A study shows that healthy people with low concentrations of "good cholesterol" in their blood are more insulin resistant

HDL influences cholesterol synthesis and absorption

August 1, 2012

By Karina Toledo

Agência FAPESP – The acronym HDL – which stands for “high-density lipoprotein,” more popularly known as “good cholesterol” – has become familiar to even those outside health care, now that several studies have demonstrated the importance that this lipoprotein has in the prevention of atherosclerosis and cardiovascular disease.

Researchers previously believed that the protective effects of HDL were due primarily to its capacity to take the cholesterol found in the walls of arteries and carry the cholesterol molecules back to the liver to be reutilized or excreted.

However, a study recently concluded at the Universidade de São Paulo Medical School (FMUSP) revealed that concentrations of this lipoprotein in the blood also influence cholesterol synthesis and absorption, in addition to being associated with the effect of insulin on glucose metabolism. The data were published in the journal Clinica Chimica Acta.

“A better understanding of the role of HDL in the metabolism of cholesterol is necessary because the benefit caused by increasing this lipoprotein in blood surpasses the harm caused by higher LDL (the bad cholesterol),” affirms Eder C. R. Quintão, coordinator of the study financed by FAPESP.

According to Quintão, the existing medications used to combat cholesterol reduce the concentrations of LDL (low-density lipoprotein) and VLDL (very-low-density lipoprotein), which are involved in increasing the cholesterol concentrations in tissues and forming atherosclerotic plaques if these lipoproteins get stuck while crossing the walls of arteries.

“The ideal would be to develop drugs capable of increasing HDL in the blood. Diet and exercise have little impact on this process. The habitual ingestion of alcoholic beverages results in an increase in mortality due to non-cardiovascular causes,” explains the researcher.

To better understand how HDL acts in the body, the team coordinated by Quintão selected a group of 66 people from among more than 800 healthy volunteers recruited in Campinas, Brazil. Half of the volunteers had plasma concentrations of this lipoprotein below 40 milligrams per deciliter (mg/dl), which is considered a high concentration.

The researchers were careful to have a balanced number of men and women in the two groups. They also selected volunteers with the same age and a body mass index (BMI) within the desired range. Diabetics, smokers and individuals with other diseases were excluded along with those who consume alcohol or take medications that influence lipoprotein metabolism, such as birth control pills.

“We created a protocol that differs from those used in all existing scientific literature. Other studies had undesirable interference factors, which included volunteers with comorbidities such as obesity or diabetes,” explains Quintão.

The researchers also conducted a detailed analysis of the eating habits of the participants. “The more vegetables the individuals ingested, the higher the blood levels of phytosterols – the equivalent of cholesterol found in vegetables. As this was one of the markers analyzed in the study, the participants had to have similar diets to avoid a bias in the results,” he said.

The FMUSP researchers collected and analyzed blood samples from volunteers, looking for steroids that serve as markers of cholesterol synthesis and intestinal absorption.

Surprises

Analysis of the results showed that the volunteers in the group with low HDL levels synthesize more cholesterol but absorb less of this substance through the intestines. In contrast, the participants with high HDL levels synthesize more cholesterol but absorb more through the intestines.

“This finding surprised us and seemed incongruent,” affirmed Quintão. This result was surprising because epidemiological studies have shown that people who absorb more cholesterol through the intestines have a higher risk of stroke.

“It is strange that these people who absorb more cholesterol are precisely those with higher HDL,” he said. To solve the new mystery, Quintão’s group intends to follow this line of investigation and are beginning a new research project.

The researchers were also surprised to find that volunteers with low HDL levels had greater resistence  to insulin than did volunteers with high HDL levels. Insulin sensitivity was evaluated based on the ratio of the insulin and glucose concentrations in the blood of fasting individuals.

“We identified this process of insulin resistance at a very early stage. These are healthy people without symptoms and normal BMI. We do not know if 10 years from now, there will be higher diabetes rates in this group. That is a possible long-term study,” says Quintão.

Data from the scientific literature reinforce the hypothesis that the higher the HDL concentration in the blood, the better the glucose metabolism in peripheral tissues in response to insulin produced in the pancreas.

The article HDL-C concentration is related to markers of absorption and of cholesterol synthesis: Study in subjects with low vs. high HDL-C can be read at: www.sciencedirect.com/science/article/pii/S0009898110006261

The article Oxidized low-density lipoproteins and their antibodies: Relationships with the reverse cholesterol transport and carotid atherosclerosis in adults without cardiovascular diseases can be read at: www.sciencedirect.com/science/article/pii/S0009898112002975.