhou, K, Donnelly, L, Yang, J, Li, M, Deshmukh, H, Van Zuydam, N, Ahlqvist, E, Spencer, C, Groop, L, Morris, A, Colhoun, H, Sham, P, McCarthy, M, Palmer, C, and Pearson, E
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Oncology ,Blood Glucose ,Genetic Markers ,Male ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Genome-wide association study ,Type 2 diabetes ,Quantitative trait locus ,Polymorphism, Single Nucleotide ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Quantitative Trait, Heritable ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Genetic Predisposition to Disease ,030304 developmental biology ,0303 health sciences ,business.industry ,Genetic Variation ,nutritional and metabolic diseases ,Articles ,Heritability ,Middle Aged ,medicine.disease ,Metformin ,3. Good health ,Diabetes Mellitus, Type 2 ,Scotland ,Data Interpretation, Statistical ,Cohort ,Female ,business ,Body mass index ,medicine.drug ,Genome-Wide Association Study - Abstract
Summary Background Metformin is a first-line oral agent used in the treatment of type 2 diabetes, but glycaemic response to this drug is highly variable. Understanding the genetic contribution to metformin response might increase the possibility of personalising metformin treatment. We aimed to establish the heritability of glycaemic response to metformin using the genome-wide complex trait analysis (GCTA) method. Methods In this GCTA study, we obtained data about HbA 1c concentrations before and during metformin treatment from patients in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) study, which includes a cohort of patients with type 2 diabetes and is linked to comprehensive clinical databases and genome-wide association study data. We applied the GCTA method to estimate heritability for four definitions of glycaemic response to metformin: absolute reduction in HbA 1c ; proportional reduction in HbA 1c ; adjusted reduction in HbA 1c ; and whether or not the target on-treatment HbA 1c of less than 7% (53 mmol/mol) was achieved, with adjustment for baseline HbA 1c and known clinical covariates. Chromosome-wise heritability estimation was used to obtain further information about the genetic architecture. Findings 5386 individuals were included in the final dataset, of whom 2085 had enough clinical data to define glycaemic response to metformin. The heritability of glycaemic response to metformin varied by response phenotype, with a heritability of 34% (95% CI 1–68; p=0·022) for the absolute reduction in HbA 1c , adjusted for pretreatment HbA 1c . Chromosome-wise heritability estimates suggest that the genetic contribution is probably from individual variants scattered across the genome, which each have a small to moderate effect, rather than from a few loci that each have a large effect. Interpretation Glycaemic response to metformin is heritable, thus glycaemic response to metformin is, in part, intrinsic to individual biological variation. Further genetic analysis might enable us to make better predictions for stratified medicine and to unravel new mechanisms of metformin action. Funding Wellcome Trust.
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- 2016
68. Trends in hypertension management in Type I diabetes across Europe, 1989/1990 – 1997/1999
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Soedamah-Muthu, S. S., Colhoun, H. M., Abrahamian, H., Chan, N. N., Mangili, R., Reboldi, G. P., Fuller, J. H., and the EURODIAB Prospective Complications Study Group
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- 2003
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69. The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control
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Casanova, F., primary, Adingupu, D. D., additional, Adams, F., additional, Gooding, K. M., additional, Looker, H. C., additional, Aizawa, K., additional, Dove, F., additional, Elyas, S., additional, Belch, J. J. F., additional, Gates, P. E., additional, Littleford, R. C., additional, Gilchrist, M., additional, Colhoun, H. M., additional, Shore, A. C., additional, Khan, F., additional, and Strain, W. D., additional
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- 2017
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70. Cardiovascular disease prevalence and risk factor prevalence in Type 2 diabetes: a contemporary analysis.
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McGurnaghan, S., Blackbourn, L. A. K., Mocevic, E., Haagen Panton, U., McCrimmon, R. J., Sattar, N., Wild, S., and Colhoun, H. M.
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SMOKING prevention ,BLOOD pressure ,CARDIOVASCULAR diseases ,CARDIOVASCULAR diseases risk factors ,CHOLESTEROL ,PEOPLE with diabetes ,GLYCOSYLATED hemoglobin ,HOSPITAL admission & discharge ,MEDICAL records ,TYPE 2 diabetes ,PATIENTS ,COMORBIDITY ,LOGISTIC regression analysis ,BODY mass index ,DISEASE prevalence ,DESCRIPTIVE statistics - Abstract
Aims: To describe the prevalence of major cardiovascular disease (CVD) and risk factor control in a contemporary population with Type 2 diabetes. Methods: We used data from the national registry in Scotland, Scottish Care Information‐Diabetes, linked to hospital admissions. Using descriptive statistics and logistic regression we described associations of risk factors with CVD. CVD was defined based on diagnostic codes in primary or secondary care data for ischaemic heart disease, cerebrovascular disease peripheral arterial disease, heart failure, cardiac arrhythmia, hypertensive heart disease and revascularization procedures. Results: Among 248 400 people with Type 2 diabetes with a median age of 67.5 years (IQR 58.2, 76.1) and median diabetes duration of 7.8 years (3.8, 13.0), 32% had prior CVD (35% of men, 29% of women). Median HbA1c overall was 55 mmol/mol (7.2%), median SBP was 132 mmHg, median total cholesterol was 4.1 mmol/l and mean BMI was 32 kg/m2. Overall two‐thirds (65% of men, 68% of women) have two or more of the following CVD risk factor thresholds: HbA1c ≥ 53 mmol/mol (7%), SBP > 130 mmHg or DBP > 80 mmHg, total cholesterol ≥ 5 mmol/l or BMI ≥ 30 kg/m2, or were currently smoking. Overall 84% were taking anti‐hypertensives and 75% a statin. Use of metformin was common at 58%, but other diabetes drugs that reduce CVD were rarely used. Conclusions: There continues to be a high prevalence of CVD among people with Type 2 diabetes and a high level of unmet need for risk factor control. This implies substantial scope for reducing the excess risk of CVD in diabetes through improved management of known risk factors. What's new?: There have been substantial advances in the management and prevention of cardiovascular disease in diabetes. To understand where unmet needs lie, it is important to understand the current burden of cardiovascular disease and the levels of treated and untreated risk factors.In this paper, we show that there continues to be a high prevalence of cardiovascular disease among people with Type 2 diabetes and a high level of unmet need for risk factor control. This implies substantial scope for reducing the excess risk of cardiovascular disease in diabetes through improved management of known risk factors. [ABSTRACT FROM AUTHOR]
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- 2019
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71. End-stage renal disease and survival in people with diabetes:a national database linkage study
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Bell, S., Fletcher, E. H., Brady, I., Looker, H. C., Levin, D., Joss, N., Traynor, J. P., Metcalfe, W., Conway, B., Livingstone, S., Leese, G., Philip, S., Wild, S., Halbesma, N., Sattar, N., Lindsay, R. S., Mcknight, J., Pearson, D., and Colhoun, H. M.
