Open Access
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
Uk-Prospective-Diabetes-Study-Group
- Vol. 352, Iss: 9131, pp 837-853
Reads0
Chats0
TLDR
The effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial were compared.Abstract:
BACKGROUND
Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial.
METHODS
3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy.
FINDINGS
Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg).
INTERPRETATION
Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)read more
Citations
More filters
Journal ArticleDOI
DURAbility of Basal Versus Lispro Mix 75/25 Insulin Efficacy (DURABLE) Trial 24-Week Results Safety and efficacy of insulin lispro mix 75/25 versus insulin glargine added to oral antihyperglycemic drugs in patients with type 2 diabetes
John B. Buse,Bruce H. R. Wolffenbuttel,William H. Herman,Natalie K. Shemonsky,Honghua H. Jiang,Jessie L. Fahrbach,Jamie Scism-Bacon,Sherry Martin +7 more
TL;DR: Compared with GL, LM75/25 resulted in slightly lower A1C at 24 weeks and a moderately higher percentage reaching A 1C target <7.0% and patients receiving LM 75/25 experienced more weight gain and higher rates of overall hypoglycemia but lower rates of nocturnal hypglycemia.
Journal ArticleDOI
Attenuation of renal injury in db/db mice overexpressing superoxide dismutase: evidence for reduced superoxide-nitric oxide interaction.
TL;DR: Evidence of increased NO responsiveness and the suppression of glomerular nitrotyrosine may both reflect reduced NO-superoxide interaction in SOD-Tg-db/db mice, implicate superoxide in the pathogenesis of diabetic nephropathy.
Journal ArticleDOI
Glomerular expression of thrombospondin-1, transforming growth factor beta and connective tissue growth factor at different stages of diabetic nephropathy and their interdependent roles in mesangial response to diabetic stimuli
Nadia Abdel Wahab,Liliana Schaefer,Benjamin S. Weston,O. Yiannikouris,A. Wright,Andrea Babelova,Roland M. Schaefer,Roger M. Mason +7 more
TL;DR: Increased glomerular expression of all three factors occurs from the earliest stage of diabetic nephropathy, and CTGF is required for mesangial synthesis of fibronectin stimulated by high glucose or glycated albumin, and is thus a potential therapeutic target.
Journal ArticleDOI
Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier function.
TL;DR: The role of DM on Sertoli/BTB glucose metabolism dynamics and the metabolic molecular mechanisms through which DM and insulin deregulation alter its functioning, affecting male reproductive potential will be discussed.
Journal ArticleDOI
Efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycaemia*.
Werner A. Scherbaum,Anja Schweizer,A. Mari,Peter M. Nilsson,G. Lalanne,S. Jauffret,J. E. Foley +6 more
TL;DR: This study was conducted to assess efficacy and tolerability of vildagliptin in drug‐naïve patients with type 2 diabetes and mild hyperglycaemia.
References
More filters
Journal Article
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
R C Turner,Rury R. Holman,Carole A. Cull,Irene M Stratton,David R Matthews,V Frighi,Susan E. Manley,Andrew Neil,K McElroy,D Wright,E. M. Kohner,Caroline S. Fox,D R Hadden,Z Mehta,Albert V. Smith,Z Nugent,Richard Peto,A I Adlel,Jim Mann,P A Bassett,S. Oakes,Tim Dornan,Stephen J Aldington,H Lipinski,R Collum,K Harrison,C MacIntyre,S Skinner,A Mortemore,D Nelson,S Cockley,S Levien,L Bodsworth,R Willox,T Biggs,S Dove,E Beattie,M Gradwell,S Staples,R Lam,F Taylor,L Leung,R D Carter,S M Brownlee,K E Fisher,K Islam,R. Jelfs,P A Williams,F A Williams,P J Sutton,A Ayres,Lisa Logie,C Lovatt,M A Evans,L A Stowell,I Ross,I A Kennedy,D. J. Croft,A H Keen,C Rose,M Raikou,A E Fletcher,Christopher J. Bulpitt,Clare Battersby,J S Yudkin,Richard Stevens,M R Stearn,S L Palmer,M S Hammersley,S L Franklin,R S Spivey,Jonathan C. Levy,C R Tidy,N J Bell,J Steemson,B A Barrow,R Coster,K Waring,L Nolan,E Truscott,N Walravens,L Cook,H Lampard,C Merle,P Parker,J McVittie,I Draisey,L E Murchison,Brunt Ahe.,M J Williams,D W Pearson,Petrie Xmp.,Lean Mej.,D Walmsley,F Lyall,E Christie,J Church,E Thomson,A Farrow,J M Stowers,M Stowers,K McHardy,N Patterson,Alex D. Wright,N A Levi,Shearer Aci.,Thompson Rjw.,G Taylor,S Rayton,M Bradbury,A Glover,A Smyth-Osbourne,C Parkes,J Graham,P England,S Gyde,C Eagle,B Chakrabarti,Josh Smith,J Sherwell,N. W. Oakley,M. Whitehead,G P Hollier,T. Pilkington,J Simpson,Michael W. Anderson,S Martin,J Kean,B Rice,A Rolland,J Nisbet,E M Kohner,A Dornhorst,M C Doddridge,M Dumskyij,S Walji,P Sharp,M Sleightholm,G Vanterpool,G Frost,M Roseblade,S Elliott,S