|Year : 2018 | Volume
| Issue : 1 | Page : 19-31
The effect of serum lipid control on diabetic retinopathy stages in Saudi adults
Abbashar M Saleem1, Mahgoub Saleem2
1 Ophthalmologist MD, Department of Retina, Makkah Eye Complex, Khartoum, Sudan
2 Ophthalmologist MD, Department of Retina, Makkah Eye Complex; Professor of Ophthalmology, Faculty of Medicine, Al Neelain University, Department of Ophthalmology and Department of Retina, Makkah Eye Complex, Khartoum, Sudan
|Date of Submission||27-Jun-2018|
|Date of Acceptance||14-Feb-2020|
|Date of Web Publication||11-Jul-2020|
Dr. Abbashar M Saleem
Department of Retina, Makkah Eye Complex, P.O. Box. 10139, Khartoum 11111
Objectives: The objective was to study the effect of serum lipid control on diabetic retinopathy (DR) stages.
Materials and Methods: Two hundred type 2 diabetic Saudi patients with or without using lipid-lowering-agents were included in this cross-sectional study (4 months: July–October 2015). All patients had standardized ophthalmological examination and fasting biochemical parameters of glycosylated hemoglobin (HbA1c) and serum lipid levels, and were then subjected to “statistical analysis by SPSS software version 20.
Results: Out of the 200 studied patients (mean age, 62.9 ± 9.43 years), 104 were male (n = 104; 52%) and 96 were female (n = 96; 48%). The mean duration of diabetes mellitus (DM) and concomitant hypertension (n = 107; 53.5%) was 16.3 and 10.3 years, respectively. A total of 106 (53%) patients had diabetic retinopathy (DR), with 66 males (33%) and 40 females (20%). Ninety-four patients had no signs of DR (no apparent DR [NDR]) (47%), with 19% of males and 28% of females. Mild nonproliferative DR (NPDR) was present in 15.5% of patients (male/female: 10%/5.5%); moderate NPDR was present in 22.5% of patients (male/female: 13.5%/9%); and severe NPDR was present in 8% of patients (male/female: 5%/3%). Proliferative DR (PDR) was present in 5% of patients (male/female: 13.5%/3%), advanced PDR was present in 2% of patients (male/female: 1%/1%), and diabetic macular edema (DME) was present in 9.5% of patients (male/female: 7%/2.5%). Total cholesterol (TC) (P = 1.292), low-density lipoprotein-cholesterol (LDL-C) (P = 1.319), and nonhigh-density lipoprotein-cholesterol (HDL-C) (P = 0.96) were found to have a statistically “nonsignificant” higher value in male DR patients. No correlation was observed between triglyceride (TG), HDL-C, and very LDL-C (VLDL-C) in different stages of DR and NDR patients, as they were exactly equal in both DR and NDR male groups. All DM females (DR + NDR) had equal values regarding TC, HDL-C, LDL-C, and VLDL-C in both female groups. TG and non-HDL-C were slightly higher in female DR groups than that in non-DR female groups (P = 0.071 and 0.072, respectively). However, TC and non-HDL-C were still higher in females than males by 4.3%. 116 (58%) “who were not using dyslipidemia medications” (NDLRx) and 84 (42%) “who were using dyslipidemia medications” (DLRx); their DM and HTN duration were 15.9 and 5 years, respectively. HbA1c and serum lipid parameters were also higher in in the NDLRx group than DLRx group.
Conclusion: Dyslipidemia could be added to DR risk factors as the development of elevated serum lipids shows some association with DR ± DME formation. Serum lipid-lowering agents may help in reducing the occurrence of retinal findings and loss of vision in diabetic patients.
Keywords: Cholesterol, diabetic macular edema, diabetic retinopathy, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, serum lipid-lowering agents, serum lipids, triglyceride
|How to cite this article:|
Saleem AM, Saleem M. The effect of serum lipid control on diabetic retinopathy stages in Saudi adults. Albasar Int J Ophthalmol 2018;5:19-31
| Introduction|| |
Diabetes mellitus (DM) is the biggest global burden disease causing significant endemicity, and morbidity and mortality rates,, with global estimates of affecting 422 million adults in 2014. It is a complex, chronic disease requiring continuous medical care with multifactorial risk reduction strategies beyond glycemic control. The clusters of risk factors apart from poor control are long DM duration, systemic hypertension (HTN), dyslipidemia, and others., Diabetic retinopathy (DR) eventually causes diabetic macular edema (DME) which is the most common DM microvascular complication affecting more than 30% of the world's population, which is a leading cause of visual disabilities in working adult populations.,,,
The World Health Organization (WHO) defines DR as a characteristic group of retinal lesions due to long-standing DM and other risk factors. The abnormalities occur in predictable progression with minor variations in the order of their appearance. The DR features occur in predictable progression manners; with minor variations in the order of their appearance. These DR features are the results of different vascular retinal circulation changes called “vascular-leakage-occlusion-dilations-new-blood vesselformation chain processes” that take place in stages. Seven percent of people with DR are at risk of blindness. WHO marked 'November 14th each year' in 2016 as “World Diabetes Day” as a new 'DM–DR theme', which appeared in 2016 WHO Global Report on Diabetes to increase the international DM–DR awareness? Then the theme for the same Day “November 14th each year” was change to 'Eyes on diabetes' in the year 2017. VISION 2020placed DR on the priority list of eye conditions which can be partly prevented and treated. It is recommended that eye care services for diabetic patients be incorporated into strategic VISION 2020 national plans. Conceptually, serum lipid disorders in diabetes could be an associated extra factor that may increase the risk of DR. However, there has been great literature disputation about this association. Many studies reported a strong correlation,,,,,,,, between Serum lipid disorders in diabetes and the increase risk of DR, which prevail over other studies that evidently showed no relationship of the two.,, There was a strong inverse correlation of DR with high-density lipoprotein (HDL) and direct correlation with non-HDLcholesterol (HDL-C).
