El descubrimiento del papel de los ácidos grasos libres en el desarrollo de la diabetes y sus complicaciones ha supuesto un cambio en el enfoque terapéutico de la diabetes. El exceso de ácidos grasos libres plasmáticos produce un estado de hiperinsulinismo que está íntimamente relacionado con la aparición de las alteraciones metabólicas y el desarrollo de hipertensión arterial y de complicaciones vasculares en pacientes diabéticos. Los receptors activadores de la proliferación peroxisomal (PPAR), al ser estimulados, favorecen la acción de la insulina al reducir las concentraciones de ácidos grasos libres plasmáticos, reducir la producción hepática de glucosa y aumentar la captación de ésta por parte del músculo esquelético. Las glitazonas, como agonistas de dichos receptores, aportan beneficios importantes en el tratamiento de pacientes con diabetes mellitus tipo 2.
Palabras clave
Diabetes mellitus
Hipertensión
PPAR gamma
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Bibliografía
[1.]
J.D. McGarry.
What if Minkowski had been ageusic? An alternative angle on diabetes.
Science, (1992), 258 pp. 766-770
[2.]
L. Guo, R. Tabrizchi.
Peroxisome proliferator-activated receptor gamma as a drug target in the pathogenesis of insulin resistance.
Pharmacol Ther, (2006), 111 pp. 145-173
[3.]
A. Chawla, J.J. Repa, R.M. Evans, D.J. Mangelsdorf.
Nuclear receptors and lipid physiology: opening the X-files.
Science, (2001), 294 pp. 1866-1870
[4.]
A. Chawla, E.J. Schwarz, D.D. Dimaculangan, M.A. Lazar.
Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation.
Endocrinology, (1994), 135 pp. 798-800
[5.]
F. Blaschke, Y. Takata, E. Caglayan, R.E. Law, W.A. Hsueh.
Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes.
Arterioscler Thromb Vasc Biol, (2006), 26 pp. 28-40
[6.]
A.R. Saltiel, J.M. Olefsky.
Thiazolidinediones in the treatment of insulin resistance and type II diabetes.
Diabetes, (1996), 45 pp. 1661-1669
[7.]
S. Schwartz, P. Raskin, V. Fonseca, J.F. Graveline.
Effect of troglitazone in insulin-treated patients with type II diabetes mellitus. Troglitazone and Exogenous Insulin Study Group.
N Engl J Med, (1998), 338 pp. 861-866
[8.]
J.P. Van Wijk, E.J. De Koning, E.P. Martens, T.J. Rabelink.
Thiazolidinediones and blood lipids in type 2 diabetes.
Arterioscler Thromb Vasc Biol, (2003), 23 pp. 1744-1749
[9.]
B.B. Kahn, J.S. Flier.
Obesity and insulin resistance.
J Clin Invest, (2000), 106 pp. 473-481
[10.]
M.I. Freed, R. Ratner, S.M. Marcovina, M.M. Kreider, N. Biswas, B.R. Cohen, et al.
Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus.
Am J Cardiol, (2002), 90 pp. 947-952
[11.]
N. Maeda, M. Takahashi, T. Funahashi, S. Kihara, H. Nishizawa, K. Kishida, et al.
PPAR gamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein.
Diabetes, (2001), 50 pp. 2094-2099
[12.]
N. Marx, J. Froehlich, L. Siam, J. Ittner, G. Wierse, A. Schmidt, et al.
Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease.
Arterioscler Thromb Vasc Biol, (2003), 23 pp. 283-288
[13.]
P. Delerive, F. Martin-Nizard, G. Chinetti, F. Trottein, J.C. Fruchart, J. Najib, et al.
Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway.
Circ Res, (1999), 85 pp. 394-402
[14.]
V.E. Crowley, M. Agostini, J.W. Schwabe, M.A. Soos, G.L. Maslen, T.D. Williams, et al.
Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension.
Nature, (1999), 402 pp. 880-883
[15.]
Y.X. Wang, C.H. Lee, S. Tiep, R.T. Yu, J. Ham, H. Kang, et al.
Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity.
Cell, (2003), 113 pp. 159-170
[16.]
J.V. Neel.
Diabetes mellitus: a «thrifty» genotype rendered detrimental by «progress»?.
Am J Human Genet, (1962), 14 pp. 353-362
[17.]
A.R. Saltiel, C.R. Kahn.
Insulin signalling and the regulation of glucose and lipid metabolism.
Nature, (2001), 414 pp. 799-806
[18.]
F.X. Pi-Sunyer.
