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1. Insulin action and skeletal muscle blood flow in patients with Type 1 diabetes and microalbuminuria

Author

Atkinson Ab, Patrick M. Bell, Wiggam Mi, B Sheridan, S.J Hunter, and C. N. Ennis

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Endocrinology, Insulin resistance, Hyperinsulinism, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Albuminuria, Humans, Insulin, Diabetic Nephropathies, Infusions, Intravenous, Muscle, Skeletal, Glycated Hemoglobin, Type 1 diabetes, Proteinuria, business.industry, General Medicine, Blood flow, Glucose clamp technique, medicine.disease, Kinetics, Diabetes Mellitus, Type 1, Glucose, Liver, Regional Blood Flow, Glucose Clamp Technique, Female, Microalbuminuria, medicine.symptom, business
Abstract

Our objective was to determine whether Type 1 diabetic patients with microalbuminuria are less sensitive to the effects of insulin on glucose metabolism and skeletal muscle blood flow, compared to those with normal albumin excretion, after careful matching for confounding variables. We recruited 10 normotensive Type 1 diabetic patients with microalbuminuria and 11 with normoalbuminuria matched for age, sex, body mass index, duration of diabetes and HbA(1c). Peripheral and hepatic insulin action was assessed using a two-step euglycaemic hyperinsulinaemic clamp (2 h at 0.4 mU x kg(-1) x min(-1), 2 h at 2.0 mU x kg(-1) x min(-1)) combined with isotope dilution methodology. Skeletal muscle blood flow was determined by venous occlusion plethysmography. During the clamps, glucose infusion rates required to maintain euglycaemia were similar in the microalbuminuric subjects and controls (step 1, 8.2+/-1.4 (SE) vs 9.2+/-1.3 micromol x kg(-1) x min(-1): step 2, 30.9+/-2.7 vs 32.0+/-3.8 micromol x kg(-1) x min(-1)), as was hepatic glucose production basally and at steady state in step 1. In step 2, hepatic glucose production was lower in the microalbuminuric group (2.9+/-0.9 vs 6.4+/-0.7 micromol x kg(-1) x min(-1), P=0.005). During step 2, skeletal muscle blood flow increased significantly above baseline in the normoalbuminuric group (4.1+/-0.5 vs 3.2+/-0.4 ml x 100-ml(-1) x min(-1), P=0.01) but not in the microalbuminuric group (2.4+/-0.3 vs 2.3+/-0.4 ml x 100-ml(-1) x min(-1)). In conclusion, microalbuminuria in Type 1 diabetes was found to be associated with impairment of insulin-mediated skeletal muscle blood flow, but not with insulin resistance.

Published
2001
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2. 2. Anti-Xa activity with local treatment protocols for acute coronary syndrome

Author

Bennett, JR, McOsker, J, Jardine, TCL, Scott, PJ, McKeown, PP, Lyons, KS, Menown, IBA, Wright, SA, O'Prey, FM, McHenry, MT, Leahey, WJ, Devine, AB, Duffy, EM, Johnston, DG, Finch, MB, McVeigh, GE, Bell, AL, Cuthbertson, J, Patterson, S, O'Harte, FPM, Bell, PM, Lewis, AS, Callender, ME, Chew, E, Courtney, CH, McDougal, N, Atkinson, AB, Morrice, K, Hastings, J, McClements, B, Scott, P, Kodoth, V, Noad, R, Bennet, J, Murphy, C, Manoharan, G, and Adgey, AAJ

Subjects
Abstracts, Presented Abstract
Published
2008

3. Mortality following Percutaneous Endoscopic Gastrostomy: results of the National Confidential Enquiry into Patient Outcome and Death

