Obesity Epidemiology

METABOLIC AND HORMONAL PREDICTORS OF OBESITY 391Among new quitters, subjects in the highest quartile of leukocytes gained 0.56 kg/yearmore than those in the lowest quartile. In multivariate analyses, the RR for a large weightgain after quitting smoking (vs. continuing) was 6.2 for those in the highest quartile ofleukocytes and 2.2 for those in the lowest quartile (P for interaction between smokingstatus and leukocytes = .03).Engstrom et al. 96 evaluated whether elevated levels of inflammation-sensitive plasmaproteins (ISPs) (fibrinogen, orosomucoid, alpha-1-antitrypsin, haptoglobin, and ceruloplasmin)were associated with future weight gain in 2,821 nondiabetic healthy men 38 to50 years of age in the Malmo Preventive Study cohort. During 6.1 years of follow-up, theproportion of subjects with a large weight gain (75th percentile ≥ 3.8 kg) increased withthe number of ISPs in the top quartile in a dose-response manner (P for trend = .0005).In a subsequent analysis of the Malmo Preventive Study cohort, Engström et al. 97 foundan association between plasma concentrations of complement factor 3 (C3) and weightgain. After adjustments for initial weight, age, height, and follow-up time, the RRs of alarge weight gain (75th percentile ≥ 3.8 kg) were 1.00 (reference), 0.96 (95% CI: 0.7 to1.2), 1.1 (0.9 to 1.5), and 1.4 (1.1 to 1.8) across increasing quartiles of C3 levels (P fortrend = .01). This relationship remained significant after further adjustments for physicalinactivity, alcohol intake, smoking, and ISP levels. Because the hepatic production of C3is stimulated by inflammatory cytokines, this study suggests that the immune responseinduced by inflammation may lead to increased weight gain.In the Cardiovascular Health Study, Barzilay et al. 98 examined several inflammatorymarkers in relation to weight change among 3,254 subjects (≥65 years old) during a3-year follow-up. They found a significant association between higher baseline concentrationsof CRP and weight change (5%, either gained or lost) during the follow-up.Other inflammatory markers (e.g., fibrinogen and factor VIIIc) were also associated withgreater weight gain, whereas white blood cell (WBC) count was associated with greaterweight loss. These analyses suggest that elevated inflammatory markers may precedeboth weight loss and gain. The relationship with weight loss may result from elevatedinflammation associated with existing and subclinical diseases.Taken together, these data indicate that inflammatory markers may predict subsequentweight gain, especially in younger subjects who are more prone to age-relatedweight gain. However, the association is modest and there could be confounding bydietary and lifestyle factors associated with inflammation if adjustment for thesefactors is inadequate. The biological mechanism for the association between inflammatorymarkers and subsequent weight change is unclear. There is some evidence fromanimal studies that infection by pathogens may have a potential etiological role inobesity, 99 and thus, it is conceivable that infection-induced inflammation may predictweight gain. So far, however, the evidence of a link between infection and obesity islargely limited to animal studies. It is also possible that the effects of inflammatoryfactors on weight gain are mediated through insulin resistance, because these cytokineshave been shown to promote insulin resistance in peripheral tissues. However, asdiscussed above, the relationship between insulin resistance and weight gain is not wellcharacterized.CortisolMore than four decades ago, Dunkelman et al. 100 suggested that increased cortisol secretionmight play a role in the development of obesity. A relationship between cortisoland obesity, especially central obesity, is well supported by clinical observations. 101 For