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REPLACEMENT THERAPY ,COMPLICATIONS ,endocrine system diseases ,NEPHROPATHY ,REGISTRY ,DIALYSIS ,DEATH ,nutritional and metabolic diseases ,EPIDEMIOLOGY ,IDDM ,urologic and male genital diseases ,female genital diseases and pregnancy complications ,PREVALENCE - Abstract
Background: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT).Aim: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival.Methods: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration and National Records of Scotland death data. Survival analyses were modelled with Cox regression.Results: Point prevalence of chronic kidney disease (CKD) 5 in 2008 was 1.63% of 19 414 people with type 1 diabetes (T1DM) compared with 0.58% of 167 871 people with type 2 diabetes (T2DM) (odds ratio for DM type 0.97, P=0.77, on adjustment for duration. Although 83% of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving RRT, there was no difference when adjusted for age, sex and DM duration (odds ratio for DM type 0.83, P = 0.432). Diabetic nephropathy was the primary renal diagnosis in 91% of people with T1DM and 58% of people with T2DM on RRT. Median survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM and 2.16 years (95% CI: 1.92, 2.38) in T2DM.Conclusion: Considerable numbers of patients with diabetes continue to progress to CKD5 and RRT. Almost half of all RRT cases in T2DM are considered to be due to conditions other than diabetic nephropathy. Median survival time for people with diabetes from initiation of RRT remains poor. These prevalence data are important for future resource planning.
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- 2015
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72. A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain
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Meng, W., Deshmukh, H. A., van Zuydam, N. R., Liu, Y., Donnelly, L. A., Zhou, K., Morris, A. D., Colhoun, H. M., Palmer, C. N A, and Smith, B. H.
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Anesthesiology and Pain Medicine - Abstract
Background: Neuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population. Method: We accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non-genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets. Results: After data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p-value of 1.77×10-7 at rs17428041. The narrow-sense heritability of this phenotype was 11.00%. Conclusion: This genome-wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level.
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- 2014
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73. Investigation of known estimated glomerular filtration rate loci in patients with Type 2 diabetes
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Deshmukh, H A, Palmer, C N A, Morris, A D, and Colhoun, H M
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Male ,Endocrinology, Diabetes and Metabolism ,urologic and male genital diseases ,Polymorphism, Single Nucleotide ,Endocrinology ,Uromodulin ,Internal Medicine ,Albuminuria ,Humans ,Diabetic Nephropathies ,Renal Insufficiency, Chronic ,Research Articles ,Adaptor Proteins, Signal Transducing ,urogenital system ,Membrane Proteins ,Reproducibility of Results ,Middle Aged ,female genital diseases and pregnancy complications ,Diabetes Mellitus, Type 2 ,Scotland ,Female ,Genome-Wide Association Study ,Glomerular Filtration Rate - Abstract
Aims: To replicate the association of genetic variants with estimated glomerular filtration rate (GFR) and albuminuria, which has been found in recent genome-wide studies in patients with Type 2 diabetes. Methods: We evaluated 16 candidate single nucleotide polymorphisms for estimated GFR in 3028 patients with Type 2 diabetes sampled from clinics across Tayside, Scotland, UK, who were included in the Genetics of Diabetes Audit and Research Tayside (GoDARTs) study. These single nucleotide polymorphisms were tested for their association with estimated GFR at entry to the study, with albuminuria, and with time to stage 3B chronic kidney disease (estimated GFR2). We also stratified the effects on estimated GFR in patients with (n = 2096) and without albuminuria (n = 613). Results: rs1260326 in GCKR (β=1.30, P = 3.23E-03), rs17319721 in SHROOM3 (β = -1.28, P-value = 3.18E-03) and rs12917707 in UMOD (β = 2.0, P-value = 8.84E-04) were significantly associated with baseline estimated GFR. Analysis of effects on estimated GFR, stratified by albuminuria status, showed that in those without albuminuria (normoalbuminura; n = 613), UMOD had a significantly stronger effect on estimated GFR (βnormo = 4.03 ± 1.23 vs βalbuminuria = 1.72 ± 0.76, P = 0.002) compared with those with albuminuria, while GCKR (βnormo = 0.45 ± 0.89 vs βalbuminuria = 1.12 ± 0.55, P = 0.08) and SHROOM3 (βnormo = -0.07 ± 0.89 vs βalbuminuria = -1.43 ± 0.53, P = 0.003) had a stronger effect on estimated GFR in those with albuminuria. UMOD was also associated with a lower rate of transition to stage 3B chronic kidney disease (hazard ratio = 0.83[0.70, 0.99], P = 0.03). Conclusion: The genetic variants that regulate estimated GFR in the general population tend to have similar effects in patients with Type 2 diabetes and in this latter population, it is important to adjust for albuminuria status while investigating the genetic determinants of renal function.
