Polymorphonuclear leucocyte dysfunction during short term metabolic changes from normo- to hyperglycemia in type 1 (insulin dependent) diabetic patients

Abstract

Polymorphonuclear leucocyte (PMN) ingestion of particles coated with lipopolysaccharide (LPS) from Escherichia coli was compared to other PMN functions in seven patients with insulin dependent diabetes mellitus (IDDM) during short-term controlled metabolic changes from normo- to hyperglycemia without ketoacidosis. Factors known to interfere with PMN functions were excluded. PMN ingestion of particles coated with both LPS and bovine serum albumin became reduced from normo- to hyperglycemia. PMN motility was impaired in IDDM, but did not seem to be affected by short-term changes in metabolic control. PMN metabolism did not change from normo-to hyperglycemia. Particle-uptake by diabetic PMN is impaired after short term hyperglycemia in the range normally occurring in diabetics in every-day life.

Augmentation of the Neutrophil Respiratory Burst Through the Action of Advanced Glycation End Products

“…The reversibility of the AGE effect may lead to neutrophils being only transiently in an activated state at sites of heavy AGE accumulation and reverting to a nearer normal state on relocation to other parts of the circulation or nonvascular compartments. Also, hyperglycemia per se is cytotoxic, impeding effective neutrophil functioning (37). Thus, neutrophil function under conditions of acute hyperglycemia differs from that during times when metabolic control is closer to physiological parameters but when the legacy of past metabolic indiscretions has led to accelerated AGE accumulation.…”

Hyperglycemia in the Intensive Care Unit: No Longer Just a Marker of Illness Severity

“…In addition, one study was able to demonstrate an increase in the number of circulating neutrophils after insulin infusion, possibly due to a decrease in their endothelial adherence [58]. Additionally, it has been well-documented both in vitro and in vivo that neutrophil phagocytic capacity is altered during brief episodes of hyperglycemia in non-diabetic patients [62]. …”

Insulin-stimulated chemokinesis in normal human neutrophils is dependent on D-glucose concentration and sensitive to inhibitors of tyrosine kinase and phosphatidylinositol 3-kinase

“…Moreover, the chemokinetic response in neutrophils can easily be measured by studying changes in neutrophil random locomotion [5]. Diabetics are well-known to suffer from impaired neutrophil chemotaxis [2,[6][7][8], whereas the random locomotion in neutrophils from diabetic patients has been found to be normal [2,7] or decreased [9].…”