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Body Mass Index: A Complex Story. Monozygotic Twin Study

Nordström et al report  of 4046 monozygotic twins with discordant body mass indexes identified from a Swedish twin registry. The study recruitment was between 1998 and 2003 and follow up to December 2013. The primary end-point was the composite of death and myocardial infarction.

The abstract follows:


Observational studies have shown that obesity is a major risk factor for
cardiovascular disease and death. The extent of genetic confounding in these associations
is unclear.


To compare the risk ofmyocardial infarction (MI), type 2 diabetes, and death
in monozygotic (MZ) twin pairs discordant for body mass index (BMI).


A cohort of 4046 MZ twin pairs with discordant BMIs
(difference >0.01) was identified using the nationwide Swedish twin registry. The study was
conducted from March 17, 1998, to January 16, 2003, with follow-up regarding incident
outcomes until December 31, 2013.


The combined primary end point of death or MI and the
secondary end point of incident diabetes were evaluated in heavier compared with leaner
twins in a co-twin control analysis using multivariable conditional logistic regression.


Mean (SD) baseline age for both cohorts was 57.6 (9.5) years (range, 41.9-91.8
years). During a mean follow-up period of 12.4 (2.5) years, 203 MIs (5.0%) and 550 deaths
(13.6%) occurred among heavier twins (mean [SD] BMI, 25.9 [3.6] [calculated as weight in
kilograms divided by height in meters squared]) compared with 209 MIs (5.2%) and 633
deaths (15.6%) among leaner twins (mean [SD] BMI, 23.9 [3.1]; combined multivariable
adjusted odds ratio [OR], 0.75; 95%CI, 0.63-0.91). Even in twin pairs with BMI discordance
of 7.0 or more (mean [SE], 9.3 [0.7]), where the heavier twin had a BMI of 30.0 or more
(n = 65 pairs), the risk of MI or death was not greater in heavier twins (OR, 0.42; 95%CI,
0.15-1.18). In contrast, in the total cohort of twins, the risk of incident diabetes was greater
in heavier twins (OR, 2.14; 95%CI, 1.61-2.84). 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, 0.89-1.05)
but were associated with the risk of incident diabetes (OR, 1.13; 95%CI, 1.01-1.26).


In MZ twin pairs, higher BMI was not associated with an
increased risk of MI or death but was associated with the onset of diabetes. 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.
JAMA Intern

Supplemental material is available here.


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