Diabetic retinopathy and dyslipidemia among patients with type 2 diabetes mellitus in the Jazan endocrine and diabetes center: A case-control study

ABSTRACT

Background:

Diabetic retinopathy (DR) is a well-known complication of diabetes mellitus (DM) that requires early diagnosis and treatment. The major risk factors for DR include older age, dyslipidemia, obesity, and higher levels of glycated hemoglobin. This study aimed to assess the type and severity of DR in type 2 patients and its correlation with dyslipidemia in Jazan, Saudi Arabia.

Methods:

This case-control study was conducted at the Jazan endocrine and diabetes center. The study included type 2 diabetic patients without DR as controls and type 2 diabetic patients with DR as cases. Version 26 of SPSS was used to analyze the data, and multivariate analysis was performed to identify the risk factors for DR.

Results:

The study included 210 patients as controls and 100 patients as cases; mild nonproliferative DR was the most common degree (52%), and 5% had maculopathy. The comparison between the two groups revealed that there was no significant difference regarding experiencing dyslipidemia (P = 0.4). On the other hand, a significantly higher proportion of patients in the case group received aspirin and statin (P < 0.001). The risk factors for developing DR included age (AOR =1.05, P < 0.001), insulin and oral hypoglycemics (AOR =4.61, P < 0.001), and statin (AOR =4.19, P < 0.001).

Conclusion:

Mild nonproliferative DR was the most dominant DR among Saudi T2DM patients. Neither dyslipidemia nor serum lipid was associated with developing DR. However, the administration of statin, older age, and a combination of insulin and oral hyperglycemics were significant risk factors for DR among T2DM patients.

Introduction

Diabetes mellitus (DM) is defined by the World Health Organization (WHO) as a metabolic disease of several etiologies that involves chronic hyperglycemia with the disturbia of metabolism of carbohydrates, proteins, and fats. DM can result from defects in insulin action, recreation, or both.[1] In Saudi Arabia, DM has emerged as a major public health issue that has reached an epidemic stage.[2] Diabetic retinopathy (DR) is an adverse result of diabetes that can be prevented[3]; it was stated that more than 77% of diabetic patients who survive for more than 20 years are affected by DR.[4] DR requires early diagnosis and suitable treatment to avoid serious further complications.[3] Therefore, The American Diabetes Association recommended screening type 2 diabetes mellitus (T2DM) patients for DR at the time of diagnosis of diabetes and then routinely annually or every 2 years if there is no evidence of retinopathy.[5]

The prevalence of DR in the globe was estimated to be 22.27%.[6] The DR prevalence in Saudi Arabia ranges from 28.1% to 45.7%, and vision-threatening DR affects 4.5% to 17.5% of diabetic patients.[7] The most common risk factors for DR include older age, dyslipidemia, higher levels of glycated hemoglobin (HbA1c), longer duration of diabetes, obesity, smoking, higher blood pressure, and nephropathy.[8,9]

Dyslipidemia is defined by the existence of one or more abnormal serum lipid concentrations, and the prescription of statin therapy can be beneficial for such conditions.[10] Serum lipids are incorporated in the occurrence and progression of DR in T2DM.[11] The high levels of lipids are known to result in endothelial dysfunction because of the reduced bioavailability of nitric oxide, and this endothelial dysfunction was proposed to play a major role in retinal exudate formation in DR.[12] However, the evidence of the correlation between DR and serum lipids is inconsistent.[11] Therefore, we conducted this study to assess the type and severity of DR in type 2 patients and its correlation with dyslipidemia in Jazan, Saudi Arabia.

Subjects and Methods

Study design, subjects, and collection of data

This case-control study included patients with T2DM with the age of 18 years and older, who were divided into a case group that involved diabetic patients with DR and a control group that involved diabetic patients without DR. The patients were recruited from the Jazan endocrine and diabetes center. On the other hand, patients with no record or lipid profile during 2019 were excluded from the study. Epi Info CDC program was used for the calculation of sample size with consideration of 1:2 cases to controls ratio, 95% confidence interval, and 80% power. The patients underwent eye examination and were classified into normal, proliferative, and nonproliferative DR. The remaining data were collected from the medical records of the patients. Confidentiality was assured to all patients included. The patients received a brief description of the study and its objectives, and their data were kept confidential, secured, and used for research purposes only. All required official permissions were fully obtained before the collection of the data.