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- 2013
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74. A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of two Dutch and two UK cohorts
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Leen 't Hart, Leeuwen, N., Zhou, K., Becker, M. L., Stricker, B. H. C., Dekker, J. M., Nijpels, G., Colhoun, H. M., Holman, R. R., Mccarthy, M. I., and Pearson, E. R.
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- 2011
75. New genetic loci link adipose and insulin biology to body fat distribution.
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ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., Carlson, OD., 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- Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
- Published
- 2015
76. C-reactive Protein and Amyloid A as Predictors of Cardiovascular Events in Type 2 Diabetes in CARDS
- Author
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Charlton-Menys, V, Colhoun, H, Betteridge, D, Soedamah-Muthu, S, Hitman, G, Neil, H, Livingstone, S, Bao, W, DeMicco, D, Preston, G, Fuller, J, Durrington, P, and Investigators, CARDS
- Published
- 2009
77. A genome‐wide association study suggests that <italic>MAPK14</italic> is associated with diabetic foot ulcers.
- Author
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Meng, W., Veluchamy, A., Hébert, H. L., Campbell, A., Colhoun, H. M., and Palmer, C. N. A.
- Subjects
DIABETIC foot ,DIABETES ,NEUROPATHY ,MEDICAL records ,GENETICS - Abstract
Summary: Background: Diabetic foot ulcers (DFUs) are a devastating complication of diabetes. Objectives: To identify genetic contributors to the development of DFUs in the presence of peripheral neuropathy in a Scottish cohort with diabetes using a genome‐wide association study. Methods: A genome‐wide association approach was applied. A case was defined as a person with diabetes (type 1 or type 2) who had ever had a foot ulcer (current or previous) in at least one foot, as well as a positive monofilament test result (i.e. evidence of peripheral neuropathy) recorded in their longitudinal e‐health records. A control was defined as an individual with diabetes (type 1 or type 2) who has never been recorded as having a foot ulcer in either foot but who had a positive monofilament test result recorded in either foot in their longitudinal e‐health records. Results: There were 699 DFU cases and 2695 controls in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) dataset. The single‐nucleotide polymorphism rs80028505 (Chr6p21·31) in
MAPK14 reached genome‐wide significance with a lowestP ‐value of 2·45 × 10−8 . The narrow‐sense heritability of this phenotype is 0·06. Conclusions: We suggest thatMAPK14 is associated with DFUs. [ABSTRACT FROM AUTHOR]- Published
- 2017
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78. Effect of atorvastatin on stroke in patients with type 2 diabetes: factors predicting the risk of stroke in the Collaborative Atorvastatin Diabetes Study (CARDS)
- Author
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Hitman, G, Newman, C, Szarek, M, Colhoun, H, Betteridge, J, Durrington, P, Neil, A, Livingstone, S, Fuller, J, and Investigators, CARDS
- Published
- 2005
79. Lipidomic profile and cardiovascular events in diabetic subjects
- Author
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McLeod, O., primary, Gertow, K., additional, Leander, K., additional, deFaire, U., additional, Tremoli, E., additional, Colhoun, H., additional, Hamsten, A., additional, and Ohrvik, J., additional
- Published
- 2014
- Full Text
- View/download PDF
80. Trends in hypertension management in Type I diabetes across Europe, 1989/1990 - 1997/1999. Diabetologia
- Author
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Soedamah Muthu, S., Colhoun, H., Abrahamian, H., Chan, N., Reboldi, Gianpaolo, and Fuller, J.