| Materials and Methods|| |
In this cross-sectional, prospective, observational, hospital-based study, all diabetic patients who referred to the Department of Ophthalmology of the tertiary care Al-Hada Armed Forces Hospital (HHRC) in Taif Region, Saudi Arabia, as part of the hospital's Diabetics' Management Protocol, were enrolled. For evaluation, screening, and management of DR, over a period of 4 months between July 2015 and October 2015, patients were shortlisted for the study.
Two hundred type 2 diabetic male and female Saudi patients were included in the present study. After obtaining informed consent from each of these 200 diabetic patients, who agreed and were fit for full ophthalmic biomicroscopic examination and extended dilated biomicroscopic fundoscopy, were included in the current study.
All the selected patients had recent medical checkup by their Dietologist and full lipid profile results; (e.g. Within the same week of referral). Some patients who refused to participate in the study; those with uveitis, opaque or poor media, high myopia, retinal vascular occlusive diseases, severe or accelerated HTN, cardiovascular diseases (CVDs), renal diseases, liver dysfunction, severe anemia and thyroid disorders, acute infections; or patients who had undergone previous vitreo-retinal surgeries were excluded from the current work. Detailed standardized ophthalmic medical history and demographic data of all participants were collected and reported in predesigned “data collection forms” at the time of examination. Best-corrected visual acuity was assessed using projected Snellen's chart by a chart projector (CP-770; Manufactured by NIDEK CO., LTD. 34-14 Maehama, Hiroishi-cho, Gamagori, Aichi 443-0038, Japan, www.nidek. com), and Intraocular Pressure measurement was routinely done by Goldmann Applanation Tonometer (Haag-Streit Diagnostics-Applanation tonometer AT 900®/870 18. Edition/2014 – 11; HAAGSTREIT AG Gartenstadtstrasse 10 3098 Koeniz, Switzerland www. haag-streit.com). Then, systematic slit-lamp (Haag-Streit Diagnostics-Slit Lamp BQ 900/870 18. /2014 – 11; HAAG-STREIT AG Gartenstadtstrasse 10 3098 Koeniz, Switzerland www.haagstreit.com) biomicroscopic examination for anterior segment was done for all patients. Then coupled by biomicroscopic fundoscopy using +90 D and +78 D lenses (V90 C, V78 C; Volk Optical Inc. 7893, OH 44060, USA, email@example.com) and indirect ophthalmoscopy with binocular indirect ophthalmoscope +20 D lens (All-Pupil Keeler BIO; 1204-P-3043; manufactured in the UK by Keeler Limited Clewer Hill Road Windsor Berkshire SL4 4AA England, www.keelerusa.c/+20 D-Volk Optical Inc. Lens Inc.) for posterior segment examination to assess the presence, types and severity of DR.
Fluorescein fundal angiography (FFA), optical coherence tomography (OCT), and B-scan ultrasonography were done for selected cases. The grading of DR severity levels was designed according to the modified Airlie House Classification system, The current study adopted the simplified classification of “The International Clinical Disease Severity Scale for diabetic retinopathy and Diabetic Macular Edema” which was designed according to: 1. the modified Airlie House Classification system, 2. the Early Treatment Diabetic Retinopathy Study and Diabetic Macular Edema, 3. the Global Diabetic Retinopathy Project Group and 4. the American Academy of Ophthalmology's “Clinical Diabetic Retinopathy Disease Severity Scale.”,,,
According to the DR severity stage, patients were divided into two main groups as follows: Group A: patients with “no apparent DR (no apparent DR [NDR])” and Group B: patients with DR of any stage (DR stage) ± DME. This “DR stage” Group “B” was subdivided into six severity-stage subgroups as follows: (i) mild nonproliferative DR (M-NPDR); (ii) moderate NPDR (Md-NPDR); (iii) severe NPDR (S-NPDR); (iv) proliferative DR (PDR); (v) advanced PDR (Ad-PDR); and (vi) DME. Then, the subgroups were re-divided into another two subdivisions. The first subgroup comprised those who were “not using lipid-lowering agents (NDLRx),” whereas the second subgroup comprised those who were “using one or another lipid-lowering agents (DLRx).” The two main drugs in use were HMG CoA reductase inhibitors from the Statin Group;, some were using atorvastatin (Lipitor®) and others were using simvastatin (Zocor®).