Statistical analysis

Version 26 of SPSS software was used for data processing; continuous data were represented using means and standard deviation (SD), whereas categorical ones were represented using percentages and frequencies. A Chi-square test for independence was used to assess the associations among the categorical data. The comparison of means of the continuous data was done using independent t-test. P value ≤ 0.05 was significant. Multivariate analysis evaluated the correlation between DR and dyslipidemia with adjustment for the potential covariates. Results were presented as adjusted odds ratio and 95% confidence interval (CI).

Results

The comparison between the control and case groups regarding sociodemographics is illustrated in Table 1. Females and married patients were more dominant in both groups with no significant difference, P = 0.1 and 0.08, respectively. Regarding working status, cases significantly tended not to work (P = 0.005). Regarding income, BMI classifications, and smoking status, patients in both groups tended to have middle income, being obese and nonsmokers, but with no significant differences, P = 0.1, 0.4, and 0.3, respectively. Regarding age, the case group was significantly older compared to the controls (P = 0.001).

Table 1.

Sociodemographics for DR among type 2 diabetic patients: Univariate analysis

Characteristic		Classification				P
		Control N=210		Cases N=100
		N	%	N	%
Gender	Male	85	(40.5)	48	(48.0)	0.122*
	Female	125	(59.5)	52	(52.0)
Marital Status	Married	181	(86.2)	93	(93.0)	0.080*
	Single	29	(13.8)	7	(7.0)
Work status	Working	85	(40.5)	24	(24.0)	0.005*
	Not Working	125	(59.5)	76	(76.0)
Income	High	19	(9.0)	5	(5.0)	0.127*
	Meddle	158	(75.2)	71	(71.0)
	Low	33	(15.7)	24	(24.0)
BMI Categories	Underweight	1	(0.5)	1	(1.0)
	Normal	29	(13.8)	20	(20.0)	0.493*
	Overweight	78	(37.1)	36	(36.0)
	Obese	102	(48.6)	43	(43.0)
Smoking Status	Smoker	66	(31.4)	37	(37.0)
	Nonsmoker	144	(68.6)	63	(63.0)
		Mean	(SD)	Mean	(SD)
Age in years		53	(13)	61	(11.0)	0.001**

* Pearson Chi-Square, ** Independent Samples t-test; Abbreviations: SD=Standard deviation, BMI=body mass index

It was revealed that mild nonproliferative DR was the most prevalent DR (52%), followed by moderate nonproliferative (32%), whereas proliferative and severe nonproliferative represented 9% and 7%, respectively [Figure 1]. Additionally, it was found that 5% of patients had maculopathy [Figure 2].

Figure 1.

Severity of DR among type 2 diabetic patients (n = 100)

Figure 2.

Prevalence of maculopathy among type 2 diabetic patients with retinopathy (n = 100)

The comparison between the two groups regarding the clinical risk factors revealed that the case group significantly tended to experience peripheral neuropathy (P < 0.001) and nephropathy (P < 0.001) compared to controls. On the other hand, the control group significantly tended to have hypertension (P < 0.001) compared to the case group. However, there was no significant difference found between the two groups regarding having a stroke (P = 0.3), heart disease (P = 0.09), or dyslipidemia (P = 0.4) [Table 2].

Table 2.

Comparison regarding clinical factors: Univariate analysis

Characteristic		Classification				P
		Control N=210		Cases N=100
		N	%	N	%
Peripheral neuropathy	No	189	(71.9)	74	(28.1)
	Yes	21	(44.7)	26	(55.3)	<0.001*
Nephropathy	No	205	(70.2)	87	(29.8)
	Yes	5	(27.8)	13	(72.2)	<0.001*
Stroke	No	208	(68.0)	98	(32.0)
	Yes	2	(50.0)	2	(50.0)	0.388**
Heart diseases	No	198	(69.0)	89	(31.0)
	Yes	12	(52.2)	11	(47.8)	0.097*
Hypertension	No	128	(80.0)	32	(20.0)
	Yes	82	(54.7)	68	(45.3)	<0.001*
Dyslipidemia	No	194	(68.3)	90	(31.7)
	Yes	16	(61.5)	10	(38.5)	0.480*

* Pearson Chi-Square, ** Fischer exact test

The comparison between the two groups regarding medications displayed that patients in control groups significantly tended to receive oral hypoglycemic only and insulin and oral hypoglycemics compared to cases (P < 0.001). Also, a significant proportion of patients without DR in the control groups received antihypertensive medications compared to the cases (P < 0.001). On the other hand, significant proportions of patients with DR in the case group received aspirin and statin compared to the controls (P < 0.001) [Table 3].