- Published
- 2002
81. Genome-wide association and functional follow-up reveals new loci for kidney function.
- Author
-
CARDIoGRAM Consortium, ICBP Consortium, CARe Consortium, Wellcome Trust Case Control Consortium 2 (WTCCC2), Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., O'Leary, DH., Pattaro, C., Köttgen, A., Teumer, A., Garnaas, M., Böger, C.A., Fuchsberger, C., Olden, M., Chen, M.H., Tin, A., Taliun, D., Li, M., Gao, X., Gorski, M., Yang, Q., Hundertmark, C., Foster, M.C., O'Seaghdha, C.M., Glazer, N., Isaacs, A., Liu, C.T., Smith, A.V., O'Connell, J.R., Struchalin, M., Tanaka, T., Li, G., Johnson, A.D., Gierman, H.J., Feitosa, M., Hwang, S.J., Atkinson, E.J., Lohman, K., Cornelis, M.C., Johansson, Å., Tönjes, A., Dehghan, A., Chouraki, V., Holliday, E.G., Sorice, R., Kutalik, Z., Lehtimäki, T., Esko, T., Deshmukh, H., Ulivi, S., Chu, A.Y., Murgia, F., Trompet, S., Imboden, M., Kollerits, B., Pistis, G., Harris, T.B., Launer, L.J., Aspelund, T., Eiriksdottir, G., Mitchell, B.D., Boerwinkle, E., Schmidt, H., Cavalieri, M., Rao, M., Hu, F.B., Demirkan, A., Oostra, B.A., de Andrade, M., Turner, S.T., Ding, J., Andrews, J.S., Freedman, B.I., Koenig, W., Illig, T., Döring, A., Wichmann, H.E., Kolcic, I., Zemunik, T., Boban, M., Minelli, C., Wheeler, H.E., Igl, W., Zaboli, G., Wild, S.H., Wright, A.F., Campbell, H., Ellinghaus, D., Nöthlings, U., Jacobs, G., Biffar, R., Endlich, K., Ernst, F., Homuth, G., Kroemer, H.K., Nauck, M., Stracke, S., Völker, U., Völzke, H., Kovacs, P., Stumvoll, M., Mägi, R., Hofman, A., Uitterlinden, A.G., Rivadeneira, F., Aulchenko, Y.S., Polasek, O., Hastie, N., Vitart, V., Helmer, C., Wang, J.J., Ruggiero, D., Bergmann, S., Kähönen, M., Viikari, J., Nikopensius, T., Province, M., Ketkar, S., Colhoun, H., Doney, A., Robino, A., Giulianini, F., Krämer, B.K., Portas, L., Ford, I., Buckley, B.M., Adam, M., Thun, G.A., Paulweber, B., Haun, M., Sala, C., Metzger, M., Mitchell, P., Ciullo, M., Kim, S.K., Vollenweider, P., Raitakari, O., Metspalu, A., Palmer, C., Gasparini, P., Pirastu, M., Jukema, J.W., Probst-Hensch, N.M., Kronenberg, F., Toniolo, D., Gudnason, V., Shuldiner, A.R., Coresh, J., Schmidt, R., Ferrucci, L., Siscovick, D.S., van Duijn, C.M., Borecki, I., Kardia, S.L., Liu, Y., Curhan, G.C., Rudan, I., Gyllensten, U., Wilson, J.F., Franke, A., Pramstaller, P.P., Rettig, R., Prokopenko, I., Witteman, J.C., Hayward, C., Ridker, P., Parsa, A., Bochud, M., Heid, I.M., Goessling, W., Chasman, D.I., Kao, W.H., Fox, C.S., CARDIoGRAM Consortium, ICBP Consortium, CARe Consortium, Wellcome Trust Case Control Consortium 2 (WTCCC2), Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., O'Leary, DH., Pattaro, C., Köttgen, A., Teumer, A., Garnaas, M., Böger, C.A., Fuchsberger, C., Olden, M., Chen, M.H., Tin, A., Taliun, D., Li, M., Gao, X., Gorski, M., Yang, Q., Hundertmark, C., Foster, M.C., O'Seaghdha, C.M., Glazer, N., Isaacs, A., Liu, C.T., Smith, A.V., O'Connell, J.R., Struchalin, M., Tanaka, T., Li, G., Johnson, A.D., Gierman, H.J., Feitosa, M., Hwang, S.J., Atkinson, E.J., Lohman, K., Cornelis, M.C., Johansson, Å., Tönjes, A., Dehghan, A., Chouraki, V., Holliday, E.G., Sorice, R., Kutalik, Z., Lehtimäki, T., Esko, T., Deshmukh, H., Ulivi, S., Chu, A.Y., Murgia, F., Trompet, S., Imboden, M., Kollerits, B., Pistis, G., Harris, T.B., Launer, L.J., Aspelund, T., Eiriksdottir, G., Mitchell, B.D., Boerwinkle, E., Schmidt, H., Cavalieri, M., Rao, M., Hu, F.B., Demirkan, A., Oostra, B.A., de Andrade, M., Turner, S.T., Ding, J., Andrews, J.S., Freedman, B.I., Koenig, W., Illig, T., Döring, A., Wichmann, H.E., Kolcic, I., Zemunik, T., Boban, M., Minelli, C., Wheeler, H.E., Igl, W., Zaboli, G., Wild, S.H., Wright, A.F., Campbell, H., Ellinghaus, D., Nöthlings, U., Jacobs, G., Biffar, R., Endlich, K., Ernst, F., Homuth, G., Kroemer, H.K., Nauck, M., Stracke, S., Völker, U., Völzke, H., Kovacs, P., Stumvoll, M., Mägi, R., Hofman, A., Uitterlinden, A.G., Rivadeneira, F., Aulchenko, Y.S., Polasek, O., Hastie, N., Vitart, V., Helmer, C., Wang, J.J., Ruggiero, D., Bergmann, S., Kähönen, M., Viikari, J., Nikopensius, T., Province, M., Ketkar, S., Colhoun, H., Doney, A., Robino, A., Giulianini, F., Krämer, B.K., Portas, L., Ford, I., Buckley, B.M., Adam, M., Thun, G.A., Paulweber, B., Haun, M., Sala, C., Metzger, M., Mitchell, P., Ciullo, M., Kim, S.K., Vollenweider, P., Raitakari, O., Metspalu, A., Palmer, C., Gasparini, P., Pirastu, M., Jukema, J.W., Probst-Hensch, N.M., Kronenberg, F., Toniolo, D., Gudnason, V., Shuldiner, A.R., Coresh, J., Schmidt, R., Ferrucci, L., Siscovick, D.S., van Duijn, C.M., Borecki, I., Kardia, S.L., Liu, Y., Curhan, G.C., Rudan, I., Gyllensten, U., Wilson, J.F., Franke, A., Pramstaller, P.P., Rettig, R., Prokopenko, I., Witteman, J.C., Hayward, C., Ridker, P., Parsa, A., Bochud, M., Heid, I.M., Goessling, W., Chasman, D.I., Kao, W.H., and Fox, C.S.