Author

Tolland, JP, McKenna, KE, Elborn, JS, Johnston, SD, Tham, TCK, Mason, M, McVeigh, CL, Passmore, AP, McSorley, A, Power, M, Gilmore, D, Steele, I, Beringer, TRO, Wiggam, MI, Kodoth, V, Hastings, J, McClements, B, Deore, R, Harte, S, Bowers, MJ, El-Agnaf, M, Ong, YL, McGuinness, B, Todd, S, Bullock, R, Mackay, EM, Mamanasiri, S, Atkinson, AB, Sheridan, B, Refetoff, S, and Courtney, CH

Subjects
Abstracts, Presented Abstract
Published
2007

4. Captopril does not improve insulin action in essential hypertension

Author

Atkinson Ab, Sheridan B, Wiggam Mi, C. N. Ennis, Henry Js, Steven J. Hunter, Bell Pm, and J. Browne

Subjects
Blood Glucose, Male, medicine.medical_specialty, Captopril, Patient Dropouts, Systole, Physiology, medicine.medical_treatment, Placebo-controlled study, Blood Pressure, Placebo, Essential hypertension, Body Mass Index, Insulin resistance, Double-Blind Method, Diastole, Internal medicine, Internal Medicine, medicine, Humans, Insulin, Antihypertensive Agents, Leg, Cross-Over Studies, biology, business.industry, Body Weight, Cholesterol, HDL, Angiotensin-converting enzyme, Fasting, Middle Aged, medicine.disease, Crossover study, Cholesterol, Endocrinology, Regional Blood Flow, Hypertension, biology.protein, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

OBJECTIVE To compare the effect of captopril with that of placebo on peripheral and hepatic insulin action in essential hypertension, in light of evidence that insulin resistance is associated with cardiovascular risk. DESIGN Randomized, double-blind, placebo-controlled, crossover trial, with 8 week treatment periods of captopril and placebo preceded and separated by 6 weeks of placebo. SETTING Belfast teaching hospital. PATIENTS Eighteen Caucasian nondiabetic patients (10 males), aged under 65 years, with essential hypertension, recruited from general practices in the greater Belfast area. INTERVENTIONS Captopril at 50 mg twice a day or placebo twice a day for two 8 week treatment periods. MAIN OUTCOME MEASURES Peripheral and hepatic insulin sensitivity assessed by glucose clamps. RESULTS Fourteen patients completed the study. Mean (+/- SEM) levels of fasting glucose, fasting insulin and postabsorptive hepatic glucose production were similar after captopril and placebo (5.4+/-0.1 versus 5.4+/-0.1 mmol/l, 10.6+/-2.2 versus 9.5+/-1.1 mU/l, 11.2+/-0.6 versus 11.0+/-0.5 mmol/kg per min, respectively). During hyperinsulinaemia, hepatic glucose production was suppressed to comparable levels after both treatments (4.8+/-0.6 versus 4.3+/-0.6 mmol/kg per min) and exogenous glucose infusion rates required to maintain euglycaemia were also similar (30.0+/-2.6 versus 30.3+/-2.6 mmol/kg per min). CONCLUSION Captopril therapy in uncomplicated essential hypertension has no effect on peripheral or hepatic insulin sensitivity.

Published
1998
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5. 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
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7. Basal and Stimulated Plasma Atrial Natriuretic Factor in Patients With Type 1 Diabetes With and Without Nephropathy

Author

McKnight Ja, Atkinson Ab, G. Roberts, B. Sheridan, and Patrick M. Bell

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Radioimmunoassay, Hemodynamics, Blood Pressure, Nephropathy, Excretion, Basal (phylogenetics), Endocrinology, Atrial natriuretic peptide, Internal medicine, Internal Medicine, medicine, Albuminuria, Humans, Diabetic Nephropathies, Type 1 diabetes, business.industry, Sodium, medicine.disease, Diabetes Mellitus, Type 1, Blood pressure, Female, Microalbuminuria, business, Atrial Natriuretic Factor
Abstract

