Mifepristone Improves Adipose Tissue Insulin Sensitivity in Insulin Resistant Individuals.

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Citation: Journal of Clinical Endocrinology & Metabolism. 106(5):1501-1515, 2021 04 23.PMID: 33507248Institution: MedStar Washington Hospital CenterDepartment: Medicine/EndocrinologyForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Adipose Tissue/de [Drug Effects] | *Glucose Intolerance/me [Metabolism] | *Insulin Resistance | *Mifepristone/pd [Pharmacology] | *Prediabetic State/me [Metabolism] | Adipose Tissue/me [Metabolism] | Adult | Aged | Cross-Over Studies | Double-Blind Method | Female | Glucose Intolerance/dt [Drug Therapy] | Humans | Insulin Resistance/ph [Physiology] | Insulin Secretion/de [Drug Effects] | Male | Middle Aged | Mifepristone/tu [Therapeutic Use] | Obesity/dt [Drug Therapy] | Obesity/me [Metabolism] | Overweight/dt [Drug Therapy] | Overweight/me [Metabolism] | Prediabetic State/dt [Drug Therapy] | United StatesYear: 2021ISSN:
  • 0021-972X
Name of journal: The Journal of clinical endocrinology and metabolismAbstract: 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.CONCLUSION: Short-term mifepristone administration improves adipose and hepatic insulin sensitivity among obese individuals with hyperglycemia without hypercortisolism. Copyright Published by Oxford University Press on behalf of the Endocrine Society 2021.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 beta-cell glucose sensitivity.All authors: Grewal S, Gubbi S, McGlotten R, Muniyappa R, Nieman LK, Sharma STOriginally published: Journal of Clinical Endocrinology & Metabolism. 106(5):1501-1515, 2021 04 23.Journal of Clinical Endocrinology & Metabolism. 106(5):1501-1515, 2021 Apr 23.Fiscal year: FY2021Fiscal year of original publication: FY2021Digital Object Identifier: Date added to catalog: 2021-02-17
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Journal Article MedStar Authors Catalog Article 33507248 Available 33507248

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.

CONCLUSION: Short-term mifepristone administration improves adipose and hepatic insulin sensitivity among obese individuals with hyperglycemia without hypercortisolism. Copyright Published by Oxford University Press on behalf of the Endocrine Society 2021.

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 beta-cell glucose sensitivity.

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