- Abstract
Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
- Published
- 2012
82. Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- Author
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Gibson, G, Pattaro, C, Koettgen, A, Teumer, A, Garnaas, M, Boeger, CA, Fuchsberger, C, Olden, M, Chen, M-H, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, MC, O'Seaghdha, CM, Glazer, N, Isaacs, A, Liu, C-T, Smith, AV, O'Connell, JR, Struchalin, M, Tanaka, T, Li, G, Johnson, AD, Gierman, HJ, Feitosa, M, Hwang, S-J, Atkinson, EJ, Lohman, K, Cornelis, MC, Johansson, A, Toenjes, A, Dehghan, A, Chouraki, V, Holliday, EG, Sorice, R, Kutalik, Z, Lehtimaeki, T, Esko, T, Deshmukh, H, Ulivi, S, Chu, AY, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Harris, TB, Launer, LJ, Aspelund, T, Eiriksdottir, G, Mitchell, BD, Boerwinkle, E, Schmidt, H, Cavalieri, M, Rao, M, Hu, FB, Demirkan, A, Oostra, BA, de Andrade, M, Turner, ST, Ding, J, Andrews, JS, Freedman, BI, Koenig, W, Illig, T, Doering, A, Wichmann, H-E, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, HE, Igl, W, Zaboli, G, Wild, SH, Wright, AF, Campbell, H, Ellinghaus, D, Nothlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Homuth, G, Kroemer, HK, Nauck, M, Stracke, S, Voelker, U, Voelzke, H, Kovacs, P, Stumvoll, M, Magi, R, Hofman, A, Uitterlinden, AG, Rivadeneira, F, Aulchenko, YS, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, JJ, Ruggiero, D, Bergmann, S, Kaehoenen, M, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Doney, A, Robino, A, Giulianini, F, Kraemer, BK, Portas, L, Ford, I, Buckley, BM, Adam, M, Thun, G-A, Paulweber, B, Haun, M, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, SK, Vollenweider, P, Raitakari, O, Metspalu, A, Palmer, C, Gasparini, P, Pirastu, M, Jukema, JW, Probst-Hensch, NM, Kronenberg, F, Toniolo, D, Gudnason, V, Shuldiner, AR, Coresh, J, Schmidt, R, Ferrucci, L, Siscovick, DS, van Duijn, CM, Borecki, I, Kardia, SLR, Liu, Y, Curhan, GC, Rudan, I, Gyllensten, U, Wilson, JF, Franke, A, Pramstaller, PP, Rettig, R, Prokopenko, I, Witteman, JCM, Hayward, C, Ridker, P, Parsa, A, Bochud, M, Heid, IM, Goessling, W, Chasman, DI, Kao, WHL, Fox, CS, Gibson, G, Pattaro, C, Koettgen, A, Teumer, A, Garnaas, M, Boeger, CA, Fuchsberger, C, Olden, M, Chen, M-H, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, MC, O'Seaghdha, CM, Glazer, N, Isaacs, A, Liu, C-T, Smith, AV, O'Connell, JR, Struchalin, M, Tanaka, T, Li, G, Johnson, AD, Gierman, HJ, Feitosa, M, Hwang, S-J, Atkinson, EJ, Lohman, K, Cornelis, MC, Johansson, A, Toenjes, A, Dehghan, A, Chouraki, V, Holliday, EG, Sorice, R, Kutalik, Z, Lehtimaeki, T, Esko, T, Deshmukh, H, Ulivi, S, Chu, AY, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Harris, TB, Launer, LJ, Aspelund, T, Eiriksdottir, G, Mitchell, BD, Boerwinkle, E, Schmidt, H, Cavalieri, M, Rao, M, Hu, FB, Demirkan, A, Oostra, BA, de Andrade, M, Turner, ST, Ding, J, Andrews, JS, Freedman, BI, Koenig, W, Illig, T, Doering, A, Wichmann, H-E, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, HE, Igl, W, Zaboli, G, Wild, SH, Wright, AF, Campbell, H, Ellinghaus, D, Nothlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Homuth, G, Kroemer, HK, Nauck, M, Stracke, S, Voelker, U, Voelzke, H, Kovacs, P, Stumvoll, M, Magi, R, Hofman, A, Uitterlinden, AG, Rivadeneira, F, Aulchenko, YS, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, JJ, Ruggiero, D, Bergmann, S, Kaehoenen, M, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Doney, A, Robino, A, Giulianini, F, Kraemer, BK, Portas, L, Ford, I, Buckley, BM, Adam, M, Thun, G-A, Paulweber, B, Haun, M, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, SK, Vollenweider, P, Raitakari, O, Metspalu, A, Palmer, C, Gasparini, P, Pirastu, M, Jukema, JW, Probst-Hensch, NM, Kronenberg, F, Toniolo, D, Gudnason, V, Shuldiner, AR, Coresh, J, Schmidt, R, Ferrucci, L, Siscovick, DS, van Duijn, CM, Borecki, I, Kardia, SLR, Liu, Y, Curhan, GC, Rudan, I, Gyllensten, U, Wilson, JF, Franke, A, Pramstaller, PP, Rettig, R, Prokopenko, I, Witteman, JCM, Hayward, C, Ridker, P, Parsa, A, Bochud, M, Heid, IM, Goessling, W, Chasman, DI, Kao, WHL, and Fox, CS
- Abstract
Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
- Published
- 2012
83. A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts
- Author
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van Leeuwen, N, Nijpels, G, Becker, Matthijs, Deshmukh, H, Zhou, K, Stricker, Bruno, Uitterlinden, André, Hofman, Bert, van Riet, E, Palmer, CNA, Guigas, B, Slagboom, PE (Eline), Durrington, P, Calle, RA, Neil, A, Hitman, G, Livingstone, SJ, Colhoun, H, Holman, RR, McCarthy, MI, Dekker, JM, 't Hart, LM, Pearson, ER, van Leeuwen, N, Nijpels, G, Becker, Matthijs, Deshmukh, H, Zhou, K, Stricker, Bruno, Uitterlinden, André, Hofman, Bert, van Riet, E, Palmer, CNA, Guigas, B, Slagboom, PE (Eline), Durrington, P, Calle, RA, Neil, A, Hitman, G, Livingstone, SJ, Colhoun, H, Holman, RR, McCarthy, MI, Dekker, JM, 't Hart, LM, and Pearson, ER
