Undiagnosed prediabetes is highly prevalent in
primary infertile men – results from a
cross-sectional study
Luca Boeri*
†
, Paolo Capogrosso*
‡
, Eugenio Ventimiglia*
‡
, Filippo Pederzoli*
‡
,
Nicola Frego*
‡
, Walter Cazzaniga*
‡
, Francesco Chierigo*
‡
, Massimo Alfano*,
Lorenzo Piemonti
‡§
, Paola Vigan
o
¶
, Marina Pontillo**, Emanuele Montanari
†
,
Francesco Montorsi*
‡
and Andrea Salonia*
‡
*Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele,
†
Department of Urology,
Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan,
‡
University Vita-Salute San Raffaele,
§
Diabetes Research Institute,
¶
Infertility Unit, Unit of Obstetrics/Gynecology, and **Laboratory Medicine Service, IRCCS
Ospedale San Raffaele, Milan, Italy
Objective
To study the prevalence and the risk associated with
prediabetes (PreDM) in primary infertile men.
Patients and methods
Data from 744 infertile men were analysed. Health-
significant comorbidities were scored with the Charlson
Comorbidity Index (CCI). Serum hormones were measured
in every man. Semen analysis was based on 2010 World
Health Organization (WHO) reference criteria. PreDM was
defined according to the clinical criteria detailed by the
American Diabetes Association (Diabetes Care 2014; 37
(Suppl. 1): S81). Descriptive statistics and logistic regression
analyses tested the association between PreDM status,
hormonal milieu and seminal parameters. The predictive
accuracy of all variables was evaluated using the area under
the curve, and the clinical net benefit estimated by decision
curve analysis (DCA).
Results
Of the 744 men, PreDM was found in 114 (15.4%). Men with
PreDM (+PreDM) were older, had higher CCI scores, lower
total testosterone and sex hormone-binding globulin but
higher follicle-stimulating hormone (FSH) and 17b-oestradiol
values compared to those without PreDM (ÀPreDM) (all P ≤
0.04). Higher sperm DNA fragmentation index (DFI; P =
0.014) and idiopathic non-obstructive azoospermia (iNOA; P
< 0.001) were found more frequently in +PreDM men. At
multivariable logistic regression analysis, older age, FSH and
iNOA (all P ≤ 0.04) were significantly associated with
+PreDM status. DCA demonstrated a clinical net benefit in
discriminating men at higher risk of a +PreDM status.
Conclusions
About 15% of primary infertile men had criteria suggestive of
undiagnosed PreDM. A PreDM status was associated with a
greater risk of hypogonadism, higher DFI values and iNOA
status. Age, FSH values and iNOA status could be considered
as useful parameters to recognise men with PreDM and
implement early preventive interventions in those men at risk
of the consequences from poor glycaemic control.
Keywords
prediabetes, infertility, risk factors, testosterone,
nonobstructive azoospermia, #Testosterone, #Infertility,
#Andrology
Introduction
Infertility is defined as the inability of a couple to achieve
pregnancy despite unprotected intercourse for a period of
>12 months [1]. About 15% of all couples are infertile, and it
is estimated that a male factor plays a role in about half of
the cases [2]. Recent data suggest that men with male factor
infertility (MFI) may have a lower general health status, with
a higher risk of developing tumours and age-related diseases,
such as cardio-vascular and metabolic disorders [3–6]. In this
context, various studies have focused on the association
between male infertility and impaired glucose metabolism [7].
Glucose metabolism has emerged to be essential not only for
testicular and epididymal function but also for sperm cell
development and quality [8,9]. Furthermore, an abnormal
glucose homeostasis has been associated with adverse
© 2018 The Authors
BJU International © 2018 BJU International | doi:10.1111/bju.14558 BJU Int 2018
Published by John Wiley & Sons Ltd. www.bjui.org wileyonlinelibrary.com