From the Guidelines
High levels of High-Density Lipoprotein (HDL) cholesterol do not necessarily protect against the negative effects of insulin resistance, and lifestyle modifications should be the primary focus to improve insulin sensitivity. The relationship between HDL cholesterol and insulin resistance is complex, and recent studies suggest that the benefits of high HDL cholesterol may be diminished in the presence of insulin resistance 1.
Key Considerations
- Insulin-resistant states, such as metabolic syndrome, pre-diabetes, and type 2 diabetes, affect over 100 million people in the United States, and are characterized by impaired skeletal muscle glucose oxidation, increased hepatic de novo lipogenesis, and atherogenic dyslipidemia after a high-carbohydrate meal 1.
- The amount of circulating saturated fatty acids (SFAs) in blood is not related to saturated fat intake from the diet, but instead tends to track more closely with dietary carbohydrate intake 1.
- Decreased accumulation of circulating SFAs in response to diets lower in carbohydrate and higher in saturated fat is partially mediated by lower production (through de novo lipogenesis), but also increased clearance 1.
Recommendations
- Focus on reducing insulin resistance through regular physical activity, adopting a Mediterranean or low-carbohydrate diet rich in vegetables, lean proteins, and healthy fats, and maintaining a consistent sleep schedule of 7-8 hours nightly.
- Weight loss of even 5-10% of body weight can significantly improve insulin sensitivity.
- Consider intermittent fasting approaches like 16:8 (16 hours fasting, 8 hours eating) to help regulate insulin levels.
- If lifestyle changes don't improve insulin sensitivity after 3-6 months, consult with your healthcare provider about medications like metformin, which can help improve insulin sensitivity without negatively impacting HDL levels.
Important Notes
- High HDL cholesterol is typically considered protective against cardiovascular disease, but its benefit may be diminished in the presence of insulin resistance, as insulin resistance can alter HDL functionality, reducing its anti-inflammatory and cholesterol efflux capabilities despite high particle numbers 1.
- The impact of dietary SFAs on health must consider the important role of carbohydrate intake and the underlying degree of insulin resistance, both of which significantly affect how the body processes saturated fat 1.
From the Research
Relationship between HDL Cholesterol and Insulin Resistance
- High levels of High-Density Lipoprotein (HDL) cholesterol have been found to have a strong negative association with insulin resistance in chronic kidney disease (CKD) patients 2.
- Insulin resistance is linked to cardiovascular disease (CVD), and CKD greatly affects the enzyme activities responsible for the metabolism of HDL, causing an abnormal composition and function of HDL 2.
- The characteristic dyslipidemia of insulin resistance consists of elevated triglyceride and triglyceride-rich lipoprotein levels, low levels of HDL cholesterol, and increased concentrations of small, dense low-density lipoprotein cholesterol 3, 4.
- Hyperinsulinemia and central obesity that typically accompany insulin resistance are thought to lead to overproduction of very low-density lipoprotein (VLDL) cholesterol, resulting in more triglyceride-rich particles, fewer HDL particles, and more small, dense LDL 4.
- Lifestyle modifications and dyslipidemia treatment in CKD might help to prevent cardiovascular events even in non-diabetic non-obese CKD patients 2.
- Interventions that improve insulin resistance, such as weight loss and exercise, can also improve the lipid profile by increasing HDL cholesterol and decreasing triglyceride levels 4, 5.
- Certain antidiabetic therapies can also improve the lipid profile by improving insulin resistance, and metformin has been shown to modestly reduce small and dense LDL and raise small and large HDL 6, 5.