DM was diagnosed if there was a self-reported history of physician diagnosis or if the participants were on drug or diet treatment for diabetes. Hyperlipidemia as the main group of dyslipidemias was taken into consideration if serum lipids were abnormally elevated in the blood and also, supported by a self-reported history of physician diagnosis or if the participants were on drug or diet treatment for hyperlipidemia. The degree of DM control was ensured by the percentage of glycosylated hemoglobin (HbA1c) levels, with targeting goal of <6.5% (4%–6%). Outcome data were obtained for all patients by reviewing the hospital's electronic laboratory records through the researcher's “official access password.” Recent laboratory investigations, within the same week of referral and examination, were requested by the DM management team, including HbA1c and the standard average five basic fasting serum lipids (lipid profile): (total cholesterol [TC], triglyceride [TG], HDL-C, low-density lipoprotein-cholesterol [LDL-C], and very-LDL-C [VLDL-C])., Non-HDL-C, a calculated parameter, was calculated by subtracting the HDL-C from the TC levels. This non-HDL-C was taken as dyslipidemia-hyperlipidemia management metric and “risk prediction” evaluation tool,, besides the TG and the conventional LDL-C levels. All serum lipid values (cholesterols and TGs) were measured according to the United Kingdom-Canadian' standards as millimoles per liter of blood, while HbA1c was measured in percentage as it is the percentage of plasma glucose concentration over a period of weeks or months.
The normal and abnormal “reference range values” of these laboratory investigational values were taken according to the HHRC's “reference range values” that include normal lower and upper limits of all the laboratory tests obtained from Saudi healthy people, adjusted to their age–sex criteria based on the National Cholesterol Education III guidelines and American Diabetes Association standards, and their values are as follows: cholesterol: 3.1–5.1 mmol/l, TG 0.00–1.70 mmol/l, HDL 1.04–1.55 mmol/l, LDL 3.0–3.6 mmol/l, VLDL 0.0–0.6 mmol/l, and HbA1c 46%. Primary targets were LDL-C and TG, whereas the secondary target was non-HDL-C. Hence, the “Optimum-Desirable” DM Target goal of LDL-C was taken as 2.6 mmol/l, non-HDL-C as 3.37 mmol/l, TC as 4.0, TG as ≤1.7, HDL-C as 1.0 for men and 1.2 for women, LDL-C as <2.0, VLDL as 0.34 mmol/L, and HbA1c as 6.5%.,,,,, Primary targets were LDL-C and TG, whereas the secondary target was non-HDL-C. Hence, the “Optimum-Desirable” DM Target goal of LDL-C was taken as 2.6 mmol/l, non-HDL-C as 3.37 mmol/l, TC as 4.0, TG as ≤1.7, HDL-C as 1.0 for men and 1.2 for women, LDL-C as <2.0, VLDL as 0.34 mmol/L, and HbA1c as 6.5%.,,,,,
The entire data were coded and entered in a Microsoft Excel spreadsheet in a personal computer, and then were subjected to “statistical analysis” by Statistical Package for the Social Sciences version 20 (IBM SPSS Inc., PASW Statistics for Windows, Version 20.0; 2009. SPSS Inc. Chicago, IL, USA). Categorical variables were analyzed using frequencies and percentages. Continuous variables were summarized using mean, percentile, range, and standard deviation. Significant differences and associations were determined by P < 0.05.
Ethical approvals were obtained from the ophthalmology department's officials. Written and verbal informed consents were obtained from the patients after full explanation of the study objectives and procedures; confidentiality and anonymity of each patient's identity were adhered.
| Results|| |
Two hundred type 2 diabetic Saudi patients in the period between July 2015 and October 2015, who presented to HHRC in Taif Region, Saudi Arabia, were included in the current study. Their mean age was 62.9 ± 9.43 years (range: 21–94 years). A total of 104 (52%) patients were male, with a mean age of 62.8 ± 11.49 years (range: 21–94 years) and 96 (48%) patients were female with a mean age of 60.8 ± 9.86 years (range: 21–85 years) [Figure 1].
