The diabetogenic effects of glucocorticoids are more pronounced in low- than in high-insulin responders.
Open accessAbstract
We investigated in six low- and six high-insulin responders (LIR and HIR) the effect of dexamethasone (Dex, 15 mg orally during 48 hr) on oral glucose tolerance (OGTT), glucose turnover under basal conditions and during glucose infusion of 2 mg.kg-1.min-1, and insulin response during hyperglycemic clamp. Dex increased fasting glucose more in LIR (P less than 0.05). During OGTT, Dex caused a more prominent increment in glucose in LIR, whereas the increment in insulin was less in LIR (P less than 0.05). After Dex, in three LIR but in no HIR, a diabetic OGTT was observed. Dex significantly increased basal hepatic glucose production (turnover measured with [6-3H]glucose), hepatic total glucose output (turnover measured with [2-3H]glucose), and glucose cycling (hepatic total glucose output--hepatic glucose production) only in LIR. Dex decreased basal glucose metabolic clearance to the same extent in LIR and HIR. Hyperglycemic clamp revealed that Dex induced a significant increase (P less than 0.05) in insulin response only in HIR. Dex effects on insulin release during hyperglycemic clamp were negatively correlated with the glucose area during Dex OGTT (P less than 0.01). Thus, the double tracer method provided a new insight into the pathogenesis of the steroid effect on carbohydrate tolerance. Dex increased basal glycemia more in LIR because only in LIR was glucose production increased. During OGTT, the LIR who were not able to counteract the effects of Dex by an appropriate enhancement in insulin secretion developed a decreased OGTT. The evaluation of insulin response after Dex may thus allow differentiation of the subset of LIR that run an increased risk of non-insulin-dependent diabetes mellitus.
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Daily administration of 36 mg prednisolone equivalent impaired glucose tolerance by reducing hepatic and peripheral insulin sensitivity.
“As such, daily administration of 36 mg prednisolone equivalent impaired glucose tolerance by reducing hepatic [8] and peripheral insulin sensitivity [9].”
From Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial (2011) · cites this paper as [8]
Previous studies have generally used high doses of long-acting glucocorticoids and assessed β-cell function with intravenous glucose tests rather than standardized meals.
“However, previous studies have generally used high doses of long-acting GCs such as dexamethasone or betamethasone that are infrequently utilized for ambulatory treatment in clinical practice, and â-cell function has been assessed by tests using intravenous glucose loads such as the intravenous glucose tolerance test or the hyperglycaemic clamp12–14 rather than standardized meals.”
From Twenty‐four‐hour profiles of plasma glucose, insulin, C‐peptide and free fatty acid in subjects with varying degrees of glucose tolerance following short‐term, medium‐dose prednisone (20 mg/day) treatment: evidence for differing effects on insulin secretion and action (2012) · cites this paper as [14]
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“As such, daily administration of 36 mg prednisolone equivalent impaired glucose tolerance by reducing hepatic [8] and peripheral insulin sensitivity [9].”
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- Authors
- Wajngot, A., Giacca, A., Grill, V, Vranic, M., & Efendic, S.
- Affiliations
- Karolinska University Hospital (SE)
- Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1992-07
- Volume
- 89
- Issue
- 13
- Pages
- 6035-6039
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC402133
- OpenAlex
- W2071240612
- Cited by
- 105
- References
- 15
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 7 · 2017: 1 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 5 · 2012: 8
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- glucocorticoids, dexamethasone, insulin secretion, insulin sensitivity, insulin resistance, hepatic glucose production, glucose turnover, hyperglycemic clamp, oral glucose tolerance, type 2 diabetes risk, steroid-induced diabetes
- MeSH terms
- Insulin Secretion, Adult, Blood Glucose, Dexamethasone, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Humans, Insulin, Male
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