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3. Effect of Interleukin-6 promoter polymorphisms in survivors of myocardial infarction and matched controls in the North and South of Europe

Author

Kelberman D, Hawe E, Luong LA, Mohamed Ali V, Lundman P, Tornvall P, Aillaud MF, Juhan Vague I, Yudkin JS, Margaglione M, Tremoli E, Humphries SE, HIFMECH study group, DI MINNO, GIOVANNI, Kelberman, D, Hawe, E, Luong, La, Mohamed Ali, V, Lundman, P, Tornvall, P, Aillaud, Mf, Juhan Vague, I, Yudkin, J, Margaglione, M, DI MINNO, Giovanni, Tremoli, E, Humphries, Se, and HIFMECH study, Group

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Genotype, Myocardial Infarction, Polymorphism, Single Nucleotide, Gastroenterology, Pathogenesis, Gene Frequency, Risk Factors, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Survivors, Myocardial infarction, Allele, Promoter Regions, Genetic, Interleukin 6, Allele frequency, Inflammation, Molecular Epidemiology, biology, Interleukin-6, business.industry, C-reactive protein, Case-control study, Hematology, Middle Aged, medicine.disease, Europe, Case-Control Studies, biology.protein, Topography, Medical, business, Biomarkers
Abstract

SummaryElevated plasma IL-6 levels have been implicated in the pathogenesis of coronary heart disease. We have investigated the association of two polymorphisms in the promoter of IL-6 (-572G>C and -174G>C) with levels of inflammatory markers and risk of myocardial infarction (MI) in a European study of MI survivors and age-matched controls from two high-risk centres in the North of Europe, and two low risk centres in the South. IL-6 and CRP levels were similar in controls in both regions, but were higher in cases. For the -174G>C polymorphism the rare -174C allele showed a regional difference in allele frequency, being more common in the North European group (0.43 vs 0.28; p < 0.0005), where -174C allele carriers showed an apparent reduced risk of MI compared to -174GG homozygotes (OR 0.53, 95%CI 0.32, 0.86). No such effect was observed in the South or with the -572G>C in either group. Neither genotype was associated with a significant effect on plasma IL-6 levels in either cases or controls. Furthermore, no regional difference was observed in the frequency of the -572G>C SNP, suggesting that these polymorphisms are unlikely to be contributing to the observed increased risk of cardiovascular disease in Northern Europe.

Published
2004

4. Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40

Author

Stearne, MR, Palmer, SL, Hammersley, MS, Franklin, SL, Spivey, RS, Levy, JC, Tidy, CR, Bell, NJ, Steemson, J, Barrow, BA, Coster, R, Waring, K, Nolan, L, Truscott, E, Walravens, N, Cook, L, Lampard, H, Merle, C, Parker, P, McVittie, J, Draisey, I, Murchison, LE, Brunt, AHE, Williams, MJ, Pearson, DW, Petrie, XMP, Lean, MEJ, Walmsley, D, Lyall, F, Christie, E, Church, J, Thomson, E, Farrow, A, Stowers, JM, Stowers, M, McHardy, K, Patterson, N, Wright, AD, Levi, NA, Shearer, ACI, Thompson, RJW, Taylor, G, Rayton, S, Bradbury, M, Glover, A, Smyth-Osbourne, A, Parkes, C, Graham, J, England, P, Gyde, S, Eagle, C, Chakrabarti, B, Smith, J, Sherwell, J, Kohner, EM, Dornhorst, A, Doddridge, MC, Dumskyj, M, Walji, S, Sharp, P, Sleightholm, M, Vanterpool, G, Rose, C, Frost, G, Roseblade, M, Elliott, S, Forrester, S, Foster, M, Myers, K, Chapman, R, Hayes, JR, Henry, RW, Featherston, MS, Archbold, GPR, Copeland, M, Harper, R, Richardson, I, Martin, S, Davison, HA, Hadden, DR, Kennedy, L, Atkinson, AB, Culbert, AM, Hegan, C, Tennet, H, Webb, N, Robinson, I, Holmes, J, Bell, PM, McCance, DR, Rutherford, J, Nesbitt, S, Spathis, AS, Hyer, S, Nanson, ME, James, LM, Tyrell, JM, Davis, C, Strugnell, P, Booth, M, Petrie, H, Clark, D, Rice, B, Hulland, S, Barron, JL, Yudkin, JS, Gould, BJ, Singer, J, Badenock, A, Eckert, M, Alibhai, K, Marriot, E, Cox, C, Price, R, Fernandez, M, Ryle, A, Clarke, S, Wallace, G, Mehmed, E, MacFarlane, S, Greenwood, RH, Wilson, J, Denholm, MJ, Temple, RC, Whitfield, K, Johnson, F, Munroe, C, Gorick, S, Duckworth, E, Flatman, M, Rainbow, S, Borthwick, LJ, Wheatcroft, DJ, Seaman, RJ, Christie, RA, Wheatcroft, W, Musk, P, White, J, McDougal, S, Bond, M, Raniga, P, Newton, RW, Jung, RT, Roxburgh, C, Kilgallon, B, Dick, L, Waugh, N, Kilby, S, Ellington, A, Burns, J, Fox, CV, Holloway, MC, Coghill, HM, Hein, N, Fox, A, Cowan, W, Richard, M, Quested, K, Evans, SJ, Paisey, RB, Brown, NPR, Tucker, AJ, Paisey, R, Garrett, F, Hogg, J, Park, P, Williams, K, Harvey, P, Wilcocks, R, Mason, S, Frost, J, Warren, C, Rocket, P, Bower, L, Roland, JM, Brown, DJ, Youens, J, Stanton-King, K, Mungall, H, Ball, V, Maddison, W, Donnelly, D, King, S, Griffin, P, Smith, S, Church, S, Dunn, G, Wilson, A, Palmer, K, Brown, PM, Humphriss, D, Davidson, AJM, Rose, R, Armistead, L, Townsend, S, Poon, P, Peacock, IDA, Culverwell, NJC, Charlton, MH, Connolly, BPS, Peacock, J, Barrett, J, Wain, J, Beeston, W, King, G, Hill, PG, Boulton, AJM, Robertson, AM, Katoulis, V, Olukoga, A, McDonald, H, Kumar, S, Abouaesha, F, Abuaisha, B, Knowles, EA, Higgins, S, Booker, J, Sunter, J, Breislin, K, Parker, R, Raval, P, Curwell, J, Davenport, J, Shawcross, G, Prest, A, Grey, J, Cole, H, Sereviratne, C, Young, RJ, Dornan, TL, Clyne, JR, Gibson, M, O'Connell, I, Wong, LM, Wilson, SJ, Wright, KL, Wallace, C, McDowell, D, Burden, AC, Sellen, EM, Gregory, R, Roshan, M, Vaghela, N, Burden, M, Sherriff, C, Clarke, J, Grenfell, J, Tooke, JE, MacLeod, K, Searnark, C, Rammell, M, Pym, C, Stockman, J, Yeo, C, Piper, J, Leighton, L, Green, E, Hoyle, M, Jones, K, Hudson, A, James, AJ, Shore, A, Higham, A, Martin, B, and Grp, UKPDS

