Research Article
Early Vascular Damage in Young Women with
DM-1 and Its Relation to Anti-Müllerian Hormone:
A Cross-Sectional Study
Annelien C. de Kat,
1
Hendrik Gremmels,
2
Marianne C. Verhaar,
2
Frank J. M. Broekmans,
1
and Felicia Yarde
1
1
Department of Reproductive Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, Netherlands
2
Department of Nephrology and Hypertension, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, Netherlands
Correspondence should be addressed to Annelien C. de Kat; a.c.dekat@umcutrecht.nl
Received 11 April 2016; Revised 2 August 2016; Accepted 2 August 2016
Academic Editor: Franco Veglio
Copyright © 2016 Annelien C. de Kat et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Vascular function is suggested to be associated with ovarian reserve, but the relationship with microvascular function has never
been studied. In this cross-sectional pilot study, the relationship of microvascular damage markers with AMH was studied in
premenopausal women. Twenty-two regularly cycling women with type 1 diabetes (DM-1) and a reference group of 20 healthy
regularly cycling women were included, from whom blood was drawn in the early follicular phase of the menstrual cycle. Te
main outcome was the correlation between circulating progenitor cells (CPCs), markers for early vascular damage, and AMH, a
marker for ovarian reserve. Secondary endpoints for early vascular impairment were circulating angiogenic cells and additional
biomarkers. Median AMH levels were 2.2 g/L [1.2–3.5] in the DM-1 group and 2.1 g/L [0.85–3.8] in the reference group. CPCs
were signifcantly decreased in women with DM-1; 1204 ± 537 CD34+/CD45dim cells were counted in the DM-1 group, compared
to 2264 ± 1124 in the reference group. CPCs and other markers of early vascular damage were not correlated with AMH levels in a
multivariable analysis. Tese results underscore previous fndings of early vascular damage in DM-1 and suggest that there may not
be a relationship between vascular function and ovarian reserve. Trial Registration. Tis trial is registered with Clinicaltrials.gov
NCT01665716.
1. Introduction
Menopause is the term used to describe the end of a woman’s
reproductive lifespan, following at least twelve consecutive
months of amenorrhea [1]. Te ovarian aging process that
dictates the onset of menopause results from a gradual
decrease in both quantity of oocytes and their quality,
altogether referred to as ovarian reserve [2]. Besides chrono-
logical age, genetic, lifestyle, and environmental factors are
thought to infuence the pacing of ovarian aging [2, 3].
However, current knowledge of contributing factors to the
decline of ovarian reserve remains scarce and determinants
of the variation in rate of decline and age at menopause still
remain to be elucidated.
In the postmenopausal state, there is an increased risk of
cardiovascular disease [4]. Tis efect is associated with age
at menopause [5] and is more profound in women with pre-
mature menopause (<40 years), suggesting a cardiovascular
protective role of the premenopausal endocrine environment
[6]. Levels of anti-M¨ ullerian hormone (AMH), a marker that
expresses ovarian reserve quantity [7, 8], were furthermore
negatively correlated with atherosclerosis development and
plaque size in a prospective primate study [9]. However,
premenopausal cardiovascular risk was associated with age at
menopause in a study with data from the Framingham Heart
Study, leading to the hypothesis that the onset of menopause
may be infuenced by cardiovascular risk status, rather than
the reverse [10]. Tis hypothesis is supported by a study
Hindawi Publishing Corporation
International Journal of Endocrinology
Volume 2016, Article ID 1487051, 7 pages
http://dx.doi.org/10.1155/2016/1487051