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Secondary diabetes mellitus due to primary aldosteronism

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Abstract

Primary aldosteronism (PA) and diabetes mellitus (DM) are clinical conditions that increase cardiovascular risk. Approximately one in five patients with PA have DM. Nevertheless, the pathophysiology linking these two entities is not entirely understood. In addition, the majority of patients with PA have glucocorticoid co-secretion, which is associated with increased risk of impaired glucose homeostasis. In the present review, we aim to comprehensively discuss all the available research data concerning the interplay between mineralocorticoid excess and glucose metabolism, with separate analysis of the sequalae in muscle, adipose tissue, liver and pancreas. Aldosterone binds both mineralocorticoid and glucocorticoid receptors and amplifies tissue glucocorticoid activity, via 11-β-hydroxysteroid dehydrogenase type 1 stimulation. A clear classification of the molecular events as per specific receptor in insulin-sensitive tissues is impossible, while their synergistic interaction is plausible. Furthermore, aldosterone induces oxidative stress and inflammation, perturbs adipokine expression, thermogenesis and lipogenesis in adipose tissue, and increases hepatic steatosis. In pancreas, enhanced oxidative stress and inflammation of beta cells, predominantly upon glucocorticoid receptor activation, impair insulin secretion. No causality between hypokalemia and impaired insulin response is yet proven; in contrast, hypokalemia appears to be implicated with insulin resistance and hepatic steatosis. The superior efficacy of adrenalectomy in ameliorating glucose metabolism vs. mineralocorticoid receptor antagonists in clinical studies highlights the contribution of non-mineralocorticoid receptor-mediated mechanisms in the pathophysiologic process. The exact role of hypokalemia, the mechanisms linking mineralocorticoid excess with hepatic steatosis, and possible disease-modifying role of pioglitazone warrant further studies.

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  1. Department of Endocrinology and Diabetes Centre, Hellenic Red Cross Hospital, Athens, Greece

    Melpomeni Moustaki, Eleni C. Vakali & Andromachi Vryonidou

  2. Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Stavroula A. Paschou

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S.A.P. and A.V. conceived the idea of this review article. Literature search and data analysis was performed by M.M. and E.C.V. The first draft of the manuscript was written by M.M. and all the authors commented on previous versions of the manuscript. The manuscript was critically revised for intellectual content by S.A.P. All authors read and approved the final manuscript.

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Moustaki, M., Paschou, S.A., Vakali, E.C. et al. Secondary diabetes mellitus due to primary aldosteronism. Endocrine 79, 17–30 (2023). https://doi.org/10.1007/s12020-022-03168-8

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