Body mass index versus surrogate measures of central adiposity as independent predictors of mortality in type 2 diabetes

Abstract

Background An “obesity paradox” for mortality has been shown in chronic disorders such as diabetes, and attributed to methodological bias, including the use of body mass index (BMI) for obesity definition. This analysis investigated the independent association of BMI versus surrogate measures of central adiposity with all-cause mortality in individuals with type 2 diabetes. Methods The Renal Insufficiency And Cardiovascular Events Italian Multicentre Study is a prospective cohort study that enrolled 15,773 patients in 19 Italian centres in 2006–2008. Exposures were BMI and the surrogate measures of central adiposity waist circumference (WC), waist-to-height ratio (WHtR), and A Body Shape Index (ABSI). Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%), Results Age- and sex-adjusted hazard ratios and 95% confidence intervals were significantly higher in BMI-based underweight (1.729 [1.193–2.505), P = 0.004), moderately obese (1.214 [1.058–1.392), P = 0.006) and severely obese (1.703 [1.402–2.068), P < 0.0001), lower in overweight (0.842 [0.775–0.915), P < 0.0001) and similar in mildly obese (0.950 [0.864–1.045), P = 0.292), compared to normal-weight individuals. When further adjusting for smoking, physical activity (PA), and comorbidities, risk was lower also in mildly obese versus normal-weight patients. The BMI-mortality relationship did not change after sequentially excluding ever smokers, individuals with comorbidities, and those died within two years from enrollment and when analyzing separately participants below and above the median age. Conversely, a paradox relationship was observed among inactive/moderately inactive, but not moderately/highly active patients. Mortality risk adjusted for age, gender, smoking, PA and comorbidities was significantly higher in the highest tertile of WC (1.279 [1.089–1.501], P = 0.003), WHtR (1.372 [1.165–1.615], P < 0.0001), and ABSI (1.263 [1.067–1.495], P = 0.007) versus the lowest tertile. However, risk was lower in the intermediate versus lowest tertile for WC (0.823 [0.693–0.979], P = 0.028), similar for WHtR, and higher, though not significantly, for ABSI. Conclusions An “overweight paradox” remained after controlling for age, smoking, and comorbidities, arguing against a collider bias or reverse causation. However, it could be partly explained by confounding from PA level, possibly through its impact on lean mass and cardiorespiratory fitness. No obesity paradox was observed with WHtR and especially ABSI, which predicted mortality risk associated with central adiposity better than WC. Trial registration ClinicalTrials.gov, NCT00715481, 15 July, 2008

Obesity indices and the risk of total and cardiovascular mortality among people with diabetes: a long-term follow-up study in Taiwan

“…In line with our observations, previous studies involving primarily white ethnic populations have consistently reported a positive relationship between ABSI and all-cause mortality in people with diabetes [ 6 , 14 , 29 ]. In the Fremantle Diabetes Study of Australian patients with type 2 diabetes, people in the fifth ABSI quintile had an elevated risk of all-cause mortality compared with those in the first quintile [ 6 ].…”

“…ABSI is the obesity indicator most strongly associated with all-cause mortality when compared with BMI, waist circumference, and WHR in their analysis [ 6 ]. Similarly, in a prospective cohort study on Italian Caucasians, the highest risk was found in the third ABSI tertile group [ 14 ]. However, none of these studies have reported data on cardiovascular mortality.…”

“…A growing body of evidence suggested that the ‘obesity-survival paradox’ may be attributed to several methodological issues [ 30 , 32 ]. One of the primary sources of bias is misclassification resulting from using BMI as an index of obesity [ 14 , 32 ]. The BMI does not distinguish between central (visceral) and peripheral (subcutaneous) fat distributions, which have differential effects on health.…”

“…The present study included a large cohort of people with diabetes, and the comprehensive assessment of potential confounders, such as smoking, physical activity, and comorbidities, helped mitigate the issues of collider bias and reverse causation [ 14 , 32 ]. Long-term follow-up allowed us to observe whether these associations changed over time.…”

“…Several studies have shown that ABSIs are associated with a greater risk of all-cause mortality than BMI or waist circumference in the general population [ 12 , 13 ]. However, very few studies have been conducted in people with diabetes to evaluate the association between ABSI and mortality, and data on cardiovascular mortality are lacking [ 6 , 14 ]. In this study, we examined the association of five adiposity indices (BMI, waist circumference, WHR, body fat percentage, and ABSI) with the risk of death from any cause or cardiovascular disease in a large cohort of individuals with diabetes in Taiwan.…”