Obesity Poses Much Bigger Risk for Diabetes Than Bad Genes

Marlene Busko

September 17, 2019

BARCELONA — Obesity is by far the greatest risk factor for developing type 2 diabetes, more than either having a genetic predisposition to diabetes or poor health habits, according to a large case-control study from Denmark.  

Specifically, among people who were mainly in their late 50s, the likelihood of developing type 2 diabetes during the next decade or so was sixfold higher if they were obese than if they were a normal weight — much greater than the risk from a poor lifestyle (related to smoking, drinking, poor diet, not exercising) or genetic predisposition.

Importantly, the study showed "individuals with an unfavorable lifestyle and obesity are at greater risk of incident type 2 diabetes regardless of their genetic risk," Hermina Jakupović, PhD fellow, MSc, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark, told Medscape Medical News.

Jakupović will present the findings in a poster here at the European Association for the Study of Diabetes (EASD) 2019 Annual Meeting.

The findings highlight "the importance of weight management in type 2 diabetes prevention...in all genetic risk groups," she stressed.

Because losing weight can delay type 2 diabetes onset among obese patients with impaired glucose tolerance, she added, "the earlier we start by implementing these interventions (favorable lifestyle behavior patterns), the better the effect."

The findings support those of a recently published meta-analysis that showed diabetes risk drops by 75% with combined lifestyle interventions.

"The [current] study again nicely recapitulates what we already know, [and] it is nice that the previous results can be extended and replicated," Louis H. Philipson, MD, PhD, president, medicine & science, American Diabetes Association (ADA), told Medscape Medical News in an email.

In general, the study by Jakupović and colleagues supports existing ADA recommendations, said Philipson, who is also director of the Kovler Diabetes Center at the University of Chicago, Illinois.

How Weight, Lifestyle, and Genes Affect Diabetes Risk

Previous research has shown that lifestyle interventions and successful weight loss can delay type 2 diabetes onset, and other studies have identified about 200 genetic mutations linked with diabetes risk.

But to what extent these three characteristics — obesity, an unhealthy lifestyle, and genetic predisposition to diabetes — are independent predictors of incident diabetes has not been clear.

And so researchers performed a case-cohort study of 57,053 participants in the Diet, Cancer, and Health study in Denmark. Of these, just under 10,000 people had available genotype data, and during a mean follow-up of 14.7 years, 49.5% developed type 2 diabetes.

Researchers matched the 4729 new cases of diabetes with 5402 participants who remained free of diabetes.

At baseline, participants were a mean age of 56.1 years (range, 50-65 years) and 49.6% were women.

About a third had a normal body mass index (BMI < 25 kg/m2), and the rest were overweight (43%; BMI > 25 to 30 kg/m2) or obese (22.8%; BMI > 30 kg/m2).

Researchers defined a favorable lifestyle as having three out of four good health habits: not smoking, doing regular physical activity, eating a healthy diet (based on 2012 Nordic nutrition recommendations), and consuming a moderate amount of alcohol (up to 1 drink/day for women and 2 drinks/day for men).

Based on these criteria, 53.3% of participants had moderate alcohol consumption; 64.1% did not smoke; 50.3% did regular physical activity; and 52.8% had a healthy diet.  

Expressed differently, 40% had a favorable lifestyle, 25% had a poor lifestyle (none or only one of these good health habits), and 35% had an "intermediate" lifestyle.

Researchers calculated a genetic risk score for diabetes for each participant based on whether they had any of 193 single nucleotide polymorphisms (SNPs) strongly associated with type 2 diabetes.

They classified participants as having low, intermediate, or high genetic risk (lowest 20%, middle 60%, and top 20% genetic risk scores, respectively).

Compared with having a low genetic risk, having a high genetic risk doubled the risk of developing diabetes (hazard ratio [HR], 2.0), after adjusting for multiple confounders.

Having an unhealthy lifestyle moderately increased the risk of developing diabetes by 18% (HR, 1.18) compared with having a healthy lifestyle.

But in comparison with having a normal body weight, being obese conferred a much larger, almost sixfold, increased risk of diabetes (HR, 5.81).

Obesity Still A Dominant Risk Factor for Diabetes Despite Good Genes

Even in the subset of people with a low genetic risk score, compared to people with a normal weight, those who were obese had a more than sixfold increased risk of developing diabetes (HR, 6.63).

In addition, in this low genetic risk subset, compared to people with a normal weight and healthy lifestyle, those who were obese and had an unhealthy lifestyle had a massive almost tenfold higher risk of developing type 2 diabetes (HR, 9.94).

"The effect of obesity on type 2 diabetes risk is dominant over other risk factors," the researchers conclude.

The Diet, Cancer and Health cohort is supported by the Danish Cancer Society. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation. Jakupović was supported by the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation.

EASD 2019 Annual Meeting. Presented September 19, 2019. Abstract 376.

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