Adipose Tissue Inflammation Is Not Related to Adipose Insulin Resistance in Humans.

The role of adipose tissue (AT) inflammation in AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression, and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC50). We studied 86 volunteers with normal weight or obesity at baseline and a subgroup of 25 volunteers with obesity before and after weight loss. There was a strong positive relationship between IC50 and abdominal subcutaneous and femoral fat cell size (FCS). The positive, univariate relationships between IC50 and abdominal AT inflammatory markers CD68, CD14, CD206 ATM/100 adipocytes, senescent cells, IL-6, and TNF-α mRNA were not significant after adjustment for FCS. A 10% weight loss significantly reduced IC50; however, there was no reduction in adipose ATM content, senescent cells, or cytokine gene expression. Our study suggests that commonly used markers of AT inflammation are not causally linked to AT insulin resistance, whereas FCS is a strong predictor of AT insulin resistance with respect to lipolysis.

Senescent cells in human adipose tissue: A cross-sectional study.

OBJECTIVE: Adipose tissue (AT) senescence is associated with AT dysfunction in rodents, but little is known about human AT senescence. The study goal was to define the distribution of senescent cells in two subcutaneous depots and understand relationships with adiposity and inflammation. METHODS: Sixty-three volunteers (48 females) underwent abdominal and femoral subcutaneous fat biopsies. Fat cell size, senescent cells using senescence-associated ß-galactosidase staining per 100 nucleated cells (percentage), and mRNA expression of four cytokines were measured. RESULTS: There was a larger proportion of senescent cells in femoral than abdominal subcutaneous AT (mean difference 1.6% [95% CI: 0.98%-2.3%], p < 0.001), and the percentage of femoral AT senescent cells was greater in women than men (median 3.9% vs. 2.1%, p < 0.01). There was a positive correlation between senescence and fat cell size in abdominal (rs  = 0.44, p < 0.001) and femoral (rs  = 0.35, p = 0.007) AT depots. Abdominal AT tumor necrosis factor alpha (rs  = 0.49, p < 0.01) and interleukin-1ß (rs  = 0.44, p = 0.01) expression was positively correlated with abdominal, but not femoral, AT senescence. CONCLUSIONS: In human subcutaneous AT, there are more senescent cells in femoral than abdominal depots; abdominal AT senescent cells are more associated with inflammatory signals than femoral AT senescent cells.

How to Measure Adipose Tissue Insulin Sensitivity.

CONTEXT AND OBJECTIVE: Adipose tissue insulin resistance may cause hepatic and skeletal muscle insulin resistance by releasing excess free fatty acids (FFAs). Because no consensus exists on how to quantify adipose tissue insulin sensitivity we compared three methods for measuring adipose tissue insulin sensitivity: the single step insulin clamp, the multistep pancreatic clamp, and the adipose tissue insulin resistance index (Adipo-IR). DESIGN AND PARTICIPANTS: We studied insulin sensitivity in 25 adults by measuring the insulin concentration resulting in 50% suppression of palmitate flux (IC50) using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-13C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations. RESULTS: Adipo-IR was reproducible (sample coefficient of variability, 10.0%) and correlated with the IC50 measured by the multistep pancreatic clamp technique (r, 0.86; P < 0.001). Age and physical fitness were significant predictors of the residual variation between Adipo-IR and IC50, with a positive relationship with age (r, 0.47; P = 0.02) and a negative association with VO2 peak (r, -0.46; P = 0.02). Likewise, IC50 measured by the multistep pancreatic clamp technique correlated with IC50 measured using the one-step hyperinsulinemic-euglycemic clamp technique (r, 0.73; P < 0.001). CONCLUSION: Adipo-IR and the one-step hyperinsulinemic-euglycemic clamp technique using a palmitate tracer are good predictors of a gold standard measure of adipose tissue insulin sensitivity. However, age and physical fitness systematically affect the predictive values. Although Adipo-IR is suitable for larger population studies, the multistep pancreatic clamp technique is probably needed for mechanistic studies of adipose tissue insulin action.

Prognosis of patients with benign thyroid nodules: a population-based study.

Most thyroid nodules are benign. The ideal follow-up of these patients should reflect their prognosis, which has been scarcely investigated. We aimed to evaluate the prognosis of patients with initial benign thyroid cytology. A population-based study, using the Rochester Epidemiology Project, identifying patients with benign thyroid cytology diagnosed between 2003 and 2006 and completely followed to 2014 using linked medical records. We identified 363 thyroid nodules with benign cytology in 327 patients after fine-needle aspiration biopsy. Patients were on average 53 years old (standard deviation 17), and 80 % were women. The median nodule size was 1.6 cm (interquartile range 1.2-2.4); 26 % had at least one suspicious ultrasound feature. During a median follow-up of 8 years, 54 patients (17 %) with 57 benign nodules underwent thyroidectomy, mostly due to compressive symptoms (44 %). Thyroidectomy was more likely in younger patients [hazard ratio (HR) 0.97, 95 % CI 0.96-0.99] and patients with larger nodules (HR 1.3, 95 % CI 1.16-1.48). Two patients were found to have follicular thyroid cancer in the index nodule (0.6 %) and 6 patients had papillary thyroid cancer detected in other nodules (1.8 %). No patient died from thyroid cancer. Patients with benign thyroid nodules are unlikely to suffer morbidity or mortality due to thyroid cancer. Follow-up strategies for these patients should consider this excellent prognosis and avoid causing unnecessary fear in patients and adding unneeded expense and burden to the healthcare system.