Relationship Between LDL-C and Diabetes Risk, Independent of Statins

Cholesterol is vital for human cells and overall bodily function. Among the different types of cholesterol, LDL-C is a significant factor in evaluating the risk of cardiovascular disease. Statins have been prescribed by healthcare professionals for years to prevent and control lipid levels. However, recent research has suggested that individuals with low LDL-C levels, whether or not they are using statins, face a higher risk of developing type 2 diabetes. Therefore, those with low LDL-C are advised to strictly monitor their blood glucose levels to better predict their risk of onset.

As we age, it is important to have our cholesterol levels checked to ensure that our LDL-C, often referred to as ‘bad’ cholesterol, is not too high, as elevated levels are linked to cardiovascular diseases such as strokes and heart attacks. To manage LDL-C levels effectively, individuals are encouraged to limit their intake of saturated fats, engage in regular exercise, and maintain a healthy weight. In some cases, statins—medications designed to lower cholesterol levels—may also be prescribed. However, research has indicated that statin use is associated with an increased risk of developing type 2 diabetes. Specifically, statins are linked to reduced insulin sensitivity and insulin secretion, which can hinder an individual's ability to manage blood glucose levels.

A recent Italian study published in Cardiovascular Diabetology found that individuals with low LDL-C levels are at greater risk of developing type 2 diabetes, regardless of whether they take statins. The researchers propose that monitoring blood glucose levels in those with low LDL-C may help predict their risk of developing type 2 diabetes. “Our results are important because they show that individuals with very low LDL-cholesterol have a higher chance of developing type 2 diabetes over time. This observation aids our understanding of metabolic risk in clinical practice and encourages a more balanced approach to cholesterol management,” noted the researchers.

Increased Diabetes Risk Among Statin Users

The researchers analyzed digital health records of over 200,000 individuals connected through a network of primary care physicians in the Naples area of southern Italy.

After excluding individuals under 18 or over 90 years old, and those with conditions that could affect life expectancy (such as cancers, peripheral vascular disease, liver cirrhosis, cardiovascular disease, diabetes, or missing medical information), the final cohort included 13,674 participants. Their ages ranged from 19 to 90, with an average age of 62, and 58% of the participants were male.

Of the cohort, 52% were on statin therapy to manage their cholesterol levels. Participants were monitored for a median of 71.6 months, during which 1,819 individuals (13%) developed type 2 diabetes.

The researchers categorized the cohort based on statin therapy. Statin users tended to be older, more likely to be overweight or obese, had higher fasting plasma glucose and serum creatinine levels, and exhibited a higher prevalence of hypertension, along with lower LDL-C levels. Among those on statin therapy, 1,424 (20%) developed type 2 diabetes, compared to 395 (6%) who were not taking statins.

Santulli cautioned against discontinuing statin therapy based on these findings, stating, “Statins should absolutely continue to be prescribed according to current guidelines. Preventing heart attacks and strokes offers a much greater benefit for most patients compared to the modest increase in diabetes risk that can occur in some individuals.”

Understanding the Link Between LDL-C Levels and Type 2 Diabetes Risk

According to the American Heart Association (AHA), the optimal LDL-C level for heart health is 100 mg/dL or lower. To further explore the relationship between LDL-C levels and the risk of type 2 diabetes, the researchers divided the cohort into four groups based on LDL-C concentrations: 

• Low: below 84 mg/dL
• Medium: between 84 mg/dL and 107 mg/dL
• High: between 107 mg/dL and 131 mg/dL
• Very High: 131 mg/dL and above 

It’s important to note that the low LDL-C group included older participants with a higher body mass index (BMI), a greater prevalence of hypertension and statin use, and a lower percentage of men.

Of the 1,819 cases of type 2 diabetes recorded during follow-up, 787 were from the low LDL-C group, 489 from the medium group, 347 from the high group, and 196 from the very high group. The incidence of type 2 diabetes was significantly lower in the very high LDL-C group compared to all others.

The researchers found that in the low LDL-C group, those with the lowest levels faced the highest risk of type 2 diabetes, and the risk decreased sharply as LDL-C levels increased. In the other groups, diabetes risk declined gradually with increasing LDL-C levels.

Could Low LDL-C Help Predict Diabetes Risk?

The researchers emphasized that very low levels of LDL-C may heighten the risk of developing type 2 diabetes. He explained that "very low LDL-C can disrupt how cells manage cholesterol, which is essential for the function of insulin-producing cells in the pancreas. This disruption can impair insulin secretion and increase insulin resistance, paving the way for type 2 diabetes."

Furthermore,  monitoring LDL-C alongside other risk factors like age, weight, and blood sugar levels can be a valuable strategy. “Very low LDL-C can help identify individuals who would benefit from intensified glucose monitoring,” he said. Although low LDL-C offers numerous benefits, Santulli stressed that the cardiovascular advantages of statin therapy outweigh the slight risk of diabetes. He asserted that lowering LDL-C is crucial for cardiovascular health.

For those already at higher diabetes risk, he recommended:

• Enhanced glucose monitoring

• Emphasis on lifestyle changes

• Careful selection of cholesterol-lowering treatments 

In conclusion, the researchers highlighted the availability of alternative medications beyond statins, such as ezetimibe and PCSK9-targeted therapies, which can effectively lower LDL-C while considering metabolic health. This flexibility can significantly improve outcomes for patients.

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MedicalNewsToday