The mean duration of DM within the whole studied diabetic population was 15.5 years, while the mean duration of the concomitant HTN was 10.3 years. HTN was found in 107 patients of the whole study population (53.5%). Forty-seven patients were hypertensive males (23.5%) and 60 patients were hypertensive females (30%) [Table 1] and [Figure 2]. The mean duration of DM for males was 16.3 years, and their mean duration for concomitant HTN was 10.6 years (range: 1–40 years). While the mean duration of DM within the whole female population was 14.7 years, and their mean duration of concomitant HTN was 10.0 years (range: 1–30 years) [Table 1] and [Figure 3] and [Figure 4].
|Table 1: Frequency and duration of diabetes mellitus and hypertension in males versus females|
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|Figure 2: Comparison between diabetes mellitus and concomitant hypertension frequency in both sexes|
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|Figure 3: Comparison between diabetes mellitus and concomitant hypertension duration in both sexes|
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|Figure 4: Comparison between diabetes mellitus and concomitant hypertension duration and frequency in both sexes|
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Diabetic retinopathy (DR) was found in 106 patients of both sexes (53%), with a definite predilection of males than females, where men with DR were 66 (33%) and women with DR were 40 (20%). In total, 94 patients (47%) were found to have No Diabetic Retinopathy (NDR), out of them; men were 38 (19%), whereas women with NDR were 56 (28%). [Table 2],[Table 3] and [Figure 5], [Figure 6], [Figure 7]. [Table 3] presented the distribution of “Diabetic Retinopathy Severity Stages” in the 106 (53%) males and females' Diabetic patients with DR. In total, all the 'Non-Proliferate Diabetic Retinopathy group (non-PDR) [Mild nonproliferative diabetic retinopathy (M-NPDR) + Moderate nonproliferative diabetic retinopathy (Md-NPDR), and + Severe nonproliferative diabetic retinopathy (S-NPDR)] were distributed as follows: 1. M-NPDR were 31 (15.5%) patients of them 20 (10%) were males and 11 (5.5%) females. 2. Md-NPDR were 45 (22.5%) patients of them 27(13.5%) were males and 18 (9%) females). 3. S-NPDR were 16 (8%) patients of them 10 (5%) males and 6 (3%) females. On the other hand, the PDR stages accounted for 14 (7%) of all Diabetic patients with DR, they were distributed as follows: 1. PDR in 10 (5%) patients of them 7 (3.5%) males and 6 (3%) females). 2. Ad-PDR in 4 (2%) patients, with equal distribution between males and females; 2 (1%) each sex. [Figure 8]. While Diabetic macular edema (DME) constituted 19 (9.5%) patients of them 14 (7%) were males and 5 (2.5%) females). [Table 3], [Figure 7] and [Figure 8].
|Table 2: Sex distribution of patients with diabetic retinopathy versus with no apparent diabetic retinopathy|
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|Table 3: Distribution of diabetic retinopathy severity stages in male and female populations|
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|Figure 5: Distribution of patients with diabetic retinopathy versus those with “no apparent diabetic retinopathy” in both sexes|
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|Figure 6: Distribution of patients with diabetic retinopathy versus “no apparent diabetic retinopathy” to total numbers in both sexes|
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|Figure 8: Distribution of diabetic retinopathy (nonproliferative diabetic retinopathy – proliferative diabetic retinopathy – diabetic macular edema) stages in both sexes|
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Diabetic retinopathy and nonapparent diabetic retinopathy patients who were using and those who were not using dyslipidemia medications
The distribution of DR stages in males and females with and without dyslipidemia medications (± DLRx) is presented in [Table 4].
|Table 4: Distribution of diabetic retinopathy severity stages in male and female patient population with and without dyslipidemia medications|
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Diabetic retinopathy and nonapparent diabetic retinopathy patients who were “not using dyslipidemia medications”
Regarding “Diabetic Retinopathy Severity Stages” in patients who were “not using dyslipidemia medications (NDLRx)” were distributed as follows: 1. Mild nonproliferative diabetic retinopathy (M-NPDR) were reported in 21 (10.5%) patients who were “not using dyslipidemia medications (NDLRx)”; 13 (6.5%) were males and 8 (4%) females. 2. Moderate nonproliferative diabetic retinopathy (Md-NPDR) in 37 (13.5%) patients who were “not using dyslipidemia medications (NDLRx)”; 19 (9.5%) were males and 18 (9%) were females). 3. Severe nonproliferative diabetic retinopathy (S-NPDR) in 16 (8%) patients who were “not using dyslipidemia medications (NDLRx)”; 10 (5%]) were males and 6 were (3%) females). 4. Proliferative Diabetic Retinopathy (PDR) was reported in 9 (4.5%) patients who were “not using dyslipidemia medications (NDLRx)”; 6 (3%) of them were males and 3(1.5%) were females). 5. Advance-Proliferative Diabetic Retinopathy (Ad-PDR) was reported in 2 (1%) patients who were “not using dyslipidemia medications (NDLRx)”; 1 (0.5%) of them was males and 1 (0.5%) was females). 6. While Diabetic macular edema (DME) constituted 14 (7 %) patients who were “not using dyslipidemia medications (NDLRx) of them 11 (5.5%) were males and 3 (1.5%) females) [Table 4].
