Big Data ‘Clinches’ Link Between High Glycemic Index Diets and CVD

People who mostly ate foods with a low glycemic index had a lower likelihood of premature death and major cardiovascular disease (CVD) events compared with those whose diet included more “poor quality” food with a high glycemic index.

The results from the global PURE study, of nearly 120,000 people, provide evidence that helps cement glycemic index as a key measure of dietary health.

This new analysis from PURE — a massive prospective epidemiological study — shows people with a diet in the highest quintile of glycemic index had a significant 25% higher rate of combined total deaths and major CVD events during a median follow-up of nearly 10 years, compared with those with a diet in the lowest glycemic index quintile, in the report published online on February 24 in the New England Journal of Medicine.

The link between lower glycemic load and fewer CVD events was even stronger among people with an established history of CVD at study entry. In this subset, which included 9% of the total cohort, people in the highest quintile for glycemic index consumption had a 51% higher rate of the composite primary endpoint compared with those in the lowest quintile, in an analysis that adjusted for several potential confounders.

David J.A. Jenkins, MD, PhD, DSc, lead author, said people do not necessarily need to closely track the glycemic index of what they eat to follow the guidance that lower is better.

A simple but accurate and effective public health message is to follow existing dietary recommendations to eat better quality food — more unprocessed fruits, vegetables, legumes, and whole grains — Jenkins advised. Those who prefer a more detailed approach could use the comprehensive glycemic index tables compiled by researchers at the University of Sydney, Australia, he noted.

All Carbohydrates Are Not the Same

“What we’re saying is that all carbohydrates are not the same. Some seem to increase the risk for CVD, and others seem protective. This is not new, but worth restating in an era of low-carb and no-carb diets,” said Jenkins.

Low glycemic index foods are generally unprocessed foods in their native state, including fruits, vegetables, legumes, and unrefined whole grains. High glycemic index foods contain processed and refined carbohydrates that deliver jolts of glucose soon after eating, as the sugar in these carbs quickly moves from the gut to the bloodstream.

An association between a diet with a lower glycemic index and better outcomes had appeared in prior reports from other studies, but not as unambiguously as in the new data from PURE, likely because of fewer study participants in previous studies.

Another feature of PURE that adds to the generalizability of the findings is the diversity of adults included in the study, from 20 countries on five continents.

“This clinches it,” Jenkins declared in an interview.

New PURE Data Tip the Evidence Balance

The NEJM article includes a new meta-analysis that adds the PURE findings to data from two large prior reports that were each less conclusive. The new calculation with the PURE numbers helps establish a clearer association between a diet with a higher glycemic index and the endpoint of CVD death, showing an overall 26% increase in the outcome.

The PURE data are especially informative because the investigators collected additional information on a range of potential confounders they incorporated into their analyses.

“We were able to include a lot of documentation on many potential confounders. That’s a strength of our data,” noted Jenkins, a professor of nutritional science and medicine at the University of Toronto, Ontario, Canada.

“The present data, along with prior publications from PURE and several other studies, emphasize that consumption of poor quality carbohydrates is likely to be more adverse than the consumption of most fats in the diet,” said senior author Salim Yusuf, MD, DPhil, professor of medicine and executive director of the Population Health Research Institute at McMaster University in Hamilton, Ontario, Canada.

“This calls for a fundamental shift in our thinking of what types of diet are likely to be harmful and what types neutral or beneficial,” Yusuf said in a statement from his institution.

Higher BMI Associated With Greater Glycemic Index Effect

Another important analysis in the new report calculated the impact of a higher glycemic index diet among people with a body mass index (BMI) of less than 25 kg/m2 as well as higher BMIs.

Among people in the lower BMI subgroup, greater intake of high glycemic index foods showed slightly more incident primary outcome events. In contrast, people with a BMI of 25 kg/m2 or greater showed a steady increment in primary outcome events as the glycemic index of their diet increased.

People with higher BMIs in the quartile that ate the greatest amount of high glycemic index foods had a significant 38% higher rate of primary outcome events compared with people with similar BMIs in the lowest quartile for high glycemic index intake.

However, the study showed no impact on the primary association of high glycemic index and increased adverse outcomes by exercise habits, smoking, use of blood pressure medications, or use of statins. 

The new report complements a separate analysis from PURE published just a few weeks earlier in BMJ that established a significant association between increased consumption of whole grains and fewer CVD events compared with people who had more refined grains in their diet, as reported by Medscape Medical News.

This prior report on whole versus refined grains, which Jenkins coauthored, looked at carbohydrate quality using a two-pronged approach, while glycemic index is a continuous variable that provides more nuance and takes into account carbohydrates from sources other than grains, Jenkins says.

PURE (Prospective Urban and Rural Epidemiological Study) enrolled roughly 225,000 people aged 35-70 years at entry. The glycemic index analysis focused on 119,575 people who had data available for the primary outcome. During a median follow-up of 9.5 years, these people had 14,075 primary outcome events, including 8780 deaths.

Analyses that looked at the individual outcomes that comprised the composite endpoint showed significant associations between a high glycemic index diet and total mortality, CVD death, non-CVD death, and stroke, but showed no significant link with myocardial infarction or heart failure. These findings are consistent with prior results of other studies that showed a stronger link between stroke and a high glycemic index diet compared with other non-fatal CVD events.

Jenkins suggested that the significant excess of non-CVD deaths linked with a high glycemic index diet may stem from the impact of this type of diet on cancer-associated mortality.

PURE received partial funding through unrestricted grants from several drug companies. Jenkins has reported receiving gifts from several food-related trade associations and food companies, as well as research grants from two legume-oriented trade associations.

N Engl J Med. Published online February 24, 2020. Abstract

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