Cholesterol-lowering gene variants linked to type 2 risk
Certain genetic variants related to reduced low-density lipoprotein cholesterol may raise the risk of type 2 diabetes, according to a new study.
More than half a million people were meta-analysed and researchers found that variants near NPC1L1 and other genes associated with the reduction of low-density lipoprotein cholesterol (LDL-C) were linked to a greater type 2 diabetes risk.
However, they also discovered there was a lower risk of coronary heart disease.
Genetic pathways
LDL-C is often referred to as “bad” cholesterol; too much LDL-C can lead to a buildup of plaque in the arteries, increasing the risk of stroke, heart attack, and heart disease.
While lifestyle changes – such as adopting a healthy diet and increasing physical activity – are the first port of call when it comes to lowering LDL-C, some people may also require treatment with cholesterol-lowering drugs, such as statins or bile acid sequestrants.
A wealth of research has demonstrated the benefits of cholesterol-lowering medications for heart health, but some studies have suggested the drugs may lead to weight gain and greater risk of type 2 diabetes.
The study was conducted by senior author Dr Luca Lotta from the University of Cambridge.
Their findings show further evidence of this association, after identifying a number of genetic pathways mediated by cholesterol-lowering drugs that may increase type 2 diabetes risk.
From a meta-analysis of genetic association studies conducted in Europe and the United States between 1991-2016, Dr Lotta identified 50,775 individuals with type 2 diabetes and 270,269 controls, alongside 60,801 people with coronary heart disease and 123,504 controls.
Adverse metabolic consequences
The analysis revealed that individuals who possessed certain LDL-C-lowering genetic variants near the genes NPC1L1, HMGCR, and PCSK9 – which encode the targets of cholesterol-lowering drugs – were at greater risk of type 2 diabetes.
The authors wrote: “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 PCSK9-inhibitors), are associated with adverse metabolic consequences and increased type 2 diabetes risk.”
Interestingly, these LDL-C-lowering genetic variants were also linked to a reduced risk of coronary artery disease.
Speaking to Medical News Today, Dr Lotta said: “On one hand, the results can be considered surprising, given that diabetes and heart disease share several risk factors that tend to affect the risk of these two diseases in a consistent direction (e.g. smoking, higher body mass index [BMI], physical inactivity).
“On the other, previous research has shown a modest increase in type 2 diabetes risk associated with statin treatment. Also, individuals with familial hypercholesterolemia, who are at high risk of heart disease, appear to have a lower prevalence of type 2 diabetes.
“Our research adds to these studies and furthers our understanding of associations between cholesterol-lowering pathways and a higher risk of diabetes.”
Dr Lotta does not think their results will have immediate clinical implications for patients taking cholesterol-lowering drugs.
He said: “The therapeutic recommendations to take statins or other drugs should not change. Our study means that we should keep monitoring the metabolic consequences of taking these drugs.”