Diabetic retinopathy and nonapparent diabetic retinopathy patients who were “using dyslipidemia medications”
Regarding “Diabetic Retinopathy Severity Stages” in patients who were “using dyslipidemia medications (DLRx)” were distributed as follows: 1. Mild nonproliferative diabetic retinopathy (M-NPDR) were reported in 10 (5%) patients who were using dyslipidemia medications (DLRx); 7 (3.5%) were males and 3 (1.5%) females). 2. Moderate nonproliferative diabetic retinopathy (Md-NPDR) were reported in 18 (9%) patients using dyslipidemia medications (DLRx); 8 (4%) were males and 10 (5%) females. 3. No patient was reported in the Severe nonproliferative diabetic retinopathy (S-NPDR) group between those males and females who were using dyslipidemia medications (DLRx). 4. Proliferative Diabetic Retinopathy (PDR) was reported in 9 (4.5%) patients who were using dyslipidemia medications (DLRx); 6 (3%) of them were males and 3(1.5%) were females). 5. Only one male patient (0.5%) from the Advance Proliferative Diabetic Retinopathy (Ad-PDR) group who was using dyslipidemia medications (DLRx) was reported. In this group [Table 4] and [Table 5], DME was 9.5% in both sexes; 7% in males and 2.5% in females (5.5 % in males, who were not using dyslipidemia medications (NDLRx) and 1.5% in those who were using dyslipidemia medications (DLRx). In females who were DLRx was 1% and 1.5% NDLRx group) [Table 4]. It was observed that some of the serum lipid parameters in males were nonsignificantly higher in NDLRx than that in DLRx (TC, HDL-C, LDL-C, and non-HDL-C), whereas others were lower in NDLRx than DLRx (TG and VLDL-C). Females reported different results of equal serum lipid values in their TC, TG, HDL-C, and VLDL-C. Nonsignificantly higher values were reported in LDL-C and non-HDL-C.
|Table 5: Association between serum lipids and stages of diabetic retinopathy in male and female patients who were Using and not Using Dyslipidemia Medications (DLRx)|
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Serum lipids of diabetic retinopathy and nonapparent diabetic retinopathy with or without using dyslipidemia medications
The association of serum lipid levels and stages of DR in male and female populations, with and without dyslipidemia medications, is presented in [Table 5],[Table 6] and [Figure 9].
|Table 6: Association of serum lipids with age, glycosylated hemoglobin, diabetes mellitus duration, and hypertension duration in male and female patients using and not using dyslipidemia medications|
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|Figure 9: Association of serum lipids with age, HbA1c%, diabetes mellitus duration, and hypertension duration in male and female patients using and not using dyslipidemia medications|
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In total, all male diabetic patients who presented with DR had nonsignificant higher values of TC (4.6 ± 0.1 vs. 4.5 ± 0.1 mmol/l; P = 1.292), LDL-C (3.0 ± 0.1 vs. 2.9 ± 0.1 mmol/l; P = 1.319), and non-HDL-C (3.6 ± 0.1 vs. 3.5 ± 0.1 mmol/l; P = 0.96) versus “NDR male patients.” While TG (1.6 vs. 1.6 mmol/l), HDL-C (1.0 vs. 0.9 mmol/l), and VLDL-C (0.7 vs. 0.7 mmol/l) were exactly equal in both DR and NDR male groups [Table 5] and [Table 6].
All female diabetic patients in both DR and NDR groups had equal values of TC, HDL-C, LDL-C, VLDL-C, and non-HDL-C (TC = 4.8 mmol/l, HDL-C = 1.0 mmol/l, LDL-C = 3.0 mmol/l, and VLDL-C = 0.7 mmol/l). TG (1.6 vs. 1.5 mmol/L) and non-HDL-C (3.8 vs. 3.7 mmol/L) were slightly higher in DR female patients than in those with no DR (P = 0.071–0.072). These results showed that TC and non-HDL-C were higher in women than men by 4.3% each (TC: 4.8 vs. 4.6 mmol/l) [Table 5] and [Table 6]. The above results highlighted that some of the serum lipid parameters in males were nonsignificantly higher in NDLRx than DLRx (TC, HDL-C, LDL-C, and non-HDL-C), while others were lower in NDLRx than DLRx (TG and VLDL-C). Females reported different results of equal serum lipid values in their TC, TG, HDL-C, and VLDL-C. Nonsignificantly higher values were reported in LDL-C and non-HDL-C.
Association between Diabetic patients who were Not Using Dyslipidemia Medications (NDLRx) and those who Were Using Dyslipidemia Medications (DLRx)
A total of 116 patients from the whole study group were “not using dyslipidemia medications (NDLRx):” 70 (35%) were male and 46 (23%) were female. Their mean age was 61.4 years, DM duration was 15.9 years, HTN duration was 5 years, and DM itself was poorly controlled which was reflected by the high HbA1C (8.5%). Regarding serum lipid levels, they were almost higher in patients who were using DLRx (TC: 4.8, TG: 1.7, LDL-C: 3.1, VLDL-C: 0.8, and non-HDL-C: 3.8 mmol/L) except HDL-C which reported an equal value in both NDLRx and DLRx groups [Table 5] and [Table 6]. On the other hand, only 84 (42%) patients were “using dyslipidemia medications (DLRx):” 34 (17%) were male and 50 (25%) were female [Table 5] and [Table 6]. Their mean age was 64.9 years, DM duration was 15.9 years, and HTN duration was 6.3 years, although HbA1c (7.9%) was slightly lower in DLRx than in NDLRx group but still reflecting their poorly controlled DM [Table 6].
