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- Title
Mifepristone Improves Adipose Tissue Insulin Sensitivity in Insulin Resistant Individuals.
- Authors
Gubbi, Sriram; Muniyappa, Ranganath; Sharma, Susmeeta T.; Grewal, Shivraj; McGlotten, Raven; Nieman, Lynnette K.
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>Short-term mifepristone administration improves adipose and hepatic insulin sensitivity among obese individuals with hyperglycemia without hypercortisolism.
- Subjects
UNITED States; INSULIN sensitivity; ALANINE aminotransferase; MIFEPRISTONE; ADIPOSE tissues; ADIPOSE tissue physiology; DIETARY supplements; MEDICAL research; GLUCOSE intolerance; OBESITY; RESEARCH; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; BLIND experiment; MENTAL health surveys; RESEARCH funding; CROSSOVER trials; INSULIN resistance; PREDIABETIC state; PHARMACODYNAMICS
- Publication
Journal of Clinical Endocrinology & Metabolism, 2021, Vol 106, Issue 5, p1501
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgab046