Autophagy and inflammasomes.

Autophagy is a ubiquitous cellular mechanism for the targeted lysosomal degradation of various cytosolic constituents, from proteins to organelles. As an essential homeostatic mechanism, autophagy is upregulated in response to numerous environmental and pharmacological stimuli, including starvation, where it facilitates the recycling of essential amino acids. In addition, autophagy plays specific roles within the immune system; it serves as a source of peptides for antigen presentation, a mechanism for the engulfment and degradation of intracellular pathogens and as a key regulator of inflammatory cytokines. In particular, autophagy has been shown to play a number of roles in regulating inflammasome activation, from the removal of inflammasome-activating endogenous signals, to the sequestration and degradation of inflammasome components. Autophagy also plays a role in determining the fate of IL-1ß, which is concentrated in autophagosomes. This review discusses a growing body of literature that suggests autophagy is a critical regulator of inflammasome activation and the subsequent release of IL-1 family cytokines.

A comparison of the Glycosylation Gap and Hemoglobin Glycation Index in patients with diabetes.

PROBLEM: The Glycosylation Gap (GGAP) based on fructosamine (F) measurement and the Hemoglobin Glycation Index (HGI) based on mean blood glucose (MBG) are two indices of between-individual differences in glycated hemoglobin (HbA1c) adjusted for glycemia. We sought to simultaneously compare GGAP with HGI and other estimates of glycemia. METHODS: HbA1c, F, and MBG level were obtained at a clinic visit from 62 patients with Type 1 diabetes. GGAP and HGI were calculated from the data as previously described. The variables were compared by correlation analysis. The concordance of patient classification by GGAP and HGI was compared by weighted kappa test. RESULTS: The mean HbA1c=11.1+/-2.7%, F=372.0+/-136.6 mol/l, MBG=186.5+/-58.4 mg/dl, HGI=0.0+/-2.0, and GGAP=0.0+/-1.9. MBG, HbA1c, and F were all highly correlated with each other. The HGI and GGAP were highly correlated (r=.73, P<.0001) and similar in both magnitude and direction. There was good agreement between HGI and GGAP classifications of patients into high, moderate, and low glycation groups (P<.0075). CONCLUSIONS: GGAP and MBG give similar information regarding between-patient differences in HbA1c among patients with diabetes. Thus, biological variation in HbA1c is not an artifact of variability in glucose measurements comprising the MBG. Individual patient factors influence the intracellular glycation of HbA1c in addition to the effect of extracellular glycemia, which is manifested as a between-individual biological variation in HbA1c.