Hypertension is linked to the development of nephropathy in Type 1 diabetes. Total exchangeable sodium is elevated in patients with Type 1 diabetes in good metabolic control, and correlates with blood pressure. Atrial natriuretic factor has been shown to have effects on sodium and blood pressure homeostasis in man. Basal and NaCl-stimulated plasma atrial natriuretic factor was therefore studied in 33 patients with Type 1 diabetes. Seventeen had no evidence of nephropathy, 11 had incipient nephropathy (albumin excretion rate 20-199 micrograms min-1) and five had overt nephropathy. Seventeen age- and sex-matched normal control subjects were also studied. Subjects fasted from 2200 h, rose at 0745 h and remained ambulant until 0945 h. After 15 min supine, 2 l 0.15 mmol l-1 NaCl was infused over 4 h. Basal erect (0945 h) plasma atrial natriuretic factor was 4.2 +/- 0.5, 3.5 +/- 0.4, 2.5 +/- 0.2, and 2.5 +/- 0.3 pmol l-1 in the control, non-nephropathic, incipient-nephropathic, and overt nephropathic diabetic groups, respectively (all NS). Levels in all groups increased in response to NaCl infusion, and the responses were not different between groups. Urinary sodium excretion for 12 h before NaCl infusion was not different between groups, but during the 12 h after the start of the infusion was significantly (p less than 0.05) less in the Type 1 diabetic group without nephropathy than in the control group. These results suggest that atrial natriuretic factor does not play a major role in the development of changes in sodium balance which are associated with Type 1 diabetes and nephropathy.

Published
1991
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9. 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

10. 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

11. 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

12. Effects of combination therapy with an angiotensin converting enzyme inhibitor and thiazide diuretic on insulin action in essential hypertension

Author

Steven J. Hunter, Sheridan B, R. Harper, Atkinson Ab, E. Crothers, C. N. Ennis, Bell Pm, and G D Johnston

Subjects
Male, medicine.medical_specialty, Captopril, Physiology, medicine.medical_treatment, Sodium Chloride Symporter Inhibitors, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Essential hypertension, Insulin resistance, Double-Blind Method, Internal medicine, Internal Medicine, medicine, Outpatient clinic, Humans, Diuretics, Thiazide, Antihypertensive Agents, Cross-Over Studies, biology, business.industry, Insulin, Angiotensin-converting enzyme, Middle Aged, medicine.disease, Endocrinology, Liver, Bendroflumethiazide, Hypertension, biology.protein, Glucose Clamp Technique, Drug Therapy, Combination, Female, Diuretic, Insulin Resistance, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

OBJECTIVE To determine whether combination of an angiotensin converting enzyme inhibitor with a high dose of thiazide diuretic avoids adverse metabolic consequences of thiazide diuretics. DESIGN Double-blind randomized crossover study of two 12-week treatment periods with captopril (up to 100 mg/day) either alone or in combination with 5 mg bendrofluazide given after a 6-week placebo run-in period. Treatment periods were separated by a 6-week placebo washout period. SETTING Outpatient clinics in greater Belfast. PATIENTS Fifteen white non-diabetic essential hypertensives (seven male) aged < 65 years recruited from general practices in greater Belfast. MAIN OUTCOME MEASURES Systolic and diastolic blood pressures and peripheral and hepatic insulin action. RESULTS Two patients failed to complete the study. Blood pressure was lowered (139/89+/-18/7 mmHg combination versus 160/97+/-21/7 mmHg captopril; P < 0.001). Fasting insulin level was raised (7.9+/-3.6 mU/l combination versus 6.2+/-3.2 mU/l baseline; P < 0.001). There were no differences between treatments for glucose, urate, cholesterol and triglyceride levels. Serum potassium level was lowered (3.8+/-0.4 mmol/l combination versus 4.2+/-0.4 mmol/l captopril, P < 0.05). Postabsorptive endogenous glucose production was raised (10.8+/-1.7 micromol/kg per min combination versus 10.0+/-1.5 micromol/kg per min captopril; P < 0.01) and was greater than baseline (9.7+/-2.1 micromol/kg per min, P < 0.05). Suppression of glucose production by insulin was similar with both treatments. Exogenous glucose infusion rates required to maintain euglycaemia did not differ (32.4+/-7.6 micromol/kg per min captopril, 32.7+/-6.2 micromol/kg per min combination, 31.5+/-7.2 micromol/kg per min baseline). CONCLUSIONS Combination therapy increased glucose production (compared with captopril alone), indicating hepatic insulin resistance. It cannot be assumed that combined preparations with angiotensin converting enzyme inhibitors will ameliorate adverse effects of high doses of thiazide diuretics on insulin action.

