Insulin resistance and metabolic syndrome in normal-weight individuals

Ghossein

Morris

et al. 2016

Cancer

Background Obesity is associated with increased adipose tissue in the tongue. Chronic white adipose tissue (WAT) inflammation commonly occurs in the obese. We investigated whether WAT inflammation in the tongue impacts survival in patients with squamous cell carcinoma (SCC) of the oral tongue. Methods In a retrospective cohort study, patients with T1–T2 oral tongue SCC who underwent curative-intent resection were included. Tongue WAT inflammation was defined by the presence of dead or dying adipocytes surrounded by macrophages forming crown-like structures. The primary and secondary endpoints were disease-specific survival (DSS) and overall survival (OS), respectively. Subgroup analyses were carried out in patients without lymph node involvement for whom adjuvant therapies were not indicated. Results Archived tissue was available from 125 patients. Median follow-up was 55 (range 3 to 156) months. Overall, 49/125 (39%) patients had tongue WAT inflammation which was associated with higher body mass index (BMI), increased tumor thickness, and vascular invasion (P<.05). The 3-year DSS rate for patients with tongue WAT inflammation was 59% (95% CI 46% to 76%) versus 82% (95% CI 73% to 92%) for those without inflammation. For patients without lymph node involvement in whom adjuvant therapy was not indicated (N=70), tongue WAT inflammation was associated with shortened DSS and OS (P<.05). When adjusted for BMI and potential prognostic covariates, the HRs for DSS and OS were 5.40 (95% CI 1.20 to 24.26) and 2.97 (95% CI 1.02 to 8.65), respectively. Conclusions Tongue WAT inflammation is associated with worse cancer specific and overall survival for patients with early stage oral tongue SCC.

Section: Discussionsupporting

confidence: 89%

White adipose tissue inflammation and cancer‐specific survival in patients with squamous cell carcinoma of the oral tongue

Ghossein

Morris

et al. 2016

Cancer

“…This finding suggests that the presence of breast WAT inflammation may provide clinically relevant information beyond that provided by BMI. It is increasingly recognized that some phenotypically obese individuals, defined by elevated BMI, are metabolically healthy (38-40), while metabolic obesity, including insulin resistance, can occur in others despite a normal BMI (41, 42). Consistent with these observations, breast WAT inflammation occurs in approximately one-third of women with normal BMI (25).…”

Section: Discussionmentioning

confidence: 99%

Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer

Clinical Cancer Research

Zhou

Gucalp

et al. 2016

170

202

Purpose Obesity, insulin resistance, and elevated levels of circulating proinflammatory mediators are associated with poorer prognosis in early-stage breast cancer. To investigate whether white adipose tissue (WAT) inflammation represents a potential unifying mechanism, we examined the relationship between breast WAT inflammation and the metabolic syndrome and its prognostic importance. Experimental Design WAT inflammation was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures of the breast (CLS-B). Two independent groups were examined in cross-sectional (Cohort 1) and retrospective (Cohort 2) studies. Cohort 1 included 100 women undergoing mastectomy for breast cancer risk reduction (n=10) or treatment (n=90). Metabolic syndrome-associated circulating factors were compared by CLS-B status. The association between CLS-B and the metabolic syndrome was validated in Cohort 2 which included 127 women who developed metastatic breast cancer. Distant recurrence free survival (dRFS) was compared by CLS-B status. Results In Cohorts 1 and 2, breast WAT inflammation was detected in 52/100 (52%) and 52/127 (41%) patients, respectively. Patients with breast WAT inflammation had elevated insulin, glucose, leptin, triglycerides, C-reactive protein, and interleukin-6; and lower HDL cholesterol and adiponectin (P<0.05) in Cohort 1. In Cohort 2, breast WAT inflammation was associated with hyperlipidemia, hypertension, and diabetes (P<0.05). Compared to patients without breast WAT inflammation, the adjusted hazard ratio for dRFS was 1.83 (95% CI, 1.07 to 3.13) for patients with inflammation. Conclusions WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis.

“…For example, insulin resistance and inflammation have been reported in individuals who have a normal BMI. [17][18][19] Conversely, a minority of individuals with elevated BMI are metabolically healthy. [20][21][22] Accordingly, the current definition of obesity on the basis of BMI has recently been called into question, 23,24 and BMI is inadequate for the identification of patients with adipose inflammation.…”

Section: Introductionmentioning

confidence: 99%

Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation

Gucalp

Dannenberg

et al. 2016

JCO

693

522

There is growing evidence that inflammation is a central and reversible mechanism through which obesity promotes cancer risk and progression. MethodsWe review recent findings regarding obesity-associated alterations in the microenvironment and the local and systemic mechanisms through which these changes support tumor growth. ResultsLocally, hyperadiposity is associated with altered adipose tissue function, adipocyte death, and chronic low-grade inflammation. Most individuals who are obese harbor inflamed adipose tissue, which resembles chronically injured tissue, with immune cell infiltration and remodeling. Within this distinctly altered local environment, several pathophysiologic changes are found that may promote breast and other cancers. Consistently, adipose tissue inflammation is associated with a worse prognosis in patients with breast and tongue cancers. Systemically, the metabolic syndrome, including dyslipidemia and insulin resistance, occurs in the setting of adipose inflammation and operates in concert with local mechanisms to sustain the inflamed microenvironment and promote tumor growth. Importantly, adipose inflammation and its protumor consequences can be found in some individuals who are not considered to be obese or overweight by body mass index. ConclusionThe tumor-promoting effects of obesity occur at the local level via adipose inflammation and associated alterations in the microenvironment, as well as systemically via circulating metabolic and inflammatory mediators associated with adipose inflammation. Accurately characterizing the obese state and identifying patients at increased risk for cancer development and progression will likely require more precise assessments than body mass index alone. Biomarkers of adipose tissue inflammation would help to identify high-risk populations. Moreover, adipose inflammation is a reversible process and represents a novel therapeutic target that warrants further study to break the obesity-cancer link.