Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance

Abstract

Context: Adipose tissue-derived adipokines may contribute to insulin resistance.

Objective: We tested the hypothesis that adipokines are associated with insulin resistance in a community-based cohort and that associations are maintained in people with and without the metabolic syndrome (high vs. low risk of diabetes).

Design, setting, and participants: We studied a cross-sectional sample of 2356 individuals attending the seventh examination (1998-2001) of the Framingham Offspring Study. We measured levels of glucose, insulin, adiponectin, resistin, and TNFalpha in fasting blood samples and defined metabolic syndrome by updated National Cholesterol Education Program criteria. We used ANOVA to test associations of adipokines with insulin resistance and multivariable logistic regression models to assess joint associations of adipokines and metabolic syndrome with insulin resistance.

Main outcome measure: Homeostasis model (HOMA-IR), with insulin resistance defined by HOMA-IR greater than the 75th percentile, was measured.

Results: Age- and sex-adjusted HOMA-IR levels were inversely related to adiponectin (r = -0.40, P < 0.0001) and positively related to resistin (r = 0.13, P < 0.0001) and TNFalpha (r = 0.12, P < 0.0001). The prevalence of insulin resistance increased with decreasing tertiles of adiponectin (from 10.9% in the third to 42.5% in the first tertile; P < 0.0001) and increasing tertiles of resistin (from 19.3 to 30.9%; P < 0.0001) and TNFalpha (from 18.8 to 32.0%; P < 0.0001). Results were similar after adjustment for body mass index. These associations were present in individuals with or without the metabolic syndrome. In multivariable regression models, metabolic syndrome and adipokines individually and jointly were significantly associated with insulin resistance.

Conclusion: Adverse levels of adipokines are associated with insulin resistance in individuals at low or high diabetes risk.

Figure 1

Adverse adipokine levels are associated with insulin resistance in individuals with metabolic syndrome (MetS) and without (no MetS). The left-hand column shows scatter plots (crude data) of plasma adiponectin (top), resistin (middle), and TNF-α (bottom) in relation to insulin resistance measured by HOMA-IR according to metabolic syndrome status (gray circle, no MetS; black circle, MetS; dashed line, no MetS; solid line, MetS). The right-hand column shows the prevalence (and ses) of insulin resistance (IR) (age-sex adjusted) defined by HOMA-IR greater than 75th percentile in relation to adipokines grouped into tertiles of increasing plasma concentration, according to metabolic syndrome status (light gray, no metabolic syndrome; dark gray, metabolic syndrome). For trends within metabolic syndrome categories, P < 0.0001 for decreasing prevalence of insulin resistance across adiponectin tertiles in both groups; for resistin (middle) and TNF-α (bottom), all P < 0.01 for trends in insulin resistance prevalence across tertiles in both groups.