Published
1998

13. Skeletal muscle blood flow is not a determinant of insulin resistance in essential hypertension

Author

Bell Pm, C. N. Ennis, R. Harper, Sheridan B, Atkinson Ab, and Steven J. Hunter

Subjects
Male, medicine.medical_specialty, Physiology, medicine.medical_treatment, Glucose uptake, Hemodynamics, Stimulation, Essential hypertension, Insulin resistance, Internal medicine, Internal Medicine, medicine, Outpatient clinic, Humans, Insulin, Muscle, Skeletal, Leg, business.industry, Blood flow, Middle Aged, medicine.disease, Plethysmography, Vasodilation, Endocrinology, Case-Control Studies, Hypertension, Female, Insulin Resistance, Cardiology and Cardiovascular Medicine, business, Blood Flow Velocity
Abstract

Objective To investigate the haemodynamic effects of insulin and their relationship to insulin resistance in essential hypertension. Design Group comparison between patients with essential hypertension and normal controls. Setting Outpatient clinics serving the greater Belfast area. Patients Eleven patients with essential hypertension and eight age-, sex- and weight-matched control subjects were recruited. Administration of all antihypertensive agents to the hypertensive patients was stopped 6 weeks prior to the study. Methods Leg blood flow was measured using venous occlusion plethysmography. Insulin action was assessed using the hyperinsulinaemic euglycaemic clamp technique. Results The hypertensive subjects were insulin-resistant compared with the normal controls. Insulin infusion resulted in similar increases in calf blood flow in the two groups. There was no correlation between calf blood flow and measurements of insulin sensitivity in either group. Conclusions Differences in whole-body glucose uptake in hypertensive and control subjects are not likely to be related to differences in insulin-induced stimulation of muscle blood flow.

Published
1997

14. Variation in left atrial anatomy in a Northern Irish population: a 64 multi-detector CT study

Author

McHenry, CM, Atkinson, AB, Hunter, SJ, Browne, J, Ennis, CN, Henry, J, Sheridan, B, Bell, PM, Cole, BRW, Purvis, JA, Hughes, SM, Morgan, DR, Donaghy, AE, McCrory, RFR, Walker, S, Convery, RP, Hall, PSJ, Taylor, M, Johnston, SD, Wazir, TU, Cairns, AP, Lewis, G, McQuillan, SL, Adgey, CH, Carl, I, Bhat, S, Lakhanpal, A, Lynch, P, Varghese, A, Scott, PJ, Smith, B, Manoharan, G, Johnson, PW, Neill, J, Douglas, H, Richardson, G, Chew, E, Walsh, S, Hanratty, C, Herity, N, Howe, AJ, Graham, UM, Ritchie, CM, McCance, DR, Donnelly, Deirdre E, McConnell, Vivienne PM, Leslie, H, Young, IS, Mullan, KR, Hunter, M, Hedderwick, S, Donnelly, C, Lewis, AS, McCourt, HJ, Boreham, CA, Courtney, CH, McKinley, MC, Murray, LJ, Woodside, JV, McKavanagh, P, Smyth, AI, Donnelly, PM, Hunter, HL, Corbett, JR, Fearon, P, Kinnaird, M, MacNair, S, Fullerton, K, and Wiggam, MI

Subjects
The Ulster Society of Internal Medicine: 82nd -84th meetings, 2009-2010, familial, three-generation, phenotypic variation, Sotos syndrome, Abstract
Abstract

