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Horm Metab Res 2012; 44(03): 208-214
DOI: 10.1055/s-0031-1295412
Review
© Georg Thieme Verlag KG Stuttgart · New York

Primary Aldosteronism and Metabolic Syndrome

F. Fallo
1   Department of Medical and Surgical Sciences, Clinica Medica 3, University of Padova, Padova, Italy
,
C. Pilon
1   Department of Medical and Surgical Sciences, Clinica Medica 3, University of Padova, Padova, Italy
,
R. Urbanet
1   Department of Medical and Surgical Sciences, Clinica Medica 3, University of Padova, Padova, Italy
› Author Affiliations
Further Information

Publication History

received 22 August 2011

accepted 11 October 2011

Publication Date:
24 November 2011 (online)

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Abstract

Hypertension is frequently associated with interrelated risk factors of metabolic origin, including abdominal obesity, dyslipidemia, and alterations in glucose homeostasis, all promoting the pathogenesis of arteriosclerosis. Clustering of these risk factors, defined as metabolic syndrome, is associated with an overall high cardiovascular risk profile. This article reviews current knowledge regarding the prevalence and characteristics of the metabolic syndrome in primary aldosteronism, and discusses a possible pathophysiological link between aldosterone and its individual components other than hypertension. An abnormal glucose metabolism due to insulin resistance appears to be linked to aldosterone overproduction, and seems the major contributor to metabolic dysfunction in primary aldosteronism. Impairment of insulin action may be also due to concurrent environmental factors (hypokalemia?), and/or it might occur in compartments other than fat tissue (liver? skeletal muscle?). Higher rates of cardiovascular events reported in primary aldosteronism could be due in part to the increased prevalence of the metabolic syndrome in this disorder. Regression of glucometabolic complications after the cure of aldosterone excess should be confirmed by larger studies, and the influence on the natural history of primary aldosteronism by using agents potentially able to correct metabolic abnormalities should be further explored.

Key words

aldosterone - hypertension - obesity - lipids - diabetes
 

  • References

  • 1 Cuspidi C, Meani S, Fusi V, Severgnini B, Valerio C, Catini E, Esposito A, Magrini F, Zanchetti A. Metabolic syndrome and target organ damage in untreated essential hypertensives. J Hypertens 2004; 22: 1991-1998
    CrossrefPubMedGoogle Scholar
  • 2 Schillaci G, Pirro M, Vaudo G, Gemelli F, Marchesi S, Porcellati C, Mannarino E. Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol 2004; 43: 1817-1822
    CrossrefPubMedGoogle Scholar
  • 3 Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S. Insulin resistance in essential hypertension. N Engl J Med 1987; 317: 350-357
    CrossrefPubMedGoogle Scholar
  • 4 Kahn R, Ferrannini E, Buse J, Stern M. American Diabetes Association; European Association for the Study of Diabetes . The metabolic syndrome: time for a critical appraisal. Diabetes Care 2005; 28: 2289-2304
    CrossrefPubMedGoogle Scholar
  • 5 National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults . Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-2497
    CrossrefPubMedGoogle Scholar
  • 6 Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith Jr SC, Spertus JA, Costa F. American Heart Association; National Heart, Lung, and Blood Institute . Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 2735-2752
