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Mifepristone Improves Adipose Tissue Insulin Sensitivity in Insulin Resistant Individuals
- Source :
- J Clin Endocrinol Metab
- Publication Year :
- 2021
- Publisher :
- The Endocrine Society, 2021.
-
Abstract
- Background Increased tissue cortisol availability has been implicated in abnormal glucose and fat metabolism in patients with obesity, metabolic syndrome, and type 2 diabetes (T2DM). Our objective was to evaluate whether blockade of glucocorticoid receptor (GR) with mifepristone ameliorates insulin resistance (IR) in overweight/obese subjects with glucose intolerance. Methods We conducted a randomized, double-blinded, placebo-controlled, crossover study in overweight/obese individuals (n = 16, 44% female) with prediabetes or mild T2DM but not clinical hypercortisolism. Mifepristone (50 mg every 6 h) or placebo was administered for 9 days, followed by crossover to the other treatment arm after a washout period of 6 to 8weeks. At baseline and following each treatment, oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIVGTT) were performed. Insulin sensitivity was measured using FSIVGTT [primary outcome: insulin sensitivity index (SI)] and OGTT [Matsuda index (MI) and oral glucose insulin sensitivity index (OGIS)]. Hepatic and adipose insulin resistance were assessed using hepatic insulin resistance index (HIRI), and adipose tissue insulin sensitivity index (Adipo-SI) and adipo-IR, derived from the FSIVGTT. Results Mifepristone administration did not alter whole-body glucose disposal indices of insulin sensitivity (SI, MI, and OGIS). GR blockade significantly improved Adipo-SI (61.7 ± 32.9 vs 42.8 ± 23.9; P = 0.002) and reduced adipo-IR (49.9 ± 45.9 vs 65.5 ± 43.8; P = 0.004), and HIRI (50.2 ± 38.7 vs 70.0 ± 44.3; P = 0.08). Mifepristone increased insulin clearance but did not affect insulin secretion or β-cell glucose sensitivity. Conclusion Short-term mifepristone administration improves adipose and hepatic insulin sensitivity among obese individuals with hyperglycemia without hypercortisolism.
- Subjects :
- medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Clinical Biochemistry
Adipose tissue
Type 2 diabetes
Biochemistry
Receptors, Glucocorticoid
Endocrinology
Insulin resistance
Internal medicine
Glucose Intolerance
medicine
Humans
Insulin
Prediabetes
Clinical Research Articles
business.industry
Biochemistry (medical)
Mifepristone
medicine.disease
Crossover study
Insulin Resistance
Metabolic syndrome
business
medicine.drug
Subjects
Details
- ISSN :
- 19457197 and 0021972X
- Volume :
- 106
- Database :
- OpenAIRE
- Journal :
- The Journal of Clinical Endocrinology & Metabolism
- Accession number :
- edsair.doi.dedup.....7c72cacd5ef02db56a47c7f047c7ec06