CANAN ERSOY, ALPARSLAN ERSOY, Gülşah ELBÜKEN, Ercan TUNCEL

The Effect of Trandolapril on Insulin Resistance is Determined by the Degree of Baseline Resistance Level

Insulin resistance (IR) is the core problem in type 2 diabetes mellitus that may lead to cardiovascular morbidity and mortality. Hypertension commonly accompanies type 2 diabetes. Antihypertensive agents improving IR may reduce the risk of cardiovascular diseases. This study was conducted to assess the effect of trandolapril on IR, glucose and lipid metabolisms in hypertensive subjects with different degrees of IR and investigate the importance of IR level in angiotensin converting enzyme inhibitor response. The subjects were nondiabetic and type 2 diabetic hypertensive patients treated with trandolapril for 12 weeks. Blood pressures (BP) and metabolic parameters were measured in all patients at baseline and after 12 weeks of trandolapril treatment and compared. Trandolapril reduced BP similarly in nondiabetic and diabetic patients. Homeostasis model assessment insulin resistance (HOMA-IR), serum glucose and hemoglobin A1C (A1C) in diabetic patients were higher than nondiabetics. HOMAsignificantly after trandolapril in diabetics, while serum glucose, insulin and A1C remained unchanged. The posttreatment HOMA-IR values were comparable in both groups. Pretreatment HOMA-IR value was found to be associated with HOMA-IR response to trandolapril while changes in BMI, A1C and BPs were unrelated. The patients with a pretreatment HOMA-IR of >4.67 responded better. In conclusion, trandolapril improved insulin sensitivity better in type 2 diabetic hypertensive patients with higher degree of IR compared with the ones with low grade IR, being independent of its hemodynamic action

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1. Ruderman NB, Carling D, Prentki M, Cacicedo JM. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest. 2013;123(7):2764-72.

2. Garcia-Touza M, Sowers JR. Evidence-based hypertension treatment in patients with diabetes. J Clin Hypertens (Greenwich). 2012;14(2):97-102.

3. Miller JL. Insulin resistance syndrome. Description, pathogenesis, and management. Postgrad Med. 2003; Spec No: 27-34.

4. Sharma SK, Ruggenenti P, Remuzzi G. Managing hypertension in diabetic patientsfocus on trandolapril/verapamil combination. Vasc Health Risk Manag. 2007;3(4):453-65.

5. Henriksen EJ, Jacob S. Angiotensin converting enzyme inhibitors and modulation of skeletal muscle insulin resistance. Diabetes Obes Metab. 2003;5(4):214-22.

6. Rayner B. Selective imidazoline agonist moxonidine plus the ACE inhibitor ramipril in hypertensive patients with impaired insulin sensitivity: partners in a successful marriage? Curr Med Res Opin. 2004;20(3):359-67.

7. Heinemann L, Heise T, Ampudia J, Sawicki P, Sindelka G, Brunner G, Starke AA. Four week administration of an ACE inhibitor and a cardioselective beta-blocker in healthy volunteers: no influence on insulin sensitivity. Eur J Clin Invest. 1995;25(8):595-600.

8. Heise T, Heinemann L, Kristahn K, Berger M, Sawicki PT. Insulin sensitivity in patients with essential hypertension: no influence of the ACE inhibitor enalapril. Horm Metab Res. 1999;31(7):418-23.

9. Park SH, Lee WY, Rhee EJ, Jeon WK, Kim BI, Ryu SH, Kim SW. Relative risks of the metabolic syndrome according to the degree of insulin resistance in apparently healthy Korean adults. Clin Sci (Lond). 2005;108(6):553-9.

10. Guay DR. Trandolapril: a newer angiotensin-converting enzyme inhibitor. Clin Ther. 2003;25(3):713-75.

11. Leighton B, Sanderson AL, Young ME, Radda GK, Boehm EA, Clark JF. Effects of treatment of spontaneously hypertensive rats with the angiotensin-converting enzyme inhibitor trandolapril and the calcium antagonist verapamil on the sensitivity of glucose metabolism to insulin in rat soleus muscle in vitro. Diabetes. 1996;45(Suppl.1):S120-4.

12. Jacob S, Henriksen EJ, Fogt DL, Dietze GJ. Effects of trandolapril and verapamil on glucose transport in insulin-resistant rat skeletal muscle. Metabolism. 1996;45(5):535- 41.

13. New JP, Bilous RW, Walker M. Insulin sensitivity in hypertensive Type 2 diabetic patients after 1 and 19 days' treatment with trandolapril. Diabet Med. 2000;17(2):134- 40.

14. Petrie JR, Morris AD, Ueda S, Small M, Donnelly R, Connell JM, Elliott HL. Trandolapril does not improve insulin sensitivity in patients with hypertension and type 2 diabetes: a double-blind, placebo-controlled crossover trial. J Clin Endocrinol Metab. 2000;85(5):1882-9.