Subjects
General Engineering, HC Economic History and Conditions, General Earth and Planetary Sciences, General Medicine, R Medicine (General), General Environmental Science
Abstract

Objectives: To estimate the economic efficiency of tight blood pressure control, with angiotensin converting enzyme inhibitors or beta blockers, compared with less tight control in hypertensive patients with type 2 diabetes. Design: Cost effectiveness analysis incorporating within trial analysis and estimation of impact on life expectancy through use of the within trial hazards of reaching a defined clinical end point. Use of resources driven by trial protocol and use of resources in standard clinical practice were both considered. Setting: 20 hospital based clinics in England, Scotland, and Northern Ireland. Subjects: 1148 hypertensive patients with type 2 diabetes from UK prospective diabetes study randomised to tight control of blood pressure (n=758) or less tight control (n=390). Main outcome measure: Cost effectiveness ratios based on (a) use of healthcare resources associated with tight control and less tight control and treatment of complications and (b) within trial time free from diabetes related end points, and life years gained. Results: Based on use of resources driven by trial protocol, the incremental cost effectiveness of tight control compared with less tight control was cost saving. Based on use of resources in standard clinical practice, incremental cost per extra year free from end points amounted to £1049 (costs and effects discounted at 6% per year) and £434 (costs discounted at 6% per year and effects not discounted). The incremental cost per life year gained was £720 (costs and effects discounted at 6% per year) and £291 (costs discounted at 6% per year and effects not discounted). Conclusions: Tight control of blood pressure in hypertensive patients with type 2 diabetes substantially reduced the cost of complications, increased the interval without complications and survival, and had a cost effectiveness ratio that compares favourably with many accepted healthcare programmes.

Published
1998

6. Common variants in the thrombomodulin gene as a risk for myocardial infarction in the north of Europe (HIFMECH Study)

Author

Konstantoulas C, Hawe E, Saut N, Yudkin JS, Margaglione M, Hamsten A, Humphries SE, Juhan Vague I, Ireland H, HIFMECH Study Group, DI MINNO, GIOVANNI, Konstantoulas, C, Hawe, E, Saut, N, Yudkin, J, DI MINNO, Giovanni, Margaglione, M, Hamsten, A, Humphries, Se, Juhan Vague, I, Ireland, H, and HIFMECH Study, Group

Subjects
Male, Risk, Linkage disequilibrium, Genotype, Thrombomodulin, Myocardial Infarction, Coronary Disease, Linkage Disequilibrium, Thrombin, Risk Factors, medicine, Odds Ratio, Humans, cardiovascular diseases, Myocardial infarction, Allele, Promoter Regions, Genetic, Alleles, Binding Sites, Polymorphism, Genetic, business.industry, Haplotype, Hematology, Odds ratio, Middle Aged, medicine.disease, Blotting, Northern, Thrombosis, Europe, Haplotypes, Immunology, cardiovascular system, business, Protein C, medicine.drug
Abstract

Common variants in the thrombomodulin gene as a risk for myocardial infarction in the north of Europe (HIFMECH Study)

Published
2004

8. The plasminogen activator inhibitor-1 -675 4G/5G genotype influences the risk of myocardial infarction associated with elevated plasma proinsulin and insulin concentrations in men from Europe: the HIFMECH study

