Can Antidiabetic Drugs Improve Male Reproductive (Dys)Function Associated with Diabetes?

2019 ◽  
Vol 26 (22) ◽  
pp. 4191-4222 ◽  
Author(s):  
R.S. Tavares ◽  
S. Escada-Rebelo ◽  
M.I. Sousa ◽  
A. Silva ◽  
J. Ramalho-Santos ◽  
...  

The alarming increase in the number of diabetic patients worldwide raises concerns regarding the impact of the disease on global health, not to mention on social and economic aspects. Furthermore, the association of this complex metabolic disorder with male reproductive impairment is worrying, mainly due to the increasing chances that young individuals, at the apex of their reproductive window, could be affected by the disease, further contributing to the disturbing decline in male fertility worldwide. The cornerstone of diabetes management is glycemic control, proven to be effective in avoiding, minimizing or preventing the appearance or development of disease-related complications. Nonetheless, the possible impact of these therapeutic interventions on male reproductive function is essentially unexplored. To address this issue, we have made a critical assessment of the literature on the effects of several antidiabetic drugs on male reproductive function. While the crucial role of insulin is clear, as shown by the recovery of reproductive impairments in insulin-deficient individuals after treatment, the same clearly does not apply to other antidiabetic strategies. In fact, there is an abundance of controversial reports, possibly related to the various study designs, experimental models and compounds used, which include biguanides, sulfonylureas, meglitinides, thiazolidinediones/glitazones, bile acid sequestrants, amylin mimetics, as well as sodiumglucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP1), α-glucosidase inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors. These aspects constitute the focus of the current review.

Reproduction ◽  
2018 ◽  
Vol 155 (1) ◽  
pp. R13-R37 ◽  
Author(s):  
R S Tavares ◽  
S Escada-Rebelo ◽  
A F Silva ◽  
M I Sousa ◽  
J Ramalho-Santos ◽  
...  

Diabetes mellitus has been increasing at alarming rates in recent years, thus jeopardizing human health worldwide. Several antidiabetic drugs have been introduced in the market to manage glycemic levels, and proven effective in avoiding, minimizing or preventing the appearance or development of diabetes mellitus-related complications. However, and despite the established association between such pathology and male reproductive dysfunction, the influence of these therapeutic interventions on such topics have been scarcely explored. Importantly, this pathology may contribute toward the global decline in male fertility, giving the increasing preponderance of diabetes mellitus in young men at their reproductive age. Therefore, it is mandatory that the reproductive health of diabetic individuals is maintained during the antidiabetic treatment. With this in mind, we have gathered the available information and made a critical analysis regarding the effects of several antidiabetic drugs on male reproductive function. Unlike insulin, which has a clear and fundamental role on male reproductive function, the other antidiabetic therapies' effects at this level seem incoherent. In fact, studies are highly controversial possibly due to the different experimental study approaches, which, in our opinion, suggests caution when it comes to prescribing such drugs to young diabetic patients. Overall, much is still to be determined and further studies are needed to clarify the safety of these antidiabetic strategies on male reproductive system. Aspects such as the effects of insulin levels variations, consequent of insulin therapy, as well as what will be the impact of the side effect hypoglycemia, common to several therapeutic strategies discussed, on the male reproductive system are still to be addressed.


2021 ◽  
Author(s):  
Carsten T. Herz ◽  
Johanna M. Brix ◽  
Bernhard Ludvik ◽  
Guntram Schernthaner ◽  
Gerit-Holger Schernthaner

