Hypertension and Diabetes Mellitus

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Activation of the RAAS also results in increased aldosterone secretion from the adrenal gland and resultant salt retention and volume expansion and consequent hypertension. Further, aldosterone also contributes to hypertension by enhancing SNS activity, decreasing parasympathetic activity, and reducing baroreceptor sensitivity.27 Other effects of aldosterone in kidney, besides the salt retension, include increased extracellular matrix deposition by glomerular cells, leading to glomerulosclerosis and hypertension.27

Blockade of the aldosterone receptor in the Randomized Aldactone Evaluation Study (RALES) using spironolactone in patients with chronic moderate to severe heart failure, corresponding to New York Heart Association (NYHA) class 3 and 4, reduced mortality by 30%.28 More recently, the selective aldosterone receptor antagonist eplerenone in heart failure patients showed a similar decrease in mortality with fewer side effects.29

Other possible causes of hypertension with diabetes and insulin resistance/hyperinsulinaemia include activation of the sympathetic nervous system, increased renal tubular sodium retention, elevated intracellular calcium concentration and vascular smooth muscle cell proliferation and atherosclerosis, and impaired NO metabolism in skeletal muscle.7,30-35 Another mechanism is the upregulation of vascular AT1Rs by post-transcriptional mechanisms enhancing the vasoconstrictive and volume-expanding actions of the RAAS.36 Some studies even suggest that excess levels of insulin can interfere with compliance of the great vessels and decrease the ability of the aorta to reflect aortic waves.37 Therapy targeted at insulin resistance, such as aerobic exercise or thiazolidenedione drugs, results in a decrease in BP.38,39

Management

In patients with diabetes, the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends a target BP of <130/80mmHg in order to prevent death and disability associated with high BP. Once hypertension is detected both pharmacological and non-pharmacological interventions should be implemented. Instituting lifestyle modifications is paramount, along with medical therapy at the earliest detection of the pre-hypertensive patient.

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References
  1. Wild S, Roglic G, Green A, Sicree R, King H, Global Prevalence of Diabetes: Estimates for the year 2000 and projections for 2030 , Diabetes Care (2004);27(5): pp. 1,047-1,053.
    Crossref | PubMed
  2. Pinhas-Hamiel O, Zeitler P, The global spread of type 2 diabetes mellitus in children and adolescents , J. Pediatr. (2005);146(5): pp. 693-700.
    Crossref | PubMed
  3. National High Blood Pressure Education Program Working Group report on hypertension in diabetes, Hypertension (1994);23(2): pp. 145-158.
    Crossref | PubMed
  4. Gress T W, Nieto F J, Shahar E, Wofford M R, Brancati F L, The Atherosclerosis Risk in Communities S. Hypertension and Antihypertensive Therapy as Risk Factors for Type 2 Diabetes Mellitus , N. Engl. J. Med. (2000);342(13): pp. 905-912.
    Crossref | PubMed
  5. Sowers J R, Epstein M, Frohlich E D, Diabetes, hypertension, and cardiovascular disease: an update , Hypertension (2001);37(4): pp. 1,053-1,059.
    Crossref | PubMed
  6. Sowers J R, Epstein M, Diabetes mellitus and associated hypertension, vascular disease, and nephropathy. An update , Hypertension (1995);26(6 Pt 1): pp. 869-879.
    Crossref | PubMed
  7. Sowers J R, Treatment of hypertension in patients with diabetes , Arch. Intern. Med. (2004);164(17): pp. 1,850-1,857.
    Crossref | PubMed
  8. El-Atat F, McFarlane S I, Sowers J R, Diabetes, hypertension, and cardiovascular derangements: pathophysiology and management , Curr. Hypertens. Rep. (2004);6(3): pp. 215-223.
    Crossref | PubMed
  9. Miettinen H, Lehto S, Salomaa V, Mahonen M, Niemela M, Haffner S M et al., Impact of diabetes on mortality after the first myocardial infarction. The FINMONICA Myocardial Infarction Register Study Group , Diabetes Care (1998);21(1): pp. 69-75.
    Crossref | PubMed
  10. Bakris G, Williams M, Dworkin L, Elliott W, Epstein M, Toto R et al., Preserving renal function in adults with hypertension and diabetes: A consensus approach , Journal of Kidney Diseases (2000);36(3): p. 646.