Author

Juhan Vague I, Morange PE, Frere C, Aillaud MF, Alessi MC, Hawe E, Boquist S, Tornvall P, Yudkin JS, Tremoli E, Margaglione M, Hamsten A, Humphries SE, HIFMECH Study Group, DI MINNO, GIOVANNI, Juhan Vague, I, Morange, Pe, Frere, C, Aillaud, Mf, Alessi, Mc, Hawe, E, Boquist, S, Tornvall, P, Yudkin, J, Tremoli, E, Margaglione, M, DI MINNO, Giovanni, Hamsten, A, Humphries, Se, and HIFMECH Study, Group

Subjects
Male, medicine.medical_specialty, Genotype, medicine.medical_treatment, Myocardial Infarction, chemistry.chemical_compound, Insulin resistance, Risk Factors, Internal medicine, Plasminogen Activator Inhibitor 1, Humans, Insulin, Medicine, Myocardial infarction, Proinsulin, Hemostasis, Polymorphism, Genetic, business.industry, Hematology, Odds ratio, Middle Aged, medicine.disease, Europe, Endocrinology, chemistry, Case-Control Studies, Plasminogen activator inhibitor-1, Insulin Resistance, business, Plasminogen activator, Body mass index
Abstract

Summary. Although the potential role of plasminogen activator inhibitor-1 (PAI-1) in the development of coronary artery disease is strongly supported by its biological characteristics, results of clinical studies remain controversial. Objectives: To investigate whether plasma PAI-1 concentrations and the −675 4G/5G polymorphism located in the PAI-1 gene could constitute risk markers for myocardial infarction (MI). Patients and methods: We used a European case–control study, the HIFMECH study, comparing 598 men with MI and 653 age-matched controls. Results: Insulin resistance explained a major part of the variation in PAI-1 (24%) whereas inflammation had only a minor contribution (0.01%). For both cases and controls plasma PAI-1 concentrations were significantly higher in the North than the South, and in both regions were higher in individuals with MI compared with control subjects [overall odds ratio (OR) for a 1 SD increase = 1.54, 95% confidence interval (CI) 1.34, 1.77]. This difference was observed in all the centers studied. Overall, the difference between cases and control subjects remained significant after controlling for inflammation variables (OR = 1.30, 95% CI 1.08, 1.57), but lost significance after controlling for insulin resistance variables (OR = 1.17, 95% CI 0.98, 1.40). The 4G allele was associated with significantly higher PAI-1 levels in cases but not controls and, taken independently, did not modify the risk of MI (P = 0.9). However, a significant interaction was observed with both insulin or proinsulin and the risk of MI (P = 0.05 and 0.02, respectively), but not with triglycerides or body mass index (BMI). The insulin or proinsulin effect on risk was observed only in the carriers of the 4G/4G genotype. This interaction appeared not to be mediated by plasma PAI-1 antigen concentrations (P = 0.01 and 0.02 after adjustment for PAI-1 plasma levels). The interaction with proinsulin but not insulin remained statistically significant after further adjustment for other factors associated with insulin resistance (triglycerides and BMI) and C-reactive protein (P = 0.01). Conclusion: This study suggests that PAI-1 has a role in risk of MI in the presence of underlying insulin resistance. A significant interaction between insulin or proinsulin and the −675 4G/5G polymorphism was observed in risk for MI. The mechanisms for these interactions remain to be determined.

Published
2003

12. The United Kingdom Prospective Diabetes Study--everything you needed to know about diabetes but were afraid to ask?

Author

Yudkin Js

Subjects
medicine.medical_specialty, business.industry, United Kingdom Prospective Diabetes Study, MEDLINE, Comorbidity, medicine.disease, United Kingdom, Diabetes Mellitus, Type 2, Ask price, Risk Factors, Family medicine, Diabetes mellitus, Hyperglycemia, medicine, Optometry, Humans, Prospective Studies, Cardiology and Cardiovascular Medicine, Prospective cohort study, business, Cardiomyopathies
Published
1999

13. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

Author

Turner, RC, Holman, RR, Cull, CA, Stratton, IM, Matthews, DR, Frighi, V, Manley, SE, Neil, A, McElroy, K, Wright, D, Kohner, E, Fox, C, Hadden, D, Mehta, Z, Smith, A, Nugent, Z, Peto, R, Adlel, AI, Mann, JI, Bassett, PA, Oakes, SF, Dornan, TL, Aldington, S, Lipinski, H, Collum, R, Harrison, K, MacIntyre, C, Skinner, S, Mortemore, A, Nelson, D, Cockley, S, Levien, S, Bodsworth, L, Willox, R, Biggs, T, Dove, S, Beattie, E, Gradwell, M, Staples, S, Lam, R, Taylor, F, Leung, L, Carter, RD, Brownlee, SM, Fisher, KE, Islam, K, Jelfs, R, Williams, PA, Williams, FA, Sutton, PJ, Ayres, A, Logie, LJ, Lovatt, C, Evans, MA, Stowell, LA, Ross, I, Kennedy, IA, Croft, D, Keen, AH, Rose, C, Raikou, M, Fletcher, AE, Bulpitt, C, Battersby, C, Yudkin, JS, Stevens, R, Stearn, MR, Palmer, SL, Hammersley, MS, Franklin, SL, Spivey, RS, Levy, JC, Tidy, CR, Bell, NJ, Steemson, J, Barrow, BA, Coster, R, Waring, K, Nolan, L, Truscott, E, Walravens, N, Cook, L, Lampard, H, Merle, C, Parker, P, McVittie, J, Draisey, I, Murchison, LE, Brunt, AHE, Williams, MJ, Pearson, DW, Petrie, XMP, Lean, MEJ, Walmsley, D, Lyall, F, Christie, E, Church, J, Thomson, E, Farrow, A, Stowers, JM, Stowers, M, McHardy, K, Patterson, N, Wright, AD, Levi, NA, Shearer, ACI, Thompson, RJW, Taylor, G, Rayton, S, Bradbury, M, Glover, A, Smyth-Osbourne, A, Parkes, C, Graham, J, England, P, Gyde, S, Eagle, C, Chakrabarti, B, Smith, J, Sherwell, J, Oakley, NW, Whitehead, MA, Hollier, GP, Pilkington, T, Simpson, J, Anderson, M, Martin, S, Kean, J, Rice, B, Rolland, A, Nisbet, J, Kohner, EM, Dornhorst, A, Doddridge, MC, Dumskyij, M, Walji, S, Sharp, P, Sleightholm, M, Vanterpool, G, Frost, G, Roseblade, M, Elliott, S, Forrester, S, Foster, M, Myers, K, Chapman, R, Hayes, JR, Henry, RW, Featherston, MS, Archbold, GPR, Copeland, M, Harper, R, Richardson, I, Davison, HA, Alexander, L, Scarpello, JHB, Shiers, DE, Tucker, RJ, Worthington, JRH, Angris, S, Bates, A, Walton, J, Teasdale, M, Browne, J, Stanley, S, Davis, BA, Strange, RC, Hadden, DR, Kennedy, L, Atkinson, AB, Bell, PM, McCance, DR, Rutherford, J, Culbert, AM, Hegan, C, Tennet, H, Webb, N, Robinson, I, Holmes, J, Nesbitt, S, Spathis, AS, Hyer, S, Nanson, ME, James, LM, Tyrell, JM, Davis, C, Strugnell, P, Booth, M, Petrie, H, Clark, D, Hulland, S, Barron, JL, Gould, BC, Singer, J, Badenoch, A, McGregor, M, Isenberg, L, Eckert, M, Alibhai, K, Marriot, E, Cox, C, Price, R, Fernandez, M, Ryle, A, Clarke, S, Wallace, G, Mehmed, E, Lankester, JA, Howard, E, Waite, A, MacFarlane, S, Greenwood, RH, Wilson, J, Denholm, MJ, Temple, RC, Whitfield, K, Johnson, F, Munroe, C, Gorick, S, Duckworth, E, Fatman, M, Rainbow, S, Borthwick, L, Wheatcroft, DJ, Seaman, RJ, Christie, RA, Wheatcroft, W, Musk, P, White, J, McDougal, S, Bond, M, Raniga, P, Day, JL, Doshi, MJ, Wilson, JG, Howard-Williams, JR, Humphreys, H, Graham, A, Hicks, K, Hexman, S, Bayliss, P, Pledger, D, Newton, RW, Jung, RT, Roxburgh, C, Kilgallon, B, Dick, L, Waugh, N, Kilby, S, Ellingford, A, Burns, J, Fox, CV, Holloway, MC, Coghill, HM, Hein, N, Fox, A, Cowan, W, Richard, M, Quested, K, Evans, SJ, Paisey, RB, Brown, NPR, Tucker, AJ, Paisey, R, Garrett, F, Hogg, J, Park, P, Williams, K, Harvey, P, Wilcocks, R, Mason, S, Frost, J, Warren, C, Rocket, P, Bower, L, Roland, JM, Brown, DJ, Youens, J, Stanton-King, K, Mungall, H, Ball, V, Maddison, W, Donnelly, D, King, S, Griffin, P, Smith, S, Church, S, Dunn, G, Wilson, A, Palmer, K, Brown, PM, Humphriss, D, Davidson, AJM, Rose, R, Armistead, L, Townsend, S, Poon, P, Peacock, IDA, Culverwell, NJC, Charlton, MH, Connolly, BPS, Peacock, J, Barrett, J, Wain, J, Beeston, W, King, G, Hill, PG, Boulton, AJM, Robertson, AM, Katoulis, V, Olukoga, A, McDonald, H, Kumar, S, Abouaesha, F, Abuaisha, B, Knowles, EA, Higgins, S, Booker, J, Sunter, J, Breislin, K, Parker, R, Raval, P, Curwell, J, Davenport, H, Shawcross, G, Prest, A, Grey, J, Cole, H, Sereviratne, C, Young, RJ, Clyne, JR, Gibson, M, O'Connell, I, Wong, LM, Wilson, SJ, Wright, KL, Wallace, C, McDowell, D, Burden, AC, Sellen, EM, Gregory, R, Roshan, M, Vaghela, N, Burden, M, Sherriff, C, Mansingh, S, Clarke, J, Grenfell, J, Tooke, JE, MacLeod, K, Seamark, C, Rammell, M, Pym, C, Stockman, J, Yeo, C, Piper, J, Leighton, L, Green, E, Hoyle, M, Jones, K, Hudson, A, James, AJ, Shore, A, Higham, A, Martin, B, Neil, HAW, Butterfield, WJH, Doll, WRS, Eastman, R, Ferris, FR, Kurinij, N, McPherson, K, Mahler, RF, Meade, TW, Shafer, G, Watkins, PJ, Keen, H, Siegel, D, Betteridge, DJ, Cohen, RD, Currie, D, Darbyshire, J, Forrester, JV, Guppy, T, Johnston, DG, McGuire, A, Murphy, M, el-Nahas, AM, Pentecost, B, Spiegelhalter, D, Alberti, KGMM, Denton, R, Home, PD, Howell, S, Jarrett, JR, Marks, V, Marmot, M, Ward, JD, and Grp, UKPDS

