High Fasting Blood Sugar and Increased Waist Circumference as Risk Factors for Diabetic Retinopathy in Type 2 Diabetes Patients Older than 45 Years

Introduction Diabetes mellitus (DM) has a long-term impact on retinal micro-blood vessels, culminating in the progression of diabetic retinopathy (DR); however; screening for DR is not widely used due to a lack of accessibility and economic constraints, especially in resource-limited settings. Thus, a longitudinal marker that is associated with the development of DR is required. This study sought to assess the association of DR with fasting blood sugar (FBS) levels and waist circumference. Methodology A cross-sectional study was conducted in a tertiary care hospital for one year. All individuals diagnosed with Type 2 DM (T2DM) and ≥45 years of age were included in the study. Individuals with fasting blood glucose levels of <126 mg/dl and <3 years of diagnosis with T2DM were excluded from the study. Individuals having one or more retinal microaneurysms or retinal blot hemorrhages, with or without any additional abnormalities, were diagnosed with DR. The results were analyzed using SPSS version 21 (IBM Corp., Armonk, NY). Results The prevalence of diabetic retinopathy among the study participants was 67.6 %. There was a significant association between increasing waist circumference (p = 0.009) and High FBS levels (p = 0.032) with the presence of DR. Conclusion Approximately two-thirds of the patients with T2DM aged >45 years and above have diabetic retinopathy. High FBS and waist circumference were associated with DR.


Introduction
Diabetes mellitus (DM) is a metabolic condition that is caused by problems in insulin production, its action, or both. It is distinguished by chronic hyperglycemia and irregularities in carbohydrate, lipid, and protein metabolism [1]. Type 2 diabetes mellitus (T2DM) is the most prevalent form of diabetes, which accounts for 90% of all diabetics worldwide [1,2]. Individuals with T2DM are more likely to develop complications, such as cardiovascular disease (CVD), neuropathy, eye disease (retinopathy), and nephropathy. This retinopathy may lead to blindness [3,4]. DM has a long-term impact on retinal tiny blood vessels, culminating in the progression to retinopathy and visual impairment. Diabetic retinopathy (DR) is the leading cause of visual impairment in adults aged 20-65 years; one in three people with diabetes have some degree of DR and one in 10 develop a vision-threatening form of the illness. Globally, the number of persons with DR is expected to rise from 126.6 million in 2010 to 191.0 million by 2030, with the number of people with visionthreatening DR rising from 37.3 to 56.3 million if immediate action is not taken [5,6]. DR is asymptomatic until it has progressed to an advanced stage; however, it is mostly preventable with frequent ocular screenings and appropriate treatment before vision impairment. Gender, unregulated DM, chronic DM, the associated complication of nephropathy, and comorbidity with hypertension are risk factors for DR in diabetic patients [7][8][9]. However, screening for DR is not widely used due to a lack of accessibility and economic constraints, especially in resource-limited settings. Thus, a longitudinal marker that is associated with the development of DR is required. To date, few studies have assessed any association with DR. Therefore, this study was conducted to assess the association between DR, fasting blood sugar (FBS) levels, and waist circumference.

Study design and sampling
A cross-sectional study was conducted in a tertiary care hospital in Salem for a duration of one year (July 2021 to July 2022). Study participants were included using a convenient sampling technique.

Sample Size
Previous studies have shown that the prevalence of DR among diabetes is 5-7%. Thus, with a 7% prevalence and 5% absolute error, the minimum sample size needed for the current study with a 95 percent confidence interval is 120 (inclusive of a 10% non-response rate). The sample size was calculated by using the formula 3.86*p*q/d 2 , where, p is prevalence, q is a compliment of p and d is absolute precision (5%).

Ethical Clearance
This study obtained ethical approval from the Institutional Ethical Committee at Vinayaka Mission's Kirupananda Variyar Medical College and Hospitals (VMKVMC&H), Salem (approval number VMKVMC&H/ICE/21/118).

Eligibility criteria
Inclusion criteria: After obtaining informed consent, all individuals who were recruited during the study period with the diagnosis of T2DM and were ≥45 years of age were included in the study. Exclusion criteria: Individuals with fasting blood glucose levels of <126 mg/dl; those diagnosed with terminally ill conditions; and those <3 years from their T2DM diagnosis were excluded from the study. Similarly, all patients who were diagnosed with impaired glucose tolerance, maturity-onset diabetes of the young (MODY), latent autoimmune diabetes in adults (LADA), and Type 1 DM were also excluded from the study.