The obesity epidemic: pathophysiology and consequences of obesity.
Obes Res, (2002), 10 pp. 97S-104S
[19.]
S.M. Haffner, M.P. Stern, H.P. Hazuda, B.D. Mitchell, J.K. Patterson.
Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes?.
JAMA, (1990), 263 pp. 2893-2898
[20.]
S.R. Crespin, W.B. Greenough, D. Steinberg.
Stimulation of insulin secretion by long-chain free fatty acids: a direct pancreatic effect.
J Clin Invest, (1973), 52 pp. 1979-1984
[21.]
R.H. Unger.
Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications.
Diabetes, (1995), 44 pp. 863-870
[22.]
Y.P. Zhou, V. Grill.
Long term exposure to fatty acids and ketones inhibits B-cell functions in human pancreatic islets of Langerhans.
J Clin Endocrinol Metab, (1995), 80 pp. 1584-1590
[23.]
M. Roden, T.B. Price, G. Perseghin, K.F. Petersen, D.L. Rothman, G.W. Cline, et al.
Mechanism of free fatty acid-induced insulin resistance in humans.
J Clin Invest, (1996), 97 pp. 2859-2865
[24.]
G. Boden, X. Chen.
Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.
J Clin Invest, (1995), 96 pp. 1261-1268
[25.]
G. Boden, P. Cheung, T.P. Stein, K. Kresge, M. Mozzoli.
FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis.
Am J Physiol Endocrinol Metab, (2002), 283 pp. 12-19
[26.]
P. Peraldi, B. Spiegelman.
TNF-alpha and insulin resistance: summary and future prospects.
Mol Cell Biochem, (1998), 182 pp. 169-175
[27.]
A.D. Pradhan, J.E. Manson, N. Rifai, J.E. Buring, P.M. Ridker.
C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus.
JAMA, (2001), 286 pp. 327-334
[28.]
C.M. Steppan, S.T. Bailey, S. Bhat, E.J. Brown, R.R. Banerjee, C.M. Wright, et al.
The hormone resistin links obesity to diabetes.
Nature, (2001), 409 pp. 307-312
[29.]
C. Weyer, T. Funahashi, S. Tanaka, K. Hotta, Y. Matsuzawa, R.E. Pratley, et al.
Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.
J Clin Endocrinol Metab, (2001), 86 pp. 1930-1935
[30.]
T. Yamauchi, J. Kamon, Y. Ito, A. Tsuchida, T. Yokomizo, S. Kita, et al.
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.
Nature, (2003), 423 pp. 762-769
[31.]
N. Ouchi, S. Kihara, Y. Arita, Y. Okamoto, K. Maeda, H. Kuriyama, et al.
Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappa B signaling through a cAMP-dependent pathway.
Circulation, (2000), 102 pp. 1296-1301
[32.]
C.D. Gardner, S.P. Fortmann, R.M. Krauss.
Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women.
JAMA, (1996), 276 pp. 875-881
[33.]
B. Lamarche, A. Tchernof, S. Moorjani, B. Cantin, G.R. Dagenais, P.J. Lupien, et al.
Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men: prospective results from the Quebec Cardiovascular Study.
Circulation, (1997), 95 pp. 69-75
[34.]
J. Jeppesen, H.O. Hein, P. Suadicani, F. Gyntelberg.
Relation of high TG-low HDL cholesterol and LDL cholesterol to the incidence of ischemic heart disease: an 8-year follow-up in the Copenhagen Male Study.
Arterioscler Thromb Vasc Biol, (1997), 17 pp. 1114-1120
[35.]
H.C. Gerstein, S. Yusuf, J. Bosch, J. Pogue, P. Sheridan, N. Dinccag, DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial, et al.
Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial.
Lancet, (2006), 368 pp. 1096-1105
[36.]
F. Heller, C. Harvengt.
Effects of clofibrate, bezafibrate, fenofibrate and probucol on plasma lipolytic enzymes in normolipaemic subjects.
Eur J Clin Pharmacol, (1983), 25 pp. 57-63
[37.]
K. Schoonjans, J. Peinado-Onsurbe, A.M. Lefebvre, R.A. Heyman, M. Briggs, S. Deeb, et al.
PPAR alpha and PPAR gamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene.
Embo J, (1996), 15 pp. 5336-5348
[38.]
B. Staels, J. Dallongeville, J. Auwerx, K. Schoonjans, E. Leitersdorf, J.C. Fruchart.
Mechanism of action of fibrates on lipid and lipoprotein metabolism.