Subjects
General Medicine
Published
1998

14. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group

Author

Stearne, MR, Palmer, SL, Hammersley, MS, Franklin, SL, Spivey, RS, Levy, JC, Tidy, CR, Bell, NJ, Steemson, J, Barrow, BA, Coster, R, Waring, K, Nolan, J, Truscott, E, Walravens, N, Cook, L, Lampard, H, Merle, C, Parker, P, McVittie, J, Draisey, I, Murchison, LE, Brunt, AHE, Williams, MJ, Pearson, DW, Petrie, XMP, Lean, MEJ, Walmsley, D, Lyall, MJ, Christie, E, Church, J, Thomson, E, Farrow, A, Stowers, JM, Stowers, M, McHardy, K, Patterson, N, Wright, AD, Levi, NA, Shearer, ACI, Thompson, RJW, Taylor, G, Rayton, S, Bradbury, M, Glover, A, Smyth-Osbourne, A, Parkes, C, Graham, J, England, P, Gyde, S, Eagle, C, Chakrabarti, B, Smith, J, Sherwell, J, Kohner, EM, Dornhurst, A, Doddridge, MC, Dumskyj, M, Walji, S, Sharp, P, Sleightholm, M, Vanterpool, G, Rose, C, Frost, G, Roseblade, M, Elliott, S, Forrester, S, Foster, M, Myers, K, Chapman, R, Hayes, JR, Henry, RW, Featherston, MS, Archbold, GPR, Copeland, M, Harper, R, Richardson, I, Martin, S, Davison, HA, Hadden, DR, Kennedy, L, Atkinson, AB, Culbert, AM, Hegan, C, Tennet, H, Webb, N, Robinson, I, Holmes, J, Bell, PM, McCance, DR, Rutherford, J, Nesbitt, S, Spathis, AS, Hyer, S, Nanson, ME, James, LM, Tyrell, JM, Davis, C, Strugnell, P, Booth, M, Petrie, H, Clark, D, Rice, B, Hulland, S, Barron, JL, Yudkin, JS, Gould, BJ, Singer, J, Badenock, A, Eckert, M, Alibhai, K, Marriot, E, Cox, C, Price, R, Fernandez, M, Ryle, A, Clarke, S, Wallace, G, Mehmed, E, MacFarlane, S, Greenwood, RH, Wilson, J, Denholm, MJ, Temple, RC, Whitfield, K, Johnson, F, Munroe, C, Gorick, S, Duckworth, E, Flatman, M, Rainbow, S, Borthwick, LJ, Wheatcroft, DJ, Seaman, RJ, Christie, RA, Wheatcroft, W, Musk, P, White, J, McDougal, S, Bond, M, Raniga, P, Newton, RW, Jung, RT, Roxburgh, C, Kilgallon, B, Dick, L, Waugh, N, Kilby, S, Ellingford, A, Burns, J, Fox, CV, Holloway, MC, Coghill, HM, Hein, N, Fox, A, Cowan, W, Richard, M, Quested, K, Evans, SJ, Paisey, RB, Brown, NPR, Tucker, AJ, Paisey, R, Garrett, F, Hogg, J, Park, P, Williams, K, Harvey, P, Wilcocks, R, Mason, S, Frost, J, Warren, C, Rocket, P, Bower, L, Roland, JM, Brown, DJ, Youens, J, Stanton-King, K, Mungall, H, Ball, V, Maddison, W, Donnelly, D, King, S, Griffin, P, Smith, S, Church, S, Dunn, G, Wilson, A, Palmer, K, Brown, PM, Humphriss, D, Davidson, AJM, Rose, R, Armistead, L, Townsend, S, Poon, P, Peacock, IDA, Culverwell, NJC, Charlton, MH, Connolly, BPS, Peacock, J, Barrett, J, Wain, J, Beeston, W, King, G, Hill, PG, Boulton, AJM, Robertson, AM, Katoulis, V, Olukoga, A, McDonald, H, Kumar, S, Abouaesha, F, Abuaisha, B, Knowles, EA, Higgins, S, Booker, J, Sunter, J, Breislin, K, Parker, R, Raval, P, Curwell, J, Davenport, H, Shawcross, G, Prest, A, Grey, J, Cole, H, Sereviratne, C, Young, RJ, Dornan, TL, Clyne, JR, Gibson, M, O'Connell, I, Wong, LM, Wilson, SJ, Wright, KL, Wallace, C, McDowell, D, Burden, AC, Sellen, EM, Gregory, R, Roshan, M, Vaghela, N, Burden, M, Sherriff, C, Clarke, J, Grenfell, J, Tooke, JE, MacLeod, K, Searnark, C, Rammell, M, Pym, C, Stockman, J, Yeo, C, Piper, J, Leighton, L, Green, E, Hoyle, M, Jones, K, Hudson, A, James, AJ, Shore, A, Higham, A, Martin, B, and Grp, USPDS

