OBJECTIVE— There is evidence that monocytes of patients with type 1 diabetes show proinflammatory activation and disturbed migration/adhesion, but the evidence is inconsistent. Our hypothesis is that monocytes are distinctly activated/disturbed in different subforms of autoimmune diabetes. RESEARCH DESIGN AND METHODS— We studied patterns of inflammatory gene expression in monocytes of patients with type 1 diabetes (juvenile onset, n = 30; adult onset, n = 30) and latent autoimmune diabetes of the adult (LADA) ( n = 30) (controls subjects, n = 49; type 2 diabetic patients, n = 30) using quantitative PCR. We tested 25 selected genes: 12 genes detected in a prestudy via whole-genome analyses plus an additional 13 genes identified as part of a monocyte inflammatory signature previously reported. RESULTS— We identified two distinct monocyte gene expression clusters in autoimmune diabetes. One cluster (comprising 12 proinflammatory cytokine/compound genes with a putative key gene PDE4B ) was detected in 60% of LADA and 28% of adult-onset type 1 diabetic patients but in only 10% of juvenile-onset type 1 diabetic patients. A second cluster (comprising 10 chemotaxis, adhesion, motility, and metabolism genes) was detected in 43% of juvenile-onset type 1 diabetic and 33% of LADA patients but in only 9% of adult-onset type 1 diabetic patients. CONCLUSIONS— Subgroups of type 1 diabetic patients show an abnormal monocyte gene expression with two profiles, supporting a concept of heterogeneity in the pathogenesis of autoimmune diabetes only partly overlapping with the presently known diagnostic categories.

The increase in surface activation marker and RAGE expression in platelets, resulting from concentrations of AGEs that occur in vivo after a meal or a drink as a source of exogenous AGEs, points to signaling mechanisms for food AGEs that could favor the precipitation of acute postprandial ischemic events.

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Background: Activated leukocytes and platelet-leukocyte interaction are involved in the pathogenesis of thrombotic and inflammatory events. Because apoptosis is a prerequisite for the successful resolution of an inflammatory response, we investigated the amount of apoptotic peripheral blood leukocytes (PBLs) in whole blood and their possible functional relation with the platelet-leukocyte interaction by a flow cytometric assay using APO 2.7 antibody for the detection of apoptosis Methods: Thirty healthy subjects volunteered for the study. PBL apoptosis in seven volunteers was induced by phorbol 12-myristate 13-acetate or while standing at rest. Results: Apoptosis was observed in all types of leukocytes (0.7% neutrophils, 1.5% monocytes, and 0.3% lymphocytes). Apoptosis was found predominantly in platelet and leukocyte coaggregates (Ͻ1% of nonaggregated leuko-

ObjectiveThe genetic polymorphism concerning the ß3-subunit of platelet integrin receptor glycoprotein IIIa is held responsible for enhanced binding of adhesive proteins resulting in increased thrombogenic potential. Whether it is associated with mortality, HbA1c or platelet volume is tested prospectively in an epidemiological cohort.Research design and methodsPopulation-based Cooperative Health Research in the Region of Augsburg (KORA) S4-Survey (N = 4,028) was investigated for prognostic value of PLA1A2-polymorphism regarding all-cause mortality, correlation with HbA1c, and mean platelet volume. Multivariate analysis was performed to investigate association between genotype and key variables.ResultsPrevalence of thrombogenic allele variant PLA2 was 15.0%. Multivariate analysis revealed no association between PLA1A2 polymorphism and mortality in the KORA-cohort. HbA1c was a prognostic marker of mortality in non-diabetic persons resulting in J-shaped risk curve with dip at HbA1c = 5.5% (37 mmol/mol), confirming previous findings regarding aged KORA-S4 participants (55–75 years). PLA1A2 was significantly associated with elevated HbA1c levels in diabetic patients (N = 209) and reduced mean platelet volume in general population. In non-diabetic participants (N = 3,819), carriers of PLA2 allele variant presenting with HbA1c > 5.5% (37 mmol/mol) showed higher relative risk of mortality with increasing HbA1c.ConclusionPLA1A2 polymorphism is associated with mortality in participants with HbA1c ranging from 5.5% (37 mmol/mol) to 6.5% (48 mmol/mol). Maintenance of euglycemic control and antiplatelet therapy are therefore regarded as effective primary prevention in this group.