Abstract Purpose Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease. Materials and Methods We included 68 non-diabetic patients who underwent bariatric surgery. Serum DPP4 activity was measured using a fluorogenic substrate before and after surgery. Results Results: After a median follow-up period of 12 (IQR 11-17) months, median serum DPP4 activity decreased from 230 (IQR: 194-273) to 193 (164-252) pmol/min (p=0.012). The decrease in DPP4 activity was significantly correlated with decreases in BMI, improved cholesterol levels, reduced hepatic injury markers as well as improved post-prandial insulin sensitivity. After multivariable adjustment, ΔDPP4 activity remained significantly associated with Δcholesterol (beta=0.341, p=0.025), ΔLDL cholesterol (beta=0.350, p=0.019), Δgamma-glutamyltransferase (beta=0.323, p=0.040) and ΔMatsuda index (beta=-0.386, p=0.045). Conclusion We demonstrated that weight loss induced by bariatric surgery results in decreased circulating DPP4 activity beyond the initial phase of weight loss. The associations between decreased DPP4 activity and improved cholesterol levels as well as hepatic injury markers point towards pleiotropic effects of DPP4 beyond glucose metabolism which warrant further investigation.


2021 ◽  
Vol 8 (4) ◽  
pp. 560-575
Author(s):  
Amina Ammar ◽  
Lindsay M. Darghali ◽  
Wassim Tarraf ◽  
Helen D. Berlie ◽  
Linda A. Jaber

To examine the impact of a pharmacist’s physical presence on (1) the achievement of individual and combined targets for hemoglobin A1c (A1C), blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) (composite target), and (2) physician practices in relation to the American Diabetes Association (ADA) standards of medical care.   Methods A retrospective, comparative study of randomly selected diabetic patients seen within an underserved primary care setting at least twice annually between June 1, 2018- December 31, 2019. Patients were allocated by whether they had received care in one of the physician-pharmacist clinics (Group A) or the physician-only clinic (Group B). Study outcomes included the proportion of patients achieving the composite and individual treatment targets for A1C, BP, and LDL-C.   Results A total of 394 patients were included; Majority were underserved African Americans. The composite target was attained by 20% of participants in Group A and 13% in Group B (p=0.09). There were no statistically significant differences in achievement of individual targets between groups. A significantly higher proportion of participants in Group A achieved better control of diastolic blood pressure control (85% vs. 74%), had microalbuminuria tested (50% vs. 12%), were prescribed aspirin (43% vs. 32%), and had lower utilization of non-insulin glucose-lowering agents relative to those in Group B.   Conclusion The impact of a pharmacist’s physical presence on physician practice demonstrated a general trend towards improvement in clinical outcomes related to diabetes management. Future studies are needed to further characterize the impact provided by the physician-pharmacist relationship.


Author(s):  
SAMIA MOHAMED ALI ◽  
YEHIA MOSTAFA GHANEM ◽  
OLA ATEF SHARAKI ◽  
WAFAA AHMED HEWEDY ◽  
ESRAA SAEED HABIBA

Objective: Vitamin D has a role in the regulation of pancreatic β-cell function and insulin sensitivity. Accordingly, Vitamin D deficiency is considered to be a risk factor for the development of type 2 diabetes mellitus (T2DM) and its complications. Therefore, the aim of the study was to assess and compare the effect of different regimens of Vitamin D3 on glucose homeostasis in patients with T2DM. Methods: The study included 80 patients with T2DM taking oral antidiabetic drugs. The patients were randomized to receive antidiabetic drugs alone or with different regimens of Vitamin D3 for 3 months. Vitamin D3-treated patients were supplemented by either daily oral 4000 IU Vitamin D3, weekly oral 50,000 IU Vitamin D3, or a single parenteral dose of 300,000 IU Vitamin D3. In addition to the assessment of patient characteristics, laboratory measurements of serum creatinine, blood urea, total and ionized calcium, serum phosphorus, fasting blood glucose, fasting serum insulin, homeostasis model assessment of insulin resistance, hemoglobin A1c, and 25(OH) Vitamin D levels were measured at the beginning and after 3 months. Results: After 3 months, the increased Vitamin D levels resulting from the daily and weekly oral doses of Vitamin D3 caused a significant decrease in metabolic parameters, whereas the parenteral dose demonstrated a non-significant decrease. Conclusion: Oral daily and weekly doses of Vitamin D3 could improve glucose homeostasis equally in patients with T2DM and better than a single parenteral dose of Vitamin D3.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Mary K. Samplaski ◽  
Trustin Domes ◽  
Keith A. Jarvi