    CrossrefPubMedGoogle Scholar
  • 7 Connell JM, MacKenzie SM, Freel EM, Fraser R, Davies E. A lifetime of aldosterone excess: long-term consequences of altered regulation of aldosterone production for cardiovascular function. Endocr Rev 2008; 29: 133-154
    Google Scholar
  • 8 Rossi GP, Sechi LA, Giacchetti G, Ronconi V, Strazzullo P, Funder JW. Primary aldosteronism: cardiovascular, renal, and metabolic implications. Trends Endocrinol Metab 2008; 19: 88-90
    Google Scholar
  • 9 Quinkler M, Born-Frontsberg E, Fourkiotis VG. Comorbidities in primary aldosteronism. Horm Metab Res 2010; 42: 429-434
    Google Scholar
  • 10 Bochud M, Nussberger J, Bovet P, Maillard MR, Elston RC, Paccaud F, Shamlaye C, Burnier M. Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension 2006; 48: 239-245
    CrossrefPubMedGoogle Scholar
  • 11 Kidambi S, Kotchen JM, Grim CE, Raff H, Mao J, Singh RJ, Kotchen TA. Association of adrenal steroids with hypertension and the metabolic syndrome in blacks. Hypertension 2007; 49: 704-711
    CrossrefPubMedGoogle Scholar
  • 12 Ingelsson E, Pencina MJ, Tofler GH, Benjamin EJ, Lanier KJ, Jacques PF, Fox CS, Meigs JB, Levy D, Larson MG, Selhub J, D’Agostino Sr RB, Wang TJ, Vasan RS. Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors: the Framingham Offspring Study. Circulation 2007; 116: 984-992
    CrossrefPubMedGoogle Scholar
  • 13 Hannemann A, Meisinger C, Bidlingmaier M, Döring A, Thorand B, Heier M, Belcredi P, Ladwig KH, Wallaschofski H, Friedrich N, Schipf S, Lüdemann J, Rettig R, Peters J, Volzke H, Seissler J, Beuschlein F, Nauck M, Reincke M. Association of plasma aldosterone with the metabolic syndrome in two german populations. Eur J Endocrinol 2011; 164: 751-758
    CrossrefPubMedGoogle Scholar
  • 14 Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, Young Jr WF, Montori VM. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008; 93: 3266-3281
    Google Scholar
  • 15 Mulatero P, Monticone S, Bertello C, Mengozzi G, Tizzani D, Iannaccone A, Veglio F. Confirmatory tests in the diagnosis of primary aldosteronism. Horm Metab Res 2010; 42: 406-410
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Douma S, Petidis K, Doumas M, Papaefthimiou P, Triantafyllou A, Kartali N, Papadopoulos N, Vogiatzis K, Zamboulis C.. Prevalence of primary aldosteronism in resistant hypertension: a retrospective observational study. Lancet 2008; 371: 1921-1926
    Google Scholar
  • 17 Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence of an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005; 45: 1243-1248
    Google Scholar
  • 18 Catena C, Colussi G, Nadalini E, Chiuch A, Baroselli S, Lapenna R, Sechi LA. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 2008; 168: 80-85
    Google Scholar
  • 19 Born-Frontsberg E, Reincke M, Rump LC, Hahner S, Diederich S, Lorenz R, Allolio B, Seufert J, Schirpenbach C, Beuschlein F, Bidlingmaier M, Endres S, Quinkler M. Participants of the German Conn’s Registry . Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: results of the German Conn’s Registry. J Clin Endocrinol Metab 2009; 94: 1125-1130
    Google Scholar
  • 20 Fallo F, Veglio F, Bertello C, Sonino N, Della Mea P, Ermani M, Rabbia F, Federspil G, Mulatero P. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab 2006; 91: 454-459
    Google Scholar
  • 21 Iacobellis G, Petramala L, Cotesta D, Pergolini M, Zinnamosca L, Cianci R, De Toma G, Sciomer S, Letizia C. Adipokines and cardiometabolic profile in primary aldosteronism. J Clin Endocrinol Metab 2010; 95: 2391-2398
