Soluble Receptor for Glycation End-products Concentration Increases Following the Treatment of Severe Diabetic Ketoacidosis

Abstract

To determine the time relationships of soluble receptor for glycation end-products (sRAGE), [a decoy of the advanced glycation end-products (AGE)-RAGE axis] and D-lactate, (a metabolite of methylglyoxal) in the inflammatory response to diabetic ketoacidosis (DKA). Methods: Sixteen children and adolescents with type 1 diabetes (T1D) had blood samples obtained, 6-12 hours into treatment, at three weeks and three months post start of treatment. sRAGE and D-lactate concentrations at three months were considered baseline. Expression of RAGE was investigated in the myocardium of a newly diagnosed and untreated young person with fatal T1D/DKA. Results: sRAGE 6-12 hours after the start of treatment was 39% lower than the values at two weeks (p=0.0036) and at three months (p=0.0023) post treatment. D-lactate was higher during treatment than at three weeks (p=0.04) and at three months (p=0.035). Conclusion: sRAGE concentration was decreased during treatment, compared to concentrations at two weeks and three months after treatment. The increased D-lactate during treatment was in keeping with the known increase in dicarbonyls at this time. The finding of RAGE expression in a young myocardium prior to DKA treatment suggested cardiovascular inflammation pre-treatment and at a young age.

Tryptophan, kynurenine pathway, and diabetic ketoacidosis in type 1 diabetes

“…The timing of the early inflammatory surge in DKA that involves the SIR [11] includes the KP. This complexity is supported by other systemic pretreatment longitudinal DKA inflammatory studies that include: TRP depletion [12]; the SIR [11,13]; alpha dicarbonyls/AGE-RAGE [8][9][10]; and the complement cascade [14]. Our study indicates KP is an early participant in the inflammation/ perturbation of DKA and likely begins prior to treatment.…”

“…interval after starting treatment) were published in 2004 [26] prior to the recent reports of the perturbing effects of oxidative [4,5] and inflammatory [8][9][10][11][12][13][14][15][16] DKA stresses.…”

“…Diabetic ketoacidosis (DKA) in type 1 diabetes (T1D) is an acute, complicated, metabolic/ immunologic condition that involves: dehydration [1]; transient hypertension [2,3]; oxidative stress [4,5]; and numerous recognizable metabolic [6][7][8][9][10][11][12] and immunologic dysregulations [13][14][15][16], in addition to a prothrombotic state [17]. The oxidative and inflammatory stresses of the hyperosmolar, acidotic milieu can cause recognized [18] and unrecognized interactions of dysregulated molecules [19,20], resulting in perturbations of various degrees to the paracellular and cellular components of the blood-brain barrier (BBB) and the brain [21,22].…”

“…Our objective was to determine the presence and initiation of the KP in DKA's metabolic and immunologic crisis, and whether it has a potential role in the pathogenesis of the acute vasogenic complication of DKA/BE [6][7][8][9][10][11][12][13][14][15][16][17] by considering: a) KP's time proximity to the transient TRP depletion; b) the transition to the formation of kynurenine metabolites and the metabolic/inflammatory cascade relative to the SIR of DKA; and c) whether these KP metabolites might serve as biomarkers of progressing subclinical BE [42,43].…”

Soluble Receptors Affecting Stroke Outcomes: Potential Biomarkers and Therapeutic Tools

“…Pharmacodynamically, soluble receptors can act as agonists or antagonists [ 5 ]. For example, in granulocyte-macrophage colony-stimulating factor (GM-CSF), soluble receptors may function as competitive antagonists with the membrane-associated receptor for the ligand [ 22 ]. This is consistent with earlier models, suggesting that soluble receptors function as binding proteins and prevent a ligand’s breakdown, which can be seen in receptor growth hormone [ 23 ].…”