Abstract

OBJECTIVE: To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes. DESIGN: Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of

Published
1998

15. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group

Author

Stearne, MR, Palmer, SL, Hammersley, MS, Franklin, SL, Spivey, RS, Levy, JC, Tidy, CR, Bell, NJ, Steemson, J, Barrow, BA, Coster, R, Waring, K, Nolan, L, Truscott, E, Walravens, N, Cook, BL, Lampard, H, Merle, C, Parker, P, McVittie, J, Draisey, I, Murchison, LE, Brunt, AHE, Williams, MJ, Pearson, DW, Petrie, XMP, Lean, MEJ, Walmsley, D, Lyall, F, Christie, E, Church, J, Thomson, E, Farrow, A, Stowers, JM, Stowers, M, McHardy, K, Patterson, N, Wright, AD, Levi, NA, Shearer, AGI, Thompson, RJW, Taylor, G, Rayton, S, Bradbury, M, Glover, A, Smyth-Osbourne, A, Parkes, C, Graham, J, England, P, Gyde, S, Eagle, C, Chakrabarti, B, Smith, J, Sherwell, J, Kohner, EM, Dornhorst, A, Doddridge, MC, Dumskyj, M, Walji, S, Sharp, P, Sleightholm, M, Vanterpool, G, Rose, C, Frost, G, Roseblade, M, Elliott, S, Forrester, S, Foster, M, Myers, K, Chapman, R, Hayes, JR, Henry, TW, Featherston, MS, Archbold, GPR, Copeland, M, Harper, R, Richardson, I, Martin, S, Davison, HA, Hadden, DR, Kennedy, L, Atkinson, AB, Culbert, AM, Hegan, C, Tennet, H, Webb, N, Robinson, I, Holmes, J, Bell, PM, McCance, DR, Rutherford, J, Nesbitt, S, Spathis, AS, Hyer, S, Nanson, ME, James, JM, Tyrell, JM, Davis, C, Strugnell, P, Booth, M, Petrie, H, Clark, D, Rice, B, Hulland, S, Barron, JL, Yudkin, JS, Gould, BJ, Singer, J, Badenock, A, Eckert, M, Alibhai, K, Marriot, E, Cox, C, Price, R, Fernandez, M, Ryle, A, Clarke, S, Wallace, G, Mehmed, E, MacFarlane, S, Greenwood, RH, Wilson, J, Denholm, MJ, Temple, RC, Whitfield, K, Johnson, F, Munroe, C, Gorick, S, Duckworth, E, Flatman, M, Rainbow, S, Borthwick, LJ, Wheatcroft, DJ, Seaman, RJ, Christie, RA, Wheatcroft, W, Musk, P, White, J, McDougal, S, Bond, M, Raniga, P, Newton, RW, Jung, RT, Roxburgh, C, Kilgallon, B, Dick, L, Waugh, N, Kilby, S, Ellingford, A, Burns, J, Fox, CV, Holloway, MC, Coghill, HM, Hein, N, Fox, A, Cowan, W, Richard, M, Quested, K, Evans, SJ, Paisey, RB, Brown, NPR, Tucker, AJ, Paisey, R, Garrett, F, Hogg, J, Park, P, Williams, K, Harvey, P, Wilcocks, R, Mason, S, Frost, J, Warren, C, Rocket, P, Bower, L, Roland, JM, Brown, DJ, Youens, J, Stanton-King, K, Mungall, H, Ball, V, Maddison, W, Donnelly, D, King, S, Griffin, P, Smith, S, Church, S, Dunn, G, Wilson, A, Palmer, K, Brown, PM, Humphriss, D, Davidson, AJM, Rose, R, Armistead, L, Townsend, S, Poon, P, Peacock, IDA, Culverwell, NJC, Charlton, MH, Connolly, BPS, Peacock, J, Barrett, J, Wain, J, Beeston, W, King, G, Hill, PG, Boulton, AJM, Robertson, AM, Katoulis, V, Olukoga, A, McDonald, H, Kumar, S, Abouaesha, F, Abuaisha, B, Knowles, EA, Higgins, S, Booker, J, Sunter, J, Breislin, K, Parker, R, Raval, P, Curwell, J, Davenport, H, Shawcross, G, Prest, A, Grey, J, Cole, H, Sereviratne, C, Young, RJ, Dornan, TL, Clyne, JR, Gibson, M, O'Connell, I, Wong, LM, Wilson, SJ, Wright, KL, Wallace, C, McDowell, D, Burden, AC, Sellen, EM, Gregory, R, Roshan, M, Vaghela, N, Burden, M, Sherriff, C, Clarke, J, Grenfell, J, Tooke, JE, MacLeod, K, Searnark, C, Rammell, M, Pym, C, Stockman, J, Yeo, C, Piper, J, Leighton, L, Green, E, Hoyle, M, Jones, K, Hudson, A, James, AJ, Shore, A, Higham, A, Martin, B, and Grp, USPDS

