High BMI Tied to T2D, but Not to Heart Troubles

Twin study suggests causal link between obesity and diabetes risk, independent of genetics

Obesity was not directly associated with myocardial infarction (MI) risk or mortality risk, but was linked to the onset of incident type 2 diabetes, according to a study done in identical twins.

In the fully adjusted model, the odds ratio for the combined primary endpoint of MI or death was 0.75 (95% CI 0.63 to 0.91) in heavier twins versus leaner twins, reported Peter Nordström, PhD, of Umea University in, Sweden, and colleagues. The minimum difference between the heavier and leaner twins was 0.01 body mass index (BMI) units.

However, incident diabetes was more likely to occur in the heavier twin than in the leaner twin (OR 2.14, 95% CI 1.61 to 2.84), they wrote in JAMA Internal Medicine.

"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," the authors wrote.

On the other hand, "these results suggest a causal link between obesity and the risk of diabetes, independent of genetic influence," they noted.

"Weight loss may be more effective to reduce the risk of diabetes than the risk of myocardial infarctions and death," Nordström wrote in an email to MedPage Today.

But not everyone was convinced by the study results. "The current study does not take into account diet, activity, or specific fat depots. It also does not control for birth weight, which may be a confounder in the interpreting results," noted Robert Lustig, MD, of the University of California San Francisco, in an email to MedPage Today. Lustig was not involved in the study.

David Katz, MD, MPH, of the Yale University School of Medicine Prevention Research Center in New Haven, Conn., pointed out that the analyses generated numerical results, despite the very small difference in average BMI between the two cohorts.

In addition, Katz, who was not involved in the study, told MedPage Today that those in the heavier cohort were more likely to have diabetes, and were in turn "treated with state-of-the-art medical care, and given more attention from physicians," such as with a personalized treatment plan that would encourage healthy changes.

The study population consisted of 4,046 pairs of Swedish twins who were all born prior to 1958. In order to be included, the twins were required to have reported discordant BMI, or BMI with a difference of at least 0.01. The baseline data was collected from 1998 until 2003, and the average follow-up period was 10 years.

The average baseline BMI of the leaner cohort group was 23.9 kg/m², and for the heavier cohort it was 25.9 kg/m².

The mean baseline age for both cohorts was 57.6. During a mean follow-up period of 12.4 years, 203 MIs (5.0%) and 550 deaths (13.6%) occurred among heavier twins compared with 209 MIs (5.2%) and 633 deaths (15.6%) among leaner twins, the authors reported.

They also found that even in twin pairs with BMI discordance of 7.0 or more where the heavier twin had a BMI of ≥30 kg/m² (n 65 pairs), the risk of MI or death was not greater in heavier twins (OR 0.42, 95% CI 0.15 to 1.18).

But in the total cohort of twins, the risk of incident diabetes was greater in heavier twins (OR 2.14, 95% CI 1.61 to 2.84).

"Finally, increases in BMI since 30 years before baseline were not associated with the later risk of MI or death (OR 0.97, 95% CI 0.89 to 1.05) but were associated with the risk of incident diabetes (OR 1.13, 95% CI 1.01 to 1.26)," the authors wrote.

"These results may suggest that lifestyle interventions to reduce obesity are more effective in decreasing the risk of diabetes than the risk of cardiovascular disease or death," they concluded.

Study limitations included the self-reporting of weight and height, the relatively small sample size, and the lack of information regarding certain confounders such as hypertension.

Another limitation was the lack of waist circumference measures, which is a better indicator of obesity associated with metabolic disturbances such as dyslipidemia or hypertension, wrote David Davidson, MD, of NorthShore University HealthSystem in Chicago, and Michael Davidson, MD, of the University of Chicago, in an accompanying commentary.

"The Framingham Heart Study found that measures of central obesity were indicators of CHD events independent of body mass index. In addition, follow-up beyond the 12 years used in this evaluation may have been necessary for the higher rates of diabetes to convert to an increased prevalence of CHD," they pointed out.

Still, Davidson and Davidson stated that the study has important clinical implications, particularly the "causal link between obesity and diabetes, which is a growing epidemic throughout the world. Therefore, weight reduction should remain the cornerstone for the prevention of diabetes."

Katz suggested that physicians take preventative action even before their overweight patients receive a diabetes diagnosis.

"Ideally, prevention could be done with lifestyle changes alone, but modifying risk factors is important, whether or not it be done through lifestyle or pharmacological interventions," he said. "The message for clinicians is to not assume that patients' weight status accurately depicts their cardiovascular profiles, and that it is important to check for signs of these diseases early on."

Nordström and co-authors disclosed no relevant relationships with industry.

Davidson and Davidson disclosed no relevant relationships with industry.

Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner

last updated 08.08.2016

Primary Source: Nordström P, et al "Risks of myocardial infarction, death, and diabetes in identical twin pairs with different body mass indexes" Jama Intern Med 2016; DOI:10.1001/jamainternmed.2016.4104.

Secondary Source: Davidson DJ, Davidson MH "Using discordance in monozygotic twins to understand causality of cardiovascular disease risk factors" Jama Intern Med 2016; DOI: 10.1001/jamainternmed.2016.4115.

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