Long-term effects of metformin on endothelial function in type 2 diabetes: A randomized controlled trial

Journal of Internal Medicine

Volumn 275, Issue 1, 2014, Pages 59-70

  de Jager, J ^a,b   Kooy, A ^a,c   Schalkwijk, C ^d   van der Kolk, J ^c   Lehert, P ^e   Bets, D ^f   Wulffele M G ^a,c   Donker, A J ^g   Stehouwer, C D A ^d  

^a Bethesda Diabetes Research Center   (Netherlands)

^b ACADEMIC MEDICAL CENTER   (Netherlands)

^c Bethesda Hospital   (Netherlands)

^d MAASTRICHT UNIVERSITY   (Netherlands)

^e Louvain Academy   (Belgium)

^f Clinical Research and Development   (Netherlands)

^g VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Cardiovascular disease outcome; Endothelial function; HOME trial; Metformin; Type 2 diabetes

Indexed keywords

ACETYLSALICYLIC ACID; ALBUMIN; ANTIHYPERTENSIVE AGENT; ANTILIPEMIC AGENT; C REACTIVE PROTEIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; HEMOGLOBIN A1C; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; INTERCELLULAR ADHESION MOLECULE 1; METFORMIN; PLACEBO; PROTEIN; SOLUBLE E SELECTIN; SOLUBLE INTERCELLULAR ADHESION MOLECULE 1; SOLUBLE VASCULAR ADHESION MOLECULE 1; TISSUE PLASMINOGEN ACTIVATOR; UNCLASSIFIED DRUG; VASCULAR CELL ADHESION MOLECULE 1; VON WILLEBRAND FACTOR;

ADULT; AGE; AGED; ARTICLE; BODY WEIGHT; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CONTROLLED STUDY; DIABETIC PATIENT; DISEASE ASSOCIATION; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG DOSE REDUCTION; DRUG EFFECT; ENDOTHELIAL DYSFUNCTION; FEMALE; FOLLOW UP; HUMAN; INFLAMMATION; INSULIN TREATMENT; LONG TERM CARE; MAJOR CLINICAL STUDY; MALE; MORBIDITY; NON INSULIN DEPENDENT DIABETES MELLITUS; OUTPATIENT DEPARTMENT; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; RISK REDUCTION; SEX DIFFERENCE; SMOKING; URINARY ALBUMIN EXCRETION; URINARY EXCRETION;

CARDIOVASCULAR DISEASE OUTCOME; ENDOTHELIAL FUNCTION; HOME TRIAL; METFORMIN; TYPE 2 DIABETES;

AGED; BIOLOGICAL MARKERS; DIABETES MELLITUS, TYPE 2; DRUG MONITORING; DRUG THERAPY, COMBINATION; ENDOTHELIUM, VASCULAR; FEMALE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; INTERCELLULAR ADHESION MOLECULE-1; MALE; METFORMIN; MIDDLE AGED; TIME; TREATMENT OUTCOME; VON WILLEBRAND FACTOR;

EID: 84890174009     PISSN: 09546820     EISSN: 13652796     Source Type: Journal    
DOI: 10.1111/joim.12128     Document Type: Article

References (42)

