- Cholesterol is vital for the functioning of human cells, but too much of one type of cholesterol — low density lipoprotein, or LDL-C — increases the risk of cardiovascular disease.
- Statins, which are prescribed to lower LDL-C, have been linked to an increased risk of type 2 diabetes.
- Now, new research suggests that people with low LDL-C, whether they are taking statins or not, are at increased risk of type 2 diabetes.
- The researchers advise that people with very low LDL-C might benefit from extra monitoring of their blood glucose levels to predict their risk of developing type 2 diabetes.
We are all encouraged to have our cholesterol levels checked as we age, to ensure that our LDL-C, or ‘bad’ cholesterol levels are not too high, as high levels are linked to cardiovascular disease, including strokes and heart attacks.
To control levels of LDL-C, people are advised to limit their intake of saturated fats, exercise regularly and maintain a healthy weight. Some may also be given statins — medications that lower cholesterol levels.
However, research has shown that use of statins is linked to an increased risk of developing type 2 diabetes. Statin use is associated with a decrease in both insulin sensitivity and insulin secretion, which may reduce a person’s ability to control their blood glucose levels.
Now, an Italian study, published in Cardiovascular Diabetology, has found that individuals with low LDL-C have an increased risk of developing type 2 diabetes whether they are taking statins or not. The researchers suggest that monitoring blood glucose levels in those with low LDL-C could help predict their risk of developing type 2 diabetes.
“Our results are important because they show that people with very low LDL-cholesterol have a higher chance of developing type 2 diabetes over time. This observation helps us better understand metabolic risk in routine clinical practice and encourages a more balanced view of cholesterol management.”
— Gaetano Santulli, senior and corresponding author of the study, Department of Medicine, Albert Einstein College of Medicine, New York City, NY.
The researchers analysed digital health records for more than 200,000 people connected via a network of primary care physicians in the Naples area in southern Italy.
After they had excluded people under the age of 18 or over 90, and those with conditions that could limit life expectancy (such as cancers, peripheral vascular disease), liver cirrhosis, cardiovascular disease, diabetes, or missing medical information, their final cohort included 13,674 people. Participants ranged in age from 19 to 90 years old, with a mean age of 62, and 58% were male.
In total, 52% of the cohort were on statin therapy to control their cholesterol levels. Participants were followed up for a median of 71.6 months, during which time 1,819 individuals (13%) developed type 2 diabetes.
Researchers stratified the cohort according to statin therapy. Statin users were, on average, older, more likely to have overweight or obesity (higher
Of those on statin therapy, 1,424 people (20%) developed type 2 diabetes, compared with 395 people who were not taking statins (6%).
Santulli cautioned that people should not give up statin therapy because of these findings:
“Statins should absolutely continue to be prescribed according to current guidelines. Preventing heart attacks and strokes provides a much greater benefit for most patients compared with the modest increase in diabetes risk that can occur in some individuals,” he told Medical News Today.
To further examine the relationship between LDL-C levels and type 2 diabetes risk, the researchers divided the cohort into 4 quartiles of LDL-C concentration:
- Low: below 84mg/dL
- Medium: 84mg/dL and above, but below 107mg/dL
- High: 107mg/dL and above, but below 131mg/dL
- Very high: 131mg/dL and above.
It should be noted that the low LDL-C group included older participants with higher BMI, a higher 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 in the low LDL-C group, 489 in the medium group, 347 in the high group and 196 in the very high group.
The incidence of type 2 diabetes was significantly lower in the very high LDL-C group than in all the others.
The researchers found that in the low LDL-C group, those at the lowest end had the highest risk of type 2 diabetes, and the risk decreased sharply as LDL-C increased. In the other groups, diabetes risk decreased gradually as LDL-C increased.
Santulli told MNT why low LDL-C might increase the risk of type 2 diabetes:
“Very low LDL-C can alter how cells handle cholesterol. Insulin-producing cells in the pancreas need cholesterol to function properly, so shifts in cholesterol balance may impair insulin secretion or increase insulin resistance. These issues create conditions that can lead to type 2 diabetes.”
He added that “when combined with other known risk factors like age, weight, and blood sugar levels” monitoring LDL-C could be a way to predict whether someone is likely to develop type 2 diabetes:
“Very low LDL-C can help identify people who may benefit from closer monitoring of their glucose over time,” he advised.
As Santulli explained, the cardiovascular benefits of statin therapy far outweigh the slightly increased risk of developing type 2 diabetes, and he emphasized that lowering LDL-C remains essential for cardiovascular protection.
“However,” he told MNT, “for people who already have a higher risk of diabetes, care should be tailored:
- Monitor glucose more closely
- Emphasize lifestyle measures
- Choose cholesterol-lowering strategies thoughtfully.”
And he added that there are now alternative medications that could be more effective:
“Importantly, we now have additional treatment options besides statins — such as ezetimibe, PCSK9-targeted therapies, and newer agents — which provide flexibility in lowering LDL-C while considering metabolic health.”