Association of inflammation with worsening HOMA-insulin resistance.
OBJECTIVE
We examined the cross-sectional and longitudinal relationships between C-reactive protein (CRP), a marker of low-grade inflammation, and insulin resistance and whether the association was independent of obesity and oxidative stress.


METHODS
CRP and insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) data were obtained in a population-based, prospective observational study, Coronary Artery Risk Development in Young Adults (CARDIA), during 1992-2006.


RESULTS
CRP showed a significant positive association with insulin resistance, both cross-sectionally and longitudinally (5 year follow-up). The estimated increment in HOMA-IR was 0.34 log(e)(pmol/l x [mmol/l]/156.25) (p value for trend <0.0001) in the highest vs lowest CRP quartiles in cross-sectional analysis, whereas the corresponding estimate was 0.12 (p trend <0.0001) in the highest vs lowest CRP quartiles longitudinally over 5 years. The gradient of HOMA-IR across CRP was attenuated but remained statistically significant after controlling for body fat measurements (0.06 in the highest vs lowest CRP in both cross-sectional [p value for trend = 0.001] and longitudinal analyses [p value for trend = 0.01]), and was little changed by further adjustment for oxidative stress markers (F(2)-isoprostanes and oxidised LDL). There were consistent increments in the levels of HOMA-IR with increasing concentrations of CRP over time. In contrast, higher HOMA-IR did not predict future increases in CRP. Findings were similar using fibrinogen as the predictor variable.


CONCLUSIONS
Although a substantial portion of this association was explained by obesity, CRP was independently related to concurrent and future insulin resistance.
Park
K
K
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, USA.
Steffes
M
M
Lee
D-H
DH
Himes
J H
JH
Jacobs
D R
DR
D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003710:Demography; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008019:Life Style; D008137:Longitudinal Studies; D008297:Male; D013997:Time Factors; D055105:Waist Circumference
D002097:C-Reactive Protein
Arterioscler Thromb Vasc Biol. 2004 May;24(5):816-23
14976002
Diabetes Care. 2007 Jun;30(6):1627-9
17372148
N Engl J Med. 2008 Oct 30;359(18):1897-908
18971492
Int J Epidemiol. 2006 Aug;35(4):1001-8
16554379
J Clin Invest. 1996 Feb 15;97(4):1111-6
8613535
JAMA. 2008 May 21;299(19):2287-93
18492970
J Clin Invest. 1995 May;95(5):2409-15
7738205
Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):972-8
10195925
Intern Med. 2005 Jun;44(6):542-7
16020877
Clin Chem. 2007 Dec;53(12):2152-9
17951292
Br J Nutr. 1974 Jul;32(1):77-97
4843734
Diabetologia. 1985 Jul;28(7):412-9
3899825
J Clin Invest. 1995 May;95(5):2111-9
7738178
Nature. 2001 Dec 13;414(6865):813-20
11742414
Science. 1993 Jan 1;259(5091):87-91
7678183
Int J Obes (Lond). 2005 Dec;29(12):1452-6
16077717