Table 3.

Medications risk factors for DR among type 2 diabetic patients: Univariate analysis

Characteristic		Classification				p*
		Control N=210		Cases N=100
		N	%	N	%
Antidiabetic medications	Oral hypoglycemics only	113	84.3	21	15.7
	Insulin only	2	66.7	1	33.3	<0.001
	Insulin and oral hypoglycemics	95	54.9	78	45.1
Antihypertensive medications	No	127	82.5	27	17.5
	Yes	83	53.2	73	46.8	<0.001
Aspirin	No	155	77.9	44	22.1
	Yes	55	49.5	56	50.5
Statin	No	142	83.0	29	17.0	<0.001
	Yes	68	48.9	71	51.1

* Pearson Chi-Square

The comparison between the diabetic patients with and those without DR revealed no significant differences regarding different laboratory parameters [Table 4].

Table 4.

Laboratory result-related risk factors for DR among type 2 diabetic patients: Univariate analysis

Characteristic	Classification				p*
	Control N=210		Cases N=100
Mean	(SD)	Mean	(SD)
HbA1c %	10.42	(4,7)	10,93	(7,7)	0.480
TC (per mmol/l)	179.83	(43.7)	171.57	(36.7)	0.103
Triglycerides (mmol/l)	151.36	(69.0)	159.22	(69.1)	0.349
LDL (mmol/l)	131.39	(418.1)	97.80	(29.0)	0.423
HDL (mmol/l)	46.84	(14.9)	44.55	(9.7)	0.161
CR (mmol/l)	1.97	(13.4)	2.00	(11.6)	0.986
Sodium	139.54	(10.3)	139.70	(4.0)	0.881
Potassium	4.63	(2.5)	4.91	(3.5)	0.420
AST (U/L)	25.23	(12.1)	26.80	(20.8)	0.404
ALT (U/L)	34.17	(15.9)	33.09	(14.9)	0.570
Albumin	4.17	(2.8)	4.25	(2.6)	0.810

*Independent Samples t-test.

Abbreviations: SD=Standard deviation, TG=triglycerides, TC=total cholesterol, CR=creatinine, ALT=alanine aminotransferase, AST=aspartate aminotransferase, HbA1C=glycated hemoglobin, LDL=low-density lipoprotein, HDL=high-density lipoprotein

Multivariate logistic regression analysis revealed that the increase in age by 1 year increased the risk of DR (AOR 1.05, 95% CI 1.03–1.08, P P < 0.001). Receiving a combination of insulin and oral hypoglycemics was associated with an increased risk of developing DR by almost fivefold (AOR 4.61, 95% CI 2.12–8.42, P < 0.001). Also, receiving statin was associated with an increased risk of developing DR by more than fourfold (AOR 4.19, 95% CI 2.38–7.36, P < 0.001), Table 5.

Table 5.

Predictors of DR

Variables	B	SE	AOR	95% CI	P
Age (years)	0.051	0.021	1.05	1.03-1.08	<0.001
Diabetic Medications*
Oral hypoglycemics	1.477	0.308	1.0	- --	- --
Insulin and oral hypoglycemics			4.61	2.12-8.42	<0.001
Statin
Noa	1.432	0.288	1.0	- --	- --
Yes			4.19	2.38-7.36	<0.001

B=Slope, SE=Standard error, AOR=Adjusted odds ratio, CI=Confidence interval

Discussion

This study was carried out to identify the severity of DR in type 2 patients and its correlation with dyslipidemia in Jazan, Saudi Arabia. In the current study, a total of 210 diabetic patients without DR were considered controls, whereas 100 diabetic patients with DR were included as a case group. Regarding the cases, the most prevalent DR was mild nonproliferative, which represented more than 50% of the cases (52%), whereas severe nonproliferative represented the least proportion of DR patients (7%). Additionally, only 5% of patients had maculopathy. A previous Saudi study from Makkah conducted on T2DM patients reported similar findings to ours, where 52.6% of DR patients had mild nonproliferative DR, and proliferative DR represented the lowest proportion of the patients (4.4%).[13] Another Saudi study revealed that mild nonproliferative DR was the major DR prevalent (57.5%), whereas proliferative was the least prevalent DR (11.6%). Out of the 146 patients with DR, 28 patients (19.2%) had maculopathy.[14] These findings reveal that the Saudi T2DM patients tended to experience mild nonproliferative DR. A previous cross-sectional study enrolled Indian patients with T2DM reported the highest prevalence of moderate nonproliferative DR (41%), followed by mild nonproliferative DR, whereas the least proportion of patients experienced proliferative DR (9.5%).[15]

