The SA Journal Diabetes & Vascular Disease Vol 12 No 1 (July 2015)

SA JOURNAL OF DIABETES & VASCULAR DISEASE

REVIEW

VOLUME 12 NUMBER 1 • JULY 2015

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.com

Marco 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): 101

S Afr J Diabetes Vasc Dis

2015;

: 19–20

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.

The disease has been

closely relatedwith awide range of long-termsystemic complications

and co-morbidities, such as renal failure or hypertension.

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.

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,

and there is a worrying number of children and adolescents with

type 2 diabetes (T2D).

Moreover, Western lifestyle habits, together

with the increasing obesity among young individuals, strongly

contribute to the high incidence of T2D in youth.

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,

which are

explained as lethargy and tiredness related to their hyperglycaemic

state. Other disorders such as erectile dysfunction (ED)

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,

as well as in sperm volume

and count,

others report only a slight, non-significant, decrease in

sperm counts, although sperm volume and motility are frequently

lower.

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.

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.

This study evidenced that T1D

effects in male fertility may be related to the disease complications

and not the disease itself.

Interestingly, the sperm of diabetic individuals is reported to

present high fructose and glucose content,

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,

while

a recent study reported no alterations in semen parameters from

T1D and T2D individuals.

Nonetheless, these authors reported that

sperm from diabetic men presented a higher level of damage in

sperm nuclear and mitochondrial DNA.

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.

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.

Recent

in vitro

studies in rat

and human

SCs showed that sex hormones are

able to modulate these cells’ metabolism. This is significant since