Throughout the Northern Trust, two different thrombolytic agents, either reteplase or tenecteplase, are used as part of the treatment of acute ST elevation myocardial infarction. Having found no other comparative studies, this retrospective study was designed to compare the efficacy of the two drugs using rate of follow-on emergency angioplasty as the primary outcome. The study retrospectively recruited 40 patients who had received reteplase and 40 who had received tenecteplase. Of the patients who received reteplase, 5 required emergency angiography. Of those who received tenecteplase, 15 required further intervention. This was a significant difference with a ratio of 37.5%:12.5% (p=0.01; significance was assumed to be p, Sotos syndrome is a relatively common overgrowth disorder, following autosomal dominant inheritance, caused by mutations and deletions in the nuclear receptor Set domain containing protein-1, NSD1 gene. Affected individuals generally have advanced bone age, macrocephaly, characteristic facial gestalt and learning difficulties. Other features include scoliosis, seizures, cardiac defects and genitourinary anomalies. Tumours are a rare occurrence. Genotype-phenotype correlations are unclear, though those with a deletion appear to have more severe mental retardation. Full penetrance is seen, although familial Sotos syndrome is extremely rare. The low vertical transmission rate, which is not fully explained by cognitive impairment, is of great importance, particularly for mildly affected patients. Here we report a 3-generation pedigree with 7 affected individuals shown to harbour the NSD1 missense mutation c. 6115C>T. To our knowledge this is the largest Sotos family to be reported. The phenotype is extremely variable, thus highlighting the clinical heterogeneity that may occur. Detailed study of individuals with NSD1 gene abnormalities will be invaluable for further clarification of the phenotype and may lead to NSD1 gene analysis having prognostic value. Long-term follow up of these rare cases of familial Sotos syndrome should make an important contribution to the clarification of these uncertainties.

Published
2011

15. The gene responsible for familial hypocalciuric hypercalcemia maps to chromosome 3q in four unrelated families

Author

Jonathan G. Seidman, Y.-H. Chou, Christine E. Seidman, Toss G, Edward M. Brown, Ghada El-Hajj Fuleihan, Atkinson Ab, Arnqvist Hj, Tatjana Levi, and G. Crowe

Subjects
Male, medicine.medical_specialty, Genetic Linkage, Molecular Sequence Data, Locus (genetics), Biology, Polymerase Chain Reaction, Genetic linkage, Internal medicine, Genetics, medicine, Humans, Gene, Metal Metabolism, Inborn Errors, Calcium metabolism, Polymorphism, Genetic, Familial hypocalciuric hypercalcemia, Base Sequence, Chromosome Mapping, DNA, medicine.disease, Urinary calcium, Chromosome Banding, Pedigree, Endocrinology, medicine.anatomical_structure, Chromosome 3, Oligodeoxyribonucleotides, Parathyroid gland, Calcium, Female, Chromosomes, Human, Pair 3, Lod Score, DNA Probes
Abstract

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant syndrome of unknown aetiology characterized by lifelong elevation in serum calcium concentration and low urinary calcium excretion. These features suggest that the causal gene is important for maintenance of extracellular calcium homeostasis by the parathyroid gland and kidney. To identify the chromosomal location of FHH gene(s), we clinically evaluated 114 individuals in four unrelated affected families and performed linkage analyses. The disease gene mapped to the long arm of chromosome 3 in each family (combined maximum multipoint lod score = 20.67). We suggest that this is the predominant FHH locus and anticipate that identification of the FHH gene will improve our understanding of the molecular basis for physiologic and pathologic regulation of calcium.

