LDL Cholesterol Lowering Genetic Variants May Increase the Risk of Diabetes

Highlights:

Cholesterol is a wax or fat like substance deposited in the cells of the body.
High levels of low density lipoprotein (LDL) or bad cholesterol may double the risk of heart disease.
A research team from University of Cambridge, UK studied the association of low density lipoprotein cholesterol lowering genetic variants with diabetes risk. The study was published in the journal JAMA.
Reducing the abnormal LDL cholesterol levels and maintaining a proper lifestyle may help manage the risk of diabetes.

Low Density Lipoprotein Cholesterol (LDL - C) lowering genetic variants were associated with an increased risk of type 2 diabetes.

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Excess LDL cholesterol causes atherosclerotic cardiovascular disease but reducing its levels prove to benefit people with this disease.

‘Exposure to LDL cholesterol lowering genetic variants near NPC1L1 gene may increase the risk of type 2 diabetes.’

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A research team from University of Cambridge, United Kingdom have examined the link between coronary artery disease of LDL-C genetic variants along with type 2 diabetes.

Statin drugs used in the treatment of lowering LDL cholesterol levels were also found to be associated with weight gain and increased onset of type 2 diabetes.

Research Study on LDL-C Lowering Genetic Variants with Type 2 Diabetes:

Genes That Increase the Risk for Cardiometabolic Disease Identified
Scientists have identified genes that are associated with cardiometabolic disease (CMD) and which could be effective as drug targets.

Research study was conducted by collecting data from Europe and United States between 1991 and 2016. Around 50,775 people with diabetes and 60,801 people with coronary artery disease were included in the meta analyses of genetic association studies with 270,269 and 123,504 individuals as controls respectively.

Luca A. Lotta, M.D., Ph.D., author of the study found that the NPC1L1 gene to be inversely associated with coronary artery disease and directly associated with type 2 diabetes.

Cholesterol - Lipoproteins - Functions - Normal Blood Cholesterol Levels - Causes - Treatment - FAQs
Cholesterol is produced by the body (liver) and is essential for normal body functioning.

Niemann Pick C1 Like 1 (NPC1L1) gene plays a major role in intestinal cholesterol absorption and is located in the brush border of the small intestines.

With a reduction in LDL-C, genetic variants were found to be linked with lower risk of coronary heart disease while there was a dissimilarity in association with type 2 diabetes which clearly stipulates the gene-specific associations with risk of LDL- C lowering genetic variants.

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The authors also wrote that “In this meta-analysis, exposure to LDL-C-lowering genetic variants in or near the NPC1L1 gene was associated with a higher risk of type 2 diabetes,”

“The results of this study show that multiple LDL-C lowering mechanisms, including those mediated by the molecular targets of available LDL-C-lowering drugs (i.e., statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors), are associated with adverse metabolic consequences and increased type 2 diabetes risk.”

In general, association of LDL - C alleles (genetic variants) with metabolic risk appears to be gene specific and also suggests that adverse effects of diabetes due to lipid lowering agents may be specific for a particular drug target. The authors also found that the drug safety might be associated with choice of the drug for a specific population.

Low Density Lipoprotein Cholesterol:

Cholesterol is a waxy, fat like substance deposited in the body. Low density lipoprotein cholesterol also known as the bad cholesterol is one of the main factors for developing coronary heart disease as it may accumulate plaque resulting in the narrowing or hardening of the arteries.

High cholesterol levels may double the risk of heart diseases. According to Centers for Disease Control and Prevention, around 73.5 million people in America were found to have high LDL Cholesterol levels in 2011.

High cholesterol levels may be due to factors like:

Age (45 - 55 years of age)
Gender
Inherited genes
Over weight
Diet and lifestyle (saturated fat, smoking habits)
Ethnicity (Non Hispanic Blacks and Mexican Americans )
Disease conditions (heart diseases, high blood pressure)

Managing Diabetes Risk in LDL Cholesterol Patients:

Diabetes is a metabolic disorder characterized by increased blood glucose levels. Patients with lower LDL cholesterol genetic variants were found to have an increased risk of diabetes.

Some of the following measures may help in managing diabetes:

Reducing the abnormal LDL cholesterol levels which are above 100mg/dL might help to lower the risk of type 2 diabetes.
Proper exercise or physical activity to control overweight or obesity can manage diabetes.

References:

What is Cholesterol? - (https://heartuk.org.uk/health-and-high-cholesterol)
Cholesterol Fact Sheet - (http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_cholesterol.htm)
Niemann Pick C1 Like 1 Protein is Critical for Intestinal Cholesterol Absorption - (https://www.ncbi.nlm.nih.gov/pubmed/14976318)

Source-Medindia