Forrester,Meredith C. Foster,K Myers,R Chapman,J R Hayes,R W Henry,M S Featherston,Archbold Gpr.,M Copeland,R Harper,I Richardson,H A Davison,L Alexander,Scarpello Jhb.,D E Shiers,R J Tucker,Worthington Jrh.,S Angris,A Bates,J Walton,M Teasdale,J Browne,S Stanley,B A Davis,R C Strange,Hadden,L Kennedy,A B Atkinson,P M Bell,D R McCance,J Rutherford,A M Culbert,C Hegan,H Tennet,N Webb,I Robinson,J Holmes,S Nesbitt,A S Spathis,S Hyer,M E Nanson,L M James,J M Tyrell,C Davis,P Strugnell,M Booth,H Petrie,D Clark,S Hulland,J L Barron,B C Gould,J Singer,A Badenoch,M McGregor,L Isenberg,M Eckert,K Alibhai,E Marriot,Christopher E. Cox,R Price,M Fernandez,A Ryle,S Clarke,G Wallace,E Mehmed,J A Lankester,E Howard,A Waite,S MacFarlane,R H Greenwood,J Wilson,M J Denholm,R C Temple,K Whitfield,F Johnson,C Munroe,S Gorick,E Duckworth,M Fatman,S Rainbow,L J Borthwick,D J Wheatcroft,R J Seaman,R A Christie,W Wheatcroft,P Musk,Jennifer White,S McDougal,M Bond,P Raniga,J L Day,M J Doshi,James G. Wilson,J. Howard-Williams,H Humphreys,A Graham,K Hicks,S Hexman,P Bayliss,D Pledger,R W Newton,R T Jung,C Roxburgh,B Kilgallon,L Dick,N Waugh,S Kilby,A Ellingford,J Burns,C Fox,M C Holloway,H M Coghill,N Hein,A J Fox,W Cowan,M Richard,K Quested,S J Evans,Richard B Paisey,Brown Npr.,A J Tucker,R Paisey,F Garrett,J Hogg,P Park,K Williams,P Harvey,R Wilcocks,S Mason,J. C. Frost,C Warren,P Rocket,L Bower,J M Roland,D J Brown,J Youens,K Stanton-King,H Mungall,V Ball,W Maddison,D Donnelly,S King,P Griffin,Sidney C. Smith,S Church,Graham Dunn,Andrew D. Wilson,K Palmer,P M Brown,D Humphriss,Davidson Ajm.,Richard Rose,L Armistead,S Townsend,P Poon,Peacock Ida.,Culverwell Njc.,M H Charlton,Connolly Bps.,J Peacock,J Barrett,J Wain,W Beeston,George L. King,P G Hill,Boulton Ajm.,A M Robertson,V Katoulis,A Olukoga,H McDonald,S Kumar,F Abouaesha,B Abuaisha,E A Knowles,S Higgins,J Booker,J Sunter,K Breislin,R Parker,P Raval,J Curwell,H Davenport,G Shawcross,A Prest,J Grey,H Cole,C Sereviratne,R J Young,J R Clyne,M Gibson,I O'Connell,L M Wong,S J Wilson,K L Wright,Chris Wallace,D McDowell,A C Burden,E M Sellen,R Gregory,M Roshan,N Vaghela,M Burden,C Sherriff,S Mansingh,J Clarke,J Grenfell,Je Tooke,K. M. MacLeod,C Seamark,M Rammell,C Pym,J Stockman,C Yeo,J Piper,L Leighton,Ellen Green,M Hoyle,K Jones,A Hudson,A J James,Angela C. Shore,A Higham,B Martin,Neil Haw.,Butterfield Wjh.,Doll Wrs.,R Eastman,F R Ferris,N Kurinij,K McPherson,R F Mahler,Tom W. Meade,G Shafer,P J Watkins,H Keen,D Siegel,D J Betteridge,R D Cohen,D Currie,Julie L Darbyshire,J V Forrester,T Guppy,D G Johnston,Alistair McGuire,Mike Murphy,A M el-Nahas,B Pentecost,D Spiegelhalter,Alberti Kgmm.,R Denton,Philip Home,S Howell,Jarrett,V Marks,Michael Marmot,J D Ward,Grp Ukpds. +398 more
TL;DR: In this article, the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial were compared.
Journal ArticleDOI
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study
Irene M Stratton,Amanda I Adler,H. Andrew W. Neil,David R. Matthews,Susan E. Manley,Carole A. Cull,D R Hadden,Robert C Turner,Rury R. Holman +8 more
TL;DR: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia, with the lowest risk being in those with HbA1c values in the normal range (<6.0%).
Journal ArticleDOI
Hyperinsulinemia as an Independent Risk Factor for Ischemic Heart Disease
Jean-Pierre Després,Benoît Lamarche,Pascale Mauriège,Bernard Cantin,Gilles R. Dagenais,Sital Moorjani,Paul-J. Lupien +6 more
TL;DR: High fasting insulin concentrations appear to be an independent predictor of ischemic heart disease in men after adjustment for other risk factors.
Journal Article
A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results.
Journal ArticleDOI
UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes
Robert C. Turner,Irene M Stratton,V A Horton,Sue Manley,Paul Zimmet,Ian R Mackay,M Shattock,Gian Franco Bottazzo,Rury R. Holman +8 more
TL;DR: In this article, the presence of either or both antibodies characterises a subtype of diabetes and provides better prediction of requirement for insulin therapy by 6 years' follow-up than clinical variables.
Related Papers (5)
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.
Anushka Patel,Stephen MacMahon,John Chalmers,Bruce Neal,Laurent Billot,Mark Woodward,Mark Woodward,Michel Marre,Mark E. Cooper,Paul Glasziou,Paul Glasziou,Diederick E. Grobbee,Pavel Hamet,Stephen B. Harrap,Simon Heller,Lisheng Liu,Giuseppe Mancia,Carl Erik Mogensen,C. Y. Pan,Neil R Poulter,Anthony Rodgers,Bryan Williams,Severine Bompoint,Bastiaan E. de Galan,Bastiaan E. de Galan,Rohina Joshi,F. Travert +26 more