Circulation, (1998), 98 pp. 2088-2093
[39.]
I. Lemieux, L. Laperriere, V. Dzavik, G. Tremblay, J. Bourgeois, J.P. Despres.
A 16-week fenofibrate treatment increases LDL particle size in type IIA dyslipidemic patients.
Atherosclerosis, (2002), 162 pp. 363-371
[40.]
Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet. 2001;357:905-10.
[41.]
C.G. Ericsson, J. Nilsson, L. Grip, B. Svane, A. Hamsten.
Effect of bezafibrate treatment over five years on coronary plaques causing 20% to 50% diameter narrowing (The Bezafibrate Coronary Atherosclerosis Intervention Trial [BECAIT]).
Am J Cardiol, (1997), 80 pp. 1125-1129
[42.]
J.K. Huttunen, V. Manninen, M. Manttari, P. Koskinen, M. Romo, L. Tenkanen, et al.
The Helsinki Heart Study: central findings and clinical implications.
Ann Med, (1991), 23 pp. 155-159
[43.]
H.B. Rubins, S.J. Robins, D. Collins, C.L. Fye, J.W. Anderson, M.B. Elam, et al.
Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group.
N Engl J Med, (1999), 341 pp. 410-418
[44.]
P.R. Devchand, H. Keller, J.M. Peters, M. Vazquez, F.J. Gonzalez, W. Wahli.
The PPAR alpha-leukotriene B4 pathway to inflammation control.
Nature, (1996), 384 pp. 39-43
[45.]
G.L. Plosker, D. Faulds.
Troglitazone: a review of its use in the management of type 2 diabetes mellitus.
Drugs, (1999), 57 pp. 409-438
[46.]
T. Meriden.
Progress with thiazolidinediones in the management of type 3 diabetes mellitus.
Clin Ther, (2004), 26 pp. 177-190
[47.]
M. St John Sutton, M. Rendell, P. Dandona, J.F. Dole, K. Murphy, R. Patwardhan, et al.
A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes.
Diabetes Care, (2002), 25 pp. 2058-2064
[48.]
J.S. Sidhu, D. Cowan, J.A. Tooze, J.C. Kaski.
Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces circulating platelet activity in patients without diabetes mellitus who have coronary artery disease.
Am Heart J, (2004), 147
[49.]
M.I. Freed, R. Ratner, S.M. Marcovina, M.M. Kreider, N. Biswas, B.R. Cohen, et al.
Rosiglitazone Study 108 investigators: effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus.
Am J Cardiol, (2002), 90 pp. 947-952
[50.]
S. Rosenblatt, B. Miskin, N.B. Glazer, M.J. Prince, K.E. Robertson.
The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus.
Coron Artery Dis, (2001), 12 pp. 413-423
[51.]
Y. Mori, Y. Murakawa, K. Okada, H. Horikoshi, J. Yokoyama, N. Tajima, et al.
Effect of troglitazone on body fat distribution in type 2 diabetic patients.
Diabetes Care, (1999), 22 pp. 908-912
[52.]
I. Kelly, T. Han, K. Walsh, M. Lean.
Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes.
Diabetes Care, (1999), 22 pp. 288-293
[53.]
C.T. Montague, S. O’Rahilly.
The perils of portliness: causes and consequences of visceral adiposity.
Diabetes, (2000), 49 pp. 883-888
[54.]
M. Adams, C.T. Montague, J.B. Prins, J.C. Holder, S.A. Smith, L. Sanders, et al.
Activators of peroxisome proliferatoractivated receptor gamma have depot specific effects on human preadipocyte differentiation.
J Clin Invest, (1997), 100 pp. 3149-3153
[55.]
C.J. De Souza, M. Eckhardt, K. Gagen, M. Dong, W. Chen, D. Laurent, et al.
Effects of pioglitazone on adipose tissue remodeling within the setting of obesity and insulin resistance.
Diabetes, (2001), 50 pp. 1863-1871
[56.]
A consensus statement from the American Heart Association and American Diabetes Association, Thiazolidinedione use, fluid retention, and congestive heart failure. Diabetes Care. 2004;27:256-63.
[57.]
S.E. Nissen, K. Wolski.
Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.
N Engl J Med, (2007), 356 pp. 2457-2471
[58.]
GSK medicine ZM2006/00207/00. Disponible en: http://ctr.gsk.co.uk/Summary/Rosiglitazone/III_CVmodeling.pdf.
[59.]
P.D. Home, S.J. Pocock, H. Beck-Nielsen, R. Gomis, M. Hanefeld, N.P. Jones, et al.
