Is HDL Cholesterol Always Beneficial?
High-density lipoprotein cholesterol (HDL-C) is generally known as “good cholesterol” due to its role in reverse cholesterol transport and cardiovascular protection. However, a 2024 study published in Scientific Reports by researchers at Jinhua Hospital, Zhejiang University, challenges this traditional view. The study analyzed 936 patients with type 2 diabetes and found that both very low and very high HDL-C levels were associated with an increased risk of diabetic kidney disease (DKD)
A U-Shaped Relationship Between HDL and Kidney Risk
Researchers classified HDL-C levels into three groups and found a U-shaped association with the risk of diabetic kidney disease:
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< 36.7 mg/dL (< 0.95 mmol/L): 77% increased risk
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36.7–59.6 mg/dL (0.95–1.54 mmol/L): Lowest risk
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> 59.6 mg/dL (> 1.54 mmol/L): 128% increased risk
This means that HDL levels that are too low or too high may increase the risk of diabetic kidney disease, rather than offering protection
Why Is the Risk Greater in Women?
Interestingly, this U-shaped relationship was statistically significant only in female patients. While a similar trend was seen in men, the association was not significant. The authors suggest that hormonal, metabolic, and physiological differences in women—especially postmenopausal changes in estrogen—may influence HDL metabolism and function.
Clinical Case Example
Case: Ms. C, a 55-year-old woman with type 2 diabetes, maintained good glycemic and blood pressure control. She proudly noted that her HDL-C level was over 65 mg/dL. However, a routine kidney evaluation revealed her UACR was 80 mg/g, and her eGFR was 58 mL/min/1.73㎡, indicating stage 2 diabetic kidney disease. She was surprised, having believed that a high HDL level meant excellent health. This case emphasizes that HDL-C levels alone do not guarantee protection.
Why Might High HDL Be Harmful?
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Dysfunctional HDL Particles
In chronic inflammation or diabetes, HDL may become oxidized and lose its anti-inflammatory properties. -
Drug- or gene-induced abnormal HDL increase
Agents like niacin and fenofibrate can raise HDL, but this does not always translate to better clinical outcomes. -
Overly high HDL linked to cardiovascular risk
Several studies have now shown that extremely high HDL levels may correlate with increased cardiovascular and kidney risk.
What Should Clinicians and Patients Do?
| Recommendation | Details |
|---|---|
| Target HDL range | 36.7–59.6 mg/dL (0.95–1.54 mmol/L) appears safest |
| Monitor kidney function | Regular eGFR and UACR tests are essential |
| Reassess medications | Be cautious with HDL-raising agents, particularly in women |
| Focus on function, not just levels | Lifestyle interventions can improve HDL function |
Common Drugs That Influence HDL Levels
| Drug | Effect | Caution |
|---|---|---|
| Fenofibrate | ↑ HDL, ↓ triglycerides | May reduce kidney function |
| Niacin | ↑ HDL | May impair liver and glucose metabolism |
| Statins (e.g., atorvastatin) | ↓ LDL, slight ↑ HDL | Kidney-protective effects |
| Pioglitazone (Actos) | ↑ HDL, ↑ insulin sensitivity | May cause fluid retention and weight gain |
Key Takeaways
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HDL-C levels outside the 36.7–59.6 mg/dL range may increase diabetic kidney disease risk
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Women with type 2 diabetes are particularly vulnerable to high-HDL-related kidney risk
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HDL levels alone are not enough—functional quality and kidney markers must be monitored
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Regular eGFR and UACR assessments are vital for early detection and prevention
Reference
Wang H, Wu J, Lin M, Hu Y, Ma Y. High levels of high-density lipoprotein cholesterol may increase the risk of diabetic kidney disease in patients with type 2 diabetes. Scientific Reports. 2024;14(15362).