    CrossrefPubMedGoogle Scholar
  • 22 Grundy SM, Brewer Jr HB, Cleeman JI, Smith Jr SC, Lenfant C. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004; 109: 433-438
    CrossrefPubMedGoogle Scholar
  • 23 Ronconi V, Turchi F, Rilli S, Di Mattia D, Agostinelli L, Boscaro M, Giacchetti G. Metabolic syndrome in primary aldosteronism and essential hypertension: relationship to adiponectin gene variants. Nutr Metab Cardiovasc Dis 2010; 20: 93-100
    Google Scholar
  • 24 Somlóová Z, Widimský Jr J, Rosa J, Wichterle D, Strauch B, Petrák O, Zelinka T, Vlková J, Masek M, Dvoráková J, Holaj R. The prevalence of metabolic syndrome and its components in two main types of primary aldosteronism. J Hum Hypertens 2010; 24: 625-630
    CrossrefPubMedGoogle Scholar
  • 25 Alberti KGMM, Zimmat P, Shaw J. Metabolic syndrome – a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 2006; 23: 469-480
    CrossrefPubMedGoogle Scholar
  • 26 Rondinone C, Rodbard MD, Baker ME. Aldosterone stimulates differentiation of mouse 3T-L1 cells into adipocytes. Endocrinology 1993; 132: 2421-2426
    CrossrefPubMedGoogle Scholar
  • 27 Fu M, Sun T, Bookout Downes M, Yu RT, Evans RM, Mangelsdorf DJ. A nuclear receptor atlas: 3T3-L1 adipogenesis. Mol Endocrinol 2005; 19: 2437-2445
    CrossrefPubMedGoogle Scholar
  • 28 Caprio M, Fève B, Claës A, Viengchareun S, Lombès M, Zennaro MC. 2007 Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis. FASEB J 2007; 21: 2185-2194
    CrossrefPubMedGoogle Scholar
  • 29 Goodfriend TL, Calhoun DA. Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and therapy. Hypertension 2004; 43: 518-524
    CrossrefPubMedGoogle Scholar
  • 30 Ronconi V, Turchi F, Bujalska IJ, Giacchetti G, Boscaro M. Adipose cell-adrenal interactions: current knowledge and future perspectives. Trends Endocrinol Metab 2008; 19: 100-103
    CrossrefPubMedGoogle Scholar
  • 31 Bentley-Lewis R, Adler GK, Perlstein T, Seely EW, Hopkins PN, Williams GH, Garg R. Body mass index predicts aldosterone production in normotensive adults on a high-salt diet. J Clin Endocrinol Metab 2007; 92: 4472-4475
    CrossrefPubMedGoogle Scholar
  • 32 Rossi GP, Belfiore A, Bernini G, Fabris B, Caridi G, Ferri C, Giacchetti G, Letizia C, Maccario M, Mannelli M, Palumbo G, Patalano A, Rizzoni D, Rossi E, Pessina AC, Mantero F. Primary Aldosteronism Prevalence in Hypertension Study Investigators . Body mass index predicts plasma aldosterone concentrations in overweight-obese primary hypertensive patients. J Clin Endocrinol Metab 2008; 93: 2566-2571
    CrossrefPubMedGoogle Scholar
  • 33 Zennaro MC, Caprio M, Fève B. Mineralocorticoid receptors in the metabolic syndrome. Trends Endocrinol Metab 2009; 20: 444-450
    CrossrefPubMedGoogle Scholar
  • 34 Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009; 360: 1509-1517
    CrossrefPubMedGoogle Scholar
  • 35 Krug AW, Ehrhart-Bornstein M. Adrenocortical dysfunction in obesity and the metabolic syndrome. Horm Metab Res 2008; 40: 515-517
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Goodfriend TL, Egan B, Stepniakowski K, Ball DL. Relationship among plasma aldosterone, high-density lipoprotein cholesterol, and insulin in humans. Hypertension 1995; 25: 30-36
    CrossrefPubMedGoogle Scholar
  • 37 Catena C, Lapenna R, Baroselli S, Nadalini E, Colussi G, Novello M, Favret G, Melis A, Cavarape A, Sechi LA. Insulin sensitivity in patients with primary aldosteronism: a follow-up study. J Clin Endocrinol Metab 2006; 91: 3457-3463
    Google Scholar
