Heme & RAGE: A new opportunistic relationship?

Heme is an iron-containing complex involved in fundamental cellular functions including oxygen transport. Free heme accumulation in blood, during intravascular hemolysis and other pathological conditions, triggers vascular dysfunction, pro-inflammatory, and prothrombotic cascade. Studies by May et al present a novel finding that heme is a ligand for RAGE and that heme binds to the V domain of RAGE and induces RAGE oligomerization. Furthermore, they show that the in vivo consequences of heme-RAGE interaction lead to a pro-inflammatory and procoagulant phenotype in the lungs. This discovery of heme as a ligand for RAGE sets the stage for probing the role of RAGE in heme homeostasis and the pathogenic role of heme-RAGE interaction in hemolytic diseases.

Three-year follow-up comparing metabolic surgery versus medical weight management in patients with type 2 diabetes and BMI 30-35. The role of sRAGE biomarker as predictor of satisfactory outcomes.

BACKGROUND: Patients with type 2 diabetes (T2D) and body mass index (BMI)<35 may benefit from metabolic surgery. The soluble form of the receptor for advanced glycation end products (sRAGE) may identify patients at greater chance for T2D remission. OBJECTIVES: To study long-term outcomes of patients with T2D and BMI 30-35 treated with metabolic surgery or medical weight management (MWM) and search for predictors of T2D remission. SETTING: University METHODS: Retrospective review of the original cohort, including patients who crossed over from MWM to surgery. Repeated-measures linear models were used to model weight loss (%WL), change in glycated hemoglobin (HbA1C) and association with baseline sRAGE. RESULTS: Fifty-seven patients with T2D and BMI 30-35 were originally randomly assigned to metabolic surgery versus MWM. Mean BMI and HbA1C was 32.6% and 7.8%, respectively. A total of 30 patients underwent surgery (19 sleeves, 8 bypasses, 3 bands). Three-year follow-up in the surgery group and MWM group was 75% and 86%, respectively. Surgery resulted in higher T2D remission (63% versus 0%; P<.001) and lower HbA1C (6.9% versus 8.4%; P<.001) for up to 3 years. There was no difference in %WL in those with versus those without T2D remission (21.7% versus 20.6%, P = .771), suggesting that additional mechanisms other than %WL play an important role for the studied outcome. Higher baseline sRAGE was associated with greater change in HbA1C and greater %WL after surgery (P< .001). CONCLUSION: Metabolic surgery was effective in promoting remission of T2D in 63% of patients with BMI 30-35; higher baseline sRAGE predicted T2D remission with surgery. Larger-scale randomly assigned trials are needed in this patient population.