Escitalopram ameliorates hypercortisolemia and insulin resistance in low birth weight men with limbic brain alterations

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikel

DOI

    Christian Selmer Buhl,
  • Hans Stødkilde-Jørgensen
  • Poul Videbech, Mental Health Centre Glostrup, Nordre Ringvej 29 - 67, 2600 Glostrup., Allan Vaag, Department of Endocrinology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark., AstraZeneca, Innovative Medicines, Early Clinical Development,
  • Niels Møller
  • Sten Lund
  • Esben Selmer Buhl, Hov Medical Centre, Sondre Land Kommune, Department of General Practice, University of Oslo

CONTEXT: Low birth weight (LBW, <2500 g) is linked to development of insulin resistance and limbic-hypothalamic-pituitary-adrenal (LHPA)-axis hyperactivity.

OBJECTIVE: First aim was to study insulin action, LHPA-axis function and limbic brain structures in young, healthy LBW-men vs. normal birth weight controls (NBW) (Part 1). Second aim was to investigate the effects of Escitalopram vs. placebo treatment in LBW with regards to LHPA-axis and insulin sensitivity (Part 2).

DESIGN SETTING, PARTICIPANTS AND INTERVENTION: Maximal (Rdmax) and sub-maximal (Rdsubmax) rates of insulin-stimulated glucose-turnover, LHPA-axis and brain morphology were examined in forty LBW-men and twenty matched NBW-men using two-stage hyper-insulinemic euglycemic clamp, 24-hour hormone plasma profiles and magnetic resonance imaging (MRI), respectively. Subsequently all LBW-subjects underwent randomized and double-blinded treatment with Escitalopram 20mg/day 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 AUC.

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). Further, these changes were related to structural alterations within left thalamus and ventromedial prefrontal cortex. LBW-men exposed to Escitalopram vs. placebo, however, normalized free cortisol levels and improved Rdsubmax by ∼24% (p=0.04).

CONCLUSIONS: LBW vs. NBW displayed alterations in key brain structures modulating 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.

OriginalsprogEngelsk
TidsskriftJournal of Clinical Endocrinology and Metabolism
Vol/bind103
Tidsskriftsnummer1
Sider (fra-til)115-124
Antal sider10
ISSN0021-972X
DOI
StatusUdgivet - jan. 2018

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