- Received December 24, 2022
- Accepted January 06, 2023
- Publication March 30, 2023
- Visibility 2 Views
- Downloads 0 Downloads
- DOI 10.18231/j.ijceo.2023.010
-
CrossMark
- Citation
Can oestrogen be a game changer in diabetic retinopathy progress: A novel study
- Author Details:
-
Asma Anjum
-
Saif Ahmed
-
Sheelu Shafiq
-
Abdul Waris *
Asma Anjum
Saif Ahmed
Introduction
Diabetic eye disease (DED) occurs as a direct result of chronic glucose levels causing damage to the retinal capillaries, leading to capillary leakage and capillary blockage. It may lead to loss of vision eventually, blindness. The spectrum of DED comprises diabetic retinopathy (DR), diabetic macular edema (DME), cataract, glaucoma, loss of focusing ability, and double vision. Diabetic macular edema is further a complication of retinopathy, which can occur at any stage. Diabetic retinopathy has a significant impact on people’s quality of life and is associated with deterioration in physical well being. Besides the burden for people with diabetes, diabetic retinopathy is also responsible for significant healthcare expenditure.[1], [2], [3] Timely intervention in case of diabetic retinopathy can lower the disease burden by limiting the progression of reversible to irreversible visual loss and the role of early identification of risk factors and screening programme are indispensable.[4], [5], [6] In recent time sex hormones has been reported to be associated with diabetes mellitus, hypertension and cardiometabolic syndrome.[7] So we conducted a hospital-based, cross-sectional study titled “Diabetic retinopathy and it's correlation with sex hormons”. The study population was drawn from the diabetic patients who attended the Rajiv Gandhi Centre for Diabetes and Endocrinology, and subsequently were referred to the Retina Clinic, Institute of Ophthalmology, of the same hospital, for their ocular evaluation. Aims of this study were
To indentify and accurately classify the patients of Diabetic Retinopathy.
To measure the levels of oestrogen in patient of Diabetic Retinopathy.
To study the relationship between Diabetic Retinopathy and Oestrogen.
Materials and Methods
A total of 60 Diabetes Type II patients were included in the study. The patients were divided into two groups:
Case group: This group served as the case group and comprised of diabetic patients with diabetic retinopathy (30 patients).
Control group: This group served as the control group and comprised of diabetic patients without diabetic retinopathy (30 patients).
Inclusion criteria
Case group: All diagnosed cases of diabetes mellitus type II (duration more than 10 years) with diabetic retinopathy and reasonably clear media who were referred to the Retina Clinic, Institute of Ophthalmology, Jawaharlal Nehru Medical College and Hospital, A.M.U., Aligarh from Rajiv Gandhi Center for Diabetes and Endocrinology, of the same hospital.
Control group: All diagnosed cases of diabetes mellitus type II without diabetic retinopathy and reasonably clear media who were referred to the Retina Clinic, Institute of Ophthalmology, Jawaharlal Nehru Medical College and Hospital, A.M.U., Aligarh from Rajiv Gandhi Center for Diabetes and Endocrinology, of the same hospital.
Exclusion criteria
The patients with media not clear (where fundus photograph is not possible).
The patients who are on medications which interfere either with sex hormones and/or treatment for diabetes.
Rheumatoid arthritis, lupus, and other autoimmune disorder
Systematic inflammation
Major depressive disorder
Malignancies or history of chemotherapy or radiotherapy within the past 1 year.
The patients where fundus photography was not possible (in any particular eye or field) due to inadequate dilatation or inability of the subject to co-operate, properly.
Serum Oestrogen for females in follicular phase 57.0 – 227.0 pg/mL Preovulatory phase 127.0 – 476.0 pg/mL was considered by Beckman Coulter, Access 2 which uses chemiluminescene immunoassay technique, as normal range.
The study was approved by the ethical committee of Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh and was according to the Declaration of Helsinki. An informed written consent was taken from each patient before their participation in the study. A clinical history was taken with the help of a structured questionnaire including: demographic data, duration of diabetes, treatment taken, addiction, dietary habits, family history of diabetes, and blood pressure. A fundus photograph using Visucam 500 was taken for every patient and was secured as an objective evidence of the subjective findings seen on 78D/90D slit lamp biomicroscopy and indirect ophthalmoscope. The photographs were graded using the ETDRS grading system for the severity of retinopathy. The data was analyzed using Statistical Package for Social Sciences SPSS) 25.0 version (Chicago, Inc., USA). The Chi-square test was used to compare categorical variables. Unpaired t-test was used to compare the continuous variables between the two strata. The one-way analysis of variance (ANOVA) was used to compare more than two means. Pearson’s correlation was done. The p-value<0.05 was considered significant. The results were shown as frequencies, percentages and mean ±SD.
