Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations

Christian Selmer Buhl; Hans Stødkilde-Jørgensen; Poul Videbech; Allan Vaag; Niels Møller; Sten Lund; Esben Selmer Buhl

doi:10.1210/jc.2017-01438

Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations

Christian Selmer Buhl, Hans Stødkilde-Jørgensen, Poul Videbech, Allan Vaag, Niels Møller, Sten Lund, Esben Selmer Buhl

Department of Clinical Medicine

4 Citations (Scopus)

Abstract

Context: Low birth weight (LBW;, 2500 g) is linked to the development of insulin resistance and limbic-hypothalamic-pituitary-adrenal (LHPA) axis hyperactivity. Objective: Our first aim was to study insulin action, LHPA axis function, and limbic brain structures in young, healthy LBW men vs normal birthweight (NBW) controls (part 1). Our second aim was to investigate the effects of escitalopram vs placebo in LBW men inthe LHPA axis and insulin sensitivity (part 2). Design Setting, Participants, and Intervention: The maximal (Rd_max) and submaximal (Rd_submax) rates of insulin-stimulated glucose turnover, LHPA axis, and brain morphology were examined in 40 LBW men and 20 matched NBW men using two-stage hyperinsulinemic euglycemic clamp, 24-hour hormone plasma profiles, and magnetic resonance imaging. Subsequently, all LBW subjects underwent randomized and double-blind treatment with escitalopram 20 mg/d or placebo for 3 months followed by a complete reexamination. Main Outcome Measures (Part 2): Changes in Rd_max/Rd_submax and plasma-free cortisol 24-hour area under the curve. Results: In LBW vs NBW, Rd_submax and Rd_max were ∼16% (P = 0.01) and ∼12% (P = 0.01) lower, respectively, and 24-hour free cortisol levels were ∼20% higher (P = 0.02), primarily driven by a ∼99% increase at 05:00 AM (P, 0.001). Furthermore, these changes were related to structural alterations within left thalamus and ventromedial prefrontal cortex. However, in LBW men, exposure to escitalopram normalized the free cortisol levels and improved the Rd_submax by ∼24% (P = 0.04) compared with placebo. Conclusions: LBW vs NBW displayed alterations in key brain structures modulating the LHPA axis, elevated free cortisol levels, and insulin resistance. Escitalopram administration ameliorated these defects, suggesting a potential for LHPA axis modulation compounds to improve insulin action in LBW subjects.

Original language	English
Journal	The Journal of clinical endocrinology and metabolism
Volume	103
Issue number	1
Pages (from-to)	115-124
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2017-01438
Publication status	Published - 2018

Keywords

Adult
Blood Glucose/metabolism
Brain Diseases/complications
Case-Control Studies
Citalopram/therapeutic use
Cushing Syndrome/drug therapy
Double-Blind Method
Follow-Up Studies
Glucose Clamp Technique
Humans
Infant, Low Birth Weight
Insulin/metabolism
Insulin Resistance
Limbic System/pathology
Male
Prognosis
Serotonin Uptake Inhibitors/therapeutic use
Young Adult

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Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations. / Buhl, Christian Selmer; Stødkilde-Jørgensen, Hans; Videbech, Poul et al.

In: The Journal of clinical endocrinology and metabolism, Vol. 103, No. 1, 2018, p. 115-124.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations",

abstract = "Context: Low birth weight (LBW;, 2500 g) is linked to the development of insulin resistance and limbic-hypothalamic-pituitary-adrenal (LHPA) axis hyperactivity. Objective: Our first aim was to study insulin action, LHPA axis function, and limbic brain structures in young, healthy LBW men vs normal birthweight (NBW) controls (part 1). Our second aim was to investigate the effects of escitalopram vs placebo in LBW men inthe LHPA axis and insulin sensitivity (part 2). Design Setting, Participants, and Intervention: The maximal (Rdmax) and submaximal (Rdsubmax) rates of insulin-stimulated glucose turnover, LHPA axis, and brain morphology were examined in 40 LBW men and 20 matched NBW men using two-stage hyperinsulinemic euglycemic clamp, 24-hour hormone plasma profiles, and magnetic resonance imaging. Subsequently, all LBW subjects underwent randomized and double-blind treatment with escitalopram 20 mg/d or placebo for 3 months followed by a complete reexamination. Main Outcome Measures (Part 2): Changes in Rdmax/Rdsubmax and plasma-free cortisol 24-hour area under the curve. Results: In LBW vs NBW, Rdsubmax and Rdmax were ∼16% (P = 0.01) and ∼12% (P = 0.01) lower, respectively, and 24-hour free cortisol levels were ∼20% higher (P = 0.02), primarily driven by a ∼99% increase at 05:00 AM (P, 0.001). Furthermore, these changes were related to structural alterations within left thalamus and ventromedial prefrontal cortex. However, in LBW men, exposure to escitalopram normalized the free cortisol levels and improved the Rdsubmax by ∼24% (P = 0.04) compared with placebo. Conclusions: LBW vs NBW displayed alterations in key brain structures modulating the LHPA axis, elevated free cortisol levels, and insulin resistance. Escitalopram administration ameliorated these defects, suggesting a potential for LHPA axis modulation compounds to improve insulin action in LBW subjects.",

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author = "Buhl, {Christian Selmer} and Hans St{\o}dkilde-J{\o}rgensen and Poul Videbech and Allan Vaag and Niels M{\o}ller and Sten Lund and Buhl, {Esben Selmer}",

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AU - Videbech, Poul

AU - Vaag, Allan

AU - Møller, Niels

AU - Lund, Sten

AU - Buhl, Esben Selmer

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Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations

Abstract

Keywords

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