    Crossref | PubMed
  11. Sowers J R, Haffner S, Treatment of cardiovascular and renal risk factors in the diabetic hypertensive , Hypertension (2002);40(6): pp. 781-788.
    Crossref | PubMed
  12. Adler A I, Stratton I M, Neil H A W, Yudkin J S, Matthews D R, Cull C A et al., Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study , BMJ (2000);321(7,258): pp. 412-419.
    Crossref | PubMed
  13. Reaven G M, Banting lecture 1988. Role of insulin resistance in human disease , Diabetes (1988);37(12): pp. 1,595-1,607.
    Crossref | PubMed
  14. Lind L, Berne C, Lithell H, Prevalence of insulin resistance in essential hypertension , J. Hypertens. (1995);13(12 Pt 1): pp. 1,457-1,462.
    Crossref | PubMed
  15. Sechi L A, Melis A, Tedde R, Insulin hypersecretion: a distinctive feature between essential and secondary hypertension , Metabolism (1992);41(11): pp. 1,261-1,266.
    Crossref | PubMed
  16. Sowers J R, Bakris G L, Antihypertensive Therapy and the Risk of Type 2 Diabetes Mellitus , N. Engl. J. Med. (2000);342(13): pp. 969-970.
    Crossref | PubMed
  17. Richey J M, Ader M, Moore D, Bergman R N, Angiotensin II induces insulin resistance independent of changes in interstitial insulin , Am. J. Physiol. Endocrinol. Metab. (1999);277(5): pp. E920-926.
    PubMed
  18. Ogihara T, Asano T, Ando K, Chiba Y, Sakoda H, Anai M et al., Angiotensin II-Induced Insulin Resistance Is Associated With Enhanced Insulin Signaling , Hypertension (2002);40(6): pp. 872-879.
    Crossref | PubMed
  19. Brenner B M, Cooper M E, de Zeeuw D, Keane W F, Mitch W E, Parving H-H et al., Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy , N. Engl. J. Med. (2001);345(12): pp. 861-869.
    Crossref | PubMed
  20. Sowers J R, Insulin resistance and hypertension , Am. J. Physiol. Heart Circ. Physiol. (2004);286(5):H pp. 1,597-1,602.
    Crossref | PubMed
  21. Sloniger J A, Saengsirisuwan V, Diehl C J, Dokken B B, Lailerd N, Lemieux A M et al., Defective insulin signaling in skeletal muscle of the hypertensive TG(mREN2)27 rat , Am. J. Physiol. Endocrinol. Metab. (2005);288(6): pp. E1,074-1,081.
    Crossref | PubMed
  22. Blendea M C, Jacobs D, Stump C S, McFarlane S I, Ogrin C, Bahtyiar G et al., Abrogation of oxidative stress improves insulin sensitivity in the Ren-2 rat model of tissue angiotensin II overexpression , Am. J. Physiol. Endocrinol. Metab. (2005);288(2): pp. E353-359.
    Crossref | PubMed
  23. Scheen A J, Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials , Diabetes Metab. (2004);30(6): pp. 487-496.
    Crossref | PubMed
  24. Niklason A, Hedner T, Niskanen L, Lanke J, Development of diabetes is retarded by ACE inhibition in hypertensive patientsÔÇöa subanalysis of the Captopril Prevention Project (CAPPP) , J. Hypertens. (2004);22(3): pp. 645-652.
    Crossref | PubMed
  25. Kjeldsen S E, Westheim A S, Os I, Prevention of cardiovascular events and diabetes with angiotensin-receptor blockers in hypertension: LIFE, SCOPE, and VALUE , Curr. Hypertens. Rep. (2005);7(3): pp. 155-157.
    Crossref | PubMed
  26. Sowers J R, Hypertension in Type II Diabetes: Update on Therapy , J. Clin. Hypertens. (Greenwich) (1999);1(1): pp. 41-47.
    PubMed
  27. McFarlane S I, Sowers J R, Cardiovascular endocrinology 1: aldosterone function in diabetes mellitus: effects on cardiovascular and renal disease , J. Clin. Endocrinol. Metab. (2003);88(2): pp. 516-523.
    Crossref | PubMed
  28. Pitt B, Zannad F, Remme W J, Cody R, Castaigne A, Perez A et al., The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure , N. Engl. J. Med. (1999);341(10): pp. 709-717.
    Crossref | PubMed
  29. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B et al., Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction , N. Engl. J. Med. (2003);348(14): pp. 1,309-1,321.
    Crossref | PubMed
  30. Modan M, Halkin H, Hyperinsulinemia or increased sympathetic drive as links for obesity and hypertension , Diabetes Care (1991);14(6): pp. 470-487.
    Crossref | PubMed
  31. DeFronzo R A, Ferrannini E, Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease , Diabetes Care (1991);14(3): pp. 173-194.
    Crossref | PubMed
  32. DeFronzo R A, The effect of insulin on renal sodium metabolism. A review with clinical implications , Diabetologia (1981);21(3): pp. 165-171.
    PubMed
  33. Anderson E A, Hoffman R P, Balon T W, Sinkey C A, Mark A L, Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans , J. Clin. Invest. (1991);87(6): pp. 2,246-2,252.
    Crossref | PubMed
  34. Berne C, Fagius J, Pollare T, Hjemdahl P, The sympathetic response to euglycaemic hyperinsulinaemia. Evidence from microelectrode nerve recordings in healthy subjects , Diabetologia (1992);35(9): pp. 873-879.
    Crossref | PubMed
  35. Rowe J W, Young J B, Minaker K L, Stevens A L, Pallotta J, Landsberg L, Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man , Diabetes (1981);30(3): pp. 219-225.
    Crossref | PubMed
  36. Nickenig G, Roling J, Strehlow K, Schnabel P, Bohm M, Insulin Induces Upregulation of Vascular AT1 Receptor Gene Expression by Posttranscriptional Mechanisms , Circulation (1998);98(22): pp. 2,453-2,460.
    Crossref | PubMed
  37. Westerbacka J, Vehkavaara S, Bergholm R, Wilkinson I, Cockcroft J, Yki-Jarvinen H, Marked resistance of the ability of insulin to decrease arterial stiffness characterizes human obesity , Diabetes (1999);48(4): pp. 821-827.
    Crossref | PubMed
  38. Raji A, Seely E W, Bekins S A, Williams G H, Simonson D C, Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients , Diabetes Care (2003);26(1): pp. 172-178.
    Crossref | PubMed
  39. Dengel D R, Hagberg J M, Pratley R E, Rogus E M, Goldberg A P, Improvements in blood pressure, glucose metabolism, and lipoprotein lipids after aerobic exercise plus weight loss in obese, hypertensive middle-aged men , Metabolism (1998);47(9): pp. 1,075-1,082.
    Crossref | PubMed
  40. Wassertheil-Smoller S, Blaufox M D, Oberman A S, Langford H G, Davis B R, Wylie-Rosett J, The Trial of Antihypertensive Interventions and Management (TAIM) study. Adequate weight loss, alone and combined with drug therapy in the treatment of mild hypertension , Arch. Intern. Med. (1992);152(1): pp. 131-136.
    Crossref | PubMed
  41. Sacks F M, Svetkey L P, Vollmer W M, Appel L J, Bray G A, Harsha D et al., Effects on Blood Pressure of Reduced Dietary Sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet , N. Engl. J. Med. (2001);344(1): pp. 3-10.
    Crossref | PubMed
  42. Halbert J A, Silagy C A, Finucane P, Withers R T, Hamdorf P A, Exercise training and blood lipids in hyperlipidemic and normolipidemic adults: a meta-analysis of randomized, controlled trials , Eur. J. Clin. Nutr. (1999);53(7): pp. 514-522.
    Crossref | PubMed
  43. Whelton S P, Chin A, Xin X, He J, Effect of Aerobic Exercise on Blood Pressure: A Meta-Analysis of Randomized, Controlled Trials , Ann. Intern. Med. (2002);136(7): pp. 493-503.
    Crossref | PubMed
  44. Whaley-Connell A, Sowers J R, Hypertension management in type 2 diabetes mellitus: recommendations of the Joint National Committee VII , Endocrinol. Metab. Clin. North Am. (2005);34(1): pp. 63-75.
    Crossref | PubMed
  45. Treatment of Hypertension in Adults With Diabetes , Diabetes Care (2003);26(90,001): pp. 80S-82.
    Crossref
  46. Chobanian A V, Bakris G L, Black H R, Cushman W C, Green L A, Izzo J L, Jr et al., The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report , JAMA (2003);289(19): pp. 2,560-2,571.
    Crossref | PubMed
  47. Arauz-Pacheco C, Parrott M A, Raskin P, The Treatment of Hypertension in Adult Patients With Diabetes , Diabetes Care (2002);25(1): pp. 134-147.