  • 38 Mosso LM, Carvajal CA, Maiz A, Ortiz EH, Castillo CR, Artigas RA, Fardella CE. A possible association between primary aldosteronism and a lower beta-cell function. J Hypertens 2007; 25: 2125-2130
    Google Scholar
  • 39 Matrozova J, Steichen O, Amar L, Zacharieva S, Jeunemaitre X, Plouin PF. Fasting plasma glucose and serum lipids in patients with primary aldosteronism: a controlled cross-sectional study. Hypertension 2009; 53: 605-610
    Google Scholar
  • 40 Conn JW. Hypertension, the potassium ion and impaired carbohydrate tolerance. N Engl J Med 1965; 273: 1135-1143
    Google Scholar
  • 41 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus . Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003; 26 (Suppl. 01) S5-S20
    CrossrefPubMedGoogle Scholar
  • 42 Corry DB, Tuck ML. The effect of aldosterone on glucose metabolism. Curr Hypertens Rep 2003; 5: 106-109
    CrossrefPubMedGoogle Scholar
  • 43 Pierluissi J, Navas FO, Ashcroft SJ. Effect of adrenal steroids on insulin release from cultured rat islets of Langerhans. Diabetologia 1986; 29: 119-121
    CrossrefPubMedGoogle Scholar
  • 44 Lastra-Lastra G, Sowers JR, Restrepo-Erazo K, Manrique-Acevedo C, Lastra-Gonzalez G. The role of aldosterone and angiotensin II in insulin resistance: an update. Clin Endocrinol (Oxf) 2009; 71: 1-6
    CrossrefPubMedGoogle Scholar
  • 45 Shamiss A, Carroll J, Rosenthal T. Insulin resistance in secondary hypertension. Am J Hypertens 1992; 10: 755-759
    PubMedGoogle Scholar
  • 46 Shimamoto K, Shiiki M, Ise T, Miyazaki Y, Higashiura K, Fukuoka M, Hirata A, Masuda A, Nakagawa M, Iimura O. Does insulin resistance participate in an impaired glucose tolerance in primary aldosteronism?. J Hum Hypertens 1994; 8: 755-759
    PubMedGoogle Scholar
  • 47 Haluzík M, Sindelka G, Widimský Jr J, Prázný M, Zelinka T, Skrha J. Serum leptin levels in patients with primary aldosteronism before and after treatment: relationship to insulin sensitivity. J Hum Hypertens 2002; 16: 41-45
    CrossrefPubMedGoogle Scholar
  • 48 Sindelka G, Widimský J, Haas T, Prázný M, Hilgertová J, Skrha J. Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. Exp Clin Endocrinol Diabetes 2000; 108: 21-25
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Widimský Jr J, Sindelka G, Haas T, Prázný M, Hilgertová J, Skrha J. Impaired insulin action in primary hyperaldosteronism. Physiol Res 2000; 49: 241-244
    PubMedGoogle Scholar
  • 50 Skrha J, Haas T, Sindelka G, Prázný M, Widimský J, Cibula D, Svacina S. Comparison of the insulin action parameters from hyperinsulinemic clamps with homeostasis model assessment and QUICKI indexes in subjects with different endocrine disorders. J Clin Endocrinol Metab 2004; 89: 135-141
    CrossrefPubMedGoogle Scholar
  • 51 Widimský Jr J, Strauch B, Šindelka G, Skrha J. Can primary hyperaldosteronism be considered as a specific form of diabetes mellitus?. Physiol Res 2001; 50: 603-607
    PubMedGoogle Scholar
  • 52 Strauch B, Widimský Jr, Šindelka G, Skrha J. Does the treatment of primary hyperaldosteronism influence glucose tolerance?. Physiol Res 2003; 52: 503-506
    PubMedGoogle Scholar
  • 53 Giacchetti G, Ronconi V, Turchi F, Agostinelli L, Mantero F, Rilli S, Boscaro M. Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism. J Hypertens 2007; 25: 177-186
    Google Scholar
  • 54 Fallo F, Della Mea P, Sonino N, Bertello C, Ermani M, Vettor R, Veglio F, Mulatero P. Adiponectin and insulin sensitivity in primary aldosteronism. Am J Hypertens 2007; 20: 855-861
    CrossrefPubMedGoogle Scholar
