A recent study published in the Journal of Diabetes and Metabolic Disorders evaluated the association between high-density lipoprotein cholesterol (HDL-C) levels and diabetic retinopathy (DR) prevalence in patients with type 2 diabetes mellitus (T2DM).
Give me some background.
HDL-C has traditionally been recognized for its protective role in cardiovascular health; however, its association with DR remains complex and controversial:
- Recent studies have shown that dyslipidemia, particularly low levels of HDL-C, correlated with the severity of DR among T2DM patients, suggesting that HDL-C may play a critical role in the pathophysiology of DR.
- Other research indicates that elevated levels of HDL-C may not confer the expected protective benefits against DR, highlighting the need for further investigation into the functional properties of HDL-C, rather than just its serum concentration.
The study authors explained that elucidating this relationship not only enhances the comprehension of DR’s pathophysiology but also paves the way for innovative therapeutic approaches that target lipid metabolism as a means to combat this debilitating complication of diabetes.
Now talk about the study.
This study is the second analysis based on a cross-sectional study and included T2DM patients who visited the diabetic clinic in the internal medicine out-patient departments of two hospitals in southern Taiwan between April 2002 and November 2004.
Demographic and clinical data were collected, serum HDL-C levels were measured, and optical coherence tomography (OCT) and fundus photos of each patient were analyzed by ophthalmologists to grade DR severity.
The data was organized into three models to aid in analyses:
- Model 1: No covariates were adjusted
- Model 2: Sex and age were adjusted
- Model 3: Sex, age, body mass index (BMI), LDL-C, triglycerides, diastolic blood pressure (DBP), ischemic heart disease, HbA1c, creatine, angiotensin-converting enzyme inhibitor (ACEI) and or angiotensin receptor blocker (ARB) use, beta-blocker use, estimated glomerular filtration rate (eGFR), calcium channel blocker use, and Ankle-Brachial Index (ABI) were adjusted
Moreover: HDL-C levels were separated into tertiles with the following values:
- Low: 15.0-42.0 mg/dL
- Middle: 43.0-52.0 mg/dL
- High: 53.0-99.0 mg/dL
Findings?
In total: 2,001 diabetic patients (858 men and 1,143 women) were included in the analysis—and of that cohort, 701 (35.0%) were diagnosed with DR.
Additionally:
- There was a significant inverse linear relationship between HDL-C levels and the presence of DR, wherein higher HDL-C was inversely associated with DR.
- Each 10 mg/dL increase in HDL-C corresponded to lower odds of DR across models, including Model 3 (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.84-0.99, P=0.027).
Anything else?
Plus: Analysis of HDL-C levels by tertiles revealed that participants in the highest tertile (53.0-99.0 mg/dL) had a lower prevalence of DR (OR: 0.78, 95% CI: 0.62-0.97) in Model 1.
This association was borderline in Model 2 (OR: 0.80, 95% CI: 0.63-1.01, P=0.055) and nonsignificant in Model 3 (OR: 0.86, 95% CI: 0.66-1.09, P=0.209).
Expert opinion?
“HDL-C has anti-inflammatory and antioxidant properties, which may protect the retina by reducing inflammation and oxidative stress in retinal vessels,” the study authors noted.
Further: “HDL-C may reduce retinal vascular damage by improving endothelial function and promoting reverse cholesterol transport,” they added.
Finally: Based on these findings, it may be advisable for physicians to enhance the monitoring of HDL-C levels and implement interventions when necessary to reduce the risk of DR.
Any limitations to note?
A few, including:
- The data analyzed was collected more than two decades ago; since then, several changes have occurred to diagnostic criteria, treatment approaches, and population characteristics for both diabetes and DR
- Meaning: Research using data from modern-day patients may be necessary to validate these findings
- The single-center design and having the primary study population comprise Chinese individuals may have reduced the generalizability of the results
- Certain confounding factors, such as genetic background and lifestyle habits, could not be controlled for and may have had an impact on the findings
- The research team conducted a sensitivity analysis by treating HDL-C as a three-level categorial variable (low, middle, and high tertiles), which decreased the per-group sample sizes (658, 635, and 699, respectively)
- This reduced the statistical power such that the p-values did not reach significance after grouping
Take home.
These findings demonstrate evidence of a linear association that higher HDL-C levels were associated with decreased odds of DR in diabetic patients.
Moving forward: Future research should further focus on elucidating the mechanistic role of HDL-C, particularly its effect across different populations, and how optimizing lipid profiles may improve ocular health in diabetic patients.