C Calhau Lab | 3‐year investigation on the role of protein, glycaemic index & physical activity for prevention of type2 diabetes

Foto_Marta Silvestre

Marta Silvestre, researcher from the ProNutri Lab led by Conceição Calhau at CINTESIS @ NOVA Medical School, published an article in the journal Diabetes, Obesity and Metabolism entitled "The PREVIEW intervention study: Results from a 3‐year randomized 2 x 2 factorial multinational trial investigating the role of protein, glycaemic index and physical activity for prevention of type 2 diabetes" (full article here).

In brief, Marta Silvestre talks about this article:

What were you trying to understand and what is the main discovery of this work?
In 2013, I was working with Professor Sally Poppitt at the University of Auckland, running the New Zealand arm of the multicentric PREVIEW study, which was a randomised controlled trial undertaken in 8 countries and led by Professor Anne Raben, from the University of Copenhagen, Denmark.
We were interested to see if a higher protein low glycaemic index diet was more effective in preventing type 2 diabetes in a high-risk group of people, meaning people with with overweight/obesity and prediabetes. Then the recommendations, established based on previous literature, a moderate protein with moderate glycaemic index diet.
Moreover, we were also interested to see the additional impact of physical activity - high versus moderate intensity.
After 3 years of follow up, with more than 2200 patients randomised to one of the two dietary interventions and one of the two physical activity interventions (resulting in a 2x2 factorial design), following a period of rapid weight loss, we found that only 3.1% of the participants developed diabetes (compared to 10% obtained in similar studies) and also that our dietary and physical activity protocols were equally effective in preventing the disease.

What discoveries led you to the research described in your publication?
There have been many important diabetes prevention trials, such as the American Diabetes Prevention Program (DPP) or the Finish Diabetes Prevention Study (DPS) showing that sustained weight loss resulting from a healthy diet may prevent or delay the onset of type 2 diabetes, even to a greater extent than pharmacological treatments (e.g. metformin). However, most individuals find difficult to maintain the weight loss. In 2008, the DioGenes study showed that a higher protein with low glycaemic index (GI) diet was better than other dietary interventions in sustaining weight change for over a period of four months, following 8 weeks of rapid weight loss, in overweight and obese individuals. The implications of these discoveries over long term (more than 1 year) and for individuals with prediabetes were unknown at the time. Our goal was to compare this newer higher protein, lower GI diet with the recommendations made years earlier, based on the DPP, DPS and other large interventions in a group of 2500 people who were at high risk of developing diabetes.

Why is this important?
Diabetes is a growing burden worldwide. It is diagnosed based on hyperglycaemia (high blood sugar levels), which results from either a defect in insulin action or in its production. In type 2 diabetes, the most prevalent form of diabetes, often both metabolic defects act concomitantly. Some of the main risk factors are hereditability, increased adiposity (being overweight or obese), age and having a sedentary lifestyle. Of these, only the lifestyle-related factors (diet, physical activity) can be modified. Hence, one must act on those urgently and in a time efficient manner. Once the disease is established there is progressive failure of the beta cells, which are the insulin producers, limiting the effectiveness of treatment. Hence, it is quite important to prevent the onset of the disease, which as we could see, is achievable with weight loss followed by adequate strategies for weight maintenance.

Can you use an analogy to help us understand your work?
Imagine that Mr X is glucose (sugar); that insulin is as key to a door (our cells) and that the insulin receptors on the cells are door locks. Now, imagine that as we put weight on the door, the door lock (cell receptor) becomes faulty. If this happens, the key (insulin) will have trouble opening the door and Mr. X (glucose) cannot go in (to the cell). So Mr X stays in the doorway (blood vessels) because he can not get into the cells with his key (insulin). To solve the problem, we must remove the weight from the door (weight loss). If we successfully do this, the lock goes back to its normal shape and insulin (the key) can finally go in, to open the door (cell) and let Mr X (glucose) go inside the house and do his work in there. The problem is that people have difficulty in sustaining the weight loss. Nutritional strategies are important to overcome this.

What questions remain to be asked?
I believe that we must better understand the pathways that regulate appetite and energy expenditure to help those who struggle to keep a healthy body weight. Among other players, the gut-brain axis appears to be critical in our appetite control and regulation of energy expenditure. I also believe that it is important to understand these mechanisms to develop further therapeutic strategies for one of the greatest problems worldwide, which is obesity-related metabolic disease. My group - Professora Conceicao Calhau's group - is currently focusing on these relationships.

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