August 3, 2016

expert reaction to genetic study looking at cholesterol levels, heart disease and type 2 diabetes

Publishing in JAMA Cardiology a group of researchers have reported an association between levels of cholesterol and triglycerides due to genetics and risk of coronary heart disease and diabetes.

Prof. Tom Sanders, Professor emeritus of Nutrition and Dietetics, King’s College London, said:

“This is an observational study which compares risk of heart disease and diabetes according to various genetic components that influence levels of blood fats; it is not a study measuring the interaction of genetics with statin use.

“This study is a Mendelian randomisation study were participants’ risk is classified according to haplotypes (a collection of genotypes associated with varying levels of lipids).  Some adjustments are made such as for age, gender etc. in the risk modelling, but the study does not measure statin exposure.

“A limitation is that lifestyle factors including diet were not properly considered – nature may well load the gun but lifestyle pulls the trigger.

“The BHF press release contains an error in suggesting that blood triglycerides are a type of dietary fat. Blood triglyceride levels generally reflect the amount of fat made in the liver, and dietary fat tends to lower the levels of fasting blood triglycerides whereas dietary carbohydrates (especially sugar) tend to increase them.

“The finding that individuals who have lower HDL levels and raised triglyceride levels are more likely to develop type 2 diabetes is already well known. This study suggests that higher LDL levels are also associated with lower risk of type 2 diabetes, which has also been suggested from previous observational studies that report a small increased incidence of type 2 diabetes in those that take statins (and whose LDL levels are therefore reduced). However, we know that many patients with type 2 diabetes also have raised LDL cholesterol and they benefit from taking statins which lower their LDL cholesterol and reduce their risk of cardiovascular disease. We also know that insulin resistance, which is the precursor to diabetes, can increase the synthesis of very low density lipoproteins (VLDL) in the liver, which in some people can raise their LDL levels, and in other people it doesn’t but instead raises blood triglycerides and lowers HDL levels.

“Drugs that have been developed to lower triglycerides and raise HDL cholesterol (e.g. fibrates, niacin and cholesteryl ester transfer protein (CETP) inhibitors) have not been shown to reduce risk of heart disease.”

Prof. Liam Smeeth, Head of the Department of Non-Communicable Disease, London School of Hygiene & Tropical Medicine, said:

“This is an interesting study that uses genetic variation in new ways to tell us about the relationship between cholesterol and diabetes.

“The study suggests that genetic factors that increase cholesterol are also associated with a lower risk of diabetes. The finding is consistent with the known small increased risk of diabetes among people taking statins. This increased risk of diabetes is greatly outweighed by the beneficial effects of statins on preventing heart attacks and strokes.

“The study does suggest that as new drugs are developed to reduce cholesterol, we will need to carefully assess them for any effect on diabetes.”

‘Association of lipid fractions with risks for coronary artery disease and diabetes’ by Jon White et al. published in JAMA Cardiology on Wednesday 3 August 2016. 

Declared interests

Prof. Tom Sanders: “Prof Tom Sanders is a Scientific Governor of the charity British Nutrition Foundation, member of the scientific advisory committee of the Natural Hydration Council (which promotes the drinking of water), and honorary Nutritional Director of the charity HEART UK. Prof. Tom Sanders is now emeritus but when he was doing research at King’s College London, the following applied: Tom does not hold any grants or have any consultancies with companies involved in the production or marketing of sugar-sweetened drinks. In reference to previous funding to Tom’s institution: £4.5 million was donated to King’s College London by Tate & Lyle in 2006; this funding finished in 2011. This money was given to the College and was in recognition of the discovery of the artificial sweetener sucralose by Prof. Hough at the Queen Elizabeth College (QEC), which merged with King’s College London. The Tate & Lyle grant paid for the Clinical Research Centre at St Thomas’ that is run by the Guy’s & St Thomas’ Trust, it was not used to fund research on sugar. Tate & Lyle sold their sugar interests to American Sugar so the brand Tate & Lyle still exists but it is no longer linked to the company Tate & Lyle PLC, which gave the money to King’s College London in 2006. Tom also used to work for Ajinomoto on aspartame about 8 years ago.  Tom was a member of the FAO/WHO Joint Expert Committee that recommended that trans fatty acids be removed from the human food chain. Tom has previously acted as a member of the Global Dairy Platform Scientific Advisory Panel and Tom is a member of the Programme Advisory Committee of the Malaysian Palm Oil Board. In the past Tom has acted as a consultant to Archer Daniel Midland Company and received honoraria for meetings sponsored by Unilever PLC. Tom’s research on fats was funded by Public Health England/Food Standards Agency.”

Prof. Liam Smeeth: “Department receives funding from GSK. Chair of a committee of a trial for a diabetes drug made by AZ. Principal investigator of an NIHR funded trial to ascertain whether statins cause muscular pain.”