Obesity Risk: Twin Study Examines Correlations Between Higher Weight And Diseases

Obesity is bad for your heart. But do genes play a role here? A twin study surprised with an unexpected result.

You live a dangerous life with too many pounds on your hips. At least it is well-known that obesity is among the largest risk factors for cardiac infarcts well as for a number of other diseases, such as diabetes. In Europe alone, extreme adiposity accounts for more than 300,000 premature deaths per year. But does it make a difference whether genes or lifestyle are responsible for the body weight?

This is exactly what scientists associated with Peter Nordström from the University of Umea in Sweden wanted to know (1). Therefore, they analyzed data from about 4,000 twin pairs that were different (discordant) in their weight.  Since the genetic outfit of identical (monozygotic) twins is nearly identical, it cannot be the genes that are responsible when weight is different between twins, it must be a different lifestyle and other environmental factors.

They sorted the twins into two groups: The group with the heavier twin had an average body mass index (BMI) of around 25.9 and were, therefore, mildly overweight. The second group had a normal weight with an average BMI of 23.9. During the course of 12 years, scientists compared the twin pairs at several time points and were surprised by one result; in both weight groups, a nearly equal number of persons suffered from a cardiac infarct. Even among twin pairs that were obese and at least 7 BMO points apart, the rate of infarcts in the more obese group did not differ from their leaner siblings. Hence, a higher BMI that is attributable nearly exclusively to lifestyle seems not to be responsible for a higher cardiac risk. This was not expected, as Norström points out in “Popular Science”; it took them three years to rerun the analyses, to wait for follow-up investigations in twins, and to accept the data.

For another disease, however, the twins’ weight had a markedly higher impact. With more pounds, the likelihood of diabetes increased. 345 of the twins in the heavier groups developed diabetes, compared to only 224 in the leaner group. Those who lose weight, therefore, can prevent diabetes, as the researchers concluded. The comparison also demonstrates that significantly more smokers die earlier than their non-smoking siblings.

And another issue surprised in the study: During the course of the 12 years, 550 of the heavier twins died, but so did 633 of the leaner ones. Most likely a subgroup of the leaner twins with a maximal BMI of 25 accounts for these differences, and maybe this group suffered specifically from chronic diseases that made them lose weight.

Two other recent studies demonstrate the large influence such factors can have. In 2013, the Center for Disease Control and Prevention (CDC) published a study in JAMA with spectacular results of a meta-analysis (2), a summary of many different previous studies: Catherine Flegal and colleagues found that people with overweight exhibited a 6 percent lower risk to die early than normal-weight people. This is called the adiposity paradox by physicians, scientists, and journalists. In the Global BMI Mortality Collaboration, a team of 500 researchers from 300 institutes came to another conclusion more recently (3): When they evaluated more than 200 studies with more than 10 million participants, they corrected them for a number of statistical biases.

Smoking, for instance, lowers body weight and distributes the risk to die in groups with lower BMI. The same holds true for people with chronic diseases that are frequently slim and haggard. If the analysis is therefore restricted to people that never smoked, have no chronic conditions, or died shortly after the recruitment for the study, the picture changes. Then it becomes evident that already a slightly higher weight increases the risk to die early.

I addition, many factors can have influenced the result of the Nordström study: the twin sample did not register the body fat at the hip. The hip circumference (or the waist-hip ratio) is a better indicator of obesity and higher weight than the BMI, which can exceed 25 with extreme muscle mass instead of fat. And maybe the observation time of 12 years was too short to identify the negative consequences of obesity. Future research will have to show whether the Nordström data will persist over time.

This is part 7 of a series covering twin health provided by Paul Enck from the Tübingen University Hospital and science writer Nicole Simon.

References:

1. Nordström P, Pedersen NL, Gustafson Y, Michaëlsson K, Nordström A. Risks of Myocardial Infarction, Death, and Diabetes in Identical Twin Pairs With Different Body Mass Indexes. JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.4104. [Epub ahead of print]
2. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013 Jan 2;309(1):71-82.
3. Global BMI Mortality Collaboration. Body-mass index and all-cause mortality: individual- participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016 Jul 13. pii: S0140-6736(16)30175-1.