Rosiglitazone evaluated for cardiovascular outcomes — an interim analysis.
N Engl J Med, (2007), Jun 5
[60.]
J.A. Dormandy, B. Charbonnel, D.J. Eckland, E. Erdmann, M. Massi-Benedetti, I.K. Moules, et al.
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.
Lancet, (2005), 8 pp. 1279-1289
[61.]
E. Ferrannini, G. Buzzigoli, R. Bonadonna, M.A. Giorico, M. Oleggini, L. Graziadei, et al.
Insulin resistance in essential hypertension.
N Engl J Med, (1987), 317 pp. 350-357
[62.]
A. Natali, A. Quinones Galvan, D. Santoro, N. Pecori, S. Taddei, A. Salvetti, et al.
Relationship between insulin release, antinatriuresis and hypokalaemia after glucose ingestion in normal and hypertensive man.
Clin Sci, (1993), 85 pp. 327-335
[63.]
L. Landsberg.
Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity-related hypertension (or, how insulin affects blood pressure, and why).
J Hypertens, (2001), 19 pp. 523-528
[64.]
M. Laakso, S.V. Edelman, G. Brechtel, A.D. Baron.
Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM.
Diabetes, (1992), 41 pp. 1076-1083
[65.]
M. Barbagallo, R.K. Gupta, O. Bardicef, M. Bardicef, L.M. Resnick.
Altered ionic effects of insulin in hypertension: role of basal ion levels in determining cellular responsiveness.
J Clin Endocrinol Metab, (1997), 82 pp. 1761-1765
[66.]
P.A. Sarafidis, A.N. Lasaridis.
Actions of peroxisome proliferatoractivated receptors-γ agonists explaining a possible blood pressure–lowering effect.
Am J Hypertens, (2006), 19 pp. 646-653
[67.]
J.S. Sidhu, D. Cowan, J.C. Kaski.
The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients.
J Am Coll Cardiol, (2003), 42 pp. 1757-1763
[68.]
C.B. Patel, J.A. De Lemos, K.L. Wyne, D.K. McGuire.
Thiazolidinediones and risk for atherosclerosis: pleotropic effects of PPAR Gamma agonism.
Diab Vasc Dis Res, (2006), 3 pp. 65-71
[69.]
G.A. Knock, S.K. Mishra, P.I. Aaronson.
Differential effects of insulin-sensitizers troglitazone and rosiglitazone on ions currents in rat vascular myocytes.
Eur J Pharmacol, (1999), 368 pp. 103-109
[70.]
F. Zhang, J.R. Sowers, J.L. Ram, P.R. Standley, J.D. Peuler.
Effects of pioglitazone on calcium channels in vascular smooth muscle.
Hypertension, (1994), 24 pp. 170-175
[71.]
R.E. Law, S. Goetz, X.P. Xi, S. Jackson, Y. Kawano, L. Demer, et al.
Expression and function of PPAR-? in rat and human vascular smooth muscle cells.
Circulation, (2000), 101 pp. 1311-1318
[72.]
S. Fujishima, Y. Ohya, Y. Nakamura, U. Onaka, I. Abe, M. Fujishima.
Troglitazone, an insulin sensitizer, increases forearm blood flow in humans.
Am J Hypertens, (1998), 11 pp. 1134-1137
[73.]
P.A. Sarafidis, A.N. Lasaridis, P.M. Nilsson, E.M. Pagkalos, A.D. Hitoglu-Makedou, C.I. Pliakos, et al.
Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase.
J Hypertens, (2004), 22 pp. 1769-1777
[74.]
A. Raji, E.W. Seely, S.A. Bekins, G.H. Williams, D.C. Simonson.
Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients.
Diabetes Care, (2003), 26 pp. 172-178
[75.]
R. Negro, D. Dazzi, H. Hassan, A. Pezzarossa.
Pioglitazone reduces blood pressure in non-dipping diabetic patients.
Minerva Endocrinol, (2004), 29 pp. 11-17
[76.]
R. Negro, T. Mangieri, D. Dazzi, A. Pezzarossa, H. Hassan.
Rosiglitazone effects on blood pressure and metabolic parameters in nondipper diabetic patients.
Diabetes Res Clin Pract, (2005), 70 pp. 20-25
[77.]
P.A. Sarafidis, A.N. Lasaridis, P.M. Nilsson, A.D. Hitoglou-Makedou, E.M. Pagkalos, J.G. Yovos, et al.
