The effect of metformin on insulin resistance and exercise parameters in patients with heart failure

European Journal of Heart Failure

Volumn 14, Issue 11, 2012, Pages 1303-1310

  Wong, Aaron K F ^a   Symon, Ruth ^a   Alzadjali, Matlooba A ^a   Ang, Donald S C ^a   Ogston, Simon ^a   Choy, Annamaria ^a   Petrie, John R ^a   Struthers, Allan D ^a   Lang, Chim C ^a  

^a UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

Chronic heart failure; Diabetes; Metformin

Indexed keywords

ADIPONECTIN; ALDOSTERONE ANTAGONIST; ANGIOTENSIN RECEPTOR ANTAGONIST; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BRAIN NATRIURETIC PEPTIDE; CALCIUM CHANNEL BLOCKING AGENT; CARBON DIOXIDE; DIGOXIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; GLUCOSE; HEMOGLOBIN A1C; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; ISOSORBIDE MONONITRATE; LACTIC ACID; LEPTIN; METFORMIN; OXYGEN; PLACEBO; RESISTIN;

ABDOMINAL DISCOMFORT; ADULT; AGED; ANOREXIA; ARTICLE; CARDIAC PATIENT; CARDIOPULMONARY EXERCISE TEST; CONTROLLED STUDY; DIARRHEA; DIET RESTRICTION; DOUBLE BLIND PROCEDURE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENDOTHELIAL DYSFUNCTION; EXERCISE; FEMALE; GAS EXCHANGE; GLUCOSE BLOOD LEVEL; HEART FAILURE; HEART LEFT VENTRICLE EJECTION FRACTION; HEART MUSCLE OXYGEN CONSUMPTION; HEART OUTPUT; HEMOGLOBIN BLOOD LEVEL; HORMONE BLOOD LEVEL; HUMAN; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; LACTATE BLOOD LEVEL; LACTIC ACIDOSIS; MAJOR CLINICAL STUDY; MALE; NAUSEA; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; TWO DIMENSIONAL ECHOCARDIOGRAPHY; WEIGHT REDUCTION;

AGED; DIABETES MELLITUS; DOUBLE-BLIND METHOD; EXERCISE; EXERCISE TEST; EXERCISE TOLERANCE; FEMALE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN RESISTANCE; MALE; METFORMIN; MIDDLE AGED; OXYGEN CONSUMPTION; STATISTICS AS TOPIC; STROKE VOLUME; VENTRICULAR FUNCTION, LEFT;

EID: 84867706737     PISSN: 13889842     EISSN: 18790844     Source Type: Journal    
DOI: 10.1093/eurjhf/hfs106     Document Type: Article

References (45)

