Pathophysiology of Diabetes Mellitus in Cushing’s Syndrome
Abstract
Cushing’s syndrome is commonly complicated with an impairment of glucose metabolism, which is often clinically manifested as diabetes mellitus. The development of diabetes mellitus in Cushing’s syndrome is both a direct and indirect consequence of glucocorticoid excess. Indeed, glucocorticoid excess induces a stimulation of gluconeogenesis in the liver as well as an inhibition of insulin sensitivity both in the liver and in the skeletal muscles, which represent the most important sites responsible for glucose metabolism. In particular, glucocorticoid excess stimulates the expression of several key enzymes involved in the process of gluconeogenesis, with a consequent increase of glucose production, and induces an impairment of insulin sensitivity either directly by interfering with the insulin receptor signaling pathway or indirectly, through the stimulation of lipolysis and proteolysis and the consequent increase of fatty acids and amino acids, which contribute to the development of insulin resistance. Moreover, the peculiar distribution of adipose tissue throughout the body, with the predominance of visceral adipose tissue, significantly contributes to the worsening of insulin resistance and the development of a metabolic syndrome, which participates in the occurrence and maintenance of the impairment of glucose tolerance. Finally, glucocorticoid excess is able to impair insulin secretion as well as act at the level of the pancreatic beta cells, where it inhibits different steps of the insulin secretion process. This phenomenon is probably responsible for the passage from an impairment of glucose tolerance to an overt diabetes mellitus in susceptible patients with Cushing’s syndrome.
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In endogenous and medication-induced hypercortisolism (Cushing's syndrome), up to 70% of patients develop impaired glycaemic control.
“This is the case in both endogenous and medication-induced hypercortisolism (Cushing's syndrome), with up to 70% of patients developing impaired glycaemic control ( 4 ).”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [4]
Chronic cortisol excess (hypercortisolism) is commonly associated with impaired glucose metabolism and the development of secondary type 2 diabetes.
“with chronic CORT excess (hypercortisolism) commonly associated with the impairment of glucose metabolism and the development of secondary type 2 diabetes ( 3, 4 ).”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [4]
Cortisol stimulates liver gluconeogenesis and glycogenolysis.
“and by stimulating liver gluconeogenesis and glycogenolysis ( 4, 15 ).”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [4]
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- Authors
- Pivonello, R., De Leo, M., Vitale, P., Cozzolino, A., Simeoli, C., De Martino, M. C., Lombardi, G., & Colao, A.
- Affiliations
- Federico II University Hospital (IT)
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2010
- Volume
- 92
- Issue
- Suppl. 1
- Pages
- 77-81
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- OpenAlex
- W2100232797
- Cited by
- 190
- References
- 24
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 14 · 2023: 13 · 2022: 8 · 2021: 15 · 2020: 14 · 2019: 13 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 17 · 2014: 13 · 2013: 16 · 2012: 14
- FWCI
- 7.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- Cushing's syndrome, diabetes mellitus, glucocorticoid excess, insulin resistance, insulin secretion, gluconeogenesis, glucose tolerance, visceral adipose tissue, metabolic syndrome, pancreatic beta cells, lipolysis
- MeSH terms
- Insulin Secretion, Cushing Syndrome, Diabetes Mellitus, Glucose, Humans, Insulin, Insulin Resistance, Insulin-Secreting Cells
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