Evidence map›Paper›PMID 40886675›Full record

Observational studyJournal of diabetes and its complications2025

Sex specific associations of sex hormones with brain volumes and cerebral blood flow: A cross sectional observational study within the look AHEAD type 2 diabetes cohort.

Dhananjay Vaidya, Yvette Yeboah-Kordieh, Marjorie Howard, Christina E Hugenschmidt, Paul A Nyquist, Erin D Michos, Rita R Kalyani, Sevil Yasar, Brian Andres Robusto, Hussein N Yassine and 3 more

Registry-linked trialAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Journal of diabetes and its complications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00017953 (Look AHEAD), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00017953 nacompletednot on this map

Look AHEAD: Action for Health in Diabetes

TypeinterventionalSponsorWake Forest University Health SciencesRan2001 to 2020Enrolled5,145ConditionsDiabetes, Myocardial Infarction, Stroke, Kidney DiseasesArmsLifestyle Intervention, Diabetes Support and Education
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Dhananjay VaidyaDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: dvaidya1@jhmi.edu.
Yvette Yeboah-KordiehMedstar Union Memorial Hospital, USA. Electronic address: Yvette.A.Yeboah-Kordieh@medstar.net.
Marjorie HowardDepartment of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA. Electronic address: mhoward@wakehealth.edu.
Christina E HugenschmidtSticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA. Electronic address: chugenscs@wakehealth.edu.
Paul A NyquistDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Electronic address: pnyquis1@jhmi.edu.
Erin D MichosDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: edonnell@jhmi.edu.
Rita R KalyaniDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: rrastogi@jhmi.edu.
Sevil YasarDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: syasar1@jhmi.edu.
Brian Andres RobustoDepartment of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA. Electronic address: brobusto@wakehealth.edu.
Hussein N YassineDepartment of Neurology and Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. Electronic address: hyassine@usc.edu.
Jeanne M ClarkDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jmclark@jhmi.edu.
Mark A EspelandDepartment of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA. Electronic address: mespelan@wakehealth.edu.
Wendy L BennettDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: wendy.bennett@jhmi.edu.

Funding

UNIVERSITY OF PITTSBURGH CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE: BPCAUL1RR024153 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2006 to 2011
$73.9M
Look AHEAD: Action for Health in DiabetesU01DK057136 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ESPELAND, MARK ANDREW, WAGENKNECHT, LYNNE E · 1999 to 2020
$54.9M
WITHIN SUBJ VARIABILITY IN MEASUREMENTS DRUG METABOL ENZYMES IN HLTY SUBJM01RR000056 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEVINE, ARTHUR S · 1985 to 2006
$29.2M
Wake Forest University School of Medicine Alzheimer's Disease Research CenterP30AG072947 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SUZANNE CRAFT · 2021 to 2026
$24.3M
ZOLEDRONATE VS AREDIA IN MULTIPLE MYELOMA/BREAST CANCER W /BONE DISORDERSM01RR001346 · NCRR · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI WALSH, NICOLAS EUGENE · 1985 to 2008
$23.1M
SHOW PROJECTU01DK057154 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI NATHAN, DAVID M · 1999 to 2020
$23.1M
Look AHEAD: Action for Health DiabetesU01DK057178 · NIDDK · ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS · PI LAFERRERE, BLANDINE B · 1999 to 2020
$21.2M
The Look AHEAD Continuation: Action for Health in DiabetesU01DK057078 · NIDDK · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI JOHNSON, KAREN C · 1999 to 2020
$20.1M
STUDY OF HEALTH OUTCOMES OF WEIGHT-LOSS (SHOW)U01DK057135 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI WADDEN, THOMAS A. · 1999 to 2020
$20.0M
The Look AHEAD Continuation: Action for Health in DiabetesU01DK056992 · NIDDK · MIRIAM HOSPITAL · PI WING, RENA R · 1999 to 2020
$20.0M
Look AHEAD: Action for Health in Diabetes ContinuationU01DK057151 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI CATENACCI, VICTORIA A · 1999 to 2020
$19.4M
STUDY OF HEALTH OUTCOMES OF WEIGHT-LOSS (SHOW) TRIALU01DK057177 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI FOREYT, JOHN P. · 1999 to 2020
$18.0M
NCRR NIH HHS M01 RR000056NCRR NIH HHS M01 RR001346NCRR NIH HHS UL1 RR024153NIA NIH HHS P30 AG072947NIA NIH HHS R01 AG058571NIA NIH HHS U01 AG073697NIDDK NIH HHS P30 DK046204NIDDK NIH HHS R01 DK092237NIDDK NIH HHS R01 DK127222NIDDK NIH HHS U01 DK056990NIDDK NIH HHS U01 DK056992NIDDK NIH HHS U01 DK057002NIDDK NIH HHS U01 DK057008NIDDK NIH HHS U01 DK057078NIDDK NIH HHS U01 DK057131NIDDK NIH HHS U01 DK057135NIDDK NIH HHS U01 DK057136NIDDK NIH HHS U01 DK057149NIDDK NIH HHS U01 DK057151NIDDK NIH HHS U01 DK057154NIDDK NIH HHS U01 DK057171NIDDK NIH HHS U01 DK057177NIDDK NIH HHS U01 DK057178NIDDK NIH HHS U01 DK057182NIDDK NIH HHS U01 DK057219
6 · The paper itself

Abstract

backgroundFemales have greater brain volume and cerebral blood flow than males when controlling for intracranial volume and age. Brain volume decreases after menopause, suggesting a role of sex hormones. We studied the association of sex hormones with brain volume, white matter hyperintensity volumes and cerebral blood flow in people with Type 2 Diabetes and with overweight and obesity conditions that accelerate brain atrophy.

methodsWe analyzed data from 215 participants with overweight or obesity and Type 2 Diabetes from the Look AHEAD Brain Magnetic Resonance Imaging ancillary study (mean age 68 years, 73 % postmenopausal female). Estradiol and total testosterone levels were measured with electrochemoluminescence assays. The ratio of brain measurements to intracranial volume was analyzed to account for body size. We analyzed sex hormones as quantitative measures in males, whereas in females we grouped those with detectable vs. undetectable hormone levels (Estradiol <73 pmol/L [20 pg/mL]: 79 %; Total Testosterone <0.07 mmol/L [0.02 ng/mL]: 37 % undetectable in females).

resultsFemales with detectable total testosterone levels had higher brain volume to intracranial volume ratio (median [25th, 75th percentile]: 0.85 [0.84, 0.86]) as compared to those with undetectable Total Testosterone levels (0.84 [0.83, 0.86]; rank sum p = 0.04). This association was attenuated after age and body mass index adjustment (p = 0.08). Neither white matter hyperintensity volumes or cerebral blood flow in females, nor any brain measures in males, were significantly associated with Estradiol or Total Testosterone.

conclusionsIn postmenopausal females with Type 2 Diabetes with overweight and obesity, detectable levels of total testosterone were associated greater brain volume relative to intracranial volume, suggesting a protective role for testosterone in female brain health. Our findings are limited by a small sample size and low sensitivity of hormone assays. Our suggestive findings can be combined with future larger studies to assess clinically important differences.

trial registrationNCT00017953.

Indexed as

BrainCerebrovascular CirculationDiabetes Mellitus, Type 2Gonadal Steroid HormonesAgedCohort StudiesCross-Sectional StudiesEstradiolFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedObesityOrgan SizeOverweightEstradiolGonadal Steroid HormonesTestosteroneBrain volumeDiabetesSex hormonesSubclinical brain disease

Identifiers

PMID40886675
PMCPMC12426787

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Registered trials

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