IMPAIRED GLUCOSE METABOLISM

EXCESS CORTISOL IMPAIRS NORMAL GLUCOSE METABOLISM AND HOMEOSTASIS

Glucocorticoid excess can impair normal glucose metabolism and homeostasis through many different mechanisms, leading to impaired fasting glucose, impaired glucose tolerance, and hyperglycemia.1

HYPERGLYCEMIA DRIVEN BY HYPERCORTISOLISM

Hyperglycemia results from a combination of systemic dysfunctions, known as the “ominous octet.” Excess cortisol can cause dysfunction in 7 of the 8 systems, which can lead to hyperglycemia and type 2 diabetes (T2D).1-3

Effect of elevated cortisol on cells and tissues

β CELL1

  • Impaired β-cell activity
  • Increased β-cell apoptosis

LIVER1,3,4

Increased

  • Gluconeogenesis
  • Glycogenolysis
  • Hepatic glucose output
  • Glucagon secretion

Decreased

  • Glycogen synthesis
  • Insulin sensitivity

BRAIN1

  • Circadian disruption of metabolism regulation
  • Neuropeptide secretion
  • Increased catecholamine signaling

FAT CELLS1

  • Increased lipolysis

  • Increased fatty acid levels

  • Increased fat deposition

α CELL1

  • Increased glucagon secretion

MUSCLE1,4

Increased

  • Proteolysis
  • Substrates for gluconeogenesis

Decreased

  • Glucose uptake
  • Glycogen synthesis

GUT1,5

  • Decreased incretin secretion

  • Decreased GLP-1 secretion

24 percent.

Nearly 1 in 4 people with difficult-to-control T2D had endogenous hypercortisolism6

UNCOVER PREVALENCE

Hypercortisolism can lead to worsening T2D and hypertension7

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References

1. Scaroni C, Zilio M, Foti M, Boscaro M. Endocr Rev. 2017;38(3):189-219. doi:10.1210/er.2016-1105 2. Defronzo RA. Banting Lecture. Diabetes. 2009;58(4):773-795. doi:10.2337/db09-9028 3. Barbot M, Ceccato F, Scaroni C. Front Endocrinol (Lausanne). 2018;9:284. doi:10.3389/fendo.2018.00284 4. Pivonello R, De Leo M, Vitale P, et al. Neuroendocrinology. 2010;92(suppl 1):77-81. doi:10.1159/000314319 5. Schernthaner-Reiter MH, Wolf P, Vila G, Luger A. Front Endocrinol (Lausanne). 2021;12:626427. doi:10.3389/fendo.2021.626427 6. Buse JB, Kahn SE, Aroda VR, et al. Prevalence of hypercortisolism in patients with difficult-to-control type 2 diabetes: updated results from CATALYST part 1 [symposium]. Presented by Fonseca, V. at the 22nd World Congress Insulin Resistance Diabetes & Cardiovascular Disease; December 12-14, 2024; Los Angeles, CA. 7. Elhassan YS, Alahdab F, Prete A, et al. Ann Intern Med. 2019;171(2):107-116. doi:10.7326/M18-3630