Regarding serum lipid levels, they were almost lower in those patients who were using dyslipidemia medications (DLRx) than those who were not using dyslipidemia medications (NDLRx) (TC: 4.7, TG: 1.6, LDL-C: 2.9, VLDL-C: 0.7, and non-HDL-C: 3.7 mmol/L) except HDL-C which reported an equal value in both NDLRx and DLRx groups [Table 5], [Table 6], [Table 7] and [Figure 9]. Also, presented the association of Serum Lipids with Age, HbA1C%, Diabetes Militus duration, Hypertension Duratin in Males and Female Patients who were Using (DLRx) and not Using Dyslipidemia Medications (NDLRx). Age never had any effect Serum Lipids as almost all the study patients in their 7th decade. HbA1C% was high allover the results, indicating poor DM control of particepants.
|Table 7: Distribution of “modified grades and reference value scales of nonhigh-density lipoprotein, in diabetic retinopathy patients with and without dyslipidemia medications|
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Regarding with (DLRx) or without dyslipidemia medications'(NDLRx) use, the average ages of all the patients in DLRx and NDLRx groups were around 60 (with an average of 63.1 years; ranging from 61–67 years). DM duration (DMD) was 15.9 years, Hypertension duration (HD) was 5.6 years. All serum lipid values [including TC (4.7: 4.5 mmol/l), HDL-C (1.0 : 0.9 mmol/l), LDLC (3.0 : 2.8 mmol/l), and non-HDL-C (3.7: 3.6 mmol/l), except VLDL-C (0.7: 0.8 mmol/l)] were nonsignificantly higher in NDLRx males' group than males in DLRx group. VLDL-C ; was lower in NDLRx than DLRx group (0.7 vs 0.8 mmol/L). Whereas, serum lipid values in both female groups; NDLRx and DLRx (including TC, TG, HDLC, and VLDL-C) were equal except non-HDL-C, which was nonsignificantly higher in NDLRx than DLRx (3.8 vs. 3.7 mmol/l) [Table 5]. HbA1c, which is an indicator of DM control, was found to be equal in both groups of males: those who were “using dyslipidemia medications” (DLRx) and those who were “not using dyslipidemia medications” (NDLRx). Both groups scored high HbA1c of 8.3% which indicated poor DM control of the current study participants [Table 6]. While in female who were “not using dyslipidemia medications” (NDLRx) the HbA1c percentage (8.7%) was higher by 1.2% than in females who were “using dyslipidemia medications” (DLRx) [Table 6].
Some serum lipid levels were almost equal in females who were using or not using dyslipidemia medications (TC: 4.8, TG: 1.6, and VLDL-C: 0.7 mmol/l) and other levels were variable: HDL-C: 1.0/1.1, LDL-C: 3.0/3.1, and non-HLD-C: 3.8/3.7 mmol/l. However, all serum lipid values were slightly lower in both male groups (DLRx vs. NDLRx) than females'. Some serum lipid levels were even nonsignificantly lower in DLRx groups than that in NDLRx groups (cholesterol: 4.5 vs. 4.7, TG: 1.6 vs. 1.7, and non-HDL-C: 3.6 vs. 3.7 mmol/l), while VLDL-C was higher (0.8 vs. 0.7 mmol/l) [Table 6].
Non-HDL-C was very high in in both sexes with Proliferative Diabetic Retinopathy (PDR). While it was “Borderline high” in diabetic patients with No Diabetic Retinopathy (NDR) or with other types of None Proliferative Diabetic Retinopathies (M-NPDR, Md-NPDR, S- NPDR) who were using dyslipidemia medications (DLRx), except few [Table 7]. Non-HDL-C values in Diabetic Females with DME who were using dyslipidemia medications (DLRx) were “Borderline”; in contrary of Non-HDL-C values in Diabetic Males with DME who were using dyslipidemia medications (DLRx), they scored “Borderline high” [Table 7].
Diabetic retinopathy and nonapparent diabetic retinopathy with or without concomitant hypertension
In the current study population, 107 patients had HTN (46 NDR + 61 DR = 107). The mean age of DLRx patients was 64.9 years, while that of NDLRx was smaller (61.4 years). HbA1c (7.9% vs. 8.5%) was slightly lower in DLRx than NDLRx group but still high enough to reflect their poorly controlled DM [Table 6]. HbA1c (7.9% vs. 8.5%) was slightly lower in DLRx than NDLRx group but still high enough to reflect their poorly controlled DM [Table 6]. According to [Table 8], the total “No Diabetic Retinopathy (NDR)” patients were 94; out of them 46 were hypotensive. While the total “Diabetic Retinopathy (DR)” patients were 106; 61 were hypotensive, which means 94 patients in the current study demonstrated high HbA1c, an indication of poor glycemic control in both groups (mean of 8.1%: 7.35% in NDRs, 8.8% in DR, with the highest in DR + HTN, 2nd in DR without HRN, 3rd in NDR + HTN, and 4th in NDR without HRN) [Figure 10].