In the current study, the comparison between controls and cases revealed that patients with DR significantly tended to be older in age compared to the controls. This finding was confirmed by multivariate analysis, where age was a significant risk factor for DR development (P < 0.001), with an adjusted odd of 1.01. In agreement with our findings, a study from India conducted on T2DM demonstrated that T2DM with DR were significantly older compared to those without DR. Additionally, there were no differences between the two diabetic groups with and without DR regarding gender,[15] which was in agreement with our findings.

Regarding the clinical conditions, DR was significantly associated with peripheral neuropathy and nephropathy; however, in multivariate analysis, there was no significant association found. Also, dyslipidemia revealed no significant association with DR (P = 0.4) in univariate analysis. It was reported that some factors displayed conflicting findings, including dyslipidemia, obesity, and smoking, where such factors reduced the risk in one study based on both univariate and multivariate analyses.[16] However, such factors, including smoking, dyslipidemia, and BMI, did not have any association with developing DR among T2DM patients in the current study. In contrast to our findings, a previous Saudi study revealed that the probability of DR development was increased by 11% by an increase of one unit in BMI, reflecting that BMI was a significant risk factor for DR among T2DM,[13] which was in contrast to our findings.

In contrast to our findings, a previous Saudi study revealed a significant association between DR and dyslipidemia among T2DM patients and a significant association between DR and hypertension.[10] In our study, no significant correlation was found between DR and dyslipidemia, and hypertension was significantly associated with T2DM patients without DR, displaying no association with DR development. Another Saudi study also reported an association between more advanced DR and dyslipidemia (r = 0.199).[17] A cross-sectional study from India found a strong association between DR and serum cholesterol in unadjusted analysis, but when adjusting factors such as gender, age, glycemic control, and duration of diabetes, there was no association found.[15]

In the current research, significant proportions of DR patients reported receiving statin and aspirin; however, on multivariate analysis, statin was significantly associated with increased risk of DR by more than fourfold (AOR =4.19, P < 0.001). In previous research conducted on T2DM patients, it was found that DR progressed among 23% of statin users and 18% of nonusers (P = 0.506), revealing no significant association between statin and developing DR,[18] which was in contrast to our findings.

Also, in the current study, receiving insulin and oral hypoglycemics was significantly associated with an increased risk of developing DR by almost fivefold (AOR =4.61). This can be explained by the previous finding that diabetic patients treated with insulin were more likely to develop DR.[19,20] We found that in comparison to oral hypoglycemics only, receiving insulin and oral hypoglycemics was a significant risk factor for DR, and this may be due to the combination with insulin that was reported in previous studies to increase the likelihood of DR.[19,20] Additionally, a previous Saudi study revealed that those not receiving insulin were 70% less likely to develop DR.[13]

In our study, none of the laboratory parameters displayed significant variations between the two groups of patients, including lipid profile parameters. In agreement with our results, there was no significant difference between patients with and without DR regarding triglycerides, total cholesterol, and high-density lipoprotein.[21]

A previous systematic review from Saudi Arabia included 12 studies to determine the prevalence and risk factors of DR among T2DM patients; it was found that DR was a common complication of T2DM with a prevalence range of 6.25%–88.1%. The identified risk factors for DR among T2DM patients included older age, longer duration of diabetes, physical inactivity, and poor glycemic and blood pressure control, with no mention of dyslipidemia.[3] Also, we found that older age was a significant risk factor for DR. Another systematic review included 13 studies that demonstrated that the baseline of triglycerides and cholesterol were significantly associated with the occurrence of DR among T2DM patients,[11] but we did not find any significant association between dyslipidemia and DR.

Conclusion

Mild nonproliferative DR was the most dominant DR among Saudi T2DM patients. There was no significant association between dyslipidemia or serum lipid and developing DR. However, the administration of statin, a combination of insulin, and oral hyperglycemics were significant risk factors for DR among T2DM patients. Also, the older age of T2DM patients was a significant predictor for DR.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.