OBJECTIVESubclinical inflammation is an important risk factor for type 2 diabetes and diabetes complications. However, data on the association between inflammation and acute diabetic foot syndrome are scarce. The aim of this study was to compare systemic immune mediators in diabetic patients with and without an ulcer and to identify modulating factors.RESEARCH DESIGN AND METHODSCirculating levels of acute-phase proteins, cytokines, and chemokines were measured in diabetic patients with an ulcer (n = 170) and without an ulcer (n = 140). Of the patients, 88% had type 2 diabetes.RESULTSPatients with an acute foot ulcer had higher levels of C-reactive protein (CRP), fibrinogen, interleukin (IL)-6, macrophage migration inhibitory factor, macrophage inflammatory protein-1α, and interferon-γ–inducible protein-10 as well as lower levels of RANTES (regulated on activation normal T-cell expressed and secreted) (all P < 0.01). No differences were found for IL-8, IL-18, and monocyte chemoattractant protein-1. Most of these associations persisted after adjustment for demographic and anthropometric data, metabolic confounders, and diabetes complications. In multivariate models, size of ulcer according to the University of Texas classification but not the grade of infection was independently associated with three markers of subclinical inflammation (CRP, IL-6, and fibrinogen).CONCLUSIONSWe demonstrate in our cross-sectional study that acute foot ulcers and their severity are associated with a marked upregulation of acute-phase proteins, cytokines, and chemokines independently of the concomitant infection. Further studies should investigate whether an activation of the immune system precedes the development of foot ulcer and whether anti-inflammatory therapies might be effective.

During acute psychological stress, the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system are activated. The released stress hormones influence glucose metabolism, can activate immune cells, and modulate subclinical inflammation. The aim of our study was to analyze the effect of acute psychological stress on glucose metabolism and the inflammatory status in patients with post-traumatic stress disorder (PTSD). We included 15 overweight male Bosnian war refugees with PTSD into the study (mean age 44+/-11 years, BMI 29.3+/-4.3 kg/m (2)). All subjects underwent an oral glucose tolerance test (OGTT) with either acute stress (trauma script exposure) or a resting period in a cross-over design. Blood was drawn over 2.5 h and metabolic markers were measured. Systemic levels of immune markers were determined using high-sensitive ELISA or bead-based multiplex assay. Immune gene expression was quantified by RT-PCR. After being exposed to acute stress, cortisol levels and heart frequency tended to be increased. Higher blood glucose and insulin levels after stress exposure were observed (p<0.05). Systemic levels of the chemokines interferon-gamma-inducible protein-10 and macrophage chemoattractant protein-1 were decreased compared to the control day (both p<0.05) and the expression of the proinflammatory regulator IKK beta was significantly reduced after stress exposure (p<0.001). In conclusion, acute stress induces postprandial blood glucose peaks and elevated insulin levels and a selective decrease of systemic immune markers and the proinflammatory regulator of the NF kappaB cascade, which are associated with type 2 diabetes. This points towards an independent effect of acute psychological stress on glucose metabolism and inflammation.

Objective: Regulated on activation, normal T-cell expressed and secreted (RANTES)/chemokine(C-C motif) ligand (CCL5) is expressed by adipocytes, and serum levels of RANTES are increased in obesity and type 2 diabetes. The aim of this study was to test the hypothesis that RANTES is involved in the pathogenesis of type 2 diabetes by analyzing the triangular association between CCL5 gene polymorphisms, systemic RANTES concentrations, and incident type 2 diabetes in a large prospective study. Subjects and methods:The study is based on 502 individuals (293 men and 209 women) and 1632 individuals (859 men and 773 women) with and without incident type 2 diabetes from the populationbased MONItoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) case-cohort study respectively (mean follow-up timeGS.D. 10.1G4.9 years). CCL5 genotypes and RANTES serum concentrations were determined and associations between genotypes, haplotypes, serum levels, and incident type 2 diabetes were assessed. Results: Minor alleles of four single nucleotide polymorphisms were associated with lower RANTES levels (P additive between 1.2!10 K9 and 3.1!10 K8), but neither genotypes, haplotypes, nor serum levels were associated with incident type 2 diabetes. Conclusions: Our data suggest that RANTES/CCL5 gene variants and serum levels are not causally related with type 2 diabetes and that elevated RANTES levels in patients with type 2 diabetes may be a consequence of hyperglycemia. However, our findings cannot preclude a local role in adipose tissue where RANTES expression may contribute to leukocyte infiltration and a proinflammatory state. European Journal of Endocrinology 158 R1-R5