Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study.
BACKGROUND
Our research group has previously shown that the geriatric syndrome of frailty is associated with features of the metabolic syndrome (MetS) on cross-sectional analysis.


METHODS
To test whether MetS and its physiologic determinants-insulin resistance as measured by homeostasis model assessment score (IR-HOMA), increased inflammation and coagulation factor levels, and elevated blood pressure-are associated with incident frailty, we studied a subcohort of participants from the Cardiovascular Health Study observed from 1989/1990 through 1998/1999: 3141 community-dwelling adults, aged 69 to 74 years, without frailty and illnesses that increase inflammation markers or mimic frailty. The association of baseline MetS, IR-HOMA, levels of inflammation and coagulation factors, and systolic blood pressure (SBP) with time to onset of frailty was adjusted for demographic and psychosocial factors and incident events. Our main outcome measure was incident frailty.


RESULTS
Metabolic syndrome was not significantly associated with incident frailty (hazard ratio, 1.16 (95% confidence interval [CI], 0.85-1.57). On the other hand, IR-HOMA and C-reactive protein levels were associated with incident frailty: for every standard deviation increment the hazard ratio for frailty was 1.15 (95% CI, 1.02-1.31) and 1.16 (95% CI, 1.02-1.32), respectively. The white blood cell count and factor VIIIc levels had a borderline association. Elevated systolic blood pressure had no association. Similar trends were found for incident prefrailty, a condition that precedes frailty.


CONCLUSIONS
Two physiologic components of MetS- IR-HOMA and inflammation-are associated with incident frailty. Based on these results, IR-HOMA can be considered part of a larger process that leads to generalized decline.
Barzilay
Joshua I
JI
Kaiser Permanente of Georgia, 200 Crescent Center Parkway, Tucker, GA 30084, USA. Joshua.barzilay@kp.org
Blaum
Caroline
C
Moore
Tisha
T
Xue
Qian Li
QL
Hirsch
Calvin H
CH
Walston
Jeremy D
JD
Fried
Linda P
LP
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D016330:Frail Elderly; D005853:Geriatrics; D006801:Humans; D007249:Inflammation / Q000150:complications*; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D011446:Prospective Studies