Abstract
Background
Obese patients have myocardial structural and functional alterations related to insulin resistance.
Hypothesis
The purpose of the study was to analyze the effects of rosiglitazone, an insulin sensitizer agent, on cardiac morphometry and functioning.
Methods
In 2 groups of sex‐ and age‐matched, nondiabetic, obese patients (5 men and 7 women, age 19–51 y; group A: body mass index [BMI] 40.6 ± 3.4 kg/m2; group B: BMI 42.6 ± 2.7 kg/m2), we evaluated the basal insulin sensitivity index (HOMA[IS]), body composition by bioelectrical impedance analysis and 24‐h blood pressure monitoring. Furthermore, all patients underwent conventional 2‐Dimensional and color Doppler echocardiography, and pulsed‐wave tissue Doppler imaging (TDI). After the baseline evaluation, all patients were put on a hypocaloric diet (70% basal metabolic rate) plus placebo if they were in group A, or plus rosiglitazone (4 mg twice daily; Avandia [GlaxoSmithKline plc., Brentford, Middlesex, United Kingdom]) if they were in group B, for 6 mo.
Results
Significant decreases in body weight, total fat mass, BMI, and systolic blood pressure were registered in both groups. Rosiglitazone administration appeared more efficient in improving HOMA(IS) (mean difference: 0.30 ± 0.19 versus 0.11 ± 0.21, p < 0.05). Left ventricular (LV) diastolic diameter (49.4 ± 7.7 versus 52.3 ± 5.4 mm, p < 0.05) and E wave (0.89 ± 0.18 versus 0.99 ± 0.20 m/sec, p < 0.05) increased in the rosiglitazone group due to a rise in preload and water content without peripheral edema. The increase in systolic (Sa) wave velocity in both groups was probably a result of the general improvement in insulin metabolism and the decrease in blood pressure.
Conclusions
We confirmed the positive effect of rosiglitazone on glucose metabolism in obese, nondiabetic patients, but changes in insulin sensitivity did not explain the cardiac effects produced by further mechanisms. Copyright © 2008 Wiley Periodicals, Inc.
Keywords: obesity, left ventricular function, rosiglitazone, tissue Doppler imaging
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References
- 1. Hirayama H, Sugano M, Abe N, Yonemoch H, Makino N: Troglitazone, an antidiabetic drug, improves left ventricular mass and diastolic function in normotensive diabetic patients. Int J Cardiol 2001; 77: 75–79. [DOI] [PubMed] [Google Scholar]
- 2. Martens FM, Visseren FL, Lemay J, de Konong EJ, Rabelink TJ: Metabolic and additional vascular effects of thiazolinediones. Drugs 2002; 62: 1463–1480. [DOI] [PubMed] [Google Scholar]
- 3. Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356: 1–15. [DOI] [PubMed] [Google Scholar]
- 4. Hollenberg NK: Considerations for management of fluid dynamic issues associated with thiazolinediones. Am J Med 2003; 115(Suppl 8A): 111S–115S. [DOI] [PubMed] [Google Scholar]
- 5. Peterson RL, Waggoner AD, Schetchman KB, Meyer T, Gropler RJ, et al.: Alterations in left ventricular structure and function in young healthy obese women. J Am Coll Cardiol 2004; 43: 1399–1404. [DOI] [PubMed] [Google Scholar]
- 6. Piccoli A, Brunani A, Savia G, Pillon L, Favaro E et al.: Discriminating between body fat and fluid overload changes in the obese adults using bioimpedance vector analysis. Int J Obes 1998; 22: 97–104. [DOI] [PubMed] [Google Scholar]
- 7. Matthews DR, Hosker JP, Rudenski AS, Naylor BA Teacher DF, et al.: Homeostasis model assessment, insulin resistance and ß cell function from fasting plasma glucose and insulin concentration in human. Diabetologia 1985; 28: 412–419. [DOI] [PubMed] [Google Scholar]
- 8. Devereux RB, Reichek N: Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation 1977; 55: 613–618. [DOI] [PubMed] [Google Scholar]
- 9. Sutton MSJ, Rendell M, Dandona P, Dole JF, Murphy K, et al.: Rosiglitazone clinical trias study froup. 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: 2058–2064. [DOI] [PubMed] [Google Scholar]
- 10. Kiryluk K, Isom R: Thiazolidinediones and fluid retention. Kidney Int 2007; 72: 762–768. [DOI] [PubMed] [Google Scholar]
- 11. Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, et al.: Thiazolidinediones use, fluid retention and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Circulation 2003; 108: 2941–1948. [DOI] [PubMed] [Google Scholar]
- 12. Kim SH, Abbassi F, Chu JW, McLaughlin TL, Lamendola C, et al.: Rosiglitazone reduces glucose‐stimulated insulin secretion rate and increases insulin clearance in nondiabetic, insulin‐resistant individuals. Diabetes 2005; 54: 2447–2452. [DOI] [PubMed] [Google Scholar]
- 13. Avandia (rosiglitazone maleate) tablets: prescribing information. Research Triangle Park, NC: GlaxoSmithKline; 2007. (package insert). [Google Scholar]
- 14. Sotiropoulos KB, Clermont A, Yasuda Y, Rask‐Madsen C, Mastumoto M et al. Adipose‐specific effect of rosiglitazone on vascular permeability and protein kinase C activation: novel mechanism for PPARgamma agonist's effects on edema and weight gain. FASEB J 2006; 20: 1203–1205. [DOI] [PubMed] [Google Scholar]
- 15. Pickavence LC, Tadayyon M, Widdowson PS, Buckingham RE, Wilding JPH: Therapeutic index for rosiglitazone in dietary obese rats: separation of efficacy and haemodilution. Br J Pharmacol 1999; 128: 1570–1576. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Rennings AJM, Smits P, Stewart MW, Tack CJ. Fluid retention and vascular effects of rosiglitazone in obese, insulin‐resistant, nondiabetic subjects. Diabetes Care 2006; 29: 581–587. [DOI] [PubMed] [Google Scholar]
- 17. Sarafidis PA, Nilsson PM: The effects of thiazolidinediones on blood pressure levels—a systemic review. Blood Press 2006; 15: 135–150. [DOI] [PubMed] [Google Scholar]
- 18. Amà R, Segers P, Roosens C, Claessens T, Verdonck P, et al.: The effects of load on systolic mitral annular velocity by tissue Doppler imaging. Anesth Analg 2004; 99: 332–338. [DOI] [PubMed] [Google Scholar]
- 19. Gondoni LA, Titon AM, Silvestri G, Nibbio F, Taronna O, et al.: Short term effects of physical exercise and low calorie diet on left ventricular function in obese subjects: a tissue Doppler study. Nutr Metab Cardiovasc Dis 2007; 17: 358–364. [DOI] [PubMed] [Google Scholar]
- 20. Buchanan J, Mazumder PK, Hu P, Chakrabarti G, Matthew WR, et al.: Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity. Endocrinology 2005; 146: 5341–5349. [DOI] [PubMed] [Google Scholar]
- 21. Kelly AS, Bank AJ: The cardiovascular effects of the thiazolidinediones: a review of the clinical data. J Diabetes Complications 2007; 21: 326–334. [DOI] [PubMed] [Google Scholar]