    Crossref | PubMed
  48. Ravid M, Lang R, Rachmani R, Lishner M, Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. A 7-year follow-up study , Arch. Intern. Med. (1996);156(3): pp. 286-289.
    Crossref | PubMed
  49. Bakris G L, Smith A C, Richardson D J, Hung E, Preston R, Goldberg R et al., Impact of an ACE inhibitor and calcium antagonist on microalbuminuria and lipid subfractions in type 2 diabetes: a randomised, multi-centre pilot study , J. Hum. Hypertens. (2002);16(3): pp. 185-191.
    Crossref | PubMed
  50. Bakris G L, Weir M R, Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? , Arch. Intern. Med. (2000);160(5): pp. 685-693.
    Crossref | PubMed
  51. Lindholm L H, Persson M, Alaupovic P, Carlberg B, Svensson A, Samuelsson O, 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(8): pp. 1,563-1,574.
    Crossref | PubMed
  52. Pfeffer M A, Swedberg K, Granger C B, Held P, McMurray J J, Michelson E L et al., Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme , Lancet (2003);362(9,386): pp. 759-766.
    Crossref | PubMed
  53. Lindholm L H, Ibsen H, Borch-Johnsen K, Olsen M H, Wachtell K, Dahlof B et al., Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study , J. Hypertens. (2002);20(9): pp. 1,879-1,886.
    Crossref | PubMed
  54. Yusuf S, Pfeffer M A, Swedberg K, Granger C B, Held P, McMurray J J et al., Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial , Lancet (2003);362(9,386): pp. 777-781.
    Crossref | PubMed
  55. Julius S, Kjeldsen S E, Weber M, Brunner H R, Ekman S, Hansson L 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(9,426): pp. 2,022-2,031.
    Crossref | PubMed
  56. Yusuf S, From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis , Am. J. Cardiol. (2002);89(2A): pp. 18A-25A; discussion pp. 25A-26A.
    Crossref | PubMed
  57. Gerstein H C, Yusuf S, Holman R, Bosch J, Pogue J, Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial , Diabetologia (2004);47(9): pp. 1,519-1,527.
    Crossref | PubMed
  58. Califf R M, Insulin resistance: a global epidemic in need of effective therapies , Eur. Heart J. Suppl. (2003);5(suppl_C): pp. C13-18.
    Crossref
  59. Scheen A J, Prevention of type 2 diabetes mellitus through inhibition of the Renin-Angiotensin system , Drugs (2004);64(22): pp. 2,537-2,565.
    Crossref | PubMed
  60. Group UKPDS, Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38 , BMJ (1998);317(7,160): pp. 703-713.
    Crossref | PubMed
  61. Group UKPDS, Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39 , BMJ (1998);317(7160): pp. 713-720.
    Crossref | PubMed
  62. Giugliano D, Acampora R, Marfella R, De Rosa N, Ziccardi P, Ragone R et al., Metabolic and Cardiovascular Effects of Carvedilol and Atenolol in Non-Insulin-Dependent Diabetes Mellitus and Hypertension: A Randomized, Controlled Trial , Ann. Intern. Med. (1997);126(12): pp. 955-959.
    Crossref | PubMed
  63. Major outcomes in high-risk 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(23): pp. 2,981-2,997.
    Crossref | PubMed
  64. Curb J D, Pressel S L, Cutler J A, Savage P J, Applegate W B, Black H et al., Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension , Systolic Hypertension in the Elderly Program Cooperative Research Group, JAMA (1996);276(23): pp. 1,886-1,892.
    Crossref | PubMed
  65. Birkenhager W H, Staessen J A, Gasowski J, de Leeuw P W, Effects of antihypertensive treatment on endpoints in the diabetic patients randomized in the Systolic Hypertension in Europe (Syst-Eur) trial , J. Nephrol. (2000);13(3): pp. 232-237.
    PubMed
  66. Hansson L, Zanchetti A, Carruthers S G, Dahlof B, Elmfeldt D, Julius S et al., Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial , HOT Study Group, Lancet (1998);351(9,118): pp. 1,755-1,762.
    Crossref | PubMed
  67. Poulter N R, Calcium antagonists and the diabetic patient: a response to recent controversies , Am. J. Cardiol. (1998);82(9B): pp. 40R-41R.
    Crossref | PubMed