Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: A cross-sectional study
Highlights
► High rates of obesity and low rates of cardiovascular disease (CVD) are observed in Mexican Americans. ► Levels of cytokines/adipokines were measured to understand biological basis of this disparity. ► Adiponectin (anti-inflammatory), IL-6 and TNF-alpha (pro-inflammatory) were elevated. ► Simultaneous upregulation of both pro- and anti-inflammatory cytokines, explain low rates of CVD.
Introduction
Type 2 diabetes, particular when poorly controlled, involves disease of the innate immune system and manifest as chronic low-grade inflammation [2], [5], [8], [28]. Consistent with this hypothesis, numerous studies have demonstrated that in individuals with impaired fasting blood glucose, circulating levels of inflammatory markers such as C-reactive protein (CRP), sialic acid and interleukin-6 (IL-6) are independent predictors of the future development of diabetes [10], [32]. Furthermore association of high levels of circulating acute phase proteins (IL-6) [32], tumor necrosis factor α (TNF-α) [35]) and other mediators of inflammation (serum-amyloid A (S-AA) [19], [39] and CRP [33]) with obesity and insulin resistance have been previously documented [10], [19]. Additionally several studies have demonstrated elevated levels of IL-6 and TNF-α among individuals with clinically diagnosed diabetes. An important factor that could potentially contribute to inflammation in diabetes is chronic hyperglycemia [2], [28]. Metabolic end products resulting from poorly controlled glucose are known to up-regulate the innate immune system leading to inflammation [4], [5], [35]. In a recent report published by Duncan and colleagues IL-6 was found to be strongly associated with levels of glucose and was a strong predictor of diabetes in at-risk individuals [10]. Inadequate glucose control and its associated inflammation in diabetes have been implicated in the pathogenesis of atherosclerosis, impaired lung function and cardiovascular disease [6], [8], [10].
This study was therefore designed to determine the association between glucose control and levels of pro- and anti-inflammatory markers. The fact that inflammation is an underlying cause of several co-morbidities associated with poorly controlled diabetes, makes it essential to understand the association between glucose control and inflammation.
We used specimens from participants from our Cameron County Hispanic Cohort (CCHC): a randomly-selected and well-characterized community-recruited cohort of Mexican Americans residing on the Texas-Mexico border [12]. This population has severe health disparities with high weighted prevalence of obesity (50.9%) and diabetes (29.7%), most of the latter poorly controlled. We first compared the pro- and anti-inflammatory profile in specimens from participants with and without diabetes for baseline characterization of chronic inflammation in this population. Secondly we determined the association between glucose control and inflammation using glycated hemoglobin (A1c) as a marker of glucose control. To our knowledge this is the first study reporting these associations in a homogenous population of Mexican Americans with diabetes.
Section snippets
Study participants
In this cross sectional study we measured adipokines and cytokines in baseline specimens from 367 CCHC participants, obtained between 2005 and 2008. Specimens were promptly aliquoted and stored at −80 °C until ready to be used. All participants completed a face-to-face administered questionnaire that includes personal and family medical history, socio-demographic data, history of medication, substance use and history of chronic illness including diabetes and heart disease. Participants also
Demographic and baseline characteristics
The analyses were performed on a total of 367 plasma specimens (67.3% female mean (M) age = 42.63 ± 15.33). The majority (80.9%), of the participants were overweight or obese and nearly one-third of the sample met the ATP III definition of metabolic syndrome [14]. A total of 13.6% had diabetes [1].
Median values (interquartile ranges IQ) were compared for gender, age, BMI, CRP, FBG, A1c, total cholesterol, high-density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides. Results of
Discussion
Inflammation both predicts and precedes diabetes. Studies performed in both the mouse model of obesity and in humans have shown that inflammatory processes occurring in the adipocytes contribute to the systemic low-grade inflammation resulting in insulin resistance and ultimately diabetes [3], [34], [37]. Further progression of diabetes particularly poorly controlled diabetes leads to the general activation of innate immune system [10], [31]. Studies by several investigators indicated that poor
Conflict of Interest
None declared.
Acknowledgments
We thank our cohort team, particularly Rocio Uribe, Elizabeth Braunstein, and Julie Ramirez at the Hispanic Health Research Center in the Lower Rio Grande Valley. We also thank Christina Villarreal at the University of Texas School of Public Health for administrative support. We would like to acknowledge the participant of the Cameron County Hispanic cohort who should tremendous enthusiasm, and support for the study. We are also grateful to the Valley Baptist Medical Center, Brownsville, for
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