Personalized dietary recommendations needed by diabetics

By JUDY SIEGEL-ITZKOVICH
Doctor with sample (photo credit: INGIMAGE)
Doctor with sample
(photo credit: INGIMAGE)
Which is more likely to raise blood sugar levels – sushi or ice cream? The answer is not obvious.
According to a Weizmann Institute of Science study just published in the journal Cell, the answer varies from one person to another. The study, which continuously monitored blood sugar levels in 800 people for a week, revealed that the bodily response to all foods was highly individual.
Called the Personalized Nutrition Project, the study was conducted by the groups of Prof. Eran Segal of the Rehovot institute’s computer science and applied mathematics department, and Dr. Eran Elinav of the immunology department.
“We chose to focus on blood sugar because elevated levels are a major risk factor for diabetes, obesity and metabolic syndrome,” Segal said. “The huge differences that we found in the rise of blood sugar levels among different people who consumed identical meals highlights why personalized eating choices are more likely to help people stay healthy than universal dietary advice.”
Indeed, the scientists found that different people responded very differently to both simple and to complex meals. For example, a large number of the participants’ blood sugar levels rose sharply after they consumed a standardized glucose meal; in many others, blood glucose levels rose sharply after they ate white bread, but not after glucose. Elinav explained: “Our aim in this study was to find factors that underlie personalized blood glucose responses to food. We used that information to develop personal dietary recommendations that can help prevent and treat obesity and diabetes, which are among the most severe epidemics in human history.”
Doctoral students David Zeevi and Tal Korem led the study, collaborating with three others. Their work was unique in its scale and in the inclusion of the analysis of gut microbes, collectively known as the microbiome, which had recently been shown to play an important role in human health and disease. Study participants, outfitted with small monitors that continuously measured their blood sugar levels, were asked to record everything they ate, as well as such lifestyle factors as sleep and physical activity. Overall, the researchers assessed the response of different people to more than 46,000 meals.
Taking these multiple factors into account, the scientists generated an algorithm for predicting individualized response to food based on the person’s lifestyle, medical background, and the composition and function of his or her microbiome. In a follow-up study of another 100 volunteers, the algorithm successfully predicted the rise in blood sugar in response to different foods, demonstrating that it could be applied to new participants.
The scientists were able to show that lifestyle also mattered. The same food affected blood sugar levels differently in the same person, depending, for example, on whether its consumption had been preceded by exercise or sleep.
They then designed a dietary intervention based on their algorithm, testing their ability to prescribe personal dietary recommendations for lowering blood glucose level responses to food. Volunteers were assigned a personalized “good” diet for one week, and a “bad” diet – also personalized – for another week. Both good and bad diets were designed to have the same number of calories, but they differed between participants. Thus, certain foods in one person’s “good” diet were part of another’s “bad” diet. The “good” diets indeed helped to keep blood sugar at steadily healthy levels, whereas the “bad” diets often induced spikes in glucose levels – all within just one week of intervention. Moreover, as a result of the “good” diets, the volunteers experienced consistent changes in the composition of their gut microbes, suggesting that the microbiome may be influenced by the personalized diets while also playing a role in participants’ blood sugar responses.
The scientists are currently enrolling Israeli volunteers for a longer-term follow-up dietary intervention study that will focus on people with consistently high blood sugar levels, who are at risk of developing diabetes, with the aim of preventing or delaying this disease.
RARE DISEASE IS A LENS ON CANCER
What can a rare genetic childhood disease teach us about cancer? Dr. Ayelet Erez of the Weizmann Institute’s biological regulation department explains that “a single-mutation disease can act as a ‘lens.’ If we find exactly what malfunctions in the sick child, we can zoom in and understand the role of the same gene among the many genetic changes that accompany cancer.”
In findings that recently appeared in the journal Nature, Erez and colleagues use this approach to reveal how a metabolic cycle that is “broken” in two childhood diseases gets hijacked to benefit cancer cells.
Erez has treated children with a disease called citrullinemia, which causes them to lack the activity of a protein named ASS1. Its absence leads to the toxic and, if untreated, fatal, buildup of ammonia in the body.
Many kinds of cancer prevent the expression of the ASS1 gene; silencing indicates a more aggressive cancer and a worse outcome, yet efforts to develop treatments based on depleting the amino acid that this gene produces have only had limited success.
Erez and her research group, led by graduate student Shiran Rabinovich, asked: What if the cancer cell, rather than silencing ASS1 because of what it makes, does so because of what it [ASSI] takes? Knowing that cancer cells often reroute the body’s normal metabolic pathways, they looked “upstream” – at the earlier connections of this protein in its metabolic cycle. The team located an amino acid called aspartate that is also required for the production of DNA and RNA. Now the connection was beginning to make sense: Cancer cells need to produce large amounts of DNA and RNA to keep dividing, so silencing ASS1 could be a way of freeing up the aspartate needed to meet the high demand.
An even rarer childhood disease – citrullinemia type II – gave the researchers an additional “therapeutic lens” on cancer. Here, rather than too much aspartate, there is too little, owing to the loss of another protein called citrin. Children with this disease tend to be smaller than average. “If the loss of citrin, and thus aspartate, could result in smaller children, we thought it might also help us achieve smaller tumors,” says Erez. The team developed a method for blocking citrin and found that certain cancer growth was indeed inhibited by the treatment.
“There are hundreds of rare, hereditary disorders caused by mutations in single genes, and more than a few show up in such common diseases as cancer,” says Erez. “So investigating the rare can truly help shed light on the common.”