Current Hypertension Reports

, Volume 7, Issue 4, pp 298–303 | Cite as

Antihypertensive treatment and new-onset diabetes mellitus

  • Tonje Amb Aksnes
  • Henrik M. Reims
  • Sverre E. Kjeldsen
  • Giuseppe Mancia


The various antihypertensive regimens have varying effects on glucose metabolism and the development of diabetes mellitus. Recent large hypertension trials have shown great differences in the development of new-onset diabetes among antihypertensive drug therapies. The incidence of diabetes is unchanged or increased by thiazide diuretics and β-adrenergic blockers, and unchanged or decreased by angiotensin-converting enzyme inhibitors, calcium channel blockers, and angiotensin-receptor blockers. The differences in new-onset diabetes mellitus have not influenced the outcome of cardiovascular mortality and morbidity in all of the large clinical trials, but drug-induced diabetes among hypertensive patients is known to carry the same cardiovascular risk as that seen in patients with previously known diabetes; however, it might take years for the increased risk to become apparent.


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References and Recommended Reading

  1. 1.
    Kannel WB, Wilson PW, Zhang TJ: The epidemiology of impaired glucose tolerance and hypertension. Am Heart J 1991, 121:1268–1273.CrossRefPubMedGoogle Scholar
  2. 2.
    Saltiel AR, Kahn CR: Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001, 414:799–806.CrossRefPubMedGoogle Scholar
  3. 3.
    Sowers JR: Insulin resistance and hypertension. Am J Physiol Heart Circ Physiol 2004, 286:H1597-H1602.CrossRefPubMedGoogle Scholar
  4. 4.
    Wheatcroft SB, Williams IL, Shah AM, Kearney MT: Pathophysiological implications of insulin resistance on vascular endothelial function. Diabet Med 2003, 20:255–268.CrossRefPubMedGoogle Scholar
  5. 5.
    Bergman RN, Finegood DT, Kahn SE: The evolution of betacell dysfunction and insulin resistance in type 2 diabetes. Eur J Clin Invest 2002, 32(Suppl3):35–45.CrossRefPubMedGoogle Scholar
  6. 6.
    Sarafidis PA, Lasaridis AN, Nilsson PM, 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, 22:1769–1777.CrossRefPubMedGoogle Scholar
  7. 7.
    Benson SC, Pershadsingh HA, Ho CI, et al.: Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension 2004, 43:993–1002.CrossRefPubMedGoogle Scholar
  8. 8.
    Padwal R, Laupacis A: Antihypertensive therapy and incidence of type 2 diabetes: a systematic review. Diabetes Care 2004, 27:247–255.CrossRefPubMedGoogle Scholar
  9. 9.
    ALLHAT Officers and Coordinators: Major outcomes in highrisk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002, 288:2981–2997. In the ALLHAT study, fewer patients developed new-onset diabetes on antihypertensive treatment with ACEI, CCB, and alpha-blocker compared with the diuretic chlorthalidone. ALLHAT was a huge study in more than 42,000 elderly patients with high cardiovascular risk.CrossRefGoogle Scholar
  10. 10.
    Brown MJ, Palmer CR, Castaigne A, et al.: Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000, 356:366–372.CrossRefPubMedGoogle Scholar
  11. 11.
    Julius S, Kjeldsen SE, Weber M, et al.: Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004, 363:2022–2031. In the VALUE trial, fewer patients developed new-onset diabetes on antihypertensive treatment with ARB compared with treatment with CCB. VALUE comprised more than 15,000 mostly elderly patients with high cardiovascular risk.CrossRefPubMedGoogle Scholar
  12. 12.
    Stamler J, Vaccaro O, Neaton JD, Wentworth D: Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993, 16:434–444.CrossRefPubMedGoogle Scholar
  13. 13.
    Verdecchia P, Reboldi G, Angeli F, et al.: Adverse prognostic significance of new diabetes in treated hypertensive subjects. Hypertension 2004, 43:963–969.CrossRefPubMedGoogle Scholar
  14. 14.
    Zimmet P, Alberti KG, Shaw J: Global and societal implications of the diabetes epidemic. Nature 2001, 414:782–787.CrossRefPubMedGoogle Scholar
  15. 15.
    Lindholm LH, Persson M, Alaupovic P, et al.: Metabolic outcome during 1 year in newly detected hypertensives: results of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE study). J Hypertens 2003, 21:1563–1574.CrossRefPubMedGoogle Scholar
  16. 16.
    Diabetes mellitus. Report of a WHO Study Group. World Health Organ Tech Rep Ser 1985, 727:1–113.Google Scholar
  17. 17.
    Hansson L, Lindholm LH, Niskanen L, 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, 353:611–616. The CAPPP study, on approximately 11,000 middle-aged hypertensive patients, was the first large, randomized trial that showed that treatment of hypertension with ACEI prevents new-onset diabetes mellitus compared with standard treatment with diruretics/β-blockers.CrossRefPubMedGoogle Scholar
  18. 18.
    Alberti KG, Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998, 15:539–553.CrossRefPubMedGoogle Scholar
  19. 19.
    Dahlof B, Devereux RB, Kjeldsen SE, et al.: Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002, 359:995–1003. The LIFE study was the first trial showing that treatment of hypertension with ARB prevents new-onset diabetes compared with standard treatment for hypertension. LIFE was done in about 9200 hypertensive patients with ECG-LVH ranging in age from 55 to 80 years.CrossRefPubMedGoogle Scholar