1. Wong AK, AlZadjali MA, Choy AM, Lang CC. Insulin resistance: a potential new target for therapy in patients with heart failure. Cardiovasc Ther 2008;26:203-213.
2. AlZadjali MA, Godfrey V, Khan F, Choy A, Doney AS, Wong AK, Petrie JR, Struthers AD, Lang CC. Insulin resistance is highly prevalent and is associated with reduced exercise tolerance in nondiabetic patients with heart failure. J Am Coll Cardiol 2009;53:747-753.
3. Suskin N, McKelvie RS, Burns RJ, Latini R, Pericak D, Probstfield J, Rouleau JL, Sigouin C, Solymoss CB, Tsuyuki R, White M, Yusuf S. Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Eur Heart J 2000;21:1368-1375.
4. Swan JW, Anker SD, Walton C, Godsland IF, Clark AL, Leyva F, Stevenson JC, Coats AJ. Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J Am Coll Cardiol 1997;30:527-532.
5. Doehner W, Rauchhaus M, Ponikowski P, Godsland IF, von Haehling S, Okonko DO, Leyva F, Proudler AJ, Coats AJ, Anker SD. Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure. J Am Coll Cardiol 2005;46:1019-1026.
6. Salpeter S, Greyber E, Pasternak G, Salpeter E. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2006;(1):CD002967.
7. Eurich DT, McAlister FA, Blackburn DF, Majumdar SR, Tsuyuki RT, Varney J, Johnson JA. Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review. BMJ 2007;335:497.
8. Evans JM, Doney AS, AlZadjali MA, Ogston SA, Petrie JR, Morris AD, Struthers AD, Wong AK, Lang CC. Effect of metformin on mortality in patients with heart failure and type 2 diabetes mellitus. Am J Cardiol 2010;106:1006-1010.
9. Goda A, Lang CC, Williams P, Jones M, Farr MJ, Mancini DM. Usefulness of noninvasive measurement of cardiac output during sub-maximal exercise to predict outcome in patients with chronic heart failure. Am J Cardiol 2009;104:1556-1560.
10. Lang CC, Agostoni P, Mancini DM. Prognostic significance and measurement of exercise-derived hemodynamic variables in patients with heart failure. J Card Fail 2007;13:672-679.
11. Gitt AK, Wasserman K, Kilkowski C, Kleemann T, Kilkowski A, Bangert M, Schneider S, Schwarz A, Senges J. Exercise anaerobic threshold and ventilatory efficiency identify heart failure patients for high risk of early death. Circulation 2002;106:3079-3084.
12. Arena R, Myers J, Abella J, Peberdy MA, Bensimhon D, Chase P, Guazzi M. Development of a ventilatory classification system in patients with heart failure. Circulation 2007;115:2410-2417.
13. Caballero AE, Delgado A, Aguilar-Salinas CA, Herrera AN, Castillo JL, Cabrera T, Gomez-Perez FJ, Rull JA. The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial. J Clin Endocrinol Metab 2004;89:3943-3948.
14. Lang CC, Karlin P, Haythe J, Tsao L, Mancini DM. Ease of noninvasive measurement of cardiac output coupled with peak VO2 determination at rest and during exercise in patients with heart failure. Am J Cardiol 2007;99:404-405.
15. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002;39:257-265.
16. Egstrup M, Schou M, Gustafsson I, Kistorp CN, Hildebrandt PR, Tuxen CD. Oral glucose tolerance testing in an outpatient heart failure clinic reveals a high proportion of undiagnosed diabetic patients with an adverse prognosis. Eur J Heart Fail 2010;13:319-326.
17. Kirpichnikov D, McFarlane SI, Sowers Jr. Metformin: an update. Ann Intern Med 2002;137:25-33.
18. Gundewar S, Calvert JW, Jha S, Toedt-Pingel I, Ji SY, Nunez D, Ramachandran A, Anaya-Cisneros M, Tian R, Lefer DJ. Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure. Circ Res 2009;104:403-411.
19. Sasaki H, Asanuma H, Fujita M, Takahama H, Wakeno M, Ito S, Ogai A, Asakura M, Kim J, Minamino T, Takashima S, Sanada S, Sugimachi M, Komamura K, Mochizuki N, Kitakaze M. Metformin prevents progression of heart failure in dogs: role of AMP-activated protein kinase. Circulation 2009;119: 2568-2577.
20. Eurich DT, Tsuyuki RT, Majumdar SR, McAlister FA, Lewanczuk R, Shibata MC, Johnson JA. Metformin treatment in diabetes and heart failure: when academic equipoise meets clinical reality. Trials 2009;10:12.
21. Wilson JR, Rayos G, Yeoh TK, Gothard P. Dissociation between peak exercise oxygen consumption and hemodynamic dysfunction in potential heart transplant candidates. J Am Coll Cardiol 1995;26:429-435.
22. Agostoni PG, Wasserman K, Perego GB, Guazzi M, Cattadori G, Palermo P, Lauri G, Marenzi G. Non-invasive measurement of stroke volume during exercise in heart failure patients. Clin Sci (Lond) 2000;98:545-551.
23. Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its antidiabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 2000;348:607-614.
