Weight Loss May Affect Diabetes Risk, but Not Future CVD Outlook

Interventions aimed at weight loss may decrease an individual’s risk of developing diabetes, but are unlikely to impact their risk of MI or death, according to a study of Swedish twins. In the study, leaner twins actually had a higher rate of death overall than their heavier brothers and sisters. 

The lack of correlation between obesity and death or MI was so unexpected, said the study’s lead author Peter Nordström, PhD (Umeå University, Umeå, Sweden), in an email, that the decision was made to increase the follow-up time by 2 more years to capture more MI or death outcomes. Nothing changed.

“The results of the present study suggest that lifestyle-obtained higher BMI with no genetic contribution, including direct genetic effects and gene-environment interactions, is not causally related to an increased risk of CVD or mortality,” Nordström and colleagues write in a JAMA Internal Medicine paper published online ahead of print on August 01, 2016.

The researchers studied 4,046 genetically identical monozygotic twin pairs as part of the Screening Across Lifespan Twin (SALT) study, begun in 1998 with follow-up through 2013, which screened for common complex disease in all twins in Sweden born before 1958. For the current study, only those with discordant BMIs were selected.

Over 12.4 years of follow-up, heavy and lean twins had similar rates of the combined primary endpoint of death and MI, as well as its individual components, even when the heavier twin had a BMI of 30 or more. After multivariable adjustment, the heavier twins had a reduced risk of MI or death (OR 0.75; 95% CI 0.63-0.91) compared with leaner twins. This reduction was most pronounced in the mildly obese subgroup of individuals with baseline BMIs of 24.9 or lower (OR 0.61; 95% CI 0.46-0.80). However, heavier twins had a higher risk of diabetes across most BMI subgroups (OR 1.94; 95% CI 1.51-2.48).

To TCTMD, Nordström said the increased risk of diabetes in the heavier twins was only associated with 31 additional cases of death or MI of the 1,438 cases in total.

“Thus, although obesity increased the risk of diabetes after adjusting for genetic factors, the heavier twins did actually [have] a lower risk of death or MI in the main analysis,” he noted.

Future Health Dependent on Choices Made Now

In an editorial accompanying the study, David J. Davidson, MD (NorthShore University HealthSystem, Chicago, IL), and Michael H. Davidson, MD (University of Chicago, Chicago, IL), say while failure to obtain waist circumference measurements is a drawback of the study, it confirms the causal link between obesity and diabetes and the importance of weight reduction to prevent diabetes.

“There is a popular misconception that obesity is the primary driver for premature CHD, and lean patients are frequently under the mistaken belief that they are protected from CHD,” they write.

Similarly, Ian J. Neeland, MD (UT Southwestern Medical Center, Dallas, TX), who was not involved with the study, told TCTMD that the death signal in the lean twins is the most interesting aspect of the study, adding that it calls to mind the obesity paradox: the concept that obese patients with chronic diseases have better outcomes than those who are normal weight or mildly obese.

Overall, the twin study provides more support for the idea that “normal weight” may not be as benign or normal as many have thought, Neeland said, stressing the importance of looking at factors other than BMI when assessing moderately obese patients for future risk of disease, and keeping in mind that all fat is not created equal.

“For example, we know that people who are obese have different amounts of visceral fat and that is a major determinant of cardiovascular disease or diabetes risk. So, you could be obese by BMI, but have very little visceral fat and have a lower risk than someone with a lower BMI but more visceral fat,” Neeland said. “On the flip side, people who are very lean, especially if they are older, may have underlying inflammatory disease, deconditioning, or poor nutrition that explains why are so lean. This is where looking at health profiles as a whole comes into play.”

As for the study, Neeland said the Swedish group cannot be easily extrapolated to the US population since even those at the higher end of the BMI spectrum were merely overweight as opposed to obese, and lean twins were much leaner than the average American.

Neeland further noted that while genetic factors play into cardiovascular disease and diabetes, the study speaks to the fact that environmental factors are probably of greater importance in the long term with regard to development of these diseases.

“Unless you have a strong family history [of a specific disease] I think a lot of what happens to you in your lifetime is dependent on lifestyle and choices that you make,” he said. “This study pretty much highlights that.”






  • Nordström, DJ Davidson, MH Davidson, and Neeland report no relevant conflicts of interest.


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  • Nordström P, Pedersen NL, Gustafson Y, et al. Risks of myocardial infarction, death, and diabetes in identical twin pairs with different body mass indexes. JAMA Intern Med. 2016;Epub ahead of print.

  • Davidson DJ, Davidson MH. Using discordance in monozygotic twins to understand causality of cardiovascular disease risk factors. JAMA Intern Med. 2016;Epub ahead of print.