Introduction. Chlamydia trachomatis is an established cause of tubal factor infertility; however its role in male fertility is not as clear. We sought to determine the prevalence of Chlamydia in infertile men and evaluate its impact on male reproductive potential. Materials and Methods. We compared the incidence of Chlamydia in our infertile male population with that reported in the literature. We then reviewed the impact of Chlamydia infection on male fertility. Results. The incidence of Chlamydia infection in our population of infertile men was 0.3%. There is considerable variability in the reported incidence, likely due to variation in the population studied, and detection technique. The optimal testing method and sample are presently unclear. The effect of Chlamydia on male reproductive function is also variable in the literature, but appears to be relatively minimal and may be related primarily to sperm DNA fragmentation or female partner transmission. Conclusions. The prevalence of Chlamydia in the infertile male population is low and routine testing is not supported by the literature. For high-risk infertile men, nucleic acid testing of urine +/− semen is the most sensitive method to detect Chlamydia. A validated testing system for semen needs to be developed, so that a standardized methodology can be recommended. In this way the full implications of Chlamydia on male fertility can be elucidated.


2020 ◽  
Author(s):  
Robert Mutagwanya ◽  
Christine Magala Nyago ◽  
Fredrick Nelson Nakwagala

Abstract Background: Consumption of a varied diet reduces the risk of developing a deficiency or excess of any one nutrient. One of the three corner stones of diabetes management is diet and therefore, dietary diversity is key among diabetes patients. Objective: The objective of this study was to establish the impact of nutrition education on the dietary diversity scores (DDS) among type 2 diabetes patients. Methods: Kant et al method was used for scoring dietary diversity. Data were analyzed using the statistical package for social sciences (SPSS version 21). Pair sample t-test was used to compare total DDS after and before nutrition education. P< 0.05 was considered as statistically significant.Subjects: One hundred type 2 diabetic patients were randomly selected and divided into two groups of intervention and control (50 patients in each group) to participate in the study. Data were collected using a pre-tested questionnaire before and after intervention every after one month for a period of four months of intervention.Results: The average age of patients who participated in the study was 48 (40–51) years. Most of the patients were females (65.39%), compared to males (34.01%). At the end of the study period of four months, DDS in the control group decreased from 40.08% to 38.49% (p=0.064) while in the intervention group, DDS increased from 35.30 % to 54.20% (p<0.001). Conclusion: Dietary diversity increased after nutrition education among type 2 diabetes patients.Trial registration: The study was registered and approved on 17th April 2013 by the Research and Ethics committee of Mulago Hospital and Institutional Review Board of Mulago hospital (Protocol MREC 113).


Author(s):  
P. A. Vuytsik

Introduction. Reproductive problems in marriage are an important component of demographic processes; therefore, attempts to resolve them have not only medical but also social significance. The state of male reproductive health plays an important role in demographic indicators, in particular, in population reproduction. This dictates the need to increase the volume of preventive measures, which requires early detection of reproductive disorders due to the impact of environmental factors, including occupational ones, that have a harmful effect on men. The aim of the study is to develop a prevention program aimed at preserving and improving the reproductive health of employees engaged in harmful working conditions. Materials and methods. To predict the quality of health of a future individual, it is necessary to consider many risk factors that can participate in the development of human pathology. Methods for studying reproductive health disorders in men include both conventional, classical methods of examining men by urologists, andrologists, and expert ones, which allow us to find out the role of harmful factors in the development of reproductive disorders of professional etiology by specialists in occupational medicine. The implementation of a reproductive health program requires monitoring the progress of the actions taken and evaluating their effectiveness. Results. Implementing a reproductive health program requires monitoring the progress of actions and evaluating their effectiveness. Conclusions. The ability to assess the risk of damage to reproductive health and the health of the offspring makes it possible to manage this risk, to prevent and reduce the levels of occupationally determined morbidity and morbidity associated with exposure to harmful factors.


2021 ◽  
Author(s):  
Benhong GU ◽  
Shangren WANG ◽  
Feng LIU ◽  
Yuxuan SONG ◽  
Jun LI ◽  
...  

