Diabetes mellitus in patients with acromegaly: pathophysiology, clinical challenges and management.

Diego Ferone, Jens Otto Lunde Jørgensen, Federico Gatto, Cesar Luiz Boguszewski, Oskar Ragnarsson, Daniela Esposito, Gudmundur Johannsson, Maria Fleseriu, Annamaria Colao

Journal: Nature reviews. Endocrinology 2024;20(9):541-552

PMID: 38844688

Full Text on Nature Publishing Group View on PubMed

Abstract

Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications.

Address: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. [email protected].; Department of Medicine (Division of Endocrinology, Diabetes and Clinical Nutrition), Sahlgrenska University Hospital, Gothenburg, Sweden. [email protected].; Department of Internal Medicine, Endocrine Division (SEMPR), University Hospital, Federal University of Parana, Curitiba, Brazil.; Endocrinlogy Unit, Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, Naples, Italy.; UNESCO Chair for Health Education and Sustainable Development, Federico II University, Naples, Italy.; Pituitary Center, Department of Medicine and Neurological Surgery, Oregon Health and Science University, Portland, OR, USA.; Endocrinology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genova, Italy.; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Department of Medicine (Division of Endocrinology, Diabetes and Clinical Nutrition), Sahlgrenska University Hospital, Gothenburg, Sweden.; Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.; Endocrinology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genova, Italy.; Endocrinology, Department of Internal Medicine and Medical Specialties, University of Genova, Genova, Italy.; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Department of Medicine (Division of Endocrinology, Diabetes and Clinical Nutrition), Sahlgrenska University Hospital, Gothenburg, Sweden.

DOI: 10.1038/s41574-024-00993-x

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MeSH Terms: Humans, Acromegaly, Diabetes Mellitus, Human Growth Hormone, Insulin Resistance