Results
Serum estrogen in patients with diabetic retinopathy
|
Groups |
Mean Estrogen ±SD (pg/mL) |
t-value |
p-value1 |
|
Case (with DR) |
42.34±34.81 |
-2.047 |
P=0.045* |
|
Control (without DR) |
64.02±46.40 |
As shown in [Table 1], the mean serum estrogen was maximum in patients without DR (64.02±46.40 pg/mL) and minimum in patients with DR (42.34±34.81 pg/mL). The results were found to be significant (t=-2.047, p<0.05).
|
Stage of Diabetic Retinopathy |
Mean Estrogen ±SD (pg/mL) |
F-value |
p-value1 |
|
Mild NPDR |
58.20±46.14 |
2.512 |
P= 0.081 |
|
Moderate NPDR |
52.20±32.57 |
||
|
Severe NPDR |
21.21±15.47 |
||
|
Mild-Moderate NPDR |
56.75±60.03 |
As shown in [Table 2], different stage of diabetic retinopathy was compared with serum estrogen and was found that serum estrogen was maximum (58.20±46.14pg/mL) in mild NPDR category, whereas minimum (21.21±15.47pg/mL) in the severe NPDR category, However results were found to be non-significant (F3 26=2.512, p>0.05).
|
Estrogen |
Age |
Duration |
SBP |
DBP |
BSF |
BSPP |
HBA1c |
TESTO |
Progent |
LH |
FSH |
|
r value1 |
.508** |
.218 |
.139 |
.099 |
.427* |
.228 |
.351 |
.891 |
.233 |
.708** |
.795** |
|
p value1 |
.004 |
.247 |
.465 |
.064 |
.019 |
.225 |
.057 |
.001 |
.215 |
.001 |
.001 |
As shown in the [Table 3], when serum estrogen of patient with diabetic retinopathy was correlated with the demographic and clinical variable then a negative correlation was found with age of patient, duration of diabetes mellitus, systolic blood pressure, diastolic blood pressure, blood sugar fasting (BSF), blood sugar post prandial (BSPP), glycated hemoglobin (HBA1c), serum testosterone, serum progesterone and a positive correlation was found with serum LH and serum FSH, However the results were found to be significant for age of patient (r = -0.508, p< 0.891), blood sugar fasting (BSF) (r = 0.427, p<0.01) and serum testosterone (r =-0.891, p<0.001), serum LH (r = 0.708, p<0.01) and serum FSH (r = 0.795, p<0.001), and found non-significant for duration if diabetes mellitus (r = -0.218, p>0.05), systolic blood pressure (r = -0.139, p>0.05), diastolic blood pressure (r = -0.009, p>0.05), blood sugar post prandial (BSPP) (r = -0.228, p>0.05), glycated hemoglobin HBA1c (r = -0.351, p>0.05) and serum progesterone (r = 0.233, p>0.05) respectively.
Discussion
In the present study the mean serum estrogen was found to be significantly (t = -2.047, p<0.05) low in patients with diabetic retinopathy (42.34±34.81pg/mL) as compared to patients without diabetic retinopathy (64.02±46.40 pg/mL) our findings show a significantly higher level of estrogen found in patients without diabetic retinopathy.[8], [9], [10] Firstly estrogen has been reported to stimulate the production of endothelial-derived nitric oxide (NO).[11], [12] Estrogen increases gene expression of endothelial NO synthase (eNOS) and enhance eNOS activity (Ross et al., 2008; Novella et al., 2012; Kim et al., 2014).[13] Secondly, estrogen has been reported to inhibit rennin release and angiotensin-converting enzyme (ACE) and expression of ICAM-1 and VCAM-1 in the vascular endothelium during inflammation (Orshal and Khalil 2004; Villa balance et al., 2010).[14] Thirdly estrogen results in increased cyclooxygenase (COX-1) expression with resulting prostacyclin synthesis that is linked to vascular relaxation (McCrohonet al., 1999).[15] Thus estrogen may attenuate numerous factors that may lead to diabetic retinopathy in the setting of hyperglycemia as supported by our finding of a significantly high level of estrogen in patients without diabetic retinopathy.[16], [17] However, no significant difference in the level of estrogen was found when the different stage of diabetic retinopathy was compared with serum estrogen. It was reported that serum estrogen was found the maximum (58.20±46.14pg/mL) in mild NPDR category, whereas minimum (21.21±15.47pg/mL) in the severe NPDR category, whereas minimum (21.21±15.47pg/mL) in the severe NPDR category and the difference in the mean value of serum estrogen in various stages of diabetic retinopathy was found to be non-significant (p > 0.05). Our finding shows a significant negative correlation of estrogen to age and postmenopausal state is significantly associated with the presence of dysglycemia independently of normal aging in this setting of dysglycemia along with deteriorating estrogen poses a risk for diabetic retinopathy. Estrogen also showed a significant negative correlation with blood sugar fasting (BSF) and testosterone which again emphasize upon the findings suggestive of increased risk for diabetic retinopathy in settings of high glucose and vascular changes mediated by testosterone in absence of ameliorating effects of estrogen.
