Can High HDL Cholesterol Increase the Risk of Diabetic Kidney Disease?

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:

< 36.7 mg/dL (< 0.95 mmol/L): 77% increased risk
36.7–59.6 mg/dL (0.95–1.54 mmol/L): Lowest risk
> 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?

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

HDL-C levels outside the 36.7–59.6 mg/dL range may increase diabetic kidney disease risk
Women with type 2 diabetes are particularly vulnerable to high-HDL-related kidney risk
HDL levels alone are not enough—functional quality and kidney markers must be monitored
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).

Balanced Meals for People with Diabetes

Health for All