  • 55 Ishimori M, Takeda N, Okumura S, Murai T, Inouye H, Yasuda K. Increased insulin sensitivity in patients with aldosterone producing adenoma. Clin Endocrinol (Oxf) 1994; 41: 433-438
    Google Scholar
  • 56 Reincke M, Meisinger C, Holle R, Quinkler M, Hahner S, Beuschlein F, Bidlingmaier M, Seissler J, Endres S. Participants of the German Conn’s Registry . Is primary aldosteronism associated with diabetes mellitus? Results of the German Conn's Registry. Horm Metab Res 2010; 42: 435-439
    Google Scholar
  • 57 Ranade K, Wu KD, Risch N, Olivier M, Pei D, Hsiao CF, Chuang LM, Ho LT, Jorgenson E, Pesich R, Chen YD, Dzau V, Lin A, Olshen RA, Curb D, Cox DR, Botstein D. Genetic variation in aldosterone synthase predicts plasma glucose levels. Proc Natl Acad Sci USA 2001; 98: 13219-13224
    CrossrefPubMedGoogle Scholar
  • 58 Colussi G, Catena C, Lapenna R, Nadalini E, Chiuch A, Sechi LA.. Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients. Diabetes Care 2007; 30: 2349-2354
    Google Scholar
  • 59 Garg R, Hurwitz S, Williams GH, Hopkins PN, Adler GK. Aldosterone production and insulin resistance in healthy adults. J Clin Endocrinol Metab 2010; 95: 1986-1990
    CrossrefPubMedGoogle Scholar
  • 60 Campion J, Maestro B, Mata F, Dávila N, Carranza MC, Calle C. Inhibition by aldosterone on insulin receptor mRNA levels and insulin binding in U-937 human promonocytic cells. J Steroid Biochem Mol Biol 1999; 70: 211-228
    CrossrefPubMedGoogle Scholar
  • 61 Campion J, Maestro B, Molero S, Dávila N, Carranza MC, Calle C. Aldosterone impairs insulin responsiveness in U-937 human promonocytic cells via the downregulation of its own receptor. Cell Biochem Funct 2002; 20: 237-245
    CrossrefPubMedGoogle Scholar
  • 62 Funder JW. Mineralocorticoid receptors: distribution and activation. Heart Fail Rev 2005; 10: 15-22
    CrossrefPubMedGoogle Scholar
  • 63 Calle C, Campion J, Garcia-Arencibia M, Maestro B, Dávila N. Transcriptional inhibition of the human insulin receptor gene. J Steroid Biochem Mol Biol 2003; 84: 543-553
    CrossrefPubMedGoogle Scholar
  • 64 Campion J, Lahera V, Cachofeiro V, Maestro B, Dávila N, Carranza MC, Calle C. In vivo tissue specific modulation or rat insulin receptor gene expression in an experimental model of mineralocorticoid excess. Mol Cell Biochem 1998; 185: 177-182
    CrossrefPubMedGoogle Scholar
  • 65 Kraus D, Jager J, Meier B, Fasshauer M, Klein J. Aldosterone inhibits uncoupling protein-1, induces insulin resistance, and stimulates proinflammatory adipokines in adipocytes. Horm Metab Res 2005; 37: 455-459
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 Guo C, Ricchiuti V, Lian BQ, Yao TM, Coutinho P, Romero JR, Li J, Williams GH, Adler GK. Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor gamma, and proinflammatory adipokines. Circulation 2008; 117: 2253-2261
    Google Scholar
  • 67 Hirata A, Maeda N, Hiuge A, Hibuse T, Fujita K, Okada T, Kihara S, Funahashi T, Shimomura I. Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice. Circulation Res 2009; 84: 164-172
    PubMedGoogle Scholar
  • 68 Wada T, Ohshima S, Fujisawa E, Koya D, Tsuneki H, Sasaoka T. Aldosterone inhibits insulin-induced glucose uptake by degradation of insulin receptor substrate (IRS) and IRS2 via a reactive oxygen species-mediated pathway in 3T3-L1 adipocytes. Endocrinology 2009; 150: 1662-1669
    Google Scholar
  • 69 Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89: 2548-2556
    CrossrefPubMedGoogle Scholar
