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Recently, SFRP4 was identified as a molecular link between islet inflammation and defective insulin secretion. Gene co-expression analysis detected a molecule associated with type 2 diabetes mellitus (T2D), elevated HbA1c, and reduced insulin secretion in mice as well as in a pilot sample of humans. To our knowledge SFRP4 has never been investigated in patients with different types of diabetes. We included 179 patients: 46 with type 1 diabetes (T1D), 30 age matched healthy controls for patients with T1D (CO-T1D), 55 with T2D, 37 with latent autoimmune diabetes of the adult (LADA) and 30 healthy controls (CO) for patients with T2D and LADA. Apart from anthropometric data, lipids and renal parameters were assessed. SFRP4 levels were measured by a commercial ELISA. Patients with diabetes had significant higher SFRP4 levels than CO: T2D vs. CO: 37.1±26.7 vs. 8.8±3.0 ng/ml, p0.001; LADA vs. CO: 15.6±6.2 vs. 8.7±3.0 ng/ml, p0.001; T1D vs. CO-T1D: 24.6±17.9 vs. 16.9±4.5 ng/ml, p=0.011. SFRP4 levels were correlated with age, BMI, HbA1c, HDL-cholesterol, and triglycerides. A multivariate model revealed HDL-cholesterol, triglycerides and BMI as predictors for SFRP4. This is the first study demonstrating that SFRP4 is significantly increased in patients with different types of diabetes suggesting that this protein is generally involved in islet dysfunction and potentially subclinical inflammation irrespective of type of diabetes.

Prevention of cardiovascular morbidity and mortality remains the key factor in the treatment of type 2 diabetes (T2DM). In the early phase of T2DM, multifactorial intervention is mandatory and glucose levels should be near normal, in particular in younger patients presenting with the highest cardiovascular risk. Anti-diabetic drugs without any risk for hypoglycaemia should be preferred in order to reduce clinical inertia and increase the long-term adherence to the treatment. In patients already presenting with cardiovascular disease, the best outcome may be expected with the triple oral therapy of metformin, pioglitazone, and empagliflozin, although a controlled prospective study versus insulin therapy is needed to confirm the expectation.

Der Typ-2-Diabetes ist eine komplexe Stoffwechselerkrankung, die mit einem deutlich erhohten Risiko fur kardiovaskulare Erkrankungen und bestimmte Krebserkrankungen einhergeht. Eine fruh einsetzende multifaktorielle Intervention ist notwendig, um die Prognose der Patienten zu verbessern. Die hochste Prioritat hat dabei die optimale Senkung des Low-density-Lipoprotein(LDL)-Cholesterins (Zielwert

Type 2 diabetes is a complex metabolic disease associated with a high risk of vascular disease and certain entities of cancer. An early starting multifactorial intervention is mandatory in order to improve the prognosis of the patients. Of highest priority is the lowering of LDL-cholesterol (Target value 100 mg/dl or 70 mg/dl when vascular complications are present) and of the very often increased blood pressure values (target values 130-135/80 mm Hg). A successful blood glucose lowering therapy is often only possible when antidiabetic drugs are used in combination. The antidiabetic therapy has to be individualized concerning the HbA1target value and the selection of the antidiabetic drugs in relation to age of the patients and presence or absence of co-morbidities. Severe events of hypoglycemia should be avoided, since these are associated with an increased cardiovascular risk and mortality.

The myelodysplastic syndromes (MDS) are a group of clonal haematological disorders characterized by cytopenia(s), reduced differentiation-capacity of myeloid cells, and impaired leukocyte function. However, little is known so far about basophil granulocytes in MDS.We have compared the numbers, phenotype and function of basophils in MDS patients with those in healthy subjects. A total numer of 23 patients with MDS (refractory anaemia, n = 8; refractory anaemia with ringsideroblasts, n = 7; refractory anaemia with excess of blasts/refractory anaemia with excess of blasts in transformation, n = 8) and 20 healthy donors were included.The numbers of blood basophils in MDS patients (34.6 +/- 62.9 microL-1) was lower compared to healthy controls (58.6 +/- 64.9 microL-1). Correspondingly, whole blood histamine levels were lower in MDS patients (MDS 34.1 +/- 29.1 ng mL-1 vs. normal donors 72.0 +/- 36.9 ng mL-1). Like "normal" basophils, basophils in MDS expressed interleukin-3 receptor alpha (CD123), E-NPP3 (CD203c), CR1 (CD35), CR3 (CD11b), CR4 (CD11c), membrane co-factor protein (CD46), decay-accelerating factor (CD55) and membrane attack complex inhibitory factor (CD59), as well as receptors for C3a, C5a (CD88), and IgE. Recombinant human (rh) C5a and anti-IgE induced significant release of histamine from basophils in both groups of donors without significant differences between MDS and healthy controls.The absolute numbers of basophils in MDS patients are lower than in normal donors. However, basophils in MDS do not differ from their "normal counterparts" in terms of complement receptor expression, IgE-receptor expression, or functional responses to respective ligands.

Mast cells (MC) are multipotent effector cells of the immune system. They contain an array of biologically active mediator substances in their granules. MC also express a number of functionally important cell surface antigens, including stem cell factor receptor (SCFR=kit=CD117), high affinity IgER (FcepsilonRI), or CSaR (CD88). Respective ligands can induce or promote degranulation, migration, or cytokine production. Other integral surface molecules can mediate adhesion or cell aggregation. Recent data suggest that a number of critical molecules are variably expressed on the surface of human MC. In fact, depending on the environment (organ), stage of cell maturation, type of disease, and other factors, MC express variable amounts of activation-linked antigens (CD25, CD63, CD69, CD88), cell recognition molecules (CD2, CD11, CD18, CD50, CD54), or cytokine receptors. At present, however, little is known about the mechanisms and regulation of expression of such antigens. The present article gives an overview of MC phenotypes in health and disease, and attempts to provide explanations for the phenotypic variability of MC.

Mast cells (MC) and blood basophils (Ba) are multifunctional effector cells of the immune system and accumulate in areas of ongoing disease. However, despite of similar morphology, MC and Ba differ from each other in terms of cell surface receptor expression, mediator content, and tissue distribution. In order to gain new insights into mechanisms and molecules responsible for the distribution and accumulation of MC and Ba, we have investigated expression of homing receptors on primary human MC (lung, n=28; uterus, n=17), Ba (healthy donors, n=64), the mast cell line HMC-1, and the basophil line KU-812. Expression of cell surface antigens on MC and Ba was analyzed by mAb and indirect immunofluorescence staining techniques. In addition to previous findings, Ba were found to react with mAb against the selectin-ligands sLe(x) (CD15s) and PSGL-1 (CD162), L-selectin (CD62L), beta7-integrin, the 'matrix-receptor' neurothelin (CD147), platelet-endothelial cell tetraspan antigen-3 (PETA-3=CD151), and BST-1 (CD157). Novel antigens detectable on MC (lung and uterus) were CD147, CD151, CD157 and CD49c (VLA-3alpha). By contrast, MC were not recognized by mAb to sLe(x), PSGL-1, L-selectin, or beta7 integrin. No reactivity of Ba or MC with mAb to syndecan-1 (CD138), VE-cadherin (CD144), MUC18/MCAM (CD146), MGC-24 (CD164), or ALCAM (CD166) was found. The cell lines HMC-1 and KU-812 expressed a similar profile of antigens when compared to primary cells. In summary, Ba and MC express a unique profile of homing molecules. Apparently, Ba differ from MC in expression of recognition receptors relevant for binding to endothelium and consecutive transmigration.