Phenotypic diversity of human adipose tissue-resident NK cells in obesity.

Natural killer (NK) cells have emerged as key mediators of obesity-related adipose tissue inflammation. However, the phenotype of NK cell subsets residing in human adipose tissue are poorly defined, preventing a detailed understanding of their role in metabolic disorders. In this study, we applied multicolor flow cytometry to characterize CD56bright and CD56dim NK cells in blood and adipose tissue depots in individuals with obesity and identified surface proteins enriched on adipose tissue-resident CD56bright NK cells. Particularly, we found that adipose tissue harbored clusters of tissue-resident CD56bright NK cells signatured by the expression of CD26, CCR5 and CD63, possibly reflecting an adaptation to the microenvironment. Together, our findings provide broad insights into the identity of NK cells in blood and adipose tissue in relation to obesity.

Distinct T cell subsets in adipose tissue are associated with obesity.

Adipose tissue inflammation is a driving factor for the development of obesity-associated metabolic disturbances, and a role of adipose tissue T cells in initiating the pro-inflammatory signaling is emerging. However, data on human adipose tissue T cells in obesity are limited, reflected by the lack of phenotypic markers to define tissue-resident T cell subsets. In this study, we performed a deep characterization of T cells in blood and adipose tissue depots using multicolor flow cytometry and RNA sequencing. We identified distinct subsets of T cells associated with obesity expressing the activation markers, CD26 and CCR5, and obesity-specific genes that are potentially engaged in activating pro-inflammatory pathway, including ceramide signaling, autophagy, and IL-6 signaling. These findings increase our knowledge on the heterogeneity of T cells in adipose tissue and on subsets that may play a role in obesity-related pathogenesis.

HbA1c predicts long-term postoperative mortality in patients with unknown glycemic status at admission for vascular surgery: An exploratory study.

BACKGROUND: Peripheral arterial disease (PAD) and diabetes mellitus (DM) represent major public health challenges and are tightly associated. To facilitate early diagnosis, HbA1c has been implemented as the preferred diagnostic tool for the diagnosis of type 2 DM. In this study, we compared and evaluated HbA1c, fasting plasma glucose (FPG), and 2-hour post-load glucose values to determine which test best predicted mortality in patients with PAD. METHODS: In all, 273 PAD patients with unknown glycemic status admitted to Haukeland University Hospital for elective surgery between October 2006 and September 2007 were included in the study. All 273 patients underwent a standard oral glucose tolerance test (OGTT) in addition to determination of HbA1c; patients were then grouped into those with DM, intermediate hyperglycemia, and normoglycemia according to World Health Organization and International Expert Committee criteria. RESULTS: All-cause mortality was 40% over a 9-year follow-up period. After adjusting for age, sex, and relevant medication, HbA1c was a predictor for mortality (hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.03-2.32]; P = 0.04). The association did not achieve statistical significance in a fully adjusted Cox regression model, although the effect estimation of HbA1c on all-cause mortality remained largely unchanged (HR 1.39; 95% CI 0.92-2.09; P = 0.13). The OGTT was not a predictor of long-term mortality. CONCLUSIONS: The results indicate that HbA1c is a useful marker in the preoperative screening of patients of unknown glycemic status at the time of admission for vascular surgery, and may identify people at high risk of long-term mortality following surgical treatment for PAD.

Correction to: HbA1c versus oral glucose tolerance test as a method to diagnose diabetes mellitus in vascular surgery patients.

The authors found errors in Table 1 after publication of the original article [1].The correct values for medical history of coronary artery disease (CAD) at baseline are 110 (40%) of all patients, 54 (35.5%) of patients categorized as having normoglycaemia, 42 (46.7%) of patients categorized as having intermediate hyperglycaemia, and 14 (42.4%) of patients categorized as having DM.All presented numbers and calculations in Table 1 are checked. No other errors were found. The presented errors did not affect results, scientific content or conclusions.The corrected Table 1 is presented in this erratum.The authors apologize for having presented this error in the original article.

HbA1c versus oral glucose tolerance test as a method to diagnose diabetes mellitus in vascular surgery patients.

BACKGROUND: The diagnosis of diabetes mellitus (DM) is based on either fasting plasma glucose levels or an oral glucose tolerance test (OGTT). Recently, an HbA1c value of ≥ 48 mmol/mol (6.5%) has been included as an additional test to diagnose DM. The purpose of this study was to validate HbA1c versus OGTT as a method to diagnose DM in vascular surgery patients. METHODS: The study population consisted of 345 patients admitted consecutively due to peripheral arterial disease. Sixty-seven patients were previously diagnosed with DM. Glucose levels of OGTT and HbA1c values were analyzed in 275 patients. The OGTT results were categorized into three groups according to the World Health Organization 1999 criteria: 1) DM defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L and/or two-hour value (2-h-value) ≥ 11.1 mmol/L; 2) intermediate hyperglycaemia, which consists of IGT (FPG < 7.0 mmol/L and a 2-h-value between 7.8 mmol/L and 11.1 mmol/L), and IFG (fasting glucose value between 6.1 mmol/L and 7.0 mmol/L with a normal 2-h-value); and 3) normal glucose metabolism defined as FPG < 6.1 mmol/L and a 2-h-value < 7.8 mmol/L. RESULTS: Of the 275 patients on whom OGTT was performed, 33 were diagnosed with DM, 90 with intermediate hyperglycaemia and 152 had normal glucose metabolism. An HbA1c value of ≥ 48 mmol/mol (6.5%) detected DM with a 45.5% sensitivity and a 90% specificity compared with the OGTT results. Combining the measurements of the HbA1c value with the fasting plasma glucose level (≥7.0 mmol/L) increased the sensitivity to 64%. The total prevalence of DM and intermediate hyperglycaemia was 85% based on HbA1c values and 45% based on the OGTT. CONCLUSIONS: Compared with the OGTT the HbA1c cut-off value of ≥ 48 mmol/mol (6.5%) had a 45.5% sensitivity to diagnose DM in patients with peripheral arterial disease. OGTT and HbA1c categorized different individuals with DM and intermediate hyperglycaemia. The total prevalence of pathologic glucose metabolism was substantially higher based on HbA1c values than based on OGTT. The high prevalence of DM and intermediate hyperglycaemia when using HbA1c in this study may reflect a high chronic glycaemic burden in patients with peripheral arterial disease. Further studies on vascular surgery patients are needed to identify which method, OGTT or HbA1c, is the better in predicting DM and future clinical development of vascular disease. TRIAL REGISTRATION: REK vest 14109.