Relationship between inflammatory biomarkers and insulin resistance
Nutrition Research Newsletter, Dec, 2005
Obesity is a known determinant of insulin resistance (IR) and a strong risk factor for type 2 diabetes. Excess central adiposity appears to be strongly associated with IR and increased risk of diabetes. Because not all studies have found that visceral fat confers a greater degree of IR than subcutaneous fat, there is a debate whether visceral fat is related to IR independently of overall fatness, especially among obese subjects.
Despite the strong associate between obesity, IR and type 2 diabetes, the mechanisms in which increased body fat impairs insulin action in other tissues are not clear. Recent research suggests that biomarkers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), or tumor necrosis factor-a (TNF-a)] or endothelial dysfunction [such as E-selectin or intercellular adhesion molecule-1 (ICAM-1)] are associated with IR and increased risk for type 2 diabetes.
In order to explore the role of inflammation and endothelial dysfunction in mediating the association of overall or central adiposity with IR and risk of type 2 diabetes, researchers classified a sample of nondiabetic women participating in the Nurses' Health Study according to overall or central adiposity, both, or neither and compared fasting insulin (FI) levels (as a surrogate measure of IR) across categories. They then controlled for levels of inflammatory and endothelial biomarkers to test the hypothesis that these account for any association of weight phenotype with IR. Additionally, the risk for incident type 2 diabetes in these women was analyzed using a nested case control design to test the hypothesis that central adiposity is an independent risk factor for type 2 diabetes and that this risk is mediated by insulin levels and levels of inflammatory and endothelial biomarkers.
A total of 519 initially nondiabetic women were divided into four phenotypes above/below median BMI (27 kg/[m.sup.2]) and waist circumference (81 cm): low BMI-low waist (LBLW; N= 190), low BMI-high waist (LBHW; N= 27), and high BMI-high waist (HBHW; N = 219).
In models assessing associations of weight phenotype with IR (FI), adjusted for age and diabetes risk factors, mean FI was higher comparing HBHW women (13.6 mieroU/mL,p < 0.0001) and LBHW (11.5 microU/mL, p = 0.02) with LBLW women (8.6 microU/mL); HBLW and LBLW women were not significantly different. Differences in FI levels were most strongly attenuated after adjustment for E-selectin comparing LBHW with LBLW women(11.7 versus 9.7 microU/mL,p = 0.2).
In logistic regression models, LBHW predicted diabetes, compared with LBLW, but was not significant after adjustment for E-selectin or CRP. Following adjustment for CRP and E-selectin, only HBHW and E-selectin were significantly associated with risk of diabetes. In women with central adiposity and low BMI, endothelial dysfunction and inflammation may promote the relationship between central fat, IR, and incident diabetes.
D. Wexler, F. Hu, J. Manson, et al. Mediating effects of inflammatory biomarkers on insulin resistance associated with obesity. Obes Res; 2005:1772-1783 (October 2005). [Correspondence: Deborah J. Wexler, Diabetes Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114. E-mail:
dwexler@partners.org].
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