  • 70 De Marco VG, Johnson MS, Whaley-Connell AT, Sowers JR. Cytokine abnormalities in the etiology of cardiometabolic syndrome. Curr Hypertens Rep 2010; 12: 93-98
    CrossrefPubMedGoogle Scholar
  • 71 Hoppmann J, Perwitz N, Meier B, Fasshauer M, Hadaschik D, Lehnert H, Klein J. The balance between gluco- and mineralo-corticoid action critically determines inflammatory adipocyte responses. J Endocrinol 2010; 204: 153-164
    CrossrefPubMedGoogle Scholar
  • 72 Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissue of obese humans. Endocrinology 2004; 145: 2273-2282
    CrossrefPubMedGoogle Scholar
  • 73 Laviola L, Cignarelli A, Natalicchio A, Leonardini A, De Stefano F, Cuscito M, De Fazio M, Memeo V, Neri V, Cignarelli M, Giorgino R, Giorgino F. Insulin signaling in human visceral and subcutaneosu adipose tissue in vivo. Diabetes 2006; S5: 952-961
    PubMedGoogle Scholar
  • 74 Carranza MC, Torres A, Calle C.. Disminucion en el numero y en la afinidad de los receptores de insulina en el tejido adiposo subcutaneo de un paciente con hiperaldosteronismo primario. Rev Clin Esp 1991; 188: 414-417
    PubMedGoogle Scholar
  • 75 Torpy DJ, Bornstein SR, Taylor W, Tauchnitz R, Gordon RD. Leptin levels are suppressed in primary aldosteronism. Horm Metab Res 1999; 31: 533-536
    Article in Thieme ConnectPubMedGoogle Scholar
  • 76 Haluzik M, Šindelka G, Widimský Jr J, Prázný M, Zelinka T, Skrha J. Serum leptin levels in patients with primary aldosteronism before and after treatment: relationship to insulin sensitivity. J Hum Hypertens 2002; 16: 41-45
    CrossrefPubMedGoogle Scholar
  • 77 Urbanet R, Pilon C, Calcagno A, Peschechera A, Hubert EL, Giacchetti G, Gomez-Sanchez C, Mulatero P, Toffanin M, Sonino N, Zennaro MC, Giorgino F, Vettor R, Fallo F. Analysis of insulin sensitivity in adipose tissue of patients with primary aldosteronism. J Clin Endocrinol Metab 2010; 95: 4037-4042
    CrossrefPubMedGoogle Scholar
  • 78 Urbanet R, Pilon C, Giorgino F, Vettor R, Fallo F. Insulin signaling in adipose tissue of patients with primary aldosteronism. J Endocrinol Invest 2011; 34: 86-89
    PubMedGoogle Scholar
  • 79 Caprio M, Antelmi A, Chetrite G, Muscat A, Mammi C, Marzolla V, Fabbri A, Zennaro MC, Fève B. Antiadipogenic effects of the mineralocorticoid receptor antagonist drospirenone: potential implications for the treatment of metabolic syndrome. Endocrinology 2011; 152: 113-125
    CrossrefPubMedGoogle Scholar
  • 80 Hitomi H, Kiyomoto H, Nishiyama A, Hara T, Moriwaki K, Kaifu K, Ihara G, Fujita Y, Ugawa T, Kohno M. Aldosterone suppresses insulin signaling via the downregulation of insulin receptor substrate-1 in vascular smooth muscle cells. Hypertension 2007; 50: 750-755
    Google Scholar
  • 81 Yamashita R, Kikichi T, Mori Y, Aoki K, Kaburagi Y, Yasuda K, Sekihara H. Aldosterone stimulates gene expression of hepatic gluconeogenic enzymes through the glucocorticoid receptor in a manner independent of protein kinase B cascade. Endocrine J 2004; 51: 243-251
    CrossrefPubMedGoogle Scholar
  • 82 Liu GH, Grifman M, Keily B, Chatterton JE, Staal FW, Li QX. Mineralocorticoid receptor is involved in the regulation of genes responsible for hepatic glucose production. Bioch Biophys Res Commun 2006; 342: 1291-1296
    CrossrefPubMedGoogle Scholar
  • 83 Goodyear LJ, Kahn BB. Exercise, glucose transport, and insulin sensitivity. Annu Rev Med 1998; 49: 235-261
    CrossrefPubMedGoogle Scholar