- Abstract
In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations. Incident users of metformin selected from the Diabetes Care System West-Friesland (DCS, n = 929) and the Rotterdam Study (n = 182) from the Netherlands, and the CARDS Trial (n = 254) from the UK were genotyped for rs11212617 and tested for an association with both HbA(1c) reduction and treatment success, defined as the ability to reach the treatment target of an HbA(1c) a parts per thousand currency sign7 % (53 mmol/mol). Finally, a meta-analysis including data from literature was performed. In the DCS cohort, we observed an association between rs11212617 genotype and treatment success on metformin (OR 1.27, 95% CI 1.03, 1.58, p = 0.028); in the smaller Rotterdam Study cohort, a numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87, 2.39, p = 0.15); while in the CARDS cohort there was no significant association. In meta-analyses of these three cohorts separately or combined with the previously published cohorts, rs11212617 genotype is associated with metfo A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetic patients from the Netherlands and the UK. This is the first robustly replicated common susceptibility locus found to be associated with metformin treatment response.
- Published
- 2012
84. Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- Author
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Pattaro, C, Kottgen, A, Teumer, A, Garnaas, M, Boger, CA, Fuchsberger, C, Olden, M, Chen, MH, Tin, A, Taliun, D, Li, M, Gao, XY, Gorski, M, Yang, Q, Hundertmark, C, Foster, MC, O'Seaghdha, CM, Glazer, N, Isaacs, Aaron, Liu, CT, Smith, AV, O'Connell, JR, Struchalin, M, Tanaka, T, Li, G (Guo), Johnson, AD, Gierman, HJ, Feitosa, M, Hwang, SJ, Atkinson, EJ, Lohman, K, Cornelis, MC, Johansson, A, Tonjes, A, Dehghan, Abbas, Chouraki, V, Holliday, EG, Sorice, R, Kutalik, Z, Lehtimaki, T, Esko, T, Deshmukh, H, Ulivi, S, Chu, AY, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Harris, TB, Launer, LJ (Lenore), Aspelund, T, Eiriksdottir, G, Mitchell, BD, Boerwinkle, E, Schmidt, Heléna, Cavalieri, M, Rao, M, Hu, FB, Demirkan, Ayse, Oostra, Ben, de Andrade, M, Turner, ST, Ding, JZ (Jing Zhong), Andrews, JS, Freedman, BI, Koenig, W, Illig, T, Doring, A, Wichmann, HE, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, HE, Igl, W, Zaboli, G, Wild, SH, Wright, AF, Campbell, H, Ellinghaus, D, Nothlings, U, Jacobs, Gunar, Biffar, R, Endlich, K, Ernst, F, Homuth, G, Kroemer, HK, Nauck, M, Stracke, S, Volker, U, Volzke, H, Kovacs, P, Stumvoll, M, Magi, R, Hofman, Bert, Uitterlinden, André, Rivadeneira, Fernando, Aulchenko, YS, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, JJ, Ruggiero, D, Bergmann, S, Kahonen, M, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Doney, A, Robino, A, Giulianini, F, Kramer, BK, Portas, L, Ford, I, Buckley, BM, Adam, M, Thun, GA, Paulweber, B, Haun, M, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, SK, Vollenweider, P, Raitakari, O, Metspalu, A, Palmer, C, Gasparini, P, Pirastu, M, Jukema, JW, Probst-Hensch, NM, Kronenberg, F, Toniolo, D, Gudnason, V, Shuldiner, AR, Coresh, J, Schmidt, R, Ferrucci, L, Siscovick, DS, Duijn, Cornelia, Borecki, I, Kardia, SLR, Liu, YM, Curhan, GC, Rudan, I, Gyllensten, U, Wilson, JF, Franke, A, Pramstaller, PP, Rettig, R, Prokopenko, I, Witteman, JCM, Hayward, C, Ridker, P, Parsa, A, Bochud, M, Heid, IM, Goessling, W, Chasman, DI, Kao, WHL, Fox, CS, Pattaro, C, Kottgen, A, Teumer, A, Garnaas, M, Boger, CA, Fuchsberger, C, Olden, M, Chen, MH, Tin, A, Taliun, D, Li, M, Gao, XY, Gorski, M, Yang, Q, Hundertmark, C, Foster, MC, O'Seaghdha, CM, Glazer, N, Isaacs, Aaron, Liu, CT, Smith, AV, O'Connell, JR, Struchalin, M, Tanaka, T, Li, G (Guo), Johnson, AD, Gierman, HJ, Feitosa, M, Hwang, SJ, Atkinson, EJ, Lohman, K, Cornelis, MC, Johansson, A, Tonjes, A, Dehghan, Abbas, Chouraki, V, Holliday, EG, Sorice, R, Kutalik, Z, Lehtimaki, T, Esko, T, Deshmukh, H, Ulivi, S, Chu, AY, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Harris, TB, Launer, LJ (Lenore), Aspelund, T, Eiriksdottir, G, Mitchell, BD, Boerwinkle, E, Schmidt, Heléna, Cavalieri, M, Rao, M, Hu, FB, Demirkan, Ayse, Oostra, Ben, de Andrade, M, Turner, ST, Ding, JZ (Jing