Subjects
cardiovascular diseases, circulatory and respiratory physiology
Abstract

OBJECTIVE: To determine whether tight control of blood pressure with either a beta blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes. DESIGN: Randomised controlled trial comparing an angiotensin converting enzyme inhibitor (captopril) with a beta blocker (atenolol) in patients with type 2 diabetes aiming at a blood pressure of =300 mg/l (5% and 9%). The proportion of patients with hypoglycaemic attacks was not different between groups, but mean weight gain in the atenolol group was greater (3.4 kg v 1.6 kg). CONCLUSION: Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications. This study provided no evidence that either drug has any specific beneficial or deleterious effect, suggesting that blood pressure reduction in itself may be more important than the treatment used.

Published
1998

16. LETTERS

Author

Yudkin Js

Subjects
medicine.medical_specialty, Endocrinology, Postprandial, business.industry, Endocrinology, Diabetes and Metabolism, Internal medicine, Internal Medicine, medicine, Cardiology, Disease, business
Published
2006

19. Leptin levels in type 2 diabetes: Associations with measures of insulin resistance and insulin secretion

Author

UCL, Wauters, M, Considine, RV, Yudkin, JS, Peiffer, F, De Leeuw, I, Van Gaal, LF, UCL, Wauters, M, Considine, RV, Yudkin, JS, Peiffer, F, De Leeuw, I, and Van Gaal, LF

Abstract

Interactions between leptin and insulin have been shown previously, in vitro and in vivo. In this study, we evaluate the associations of leptin levels with insulin secretion and insulin sensitivity in type 2 diabetes. Fasting leptin levels, HbA(1C), glucose, insulin, C-peptide, intact and des-31,32-proinsulin were measured in 100 non-insulin-treated type 2 diabetic patients. Glucose, insulin and C-peptide were measured 2 hours after an oral glucose load. Insulin resistance and beta-cell function were calculated using HOMA. Leptin levels were found to be associated with all measures of beta-cell secretion: with fasting and 2 hours insulin and C-peptide, with intact and des-31,32-proinsulin concentrations, and with beta-cell secretion estimated with HOMA. This association was independent of age and body fat in women, but in men, associations with insulin and C-peptide weakened after controlling for fat mass, whereas those with intact and des-31,32-proinsulin disappeared. Fasting insulin and C-peptide levels were also significant in multiple regression analyses, besides gender and fat mass. Insulin resistance, as assessed by HOMA, was strongly correlated with leptin, also after correction for age and fat mass in both genders. We conclude that, besides fat mass and gender the main determinants for leptin levels in type 2 diabetic subjects as in healthy subjects - insulin secretion and the degree of insulin resistance also seem to contribute significantly to leptin levels.

Published
2003

27. Perivascular adipose tissue and its role in type 2 diabetes and cardiovascular disease.

Author

Meijer RI, Serne EH, Smulders YM, van Hinsbergh VW, Yudkin JS, Eringa EC, Meijer, Rick I, Serne, Erik H, Smulders, Yvo M, van Hinsbergh, Victor W M, Yudkin, John S, and Eringa, Etto C

Abstract

Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity. Adipose tissue-derived substances (adipokines) and especially inflammatory products of adipose tissue control insulin sensitivity and vascular function. In the past years, adipose tissue associated with the vasculature, or perivascular adipose tissue (PAT), has been shown to produce a variety of adipokines that contribute to regulation of vascular tone and local inflammation. This review describes our current understanding of the mechanisms linking perivascular adipose tissue to vascular function, inflammation, and insulin resistance. Furthermore, we will discuss mechanisms controlling the quantity and adipokines secretion by PAT. [ABSTRACT FROM AUTHOR]

Published
2011
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30. Life-course socio-economic factors, skin colour and abdominal obesity in adulthood in a Brazilian birth cohort.

Author

González DA, Nazmi A, Yudkin JS, Victora CG, González, David A, Nazmi, Aydin, Yudkin, John S, and Victora, Cesar G

Abstract

Objective: Obesity is an increasingly prevalent nutritional disorder throughout the world. In particular, abdominal obesity is associated with cardiovascular and metabolic risk. The present study aimed to evaluate the effects of skin colour and life-course socio-economic indicators on waist circumference (WC), hip circumference (HC) and waist:hip ratio (WHR) in young adults.Design: Population-based birth cohort study. Individuals born in 1982 in Pelotas (southern Brazil) were visited on a number of occasions from birth to age 23-24 years. A sample of the cohort was sought in 2006 and 972 individuals were located. The analysis was restricted to individuals with complete data available (442 males, 414 females).Results: In men, family income at birth and in 2004-5 were positively associated with WC and HC, but not with WHR. Regardless of current income, men born to wealthier families had larger WC and HC as adults. Skin colour was not associated with any of the outcomes. In women, early poverty was associated with smaller HC, and current poverty with larger WC. Poverty at any age thus led to higher WHR. Black women had larger WC and HC than white women, but there were no differences in WHR. All the associations were partially mediated by education and behavioural variables.Conclusions: The effects of early socio-economic position on WC and HC persist even after adjustment for adult socio-economic position, highlighting the importance of interventions during the first years of life. [ABSTRACT FROM AUTHOR]

Published
2009
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34. Access to care for patients with insulin-requiring diabetes in developing countries: case studies of Mozambique and Zambia.