  • 84 Lastra G, Whaley-Connell A, Manrique C, Habibi J, Gutweiler AA, Appesh L, Hayden MR, Wei Y, Ferrario C, Sowers JR. Low-dose spironolactone reduces reactive oxygen species generation and improves insulin-stimulated glucose transport in skeletal muscle in the TG(mRen2)27 rat. Am J Physiol Endocrinol Metab 2008; 295: E110-E116
    CrossrefPubMedGoogle Scholar
  • 85 Ndisang JF, Jadhav A. The heme oxygenase system attenuates pancreatic lesions and improves insulin sensitivity and glucose metabolism in deoxycorticosterone acetate hypertension. Am J Physiol Regul Integr Comp Physiol 2010; 298: R211-R223
    CrossrefPubMedGoogle Scholar
  • 86 Selvaraj J, Muthusamy T, Srinivasan C, Balasubramanian K. Impact of aldosterone on glucose homeostasis in adult male rat. Clin Chim Acta 2009; 407: 51-57
    Google Scholar
  • 87 Lastra G, Dhuper S, Johnson MS Sowers JR Salt, aldosterone, and insulin resistance: impact on the cardiovascular system. Nat Rev Cardiol 2010; 7: 577-584
    CrossrefPubMedGoogle Scholar
  • 88 Kotronen A, Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol 2008; 28: 27-38
    CrossrefPubMedGoogle Scholar
  • 89 Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010; 363: 1341-1350
    CrossrefPubMedGoogle Scholar
  • 90 Fallo F, Dalla Pozza A, Tecchio M, Tona F, Sonino N, Ermani M, Catena C, Bertello C, Mulatero P, Sabato N, Fabris B, Sechi LA. Nonalcoholic fatty liver disease in primary aldosteronism: a pilot study. Am J Hypertens 2010; 23: 2-5
    CrossrefPubMedGoogle Scholar
  • 91 Wada T, Kenmochi H, Miyashita Y, Sasaki M, Ojima M, Sasahara M, Koya D, Tsuneki H, Sasaoka T. Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet. Endocrinology 2010; 151: 2040-2049
    Google Scholar
  • 92 Giacchetti G, Sechi LA, Rilli S, Carey RM. The renin-angiotensin-aldosterone system, glucose metabolism and diabetes. Trends Endocrinol Metab 2005; 16: 120-125
    CrossrefPubMedGoogle Scholar
  • 93 Luther JM, Luo P, Kreger MT, Brissova M, Dai C, Whitfield TT, Kim HS, Wasserman DH, Powers AC, Brown NJ. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia 2011; 54: 2152-2163
    Google Scholar
  • 94 Gomez-Sanchez CE, Rossi GP, Fallo F, Mannelli M. Progress in primary aldosteronism. present challenges and perspectives Horm Metab Res 2010; 42: 374-381
    Article in Thieme ConnectPubMedGoogle Scholar
  • 95 Fallo F, Sonino N. Metabolic syndrome and primary aldosteronism: time for reappraisal?. J Hum Hypertens 2010; 24: 623-624
    CrossrefPubMedGoogle Scholar
  • 96 Literáti-Nagy B, Kulcsár E, Literáti-Nagy Z, Buday B, Péterfai E, Horváth T, Tory K, Kolonics A, Fleming A, Mandl J, Korányi L. Improvement of insulin sensitivity by a novel drug, BGP-15, in insulin-resistant patients: a proof of concept randomized double-blind clinical trial. Horm Metab Res 2009; 41: 374-380
    Article in Thieme ConnectPubMedGoogle Scholar
  • 97 Fogari R, Zoppi A, Ferrari I, Mugellini A, Preti P, Lazzari P, Derosa G. Comparative effects of telmisartan and eprosartan on insulin sensitivity in the treatment of overweight hypertensive patients. Horm Metab Res 2009; 41: 893-898
    Article in Thieme ConnectPubMedGoogle Scholar
  • 98 Kurtz TW, Klein U. Next generation multifunctional angiotensin receptor blockers. Hypertens Res 2009; 32: 826-834
    CrossrefPubMedGoogle Scholar
  • 99 Sechi LA, Colussi G, Di Fabio A, Catena G. Cardiovascular and renal damage in primary aldosteronism: outcomes after treatment. Am J Hypertens 2010; 23: 1253-1260
    Google Scholar
  • 100 Tirosh A, Garg R, Adler GK. Mineralocorticoid receptor antagonists and the metabolic syndrome. Curr Hypertens Rep 2010; 12: 252-257
    CrossrefPubMedGoogle Scholar