High-Fat Diet Best for Diabetes Prevention in Obesity Prone

Marlene Busko

June 29, 2016

NEW ORLEANS — In a study of mainly white, overweight or obese, nondiabetic Americans on reduced-calorie diets, those who had a high genetic susceptibility to obesity who were on a high-fat as opposed to a low-fat diet had improved beta-cell function and insulin resistance at the end of 2 years.

These preliminary findings suggest that a diet such as the Mediterranean diet, which is high in polyunsaturated fat, would be especially beneficial for people who have a greater number of genetic variants that are associated with obesity and could help prevent them from progressing to prediabetes and type 2 diabetes, the researchers say.

Tao Huang, PhD, assistant professor, National University of Singapore, presented this study in an oral moderated poster session on June 11 here at the American Diabetes Association (ADA) 2016 Scientific Sessions.

Dr Huang and colleagues analyzed data from 744 participants in the Preventing Overweight Using Dietary Strategies (POUNDS LOST) trial who had been randomized to one of four weight-loss diets, including two that were high fat (40% fat) and two that were low fat (20% fat) and for whom data were available on body mass index (BMI)–associated genetic variants.

"We tested 32 single nucleotide polymorphisms [SNPs]," or genetic variants in DNA, that are associated with a risk of obesity (high BMI), Dr Huang explained to Medscape Medical News. If genetic testing is done "in 10 people, maybe two people carry 2 SNPs of high-risk genes; another five people carry eight high-risk SNPs. The others [are at the highest risk and] may have more than 20 high-risk SNPs — and this group with high genetic risk may benefit more from the high-fat diet," he noted.

This is an example of how DNA testing can lead to personalized medicine (or in this case, a personalized diet), according to Dr Huang.

To Medscape Medical News, the moderator of the oral poster session, Mary Beth Weber, PhD, assistant professor, Global Diabetes Research Center, Emory University, Atlanta, Georgia, commented that the FTO gene has a strong association with obesity, and a couple of other genes have a somewhat strong association with obesity, but others have a much lesser effect, so a few genetic variants are probably driving the results.

She agreed that the study shows that "following a Mediterranean diet that, although is higher in fat, is healthy polyunsaturated fat, could be beneficial," especially if for those with a high genetic risk for obesity.

However, although a lot of people are arguing for genetic testing and personalized medicine, "I would tend to agree that we are not [yet] at that point clinically," she cautioned.

"Unless we have a very certain link between the gene and the outcome, something like BRCA [in breast/ovarian cancer], you should consider very carefully whether taking a genetic test is worth it," she added.

In the meantime, this study adds to the knowledge that is already understood, that a Mediterranean type high-fat, lower-calorie diet can be very beneficial in general, she noted.

POUNDS LOST Trial Included Two High-Fat, Two Low-Fat Diets

Dr Huang explained that diet interventions have shown effectiveness in improvement of insulin resistance and beta-cell function; however, little is known about whether the overall genetic susceptibility to obesity modifies the dietary effects.

So he and his colleagues analyzed data from the POUNDS LOST trial that was conducted from 2004 through 2007 in Boston, Massachusetts and Baton Rouge, Louisiana among adults who had a BMI of 25 to 40 who were randomly assigned to one of the four diets with differences in fat, protein, and carbohydrate content.

On average, the participants were 51 years old and had a BMI of 33, and 60% were women.

The investigators calculated the participants' risk score, based on the presence of 32 obesity–associated genetic variants, which were determined from DNA analysis from a blood or saliva sample.

The participants were divided into tertiles, based on their genetic risk score for obesity.

Dietary fat significantly interacted with the BMI genetic risk score on changes in fasting insulin, the homeostatic model assessment of beta-cell function (HOMA-B), and insulin resistance (HOMA-IR) at 6 months (P for interaction = .006, .005, and .01, respectively).

Among those in the highest tertile of genetic risk scores for obesity, those who consumed a low-calorie, high-fat diet had a greater decrease in fasting insulin (P = .05) and insulin resistance (P = .04) compared with those who consumed a low-fat diet, along with a greater increase in beta-cell function (P = .09) during the 6-month weight-loss period.

Similar but attenuated patterns were observed for fasting insulin, HOMA-B, and HOMA-IR at 2 years (P = .06, .05, and .06, respectively).

"Our data suggest that individuals with a higher genetic susceptibility to obesity may benefit more from consuming a hypocaloric and high-fat weight-loss diet in improving insulin resistance and beta-cell function during the long-term weight-loss period," Dr Huang and colleagues concluded.

The authors have no relevant financial relationships.

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American Diabetes Association 2016 Scientific Sessions; June 12, 2016; New Orleans, Louisiana. Abstract 1497-P

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