The effect of rosiglitazone on urine albumin excretion in patients with type 2 diabetes mellitus and hypertension.
Am J Hypertens, (2005), 18 pp. 227-234
[78.]
J.S. Sidhu, Z. Kaposzta, H.S. Markus, J.C. Kaski.
Effect of rosiglitazone on common carotid intima-media thickness progression in coronary artery disease patients without diabetes mellitus.
Arterioscler Thromb Vasc Biol, (2004), 24 pp. 930-934
[79.]
W.J. Elliott, P.M. Meyer.
Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis.
Lancet, (2007), 369 pp. 201-207
[80.]
L. Hansson, L.H. Lindholm, L. Niskanen, J. Lanke, T. Hedner, A. Niklason, et al.
Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.
Lancet, (1999), 353 pp. 611-616
[81.]
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group.
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT).
JAMA, (2002), 288 pp. 2998-3007
[82.]
S. Yusuf, P. Sleight, J. Pogue, J. Bosch, R. Davies, G. Dagenais.
Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.
N Engl J Med, (2000), 342 pp. 145-153
[83.]
B. Dahlof, R.B. Devereux, S.E. Kjeldsen, S. Julius, G. Beevers, U. De Faire, LIFE Study Group, et al.
Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.
Lancet, (2002), 359 pp. 995-1003
[84.]
S. Julius, Se. Kjeldesen, M. Weber, H.R. Brunner, S. Ekman, L. Hansson, et al.
VALUE trial group Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial.
Lancet, (2004), 363 pp. 2022-2031
[85.]
M.A. Pfeffer, K. Swedberg, C.B. Granger, P. Held, J.J. McMurray, E.L. Michelson, CHARM Investigators and Committees, et al.
Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme.
Lancet, (2003), 362 pp. 759-766
[86.]
S.C. Benson, H.A. Pershadsingh, C.I. Ho, A. Chittiboyina, P. Desai, M. Pravenec, et al.
Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR gamma-modulating activity.
Hypertension, (2004), 43 pp. 993-1002
[87.]
M.C. Michel, H. Bohner, J. Koster, R. Schafers, U. Heemann.
Safety of telmisaran in patients with arterial hypertension: an open-label observational study.
Drug Saf, (2004), 27 pp. 335-344
[88.]
C. Vitale, G. Mercuro, C. Castiglioni, A. Cornoldi, A. Tulli, M. Fini, et al.
Metabolic effect of termisartan and losartan in hypertensive patients with metabolic syndrome.
Cardiovasc Diabetol, (2005), 15 pp. 5-6
[89.]
G. Derosa, P.D. Ragonesi, A. Mugellini, L. Ciccarelli, R. Fogari.
Effects of telmisartan compared with eprosartan on blood pressure control, glucose metabolism and lipid profile in hypertensive, type 2 diabetic patients: a randomized, double-blind, placebocontrolled 12-month study.
Hypertens Res, (2004), 27 pp. 457-464
[90.]
R.C. Turner, H. Millns, H.A. Neil, I.M. Stratton, S.E. Manley, D.R. Matthews, et al.
Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23).
BMJ, (1998), 316 pp. 823-828
[91.]
L. Ryden, E. Standl, M. Bartnik, G. Van den Berghe, J. Betteridge, M.J. De Boer, Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC); European Association for the Study of Diabetes (EASD), et al.
Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the study of Diabetes (EASD).
Eur Heart J, (2007), 28 pp. 88-136
[92.]
J. Lindström, P. Ilanne-Parikka, M. Peltonen, S. Aunola, J.G. Eriksson, K. Hemiö, et al.
Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study.
Lancet, (2006), 368 pp. 1673-1679
[93.]
D. Nathan, M. Berkwits.
Trials that matter: rosiglitazone, ramipril and the prevention of type 2 diabetes.
Ann Intern Med, (2007), 146 pp. 461-463
[94.]
B. Ljung, K. Bamberg, B. Dahllof, A. Kjellstedt, N.D. Oakes, J. Ostling, et al.
AZ 242, a novel PPARa/g agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats.
J Lipid Res, (2002), 43 pp. 1855-1863
[95.]
B.K. Skrumsager, K.K. Nielsen, M. Muller, G. Pabst, P.G. Drake, B. Edsberg.
Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPAR alpha and gamma agonist in healthy subjects and patients with type 2 diabetes.
J Clin Pharmacol, (2003), 43 pp. 1244
[96.]
S.E. Nissen, K. Wolski, E.J. Topol.
Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus.
JAMA, (2005), 294 pp. 2581-2586
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