24. Braun B, Eze P, Stephens BR, Hagobian TA, Sharoff CG, Chipkin SR, Goldstein B. Impact of metformin on peak aerobic capacity. Appl Physiol Nutr Metab 2008;33: 61-67.
25. Beck-da-Silva L, Higginson L, Fraser M, Williams K, Haddad H. Effect of orlistat in obese patients with heart failure: a pilot study. Congest Heart Fail 2005;11: 118-123.
26. Seibaek M, Vestergaard H, Burchardt H, Sloth C, Torp-Pedersen C, Nielsen SL, Hildebrandt P, Pedersen O. Insulin resistance and maximal oxygen uptake. Clin Cardiol 2003;26:515-520.
27. Regensteiner JG, Bauer TA, Reusch JE. Rosiglitazone improves exercise capacity in individuals with type 2 diabetes. Diabetes Care 2005;28:2877-2883.
28. Cohen B, Novick D, Rubinstein M. Modulation of insulin activities by leptin. Science 1996;274:1185-1188.
29. Doehner W, Rauchhaus M, Godsland IF, Egerer K, Niebauer J, Sharma R, Cicoira M, Florea VG, Coats AJ, Anker SD. Insulin resistance in moderate chronic heart failure is related to hyperleptinaemia, but not to norepinephrine or TNF-alpha. Int J Cardiol 2002;83:73-81.
30. Liu YL, Emilsson V, Cawthorne MA. Leptin inhibits glycogen synthesis in the isolated soleus muscle of obese (ob/ob) mice. FEBS Lett 1997;411:351-355.
31. Glueck CJ, Fontaine RN, Wang P, Subbiah MT, Weber K, Illig E, Streicher P, Sieve-Smith L, Tracy TM, Lang JE, McCullough P. Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism 2001;50:856-861.
32. Klein J, Westphal S, Kraus D, Meier B, Perwitz N, Ott V, Fasshauer M, Klein HH. Metformin inhibits leptin secretion via a mitogen-activated protein kinase signalling pathway in brown adipocytes. J Endocrinol 2004;183:299-307.
33. George J, Patal S, Wexler D, Sharabi Y, Peleg E, Kamari Y, Grossman E, Sheps D, Keren G, Roth A. Circulating adiponectin concentrations in patients with congestive heart failure. Heart 2006;92:1420-1424.
34. Kistorp C, Faber J, Galatius S, Gustafsson F, Frystyk J, Flyvbjerg A, Hildebrandt P. Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 2005;112:1756-1762.
35. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N, Walsh K. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK-and COX-2-dependent mechanisms. Nat Med 2005; 11:1096-1103.
36. Watanabe S, Tamura T, Ono K, Horiuchi H, Kimura T, Kita T, Furukawa Y. Insulinlike growth factor axis (insulin-like growth factor-I/insulin-like growth factorbinding protein-3) as a prognostic predictor of heart failure: association with adiponectin. Eur J Heart Fail 2010;12:1214-1222.
37. Kim HJ, Kang ES, Kim DJ, Kim SH, Ahn CW, Cha BS, Nam M, Chung CH, Lee KW, Nam CM, Lee HC. Effects of rosiglitazone and metformin on inflammatory markers and adipokines: decrease in interleukin-18 is an independent factor for the improvement of homeostasis model assessment-beta in type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2007;66:282-289.
38. Takeishi Y, Niizeki T, Arimoto T, Nozaki N, Hirono O, Nitobe J, Watanabe T, Takabatake N, Kubota I. Serum resistin is associated with high risk in patients with congestive heart failure-a novel link between metabolic signals and heart failure. Circ J 2007;71:460-464.
39. Shuldiner AR, Yang R, Gong DW. Resistin, obesity and insulin resistance-the emerging role of the adipocyte as an endocrine organ. N Engl J Med 2001;345: 1345-1346.
40. Gomez-Diaz RA, Talavera JO, Pool EC, Ortiz-Navarrete FV, Solorzano-Santos F, Mondragon-Gonzalez R, Valladares-Salgado A, Cruz M, Aguilar-Salinas CA, Wacher NH. Metformin decreases plasma resistin concentrations in pediatric patients with impaired glucose tolerance: a placebo-controlled randomized clinical trial. Metabolism 2012;in press.
41. Ventura-Clapier R, Garnier A, Veksler V. Energy metabolism in heart failure. J Physiol 2004;555:1-13.
42. Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol 2001;37:1344-1350.
43. Vitale C, Mercuro G, Cornoldi A, Fini M, Volterrani M, Rosano GM. Metformin improves endothelial function in patients with metabolic syndrome. J Intern Med 2005;258:250-256.
44. Naka KK, Papathanassiou K, Bechlioulis A, Pappas K, Kazakos N, Kanioglou C, Kostoula A, Vezyraki P, Makriyiannis D, Tsatsoulis A, Michalis LK. Effects of pioglitazone and metformin on vascular endothelial function in patients with type 2 diabetes treated with sulfonylureas. Diab Vasc Dis Res 2012;9:52-58.
45. Ingle L, Sloan R, Carroll S, Goode K, Cleland JG, Clark AL. Prognostic significance of different measures of the ventilation-carbon dioxide relation in patients with suspected heart failure. Eur J Heart Fail 2011;13:537-542.