Insulin resistance and systemic inflammation, but not metabolic syndrome phenotype, predict 9 years mortality in older adults

Background: Although metabolic syndrome (MS) is a typical condition of middle-aged/older person, the association between MS and mortality risk has not been confirmed in people over 65 years. We hypothesized that while in the elderly MS phenotype might lose its value in predicting mortality risk, the two core factors of MS, i.e. insulin resistance (IR) and low grade systemic inflammation (LGSI) would not.

Methods: 1011 community-dwelling older individuals (InCHIANTI study) were included. MS phenotype was defined by NCEP-ATP-III criteria. IR was calculated by HOMA; high-sensitivity C reactive protein was measured by ELISA. Subjects were divided into four groups based on presence/absence of IR (HOMA ≥ 2.27) and LGSI (hs-CRP ≥ 3 g/L): Group 1: no IR/LGSI (reference); Group 2: LGSI only; Group 3: IR only; Group 4: IR + LGSI. Hazard Ratios (HR) for 9-years cardiovascular (CVD) and total mortality, according to IR/LGSI groups, were estimated in subjects with (n.311) and without MS by Cox model.

Results: 31.8% of subjects with MS phenotype had no IR, 45.3% had no LGSI; moreover, 51% of subjects with both IR and LGSI didn't display the MS phenotype. MS phenotype was not associated with CVD (HR: 1.29; 95%C.I.:0.92-1.81) or total (HR: 1.07; 95%C.I.:0.86-1.34) mortality risk, whereas the presence of IR plus LGSI was associated with increased CVD (no MS: HR 2.07, 95%CI: 1.12-3.72; MS: HR 9.88, 95%CI: 2.18-4), and overall (no MS: HR 1.72, 95%CI: 1.001-3.17; MS: HR 1.51, 95%CI: 1.02-2.28) mortality risk. The presence of IR (HR: 6.90, 95%CI: 1.45-32) or LGSI (HR 7.56, 95%CI: 1.63-35) was associated with CVD mortality, only among individuals with MS phenotype.

Conclusions: Among community-dwelling older individuals, IR and LGSI, but not MS phenotype, was associated with 9-years overall and CVD mortality risk. Since a reduced "overlap" between MS phenotype and its physiopathological core (IR and LGSI) might be present with aging, we suggest that the definition of MS might be more holistic in advanced age, and probably comprise the measurement of IR and LGSI.