Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes
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TLDR
It is believed that the most important consideration is to select antidiabetes agents that correct specific pathophysiologic disturbances present in T2DM and that have complementary mechanisms of action.Abstract:
Two general approaches to the treatment of type 2 diabetes mellitus (T2DM) have been advocated. 1 ) A “guideline” approach that advocates sequential addition of antidiabetes agents with “more established use” (1); this approach more appropriately should be called the “treat to failure” approach, and deficiencies with this approach have been discussed (2). And 2 ) a “pathophysiologic” approach using initial combination therapy with agents known to correct established pathophysiologic defects in T2DM (3). Within the pathophysiologic approach, choice of antidiabetes agents should take into account the patient’s general health status and associated medical disorders. This individualized approach, which we refer to as the ABCD(E) of diabetes treatment (4), has been incorporated into the updated American Diabetes Association (ADA) guidelines (5).
Even though physicians must be cognizant of these associated conditions (ABCDE) when initiating therapy in newly diagnosed T2DM patients, we believe that the most important consideration is to select antidiabetes agents that correct specific pathophysiologic disturbances present in T2DM and that have complementary mechanisms of action. Although it has been argued that the pathogenesis of T2DM differs in different ethnic groups (6), evidence to support this is weak. Although the relative contributions of β-cell failure and insulin resistance to development of glucose intolerance may differ in different ethnic groups (6), the core defects of insulin resistance in muscle/liver/adipocytes and progressive β-cell failure (3) are present in virtually all T2DM patients and must be treated aggressively to prevent the relentless rise in HbA1c that is characteristic of T2DM.
In subsequent sections, we provide a review of the natural history of T2DM, specific pathophysiologic abnormalities responsible for T2DM, currently …read more
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References
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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 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). UK Prospective Diabetes Study (UKPDS) Group.
R C Turner,C Fox,Matthews,H McElroy,Carole A. Cull,Rury R. Holman,P. A. Neil,D R Hadden,D Wright,E Manley,Irene M Stratton,UK Prospective Diabetes,E M Kohner,Frighi,Michael Gnant +14 more
TL;DR: 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 Article
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
R C Turner,Rury R. Holman,Irene M Stratton,Carole A. Cull,David R Matthews,Susan E. Manley,V Frighi,D Wright,Andrew Neil,E M Kohner,H McElroy,C Fox,D R Hadden,Grp Ukpds. +13 more
TL;DR: Since intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints in overweight diabetic patients, and is associated with less weight gain and fewer hypoglycaemic attacks than are insulin and sulphonylureas, it may be the first-line pharmacological therapy of choice in these patients.
Journal ArticleDOI
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes
Steven E. Nissen,Kathy Wolski +1 more
TL;DR: Patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes mellitus as well as the availability of outcome data for myocardial infarction and death from cardiovascular causes.
Journal ArticleDOI
Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
Silvio E. Inzucchi,Richard M. Bergenstal,John B. Buse,Michaela Diamant,Ele Ferrannini,Michael A. Nauck,Anne L. Peters,Apostolos Tsapas,Richard C. Wender,David R. Matthews,David R. Matthews,David R. Matthews +11 more
TL;DR: Properties of currently available glucose-lowering agents that may guide treatment choice in individual patients with type 2 diabetes mellitus are explored.
Related Papers (5)
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