OBJECTIVE: Studies in type 2 @entity6 report both increased mortality for normal weight and no evidence of an @entity28 paradox. We aimed to examine whether adipose tissue, muscle size, and physical function, which are known to vary by weight, mediate associations between BMI and mortality. RESEARCH DESIGN AND METHODS: The AGES-Reykjavik cohort comprised @entity1 aged 66-96 years with @entity6 defined by fasting @entity413 , medications, or self-report. BMI was determined from measured height and weight and classified as normal (18.5-24.9 kg/m(2), n = 117), overweight (25.0-29.9 kg/m(2), n = 293, referent group) or @entity28 (>= 30.0 kg/m(2), n = 227). Thigh muscle area and intermuscular, visceral, and subcutaneous adipose tissues were assessed with computed tomography. Function was assessed from gait speed and knee extensor strength. Hazard ratios (HRs) and 95% CIs were estimated by Cox proportional hazards regression adjusted for demographics and @entity6 -related risk factors. RESULTS: The median follow-up was 6.66 years, and there were 85, 59, and 44 @entity204 among normal weight, overweight, and @entity28 @entity1 , respectively. There was no mortality risk for @entity28 @entity1 and an increased risk among normal weight compared with overweight @entity1 (HR 1.72 [95% CI 1.12-2.64]). Associations remained with adjustment for adipose tissues and knee extensor strength; however, mortality risk for normal weight was attenuated following adjustment for thigh muscle (HR 1.36 [95% CI 0.87-2.11]) and gait speed (HR 1.44 [95% CI 0.91-2.27]). Linear regression confirmed with bootstrapping indicated that thigh muscle size mediated 46% of the relationship between normal weight and mortality. CONCLUSIONS: Normal weight @entity1 had elevated mortality risk compared with overweight @entity1 . This paradoxical association was mediated in part by muscle size.

Adipose tissue, muscle, and function: potential mediators of associations between body weight and mortality in older adults with type 2 XXXX .

@entity1 :: ('9606', 'Species') :: ['participants'] @entity28 :: ('MESH:D009765', 'Disease') :: ['obese', 'obesity'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity204 :: ('MESH:D003643', 'Disease') :: ['deaths'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity6 :: (MESH:D003920,Disease) :: ['diabetes']
