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 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.

• Authors: Christian Selmer Buhl, Hans Stødkilde-Jørgensen, Poul Videbech, Allan Vaag, Niels Møller, Sten Lund, Esben Selmer Buhl
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 103 Issue 1 Pg. 115-124 (01 01 2018) ISSN: 1945-7197 [Electronic] United States
• PMID: 29053851 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Endocrine Society

Chemical References

• Blood Glucose
• Insulin
• Serotonin Uptake Inhibitors
• Citalopram

Topics

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