|Table 8: Serum lipid spectra on diabetic retinopathy with and without hypertension|
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|Figure 10: Association of ± hypertension with diabetic retinopathy and nondiabetic retinopathy|
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Both Diabetic female patients with (DR) and without Diabetic retinopathy (NDR) reported equal values of serum lipids. [Tables 5] While Both Diabetic male patients with (DR) and without Diabetic retinopathy (NDR) reported almost equal values of serum lipids except minor differences in TC and nonHDLC values (Males' TC was 4.6 mmol/l in DR group vs, 4.5 mmol/l in NDR group. NonHDLC was 3.6 mmol/l in DR group vs, 3.5 mmol/l in NDR group). [Table 5].
Diabetic Macular Edema (DME): [Table 9]a, [Table 9]b, [Table 9]c and [Table 10]
|Table 10: “Modified grades and reference value scales” of serum lipid-glycosylated hemoglobin in patients with and without dyslipidemia medications|
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Association of DME in Males' and Females' with the serum lipids parameters in NDLRx and DLRx groups; were inconsistent due to the following findings:
- TC was equal in both groups regardless of the DLRx with 15% higher records in male patients (5.0 mmol/l in males vs. 4.3 mmol/l in females) and even slightly exceeding the recommended “DM Target Goal of TC” [Table 10].
- TG was higher in DLRx rather than in NDLRx group with DME. Females TG values were even more than males' TG (1.9 mmol/l in female's vs 1.6 mmol/l in males'). However, both females and males' values were still exceeding the recommended “DM Target Goal of TG” levels. DLRx female's values were at the “High” grade.
- HDL-C values were equal in both DLRx/NDLRx groups which were at the zones of nrrv
- LDL-C values were almost equal in both sexes with slightly higher scores in males (M/F: 1.0:0.9 mmol/l)
- Non-HDL-C values were equal in both NDLRx and DLRx males' diabetic patients (both reported “Borderline high” values of 4.0 mmol/l, a pit higher than in females' patients (3.4 and 3.5 mmol/l respectively). However, all values were within non-HDLC “Borderline high scale” of Al-Hada Armed Forces Hospitals Laboratories adjusted “Borderline High Reference Range Values” (3.8 mmol/l). [Table 8] and [Table 9]a Females patients “using dyslipidemia medications (DLRx)” scored slightly higher non-HDL-C mean values (3.5 mmol/l) than females' patients who were “not using dyslipidemia medications (NDLRx)” (3.4 mmol/l) although both they were within the normal Reference Values scales “of non-HDL-C in DR. [Table 8] and [Table 9]b
- HbA1c values were high in all patients with a mean of 9.5% in the entire DME population (range from 8.4% to 10.3%) indicating poor glycemic control [Table 9]a, [Table 9]b, [Table 9]c.
| Discussion|| |
Serum lipid abnormalities are largely manifested during the asymptomatic diabetic prodromal phases, which may increase the risk of diabetic macrovascular insults during the long course of DM. Consequently, there is a high risk for CVD and DR. HbA1c level indicates the estimated average glucose level and is believed to assist in determining the effectiveness of blood glucose control measures. Associations between poor control of type 2 DM (T2DM) and serum lipids were noticed by many researchers (Khan HA, 2007), which raised the benefit of HbA1c level as an indirect marker of dyslipidemia and greater risk of DR in T2DM. Therefore, correction of dyslipidemia is important in preventing the development and progression of DR.
Although studies concerned with the association between the serum lipid levels and DR produced disputable and controversial results, some showed a positive relationship, whereas certain other studies showed no relationship at all. Jonathan et al.'s review (2016) supported the concept of using “dyslipidemia medications in patients with DM and high total serum lipid levels” does result in an improvement in their DR severity levels,, a matter which had been supported and recommended by the Joint British Societies' consensus recommendations for the prevention of CVD (JBS3) in 2014, and the recent “Guidelines of the American Association of Clinical Endocrinologists and the American College of Endocrinology Guidelines (AACE 2017).”
The incidence of DR in this study was 53% at a mean duration of 15.5 years which is better than that in the literature where Fong DS and collegues (2003) estimated DR incidence up to 80% at 15 years, a matter which could explain the use of DLRx in nearly half of the studied patients (42%), as this was not so clear in Fong DS' and collegues results. Genetic aspects can be raised as an added factor which may lead to variations in DR prevalence between populations.
The current work reported that 107 patients (53.5%) had DM with long-standing duration (10.6 years) coexisted with HTN. Out of these 107 patients, about 1/3rd of the patients (60, 30.5%) developed DR, a condition which supports the concept of the “role of HTN” as an additional risk factor for DR, especially in poorly controlled DM, as in the case of the present study where the mean HbA1c% was 8.0% (”No DR” patients 7.4% and “DR” patients 8.5%). This conception can even explain the positive association of the DR prevalence with HTN as mentioned by van Leiden et al.