Conclusion
The mean serum estrogen found to be significantly lower in patients with diabetic retinopathy (42.34±34.81pg/mL) as compared to patients without diabetic retinopathy (64.02±46.40pg/mL). The serum estrogen was found maximum in mild NPDR category (58.20±46.14pg.mL) and minimum in severe NPDR category (21.21±15.47pg.mL). With estrogen, a significant negative correlation was found with age of patient (r = -0.508, p<0.01), blood sugar fasting (BSF) (r = -0.427, p<0.05), serum testosterone (r = -0.891, p<0.001) and a significant positive correlation was found with serum LH (r = 0.708, p<0.01) and serum FSH (r = 0.795, p<0.01) respectively.
Carry Home Massage
Oestrogen has a protective impact on development of diabetic retinopathy.
Though it has no significant relation with severity of diabetic retinopathy.
Once oestrogen level falls after menopause the risk of DR increase.
Low level oestrogen therapy may have a positive impact on DR acuity in post menopause. Warrants a prospective study.
Source of Funding
None.
Conflict of Interest
None.
References
- R Dandona, L Dandona, TJ Naduvilath, A Nanda, CA Mccarty, G Rao. Population-based assessment of diabetic retinopathy in an urban population in southern India. Br J Ophthalmol 1999. [Google Scholar]
- Y Zheng, M He, N Congdon. The worldwide epidemic of diabetic retinopathy. Indian J Ophthalmol 2012. [Google Scholar]
- SS Gadkari, QB Maskati, BK Nayak. Prevalence of diabetic retinopathy in India: The All India Ophthalmological Society Diabetic Retinopathy Eye Screening Study 2014. Indian J Ophthalmol 2016. [Google Scholar]
- JE Grunwald, AJ Brucker, SS Schwartz, SN Braunstein, L Baker, BL Petrig. Diabetic glycemia control and retinal blood flow. Diabetes 1990. [Google Scholar]
- B Hemmingsen, SS Lund, C Gluud, A Vaag, TP Almdal, C Hemmingsen. Targeting intensive glycaemic control versus targeting conventional glycemic control for type 2 diabetic mellitus. Cochrane Database Syst Rev 2013. [Google Scholar] [Crossref]
- SR Joshi, RM Parikh. India; the diabetes capital of the world: Now heading towards hypertension. J-Assoc Physicians India 2007. [Google Scholar]
- PD Gupta, K Johar, K Negpal, AR Vasavada. Sex hormone receptors in the human eye. Surv Ophthalmol 2005. [Google Scholar]
- KH Kim, Young Bd, JR Bender. Endothelial estrogen receptor isoforms and cardiovascular disease. Mol Cell Endocrinol 2014. [Google Scholar]
- SM Haffiner, R Klein, SE Moss, BE Klein. Sex hormones and the incidence of severe retinopathy in male subjects with type I diabetes. Ophthalmology 1993. [Google Scholar]
- RP Maurya, A Gupta, A Singh, VP Singh, S Bosak, A Kumar. Gender, Sex hormones and Diabetic retinopathy. Indian J Clin Exp Ophthalmol 2021. [Google Scholar]
- SB Ogueta, SD Schwartz, CK Yamashita, DB Farber. Estrogen receptor in the human eye: influence of gender and age on gene expression. Invest Ophthalmol Vis Sci 1999. [Google Scholar]
- ME Marin-Castaño, SJ Elliot, M Potier, M Karl, LJ Striker, GE Striker. Regulation of Estrogen Receptors and MMP-2 Expression by Estrogen in Human Retinal Pigment Epithelium. Invest Ophthalmol Vis Sci 2003. [Google Scholar]
- RL Ross, MR Serock, RA Kahlil. Experimental benefits of sex hormones on vascular function and the outcome of hormone therapy in cardiovascular disease. Curr Cardiol Rev 2008. [Google Scholar]
- JM Orshal, RA Khalil. Gender, sex hormones, and vascular tone. Am J Physiol Regul Integr Comp Physiol 2004. [Google Scholar]
- RH Mccrohon, SD West, CA Kiire, DC Groves, HJ Lipinski, A Jaycock. High prevalence of sleep disorder breathing in patients with diabetic muscular edema. Retina 2012. [Google Scholar]
- S Novella, AP Dantas, G Segarra, P Medina, C Hermenegildo. Vascular Aging in Women: is Estrogen the Foundation of Youth?. Front Physiol 2012. [Google Scholar]
- KK Yuen, HA Kahn. The association of femal hormones with blindness from diabetic retinopathy. Am J Ophthalmol 1976. [Google Scholar]