15. Schneider M, Lerch M, Papiri M, Buechel P, Boehlen L, Shaw S, Risen W, Weidmann P. Metabolic neutrality of combined verapamil-trandolapril treatment in contrast to beta-blocker-low-dose chlortalidone treatment in hypertensive type 2 diabetes. J Hypertens. 1996;14(5):669-77. 16. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of lowdensity lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499-502.

17. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9.

18. Gokcel A, Baltali M, Tarim E, Bagis T, Gumurdulu Y, Karakose H, Yalcin F, Akbaba M, Guvener N. Detection of insulin resistance in Turkish adults: a hospital-based study. Diabetes Obes Metab. 2003;5(2):126-30.

19. Foianini KR, Steen MS, Kinnick TR, Schmit MB, Youngblood EB, Henriksen EJ. Effects of exercise training and ACE inhibition on insulin action in rat skeletal muscle. J Appl Physiol. 2000;89(2):687-94.

20. Reneland R, Alvarez E, Andersson PE, Haenni A, Byberg L, Lithell H. Induction of insulin resistance by beta-blockade but not ACE-inhibition: long-term treatment with atenolol or trandolapril. J Hum Hypertens. 2000;14(3):175-80.

21. Galletti F, Strazzullo P, Capaldo B, Carretta R, Fabris F, Ferrara LA, Glorioso N, Semplicini A, Mancini M. Controlled study of the effect of angiotensin converting enzyme inhibition versus calcium-entry blockade on insulin sensitivity in overweight hypertensive patients: Trandolapril Italian Study (TRIS). J Hypertens. 1999;17(3):439- 45.

22. Rubio-Guerra AF, Vargas-Robles H, Lozano Nuevo JJ, Elizalde-Barrera CI, HuertaRamirez S, Escalante-Acosta BA. Beneficial effect of combination therapy using an angiotensin-converting enzyme inhibitor plus verapamil on circulating resistin levels in hypertensive patients with type 2 diabetes. Exp Clin Cardiol. 2012;17(4):202-4.

23. Rubio-Guerra AF, Vargas-Robles H, Vargas-Ayala G, Rodríguez-Lopez L, CastroSerna D, Escalante-Acosta BA. Impact of trandolapril therapy and its combination with a calcium channel blocker on plasma adiponectin levels in patients with type 2 diabetes and hypertension. Ther Adv Cardiovasc Dis. 2011;5(4):193-7.

24. Fukuzawa M, Satoh J, Sagara M, Muto G, Muto Y, Nishimura S, Miyaguchi S, Qiang XL, Sakata Y, Nakazawa T, Ikehata F, Ohta S, Toyota T. Angiotensin converting enzyme inhibitors suppress production of tumor necrosis factorImmunopharmacology. 1997;36(1):49-55.

25. Mishima Y, Kuyama A, Tada A, Takahashi K, Ishioka T, Kibata M. Relationship between serum tumor necrosis factor- 2 diabetes mellitus. Diabetes Res Clin Pract. 2001; 52(2): 119-23.

26. Seghieri G, Yin W, Boni C, Sanna G, Anichini R, Bartolomei G, Ferrannini E. Effect of chronic ACE inhibition on glucose tolerance and insulin sensitivity in hypertensive type 2 diabetic patients. Diabet Med. 1992;9(8):732-8.

27. Pollare T, Lithell H, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med. 1989;321(13):868-73.

28. Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A, Luomanmäki K, Dahlöf B, de Faire U, Mörlin C, Karlberg BE, Wester PO, Björck JE. 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(9153):611-6.

29. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in highrisk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342(3):145-53.

30. Bakris G, Stockert J, Molitch M, Zhou Q, Champion A, Bacher P, Sowers J; STAR Investigators. Risk factor assesment for new onset diabetes: Literature review. Diabetes Obes Metab. 2009;11(3):177-87.

31. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. United Kingdom Prospective Diabetes Study Group. BMJ. 1998;317(7160):713-20.

32. Holzgreve H, Nakov R, Beck K, Janka HU. Antihypertensive therapy with verapamil SR plus trandolapril versus atenolol plus chlorthalidone on glycemic control. Am J Hypertens. 2003;16(5 Pt 1):381-6.

33. Gavras HP. Issues in Hypertension: drug tolerability and special populations. Am J Hypertens. 2001;14(7 Pt 2):231S-6S.

34. O’Keefe JH, Wetzel M, Moe RR, Bronsnahan K, Lavie CJ. Should an angiotensinconverting enzyme inhibitor be standard therapy for patients with atherosclerotic disease? J Am Coll Cardiol. 2001;37(1):1-8.