Author

Beran D, Yudkin JS, de Courten M, Beran, David, Yudkin, John S, and de Courten, Maximilian

Abstract

Objective: The objective of this study was to assess the barriers to care for patients with insulin-requiring diabetes in Mozambique and Zambia.Research Design and Methods: We used the Rapid Assessment Protocol for Insulin Access to collect information through interviews, discussions, site visits, and document reviews. Government organizations, health facilities, care givers, and patients were asked about care for people with insulin-requiring diabetes. Between 100 and 200 interviews/discussions per country were undertaken in and around the capital city and the regional capital and in a rural area.Results: Insulin was present in both countries in sufficient quantities, although the financial burden for health services and patients meant that problems with supply exist. There are problems with quantification of needs and equitable distribution of insulin. Problems with availability of syringes and testing equipment were noted, particularly in Mozambique. This lack of tools and infrastructure for diagnosis and follow-up coupled with low levels of health care worker training and lack of diagnostic reagents resulted in a substantial risk of misdiagnosis or failure to detect diabetes. The estimated prevalence of insulin-requiring diabetes differs more than 10-fold between urban and rural areas in Mozambique and 4-fold between Mozambique and Zambia, suggesting that problems in diagnosis and care result in substantial worsening of prognosis for such patients.Conclusions: Insulin is necessary but not sufficient to improve prognosis for diabetic patients. A Rapid Assessment Protocol methodology can be used to define problems in health care delivery for diabetes. Proper care for insulin-requiring diabetes necessitates health systems able to provide trained personnel, medicines in sufficient quantity, and diagnostic and monitoring facilities. [ABSTRACT FROM AUTHOR]

Published
2005
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46. Drug control: a prerequisite for health

Author

Yudkin Js

Subjects
Drug, media_common.quotation_subject, Developing country, Rural Health, World Health Organization, Procurement, Drug control, Environmental health, Health care, Medicine, Humans, Technology, Pharmaceutical, Marketing, Developing Countries, Health policy, General Environmental Science, media_common, business.industry, Rural health, Health Policy, General Engineering, Pharmaceutical Preparations, General Earth and Planetary Sciences, Drug and Narcotic Control, Rural area, business, Delivery of Health Care
Abstract

The purchase of drugs employs an increasingly large part of the health budget of many Third World countries. Like health care expenditure as a whole, drug spending is heavily biased in favour of urban hospitals, often for expensive proprietary drugs that offer little benefit over cheaper preparations. As a result, because limited funds are available, vaccines and drugs for prevention and primary care are sometimes unavailable, especially in rural areas. The World Health Organization and many individual countries have responded to the problem of drug costs by creating a limited list of drugs considered essential for health care needs. Other methods of curtailing spending on drugs have included tendering for supplies and the establishment of plants to manufacture and formulate drugs. Controls of this type meet enormous resistance from doctors and pharmaceutical manufacturers, but are vital for the implementation of policies for appropriate health care.

Published
1980

48. Associations of stunting in early childhood with cardiometabolic risk factors in adulthood

Author

De Lucia Rolfe, E, Vinícius Araújo De França, G, Avila Vianna, C, Gigante, DP, Miranda, JJ, Yudkin, JS, Lessa Horta, B, and Ong, KK

Subjects
4. Education, 3. Good health
Abstract

Early life stunting may have long-term effects on body composition, resulting in obesity-related comorbidities. We tested the hypothesis that individuals stunted in early childhood may be at higher cardiometabolic risk later in adulthood. 1753 men and 1781 women participating in the 1982 Pelotas (Brazil) birth cohort study had measurements of anthropometry, body composition, lipids, glucose, blood pressure, and other cardiometabolic traits at age 30 years. Early stunting was defined as height-for-age Z-score at age 2 years below -2 against the World Health Organization growth standards. Linear regression models were performed controlling for sex, maternal race/ethnicity, family income at birth, and birthweight. Analyses were stratified by sex when p-interaction, The last phase of the 1982 Pelotas (Brazil) birth cohort study was supported by the Wellcome Trust and the Fundação de Aparo à Pesquisa do Estado do Rio Grande do Sul; Brazil (Edital 04/2012 – PQG; Processo 12/2185-9). Earlier phases were funded by the International Development Research Centre (Canada), the WHO (Department of Child and Adolescent Health and Development and Human Reproduction Programme) to BLH, the Overseas Development Administration (currently the Department for International Development, United Kingdom), the European Union, the United Nations Development Fund for Women, the National Program for Centres of Excellence, the Pastorate of the Child (Brazil), the National Council for Scientific and Technological Development (CNPq; Brazil), and the Ministry of Health (Brazil). GVAF was supported by the Brazilian Coordination of Improvement of Higher Education Personnel (scholarship process BEX 5077/13-3). EDLR and KKO are supported by the Medical Research Council [Unit Programme number MC_UU_12015/2]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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