  20. 20.
    Lindholm LH, Ibsen H, Borch-Johnsen K, et al.: Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study. J Hypertens 2002, 20:1879–1886.CrossRefPubMedGoogle Scholar
  21. 21.
    Yusuf S, Sleight P, Pogue J, et al.: 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, 342:145–153.CrossRefPubMedGoogle Scholar
  22. 22.
    Yusuf S, Gerstein H, Hoogwerf B, et al.: Ramipril and the development of diabetes. JAMA 2001, 286:1882–1885.CrossRefPubMedGoogle Scholar
  23. 23.
    Hansson L, Hedner T, Lund-Johansen P, et al.: Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Lancet 2000, 356:359–365.CrossRefPubMedGoogle Scholar
  24. 24.
    Hansson L, Lindholm LH, Ekbom T, et al.: Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet 1999, 354:1751–1756.CrossRefPubMedGoogle Scholar
  25. 25.
    Pfeffer MA, Swedberg K, Granger CB, et al.: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003, 362:759–766.CrossRefPubMedGoogle Scholar
  26. 26.
    Fletcher A, Amery A, Birkenhager W, et al.: Risks and benefits in the trial of the European Working Party on High Blood Pressure in the Elderly. J Hypertens 1991, 9:225–230.CrossRefPubMedGoogle Scholar
  27. 27.
    Lithell H, Hansson L, Skoog I, et al.: The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003, 21:875–886.CrossRefPubMedGoogle Scholar
  28. 28.
    Savage PJ, Pressel SL, Curb JD, et al.: Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group. Arch Intern Med 1998, 158:741–751.CrossRefPubMedGoogle Scholar
  29. 29.
    The SOLVD Investigators: Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991, 325:293–302.CrossRefGoogle Scholar
  30. 30.
    Vermes E, Ducharme A, Bourassa MG, et al.: Enalapril reduces the incidence of diabetes in patients with chronic heart failure: insight from the Studies of Left Ventricular Dysfunction (SOLVD). Circulation 2003, 107:1291–1296.CrossRefPubMedGoogle Scholar
  31. 31.
    Braunwald E, Domanski MJ, Fowler SE, et al.: Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 2004, 351:2058–2068.CrossRefPubMedGoogle Scholar
  32. 32.
    Henriksen EJ, Jacob S: Modulation of metabolic control by angiotensin converting enzyme (ACE) inhibition. J Cell Physiol 2003, 196:171–179.CrossRefPubMedGoogle Scholar
  33. 33.
    Jacob S, Henriksen EJ, Fogt DL, Dietze GJ: Effects of trandolapril and verapamil on glucose transport in insulin-resistant rat skeletal muscle. Metabolism 1996, 45:535–541.CrossRefPubMedGoogle Scholar
  34. 34.
    Sharma AM, Janke J, Gorzelniak K, et al.: Angiotensin blockade prevents type 2 diabetes by formation of fat cells. Hypertension 2002, 40:609–611.CrossRefPubMedGoogle Scholar
  35. 35.
    Ferrannini E, Seghieri G, Muscelli E: Insulin and the reninangiotensin-aldosterone system: influence of ACE inhibition. J Cardiovasc Pharmacol 1994, 24(Suppl3):S61-S69.PubMedGoogle Scholar
  36. 36.
    Carlsson PO, Berne C, Jansson L: Angiotensin II and the endocrine pancreas: effects on islet blood flow and insulin secretion in rats. Diabetologia 1998, 41:127–133.CrossRefPubMedGoogle Scholar
  37. 37.
    Leung PS, Carlsson PO: Tissue renin-angiotensin system: its expression, localization, regulation and potential role in the pancreas. J Mol Endocrinol 2001, 26:155–164.CrossRefPubMedGoogle Scholar
  38. 38.
    Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al.: A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA 2003, 290:2805–2816.CrossRefPubMedGoogle Scholar
  39. 39.
    Conn JW: Hypertension, the potassium ion and impaired carbohydrate tolerance. N Engl J Med 1965, 273:1135–1143.CrossRefPubMedGoogle Scholar
  40. 40.
    Shamiss A, Carroll J, Peleg E, et al.: The effect of enalapril with and without hydrochlorothiazide on insulin sensitivity and other metabolic abnormalities of hypertensive patients with NIDDM. Am J Hypertens 1995, 8:276–281.CrossRefPubMedGoogle Scholar
  41. 41.
    Gress TW, Nieto FJ, Shahar E, et al.: Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. N Engl J Med 2000, 342:905–912.CrossRefPubMedGoogle Scholar
  42. 42.
    Jacob S, Rett K, Henriksen EJ: Antihypertensive therapy and insulin sensitivity: Do we have to redefine the role of betablocking agents? Am J Hypertens 1998, 11:1258–1265.CrossRefPubMedGoogle Scholar
  43. 43.
    Gerstein HC, Yusuf S, Holman R, et al.: Rationale, design, and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial. Diabetologia 2004, 47:1519–1527.CrossRefPubMedGoogle Scholar
  44. 44.
    NAVIGATOR information site: http:/ news/novartis_2.htm. Accessed September 10, 2001.Google Scholar
  45. 45.
    Opie LH, Schall R: Old antihypertensives and new diabetes. J Hypertens 2004, 22:1453–1458.CrossRefPubMedGoogle Scholar
  46. 46.
    Kjeldsen SE, Reims HR, Fagard R, Mancia G: Hypertension. In European Society of Cardiology Textbook of Cardivascular Medicine. Oxford: Blackwell Publishing; 2005:In press.Google Scholar

Copyright information

© Current Science Inc 2005

Authors and Affiliations

  • Tonje Amb Aksnes
    • 1
  • Henrik M. Reims
    • 1
  • Sverre E. Kjeldsen
    • 1
  • Giuseppe Mancia
    • 1
  1. 1.Clinica Medica, Ospedale S GerardoUniversity of Milan-BicoccaMonzaItaly

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