1. Bonow RO, Gheorghiade M. The diabetes epidemic: a national and global crisis. Am J Med 2004; 116: 2S-10S.
2. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999; 340: 115-26.
3. Jager A, van Hinsbergh VWM, Kostense PJ et al. Von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and non-diabetic subjects. The Hoorn study. Arterioscler Thromb Vasc Biol 1999; 19: 3071-8.
4. U.K. Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-65.
5. Kooy A, de Jager J, Lehert P et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med 2009; 169: 616-25.
6. Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol 2001; 37: 1344-50.
7. Nagi DK, Yudkin JS. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups. Diabetes Care 1993; 16: 621-9.
8. Charles MA, Morange P, Eschwège E, André P, Vague P, Juhan-Vague I. Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects. The BIGPRO1 Study. Diabetes Care 1998; 21: 1967-72.
9. Grant PJ. The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes. Diabetes Care 1996; 19: 64-6.
10. Wulffelé MG, Kooy A, Lehert P et al. Combination of insulin and metformin in the treatment of type 2 diabetes. Diabetes Care 2002; 25: 2133-40.
11. Wulffelé MG, Kooy A, Lehert P, Bets D, Donker AJM, Stehouwer CDA. Does metformin reduce blood pressure in patients with type 2 diabetes intensively treated with insulin? Diabet Med 2005; 22: 907-13.
12. de Jager J, Kooy A, Lehert P, Bets D, Donker AJM, Stehouwer CDA. Effects of short-term treatment with metformin on markers of endothelial function an inflammatory activity in type 2 diabetes: a randomised, controlled trial. J Intern Med 2005; 257: 100-9.
13. Passing H, Bablok W. A new biometrical procedure for testing the equality of measurements from two different analytical methods. I. Application of linear regression procedures for method comparison studies in clinical chemistry. J Clin Chem Clin Biochem 1983; 21: 709-20.
14. Passing H, Bablok W. Comparison of several regression procedures for method comparison studies and determination of sample sizes. II. Application of linear regression procedures for method comparison studies in clinical chemistry. J Clin Chem Clin Biochem 1984; 22: 431-45.
15. Stehouwer CDA, Lambert J, Donker AJM, van Hinsbergh VWM. Endothelial dysfunction and pathogenesis of diabetic angiopathy. Cardiovasc Res 1997; 34: 55-68.
16. Mannucci PM. Von Willebrand Factor: a marker of endothelial damage? Arterioscler Thromb Vasc Biol 1998; 18: 1359-62.
17. Vapaatalo H, Mervaala E. Clinically important factors influencing endothelial function. Med Sci Monit 2001; 7: 1075-85.
18. Blake GJ, Ridker PM. Novel clinical markers of vascular wall inflammation. Circ Res 2001; 89: 763-71.
19. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836-43.
20. Brevetti G, Martone VD, de Cristofano T et al. High levels of adhesion molecules are associated with impaired endothelium-dependent vasodilation in patients with peripheral arterial disease. Thromb Haemost 2001; 85: 63-6.
21. Preacher KJ, Hayes AF. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Met 2008; 40: 879-91.
22. Brown RL. Assessing specific mediational effects in complex theoretical models. Struct Equat Model 1997; 4: 142-56.
23. Briggs N. Estimation of the standard error and confidence interval of the indirect effect in multiple mediator models. Dissert Abst Int 2006; 37: 4755B.
24. de Jager J, Dekker JM, Kooy A et al. Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: the Hoorn study. Arterioscler Thromb Vasc Biol 2006; 26: 1086-93.
25. Lund S, Tarnow L, Stehouwer CDA et al. Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. Eur J Endocrinol 2008; 158: 631-41.
26. Ryysy L, Yki-Järvinen H. Improvement of glycemic control by 1 year of insulin therapy leads to a sustained decrease in sE-Selectin concentrations in type 2 diabetes. Diabetes Care 2001; 24: 549-54.
27. Diamanti-Kandarakis E, Paterakis T, Alexandraki K et al. Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin. Hum Reprod 2006; 21: 1426-31.
28. Skrha J, Prazny M, Hilgertova J, Kvasnicka J, Kalousova M, Zima T. Oxidative stress and endothelium influenced by metformin in type 2 diabetes mellitus. Eur J Clin Pharmacol 2007; 63: 1107-14.
29. Vischer UM, Emeis JJ, Bilo HJG et al. Von Willebrand factor (vWf) as a plasma marker of endothelial activation in diabetes: improved reliability with parallel determination of the vWf propeptide (vWf:agII). Thromb Haemost 1998; 80: 1002-7.
30. Amador-Licona N, Guizar-Mendoza J-M, Vargas E, Sanchez-Camargo G, Zamora-Mata L. The short-term effects of a switch from glibenclamide to metformin on blood pressure and microalbuminuria in patients with type 2 diabetes mellitus. Arch Med Res 2000; 31: 571-5.
31. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 1989; 32: 219-26.
32. Hattori Y, Suzuki K, Hattori S, Kasai K. Metformin inhibits cytokine-induced nuclear factor kB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension 2006; 47: 1183-8.
33. Ewart M, Kohlhaas C, Salt I. Inhibition of tumor necrosis factor alpha-stimulated monocyte adhesion to human aortic endothelial cells by AMP-activated protein kinase. Arterioscler Thromb Vasc Biol 2008; 28: 2255-7.
34. van Bussel BC, Henry RM, Schalkwijk CG, Dekker JM, Nijpels G, Stehouwer CD. Low-grade inflammation, but not endothelial dysfunction, is associated with greater carotid stiffness in the elderly: the Hoorn Study. J Hypertens 2012; 30: 744-52.
35. Beiswenger PJ, Howell SK, Touchette AD, Lal S, Swerzgold BS. Metformin reduces systemic methylglyoxal levels in type 2 diabetes. Diabetes 1999; 48: 198-202.
36. Ruggiero-Lopez D, Lecomte M, Moinet G, Patereau G, Lagarde M, Wiernsperger N. Reaction of metformin with dicarbonyl compounds. Possible implication in the inhibition of advanced glycation end product formation. Biochem Pharmacol 1999; 58: 1765-73.
37. Tanaka Y, Uchino H, Shimizu T et al. Effect of metformin on advanced glycation endproduct formation and peripheral nerve function in streptozotocin-induced diabetic rats. Eur J Pharmacol 1999; 376: 17-22.
38. Fujita H, Fujishima H, Morii T et al. Effect of metformin on adipose tissue resistin expression in db/db mice. Biochem Biophys Res Commun 2002; 298: 345-9.
39. Fruehwald-Schultes B, Oltmanns KM, Toschek B et al. Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men. Metabolism 2002; 51: 531-6.
40. Phillips SA, Ciaraldi TP, Kong APS et al. Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy. Diabetes 2003; 52: 667-74.
41. Bruun JM, Pedersen SB, Richelsen B. Interleukin-8 production in human adipose tissue. Inhibitory effects of anti-diabetic compounds, the thiazolidinedione ciglitazone and the biguanide metformin. Horm Metab Res 2000; 32: 537-41.
42. Solomon SS, Mishra SK, Cwik C, Rajanna B, Postlethwaite AE. Pioglitazone and metformin reverse insulin resistance induced by tumor necrosis factor-alpha in liver cells. Horm Metab Res 1997; 29: 379-82.