Zhong), Andrews, JS, Freedman, BI, Koenig, W, Illig, T, Doring, A, Wichmann, HE, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, HE, Igl, W, Zaboli, G, Wild, SH, Wright, AF, Campbell, H, Ellinghaus, D, Nothlings, U, Jacobs, Gunar, Biffar, R, Endlich, K, Ernst, F, Homuth, G, Kroemer, HK, Nauck, M, Stracke, S, Volker, U, Volzke, H, Kovacs, P, Stumvoll, M, Magi, R, Hofman, Bert, Uitterlinden, André, Rivadeneira, Fernando, Aulchenko, YS, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, JJ, Ruggiero, D, Bergmann, S, Kahonen, M, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Doney, A, Robino, A, Giulianini, F, Kramer, BK, Portas, L, Ford, I, Buckley, BM, Adam, M, Thun, GA, Paulweber, B, Haun, M, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, SK, Vollenweider, P, Raitakari, O, Metspalu, A, Palmer, C, Gasparini, P, Pirastu, M, Jukema, JW, Probst-Hensch, NM, Kronenberg, F, Toniolo, D, Gudnason, V, Shuldiner, AR, Coresh, J, Schmidt, R, Ferrucci, L, Siscovick, DS, Duijn, Cornelia, Borecki, I, Kardia, SLR, Liu, YM, Curhan, GC, Rudan, I, Gyllensten, U, Wilson, JF, Franke, A, Pramstaller, PP, Rettig, R, Prokopenko, I, Witteman, JCM, Hayward, C, Ridker, P, Parsa, A, Bochud, M, Heid, IM, Goessling, W, Chasman, DI, Kao, WHL, and Fox, CS
- Abstract
Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
- Published
- 2012
85. Common variant in the HMGA2 gene increases susceptibility to nephropathy in patients with type 2 diabetes
- Author
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Alkayyali, S., primary, Lajer, M., additional, Deshmukh, H., additional, Ahlqvist, E., additional, Colhoun, H., additional, Isomaa, B., additional, Rossing, P., additional, Groop, L., additional, and Lyssenko, V., additional
- Published
- 2012
- Full Text
- View/download PDF
86. Common Nonsynonymous Substitutions in SLCO1B1 Predispose to Statin Intolerance in Routinely Treated Individuals With Type 2 Diabetes: A Go-DARTS Study
- Author
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Donnelly, L A, primary, Doney, A S F, additional, Tavendale, R, additional, Lang, C C, additional, Pearson, E R, additional, Colhoun, H M, additional, McCarthy, M I, additional, Hattersley, A T, additional, Morris, A D, additional, and Palmer, C N A, additional
- Published
- 2010
- Full Text
- View/download PDF
87. Apolipoproteins, cardiovascular risk and statin response in type 2 diabetes: the Collaborative Atorvastatin Diabetes Study (CARDS)
- Author
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Charlton-Menys, V., primary, Betteridge, D. J., additional, Colhoun, H., additional, Fuller, J., additional, France, M., additional, Hitman, G. A., additional, Livingstone, S. J., additional, Neil, H. A. W., additional, Newman, C. B., additional, Szarek, M., additional, DeMicco, D. A., additional, and Durrington, P. N., additional
- Published
- 2008
- Full Text
- View/download PDF
88. Risk of myocardial infarction in men and women with type 2 diabetes in the UK: a cohort study using the General Practice Research Database
- Author
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Mulnier, H. E., primary, Seaman, H. E., additional, Raleigh, V. S., additional, Soedamah-Muthu, S. S., additional, Colhoun, H. M., additional, Lawrenson, R. A., additional, and de Vries, C. S., additional
- Published
- 2008
- Full Text
- View/download PDF
89. Antibodies to periodontal pathogens and coronary artery calcification in type 1 diabetic and nondiabetic subjects
- Author
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Colhoun, H. M., primary, Slaney, J. M., additional, Rubens, M. B., additional, Fuller, J. H., additional, Sheiham, A., additional, and Curtis, M. A., additional
- Published
- 2007
- Full Text
- View/download PDF
90. Mo-W14:4 Apolipoproteins as predictors of cardiovascular risk in the collaborative atorvastatin diabetes study (Cards)
- Author
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Durrington, P.N., primary, Livingstone, S., additional, Charlton-Menys, V., additional, Colhoun, H., additional, Betteridge, D.J., additional, Fuller, J., additional, Hitman, G., additional, Neil, H.A.W., additional, Newman, C., additional, and Szarek, M., additional
- Published
- 2006
- Full Text
- View/download PDF
91. W12-P-066 Insight into the nature of the CRP-coronary event association using mendelian randomisation
- Author
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Shah, T., primary, Casas, J., additional, Cooper, J., additional, Hawe, E., additional, Stephens, J., additional, Yudkin, J., additional, Colhoun, H., additional, Bautista, L., additional, Meade, T., additional, Gaffney, D., additional, McMahon, A., additional, Hamsten, A., additional, Sattar, N., additional, Humphries, S., additional, and Hingorani, A., additional
- Published
- 2005
- Full Text
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92. 3WS20-1 Increased atherosclerosis in type 1 diabetes — Are lipids and lipoproteins irrelevant?
