Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations
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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; Vaag, Allan; Møller, Niels; Lund, Sten; Buhl, Esben Selmer.
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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TY - JOUR
T1 - Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations
AU - Buhl, Christian Selmer
AU - Stødkilde-Jørgensen, Hans
AU - Videbech, Poul
AU - Vaag, Allan
AU - Møller, Niels
AU - Lund, Sten
AU - Buhl, Esben Selmer
N1 - Copyright © 2017 Endocrine Society
PY - 2018
Y1 - 2018
N2 - 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 in the 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.
AB - 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 in the 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.
KW - Adult
KW - Blood Glucose/metabolism
KW - Brain Diseases/complications
KW - Case-Control Studies
KW - Citalopram/therapeutic use
KW - Cushing Syndrome/drug therapy
KW - Double-Blind Method
KW - Follow-Up Studies
KW - Glucose Clamp Technique
KW - Humans
KW - Infant, Low Birth Weight
KW - Insulin/metabolism
KW - Insulin Resistance
KW - Limbic System/pathology
KW - Male
KW - Prognosis
KW - Serotonin Uptake Inhibitors/therapeutic use
KW - Young Adult
U2 - 10.1210/jc.2017-01438
DO - 10.1210/jc.2017-01438
M3 - Journal article
C2 - 29053851
VL - 103
SP - 115
EP - 124
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 1
ER -
ID: 215784635