Data collection
All study participants provided 12-hour overnight fasting blood samples, which were sent for laboratory analysis. The circumference line connecting the narrowest point between the inferior border of the lower rib, iliac crest, and umbilicus was used to measure the waist circumference. The normal waist circumference range for men and women is less than 90 and less than 80 centimeters respectively. Individuals presented with ≥1 retinal micro-aneurysm or retinal blot hemorrhages, with or without any additional abnormalities, while doing ophthalmoscopy, were diagnosed as DR.

Data analysis
The data obtained from the study were entered in Microsoft Excel. The results were analyzed using SPSS version 21 (IBM Corp., Armonk, NY). Continuous variables were expressed as mean and standard deviation. The association between FBS and waist circumference with DR was assessed by using an independent t-test. Data were considered statistically significant with a 95% confidence interval when p < 0.05.

Results
This study included 213 individuals. The mean age, duration of diabetes, height, and weight were 60.46 years, 10.02 years, 161.24 cm, and 61.6 kg, respectively ( Table 1).  The general characteristics of the study participants are described in Table 2. Approximately 55.9% of the study participants were males (n = 119). The prevalence of hypertension and being overweight was 13.6% and 24.9%, respectively. The prevalence of diabetic retinopathy among the study participants was 67.6%.

FBS: Fasting blood sugar
The mean FBS value for participants with and without DR was 203.36 and 187.93, respectively ( Table 5), which was a significant difference (p = 0.032). The mean waist circumference for participants with and without DR was 39.72 and 37.64, respectively, which was also a significant difference (p = 0.009).   N = 11,182) found a prevalence of 33% DR in the study population with a mean age of 58 years [11]. This difference may be due to sample size differences and a multi-centric approach. A population-based study (N = 63,000, age ≥50 years) involving 31 districts showed a prevalence of only 16.9% [12]. This study used data from a national survey from 2015-2019. This big difference could be due to differences in the study setting and sample size. Further research is required to confirm the true prevalence.
Our study showed a significant association between increased waist circumference and the presence of DR. Similar results have been reported in a Chinese population (N = 511) study [13]. That study assessed the association between central obesity (defined by waist circumference) and DR. Results indicated that individuals with central obesity are 1.07X more likely to have DR (95% confidence interval, 1.03-1.10). Further, Man et al. have shown that obesity, as defined by BMI, is protective against developing DR, whereas central obesity, as defined by waist circumference, is significantly associated with DR [14]. This indicates the importance of waist circumference among diabetic patients when considering the risk of developing DR. In contrast to our study, Wat et al. have reported no significant association between obesity and DR [15]. A review article by Mbata et al. has discussed a significant association between metabolic syndrome and the development of DR; however, there are conflicting data regarding the individual factors of metabolic syndrome on the development of DR, especially in non-diabetic individuals [16]. Taken together, these data highlight that central obesity/obesity among individuals with T2DM diabetics does not have a confirmed association with the presence of DR. Our study showed a significant association between increased waist circumference and DR; however, further evaluation is required.
Moreover, we found a significant association between high FBS and the presence of DR. Similarly, a study by Yin et al. has found a significant association between FBS and the prevalence of DR among individuals with diabetes [17]. Another cross-sectional study undertaken in China by Cui et al. found a similar association among 17,985 participants [18]. Further, Kumar et al. have shown that FBS and post-prandial blood sugar (PPBS) levels along with triglyceride levels are significantly associated with the prevalence of DR [19]. An indirect association was shown by Mujeeb et al. with 150 diabetes patients; FBS is associated with the urinary protein-creatine ratio, which in turn is associated with the prevalence of DR [20]. Therefore, our data add to the strength of the association between FBS and the presence of DR.

Strengths and limitations of the study
This study follows a convenient sampling technique; however, a fair number of study participants were included in the study. All the data and measurements were collected by a single investigator, which eliminated any inter-observer bias. This study was performed in a tertiary care setting alone, which may cause Berksonian Bias. A multicentric or a community-based study would provide more reliable results when assessing the prevalence of DR.

Conclusions
Approximately two-thirds of individuals with diabetes who were ≥45 years of age had DR in our study sample. High FBS levels and increased waist circumference were significantly associated with the presence of DR. Therefore, FBS and waist circumference may be useful tools to indicate further screening for DR, especially in low-resource settings. In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.

Additional Information Disclosures
Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.