- Author
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Colhoun, H., primary
- Published
- 2003
- Full Text
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93. Cross sectional study of differences in coronary artery calcification by socioeconomic status
- Author
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Colhoun, H. M, primary
- Published
- 2000
- Full Text
- View/download PDF
94. Letters to the Editor
- Author
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Colhoun, H, primary
- Published
- 1999
- Full Text
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95. Prevalence and management of hypertension in Type 1 diabetes mellitus in Europe: the EURODIAB IDDM Complications Study
- Author
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Collado-Mesa, F., primary, Colhoun, H. M., additional, Stevens, L. K., additional, Boavida, J., additional, Ferriss, J. B., additional, Karamanos, B., additional, Kempler, P., additional, Michel, G., additional, Roglic, G., additional, Fuller, J. H., additional, and Group, the Eurodiab Iddm Complications Stu, additional
- Published
- 1999
- Full Text
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96. The scope for cardiovascular disease risk factor intervention among people with diabetes mellitus in England: a population-based analysis from the Health Surveys for England 1991-94
- Author
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Colhoun, H. M., primary, Dong, W., additional, Barakat, M. T., additional, Mather, H. M., additional, and Poulter, N. R., additional
- Published
- 1999
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97. Hormone replacement therapy use and blood pressure: Results from the health surveys for England 1993 and 1994
- Author
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COLHOUN, H, primary
- Published
- 1998
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- View/download PDF
98. P035 Socio-economic status and blood pressure; overview of published data: 1966?1996
- Author
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COLHOUN, H, primary
- Published
- 1998
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99. Ecological analysis of collectivity of alcohol consumption in England: importance of average drinker
- Author
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Colhoun, H., primary, Ben-Shlomo, Y., additional, Dong, W., additional, Bost, L., additional, and Marmot, M., additional
- Published
- 1997
- Full Text
- View/download PDF
100. The methylglyoxal-derived AGE tetrahydropyrimidine is increased in plasma of individuals with type 1 diabetes mellitus and in atherosclerotic lesions and is associated with sVCAM-1.
- Author
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Eupen, M., Schram, M., Colhoun, H., Hanssen, N., Niessen, H., Tarnow, L., Parving, H., Rossing, P., Stehouwer, C., and Schalkwijk, C.
- Abstract
Aims/hypothesis: Methylglyoxal (MGO) is a major precursor for advanced glycation end-products (AGEs), which are thought to play a role in vascular complications in diabetes. Known MGO-arginine-derived AGEs are 5-hydro-5-methylimidazolone (MG-H1), argpyrimidine and tetrahydropyrimidine (THP). We studied THP in relation to type 1 diabetes, endothelial dysfunction, low-grade inflammation, vascular complications and atherosclerosis. Methods: We raised and characterised a monoclonal antibody against MGO-derived THP. We measured plasma THP with a competitive ELISA in two cohort studies: study A (198 individuals with type 1 diabetes and 197 controls); study B (individuals with type 1 diabetes, 175 with normoalbuminuria and 198 with macroalbuminuria [>300 mg/24 h]). We measured plasma markers of endothelial dysfunction and low-grade inflammation, and evaluated the presence of THP and N-(carboxymethyl)lysine (CML) in atherosclerotic arteries. Results: THP was higher in individuals with type 1 diabetes than in those without (median [interquartile range] 115.5 U/μl [102.4-133.2] and 109.8 U/μl [91.8-122.3], respectively; p = 0.03). THP was associated with plasma soluble vascular cell adhesion molecule 1 in both study A (standardised β = 0.48 [95% CI 0.38, 0.58]; p < 0.001) and study B (standardised β = 0.31 [95% CI 0.23, 0.40]; p < 0.001), and with secreted phospholipase A2 (standardised β = 0.26 [95% CI 0.17, 0.36]; p < 0.001) in study B. We found no association of THP with micro- or macro-vascular complications. Both THP and CML were detected in atherosclerotic arteries. Conclusions/interpretation: Our results suggest that MGO-derived THP may reflect endothelial dysfunction among individuals with and without type 1 diabetes, and therefore may potentially play a role in the development of atherosclerosis and vascular disease. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
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