Abstract Male infertility may be caused by genetic and/or environmental factors that impair spermatogenesis and sperm maturation. High-altitude (HA) hypoxic environments represent one of the most serious challenges faced by humans that reside in these areas. To assess the influence of the plateau environment on semen parameters, 2,798 males, including 1,111 native Tibetans and 1,687 Han Chinese individuals living in the plains(HCILP) who underwent pre-pregnancy checkups, were enrolled in this study. The semen samples of males were evaluated to determine conventional sperm parameters, sperm morphology, and sperm movement. Reproductive endocrine hormones (REHs) were detected in 474 males, including 221 Tibetans and 253 HCILP. Due to recurrent abortions in partners, the DNA fragmentation index (DFI) of 133 native Tibetans and 393 HCILP individuals was further compared. Luteinizing hormone (LH) (4.94 ± 2.12 vs. 3.29 ± 1.43 U/L), prolactin (11.34 ± 3.87 vs. 8.97 ± 3.48 nmol/L), E2/T (0.22 ± 0.11 vs 0.11 ± 0.05), median total sperm motility (61.20% vs. 51.56%), and DFI (23.11% vs. 7.22%) were higher in males from plateau areas while median progressive motility (PR) (35.60% vs. 41.12%), total number of PR sperms (51.61 vs. 59.63 mil/ejaculate), percentage of normal form sperms (3.70% vs. 6.00%), curvilinear velocity (36.10 vs. 48.97 μm/s), straight-line (rectilinear) velocity (14.70 vs. 31.52 μm/s), estradiol (103.82 ± 45.92 vs. 146.01 ± 39.73 pmol/L), progesterone (0.29 ± 0.27 vs. 2.22 ± 0.84 nmol/L), testosterone (4.90 ± 1.96 vs. 14.36 ± 5.24 nmol/L), and testosterone secretion index (ratio of testosterone to LH) (33.45 ± 22.86 vs 145.78 ± 73.41) were lower than those in males from the plains. There was no difference in median total sperm number (157.76 vs. 151.65 mil/mL), sperm concentration (52.40 vs. 51.79 mil/mL), volume (3.10 vs. 3.10 mL), total normal form sperms (5.91 vs. 6.58 mil/ejaculate, p50), and follicle-stimulating hormone (FSH) levels (4.13 ± 2.55 U/L vs 3.82 ± 2.35 U/L) between the two groups of males. The REH and sperm parameters of males from HA hypoxic environments were adaptively altered. Although the total number of PR sperm decreased and DFI increased, the Tibetan population that lives at HAs has been found to grown continuously and rapidly. These results supplement prior findings regarding the impact of HA on male reproductive function.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 860
Author(s):  
Grace Cooksley ◽  
Joseph Lacey ◽  
Marcus K. Dymond ◽  
Susan Sandeman

Posterior capsule opacification (PCO) is the most common complication arising from the corrective surgery used to treat cataract patients. PCO arises when lens epithelial cells (LEC) residing in the capsular bag post-surgery undergo hyper-proliferation and transdifferentiation into myofibroblasts, migrating from the posterior capsule over the visual axis of the newly implanted intraocular lens (IOL). The developmental pathways underlying PCO are yet to be fully understood and the current literature is contradictory regarding the impact of the recognised risk factors of PCO. The aim of this review is firstly to collate the known biochemical pathways that lead to PCO development, providing an up-to-date chronological overview from surgery to established PCO formation. Secondly, the risk factors of PCO are evaluated, focussing on the impact of IOLs’ properties. Finally, the latest experimental model designs used in PCO research are discussed to demonstrate the ongoing development of clinical PCO models, the efficacy of newly developed IOL technology, and potential therapeutic interventions. This review will contribute to current PCO literature by presenting an updated overview of the known developmental pathways of PCO, an evaluation of the impact of the risk factors underlying its development, and the latest experimental models used to investigate PCO. Furthermore, the review should provide developmental routes for research into the investigation of potential therapeutic interventions and improvements in IOL design in the aid of preventing PCO for new and existing patients.


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