SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 12 NUMBER 1 • JULY 2015
19
Diabetes mellitus and male reproductive function:
where do we stand?
MARCO G ALVES, PEDRO F OLIVEIRA
Correspondence to: Pedro F Oliveira
CICS, UBI, Health Sciences Research Centre, University of Beira Interior,
Covilhã, Portugal
e-mail:
pfobox@gmail.comMarco G Alves
CICS, UBI, Health Sciences Research Centre, University of Beira Interior,
Covilhã, Portugal
Originally published in International
Journal of Diabetology & Vascular
Disease Research
2013;
1
(1): 101
S Afr J Diabetes Vasc Dis
2015;
12
: 19–20
D
iabetes mellitus (DM) is a metabolic disorder caused by
absolute (type 1 diabetes) or relative (type 2 diabetes)
deficiency of insulin and is associated with alterations in
carbohydrate, lipid and protein metabolism.
1
The disease has been
closely relatedwith awide range of long-termsystemic complications
and co-morbidities, such as renal failure or hypertension.
2
Therefore,
the study of DM implications in human health is a challenge to
experts in any field of research.
According to the latest fact sheets from World Health
Organisation (WHO), DM is one of the most rapidly growing
threats to public health in modern societies. Over the past 20 years,
the global prevalence of DM has increased approximately six-fold
and nearly 350 million people worldwide suffer with the disease.
The WHO estimated that, in 2004, over three million people died
from consequences of high blood sugar levels and estimates
that DM-related deaths will increase by two-thirds between
2008 and 2030.
1,3
Nonetheless, the existing statistical data can
be underestimated since the factors known to be responsible for
the disease progression, such as obesity and lifestyle habits, may
aggravate these numbers.
2
When we take a close look at fertility rates in modern societies,
we observe that the increased incidence of DM is concurrent with
the falling birth rates and decreased fertility.
4,5
This fact is partly
due to the alarming increase in the number of men developing DM
during the reproductive age. Indeed, the great majority of patients
with type 1 diabetes (T1D) are diagnosed before the age of 30,
6
and there is a worrying number of children and adolescents with
type 2 diabetes (T2D).
7
Moreover, Western lifestyle habits, together
with the increasing obesity among young individuals, strongly
contribute to the high incidence of T2D in youth.
2
DM is responsible
for several biochemical and homeostasis alterations that may result
in male subfertility and or infertility, yet the real impact of DM on
male reproductive health remains undisclosed.
Although there is some controversy on the subject, diabetic
individuals are frequently described as possessing some sexual
neuropathies, such as reduction in sexual appetite,
8
which are
explained as lethargy and tiredness related to their hyperglycaemic
state. Other disorders such as erectile dysfunction (ED)
9
or retrograde
ejaculation
10,11
are also well known to occur in male diabetics.
Nonetheless, when examining sperm parameters and sperm
quality markers, the literature shows some conflicting results.
There are several studies since the 1970s comparing young or adult
diabetics with control individuals. While some studies report that
diabetic men present lower sperm counts and significant differences
in sperm motility and morphology,
12
as well as in sperm volume
and count,
13
others report only a slight, non-significant, decrease in
sperm counts, although sperm volume and motility are frequently
lower.
14
Others have reported that sperm count and concentration
were increased in the ejaculatant of diabetic individuals, although
sperm motility and semen volume were decreased. Noteably, in
these last studies, sperm morphology and motility were described
to remain unaffected.
15
Another more recent study reported no correlations between
sperm motility and age, age of onset of T1D and duration. The
same study reported that several sperm motility parameters such
as track speed, path velocity, progressive velocity, and lateral head
displa cement remained unchanged, while others, such as linearity
and linear index (which reveal the straightness of sperm swimming),
were increased in diabetic men.
16
This study evidenced that T1D
effects in male fertility may be related to the disease complications
and not the disease itself.
16
Interestingly, the sperm of diabetic individuals is reported to
present high fructose and glucose content,
14
but the relationship
between an ineffective metabolic control and the observed
alterations in the semen was never established and therefore should
deserve a special focus in the next years.
Anextensive study of spermatozoa cryopreservation frompatients
with various pathologies reported that only sperm from diabetic
men presented significant differences in sperm parameters,
17
while
a recent study reported no alterations in semen parameters from
T1D and T2D individuals.
6
Nonetheless, these authors reported that
sperm from diabetic men presented a higher level of damage in
sperm nuclear and mitochondrial DNA.
6
Although most of the studies have focused on analysis of sperm
parameters, there is an important study from 1985, performed
using testicular biopsies from impotent men with DM that reported
ultrastructural lesions in the cytoplasm of Sertoli cells (SCs) and
morphological changes in the interstitial compartment of diabetic
men’s testes.
18
These anatomical, structural and morphological
alterations suggested that diabetic men may suffer from disruption
of the spermatogenic event, resulting in the subfertility and/or
infertility often associated with DM.
Even though there are apparent contradictory results concerning
sperm parameters and the real impact of DM in male reproductive
function, it is not consensual that DM effects are only reflected
in sperm or in the ejaculatant. Moreover, apart from the direct
studies of sperm, new important findings have been reported using
in vitro
strategies. For instance, diabetic individuals are known to
have fluctuations in sex hormone concentrations.
19
Recent
in vitro
studies in rat
20
and human
21
SCs showed that sex hormones are
able to modulate these cells’ metabolism. This is significant since