Published
1992

16. Variations in the plasma concentration of atrial natriuretic factor across 24 hours

Author

McKnight Ja, Brian Sheridan, G. Roberts, Atkinson Ab, H. Leslie, D.R. McCance, and Merrett Jd

Subjects
Adult, Employment, Male, medicine.medical_specialty, Supine position, Hydrocortisone, Endocrinology, Diabetes and Metabolism, Posture, Plasma renin activity, chemistry.chemical_compound, Endocrinology, Internal medicine, Renin, Medicine, Humans, Circadian rhythm, Aldosterone, Exercise, business.industry, General Medicine, Feeding Behavior, Circadian Rhythm, Normal variation, chemistry, Plasma concentration, Female, business, Nadir (topography), Atrial Natriuretic Factor, Hormone
Abstract

There is little information available concerning the presence or absence of a normal variation in the circulating concentration of atrial natriuretic homone throughout a 24 h period. We have examined this in 8 normal subjects (aged 23–35 years) on a fixed 120 mmol Na+ diet. Circulating levels of ANH, plasma renin activity, serum aldosterone and serum cortisol were determined two-hourly during 24 h in a supine position. There was a significant change in the concentration of each of these four hormones during the study period (P< 0.05). ANH: peak 8.5 (22.00 h), nadir 4.0 (12.00 h) (pmol/l); PRA: peak 1.7 (04.00 h), nadir 0.8 (22.00 h) (μg · l−1 · h−1); aldosterone: peak 350 (14.00 h), nadir 143 (22.00 h) (pmol/l); cortisol: peak 346 (08.00 h), nadir 51 (22.00 h) (nmol/l). Peak plasma ANH occurred at 22.00 h and with the exception of times 20.00 h and 10.00 h this value was significantly higher than all the other time means (P< 0.05). The only other significant differences were between plasma ANH at 20.00 h and 06.00 h, 08.00 h, 12.00 h and 14.00 h, respectively (P< 0.05). From midnight until 18.00 h, there was no significant difference between any of the time means. There was a peak in PRA at 04.00 h, while peak serum aldosterone and serum cortisol occurred at 14.00 h and 08.00 h, respectively. This study suggests that ANH may display a diurnal rhythm. Our findings provide further physiological evidence that plasma ANH and PRA may have a reciprocal relationship.

Published
1989

17. Diagnosis and Complications of Cushing’s Syndrome: A Consensus Statement

Author

Xavier Bertagna, Ashley B. Grossman, Franco Mantero, André Lacroix, John Newell-Price, Blerina Kola, Marco Boscaro, Andrea Giustina, Mary Lee Vance, Rolf C. Gaillard, Giorgio Arnaldi, Tatiana Mancini, Lynnette K. Nieman, Giovanni A. Fava, George P. Chrousos, Nicoletta Sonino, Alberto Angeli, James W. Findling, A. B. Atkinson, F. Cavagnini, Arnaldi, G, Angeli, A, Atkinson, Ab, Bertagna, X, Cavagnini, F, Chrousos, Gp, Fava, Ga, Findling, Jw, Gaillard, Rc, Grossman, Ab, Kola, B, Lacroix, A, Mancini, T, Mantero, F, NEWELL PRICE, J, Nieman, Lk, Sonino, N, Vance, Ml, Giustina, Andrea, and Boscaro, M.

Subjects
medicine.medical_specialty, Statement (logic), Endocrinology, Diabetes and Metabolism, education, Clinical Biochemistry, MEDLINE, Biochemistry, Diagnosis, Differential, Cushing syndrome, Endocrinology, Internal medicine, Humans, Medicine, Cushing Syndrome, S syndrome, business.industry, Mental Disorders, Pituitary ACTH hypersecretion, Biochemistry (medical), Cushing's disease, medicine.disease, Cushing Disease, Inferior petrosal sinus sampling, Cardiovascular Diseases, Osteoporosis, Cognition Disorders, business
Abstract

In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on the management of Cushing's syndrome. The workshop was organized by the University of Ancona and sponsored by the Pituitary Society, the European Neuroendocrine Association, and the Italian Society of Endocrinology. Invited international participants included almost 50 leading endocrinologists with specific expertise in the management of Cushing's syndrome. The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.

Published
2003
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