Still, in some way or another, the finding was in agreement with that of Kajiwara et al. and Lee et al.
NonHDLC recorded lower values (3.7 mmol/l) in Diabetic patients with DR and Hypertension (HTN) and slightly higher values (3.8 mmol/l) in Diabetic patients without DR (NDR) [Table 8].
In the present study, serum lipid profile showed that the “overall” average values for TC, TG, HDL-C, LDL-C, and VLDL-C were almost equal in both groups of patients with DR and without DR (NDR): TC 4.8 mmol/l, TGs 1.8 mmol/l, and HDL-C 1.0 mmol/l. To some extent, it may conquer the concept of dyslipidemia's role (cholesterolemia and triglyceridemia) in DR severity levels that reported its inevitability in worsening the DR state. On the contrary, Rema et al. reported significant increase of serum lipids in patients with DR compared with those without DR (NDR). Furthermore, the current study results, which couldn't observe a strong correlation between serum lipids with different stages of DR, to some extents; were compatible with the results by Chang and Wu' mass literature review who reported the lack of definite associations between traditional lipid markers and DR. In contrary with van Leiden and colleagues' in the Netherlands popular Hoorn Cohort study (2002) who reported that “the prevalence of DR was positively associated with serum cholesterol, TG, and LDL-C level.” Moreover, Busik JV, Esselman WJ and Reid GE of Michigan State University, USA demonstrated even stronger association between dyslipidemia and development of DR, in contrary to the current study.
The current study reported that the serum lipid levels in male patients were non-significantly associated with the DR severity levels (P = 1.319) and even in female patients, most of the serum lipid parameters were exactly equal in both DR and NDR patients, a condition which had been agreed with the results of Ajith et al., Cetin et al., Lyons et al., and Aclan Ozder (2014, in Turkey) who reported a non-statistically significant difference between diabetic females and males in TC, TG, HDL, and LDL, with higher values than reported in the current study.
The current study revealed higher LDL-C (3.1 mmol/l) in patients who were “not using dyslipidemia medications (NDLRx),” in conjunction with 13 (6.5%) cases of DME, as compared with LDL-C (2.9 mmol/l) and no cases of DME in patients who were “using dyslipidemia medications (DLRx).” This result was in line with Chowdhury et al., who reported high LDL with DME as relative risk factors for DME.
TC, TG, VLDL-C, and non-HDL-C levels had similar higher scores and diabetic retinal insults. Hence, TC levels were slightly “nonsignificantly” higher in those who were not using NDLRx (5 mmol/l vs. 4.9 mmol/l) in comparison with those using DLRx. This is weakly in alignment with the findings of Klein et al. who reported a higher but significant serum TC level that gave Klein et al. an impression of a strong association with a higher prevalence of DR and DME.
Non-HDL-C and serum TC levels provided the highest serum lipid scores (4.9 mmol/l and 5.8 mmol/l, respectively) with the PDR in DR severity level scale. Hence, they were well associated with PDR in males and females and directly associated with increased DME. Serum HDL-C was inversely associated with the prevalence of DME and PDR, while TC was associated directly with an increased risk of both DR severity scales. This was in alignment with the famous 35-year long Cohort Wisconsin Epidemiologic Study of Diabetic Retinopathy (1979–2014) in 11 counties where TC was associated with an increased risk of PDR.
- The types and severity of DR were diagnosed by clinical biomicroscopic fundoscopy. But due to high coast of the fundal imaging techniques, only in some selected cases, the diagnoses were confirmed by fundal imaging techniques like: Fundus Fluorescein Angiography (FFA), Optical Coherence tomography (OCT), and Ultrasonography (Bscan)
- Variable sample sizes in various stages of DR, as some DR stages may not be enough
- Data were obtained from the hospital's laboratory records without knowing the real methods of serum lipid assay: direct methods (that usually give a better estimate of these serum lipids than the indirect methods) versus indirect methods.
| Conclusion|| |
The current study findings have weakly appended an evidence that dyslipidemia could be added to the list of DR risk factors, as the development of elevated serum lipids showed some association with DR ± DME formation. Hence, it can be concluded that serum lipid-lowering agents may help in reducing the occurrence of retinal findings and loss of vision in diabetic patients.
- Initiate more future prospective clinical studies supporting the role of lipids on DR
- Implement well-funded DR cost-effective screening strategies that depend on the rates of appearance and progression of DR and on risk factors that alter these rates
- Optimize national-level better screening and therapeutic options of serum lipid as part of DR management protocols
- Optimize glycemic control to reduce the risk or slow the progression of DR
- Optimize blood pressure and serum lipid control to reduce the risk or slow the possible progression of DR
- Prompt DM patients' referral to the concerned ophthalmologist for screening and treatment of DR.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]