Diabetic Hyperglycemia: A Facilitating Factor in Systemic Capillary Leak

Lawson, Stephen; Ward, David T.; Conner, Chance; Gallagher, Christopher; Tsokos, George C.; Shea‐Donohue, Terez

doi:10.1006/jsre.2002.6370

Cited by 10 publications

(6 citation statements)

References 18 publications

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“…Chronic extravasation of albumin modifies the size and composition of the interstitium, which causes disturbances in the traffic of fluid and vital substrates to the cellular mass and in the removal of waste products in the opposite direction (6). Accordingly, capillary leakage contributes to the increased susceptibility to local and systemic injury of diabetic organs (39).…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation

et al. 2007

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Increased permeability to albumin is a well-known feature of diabetic microvasculature and a negative prognostic factor of vascular complications. The mechanisms responsible for loss of the physiological albumin barrier in diabetic organs remain only partially understood. We have recently demonstrated that the protease -calpain is activated in hyperglycemia, which causes endothelial dysfunction and vascular inflammation. In the present study, we investigated whether -calpain is involved in the hyperpermeability of the diabetic vasculature. We also investigated the mechanistic roles of hyperglycemia and leukocyte adhesion in this process. Albumin permeability in the intact microcirculation of the Zucker diabetic fatty (ZDF) rat was quantified by intravital microscopy. Extravasation of albumin in the microcirculation of ZDF rats was significantly increased when compared with nondiabetic Zucker lean (ZL) rats. Microvascular albumin leakage was prevented by either antisense depletion of -calpain or pharmacological inhibition of calpain in vivo. Calpain inhibition also attenuated urinary albumin excretion in ZDF rats. Glucose concentrations in the range of those found in the blood of ZDF rats increased albumin permeability in nondiabetic ZL rats. Thus, this demonstrates a mechanistic role for hyperglycemia in the hypermeability of diabetes. Depletion of polymorphonuclear leukocytes in vivo failed to prevent glucose-induced hypermeability, which suggests that hyperglycemia can disrupt the physiological endothelial cell barrier of the microcirculation, even in the absence of increased overt leukocyte-endothelium interactions.

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Section: Discussionmentioning

confidence: 99%

Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation

et al. 2007

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“…The respiratory burst of neutrophils from diabetic patients is primed , and p47phox is phosphorylated and translocates to the plasma membrane. This primed neutrophil state could be the result of hyperglycemia itself , hyperlipidemia , or advanced glycation end products (AGEs) , all associated with diabetes.…”

Section: Role Of Priming In Pathological Inflammation: ‘When the Goodmentioning

confidence: 99%

Priming of the neutrophil respiratory burst: role in host defense and inflammation

El-Benna

Hurtado-Nédelec

Marzaioli

et al. 2016

Immunological Reviews

377

328

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Neutrophils are the major circulating white blood cells in humans. They play an essential role in host defense against pathogens. In healthy individuals, circulating neutrophils are in a dormant state with very low efficiency of capture and arrest on the quiescent endothelium. Upon infection and subsequent release of pro-inflammatory mediators, the vascular endothelium signals to circulating neutrophils to roll, adhere, and cross the endothelial barrier. Neutrophils migrate toward the infection site along a gradient of chemo-attractants, then recognize and engulf the pathogen. To kill this pathogen entrapped inside the vacuole, neutrophils produce and release high quantities of antibacterial peptides, proteases, and reactive oxygen species (ROS). The robust ROS production is also called 'the respiratory burst', and the NADPH oxidase or NOX2 is the enzyme responsible for the production of superoxide anion, leading to other ROS. In vitro, several soluble and particulate agonists induce neutrophil ROS production. This process can be enhanced by prior neutrophil treatment with 'priming' agents, which alone do not induce a respiratory burst. In this review, we will describe the priming process and discuss the beneficial role of controlled neutrophil priming in host defense and the detrimental effect of excessive neutrophil priming in inflammatory diseases.

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“…However, there are some reports claiming hyperglycemia is an independent risk factor for ISCLS in newborns [ 22 ]. Diabetic rats exhibited significant mucosal injury after 10 min of ischemia and 1 hour of reperfusion that was associated with significant capillary leak [ 23 ]. Transient hyperglycemia was reported during acute attacks of ISCLS, but the relationship between DM and ISCLS is obscure [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

A Remarkable Coexistence of Systemic Capillary Leak Syndrome and Diabetes in an 11-Year-Old Boy: A Case Report and Review of the Literature

Ata

Özen

Gökşen

et al. 2020

Case Reports in Immunology

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Systemic capillary leak syndrome (ISCLS) is a rare disease characterized by unexplained reversible capillary hyperpermeability followed by hypoperfusion, hemoconcentration, and either hypoalbuminemia or total hypoproteinemia. An 11-year-old boy was admitted with vomiting, generalized edema, and hyperglycemia, which was preceded by 5 days of coryzal symptoms, lethargy, and oral aft, without fever. On physical examination, he had tachycardia and hypotension, with severe generalized systemic nonitchy edema, and the laboratory tests supported the conclusion that he had severe hemoconcentration with hemoglobin: 184 g/L, hematocrit: 51.3 %, urea: 20 mmol/L, blood glucose: 11.1 mmol/L, and albumin: 19 gr/L, with normal urine analysis. On the fourth day, the patient was diagnosed with ISCLS, by ruling out other causes of shock and hypoalbuminemia. Intravenous immunoglobulin (IVIG) treatment regimen was administered on two consecutive days (day five and day six). His edema decreased on the fifth day, and the patient was deemed clinically well. There was no compartment syndrome, rhabdomyolysis, or pulmonary edema in the recovery period. However, respiratory virus panel PCR was positive for respiratory syncytial virus (RSV) and enterovirus, which were thought to be the triggering cause of ISCLS. For the differential diagnosis of diabetes, his fasting serum glucose was 13.4 mmol/L, simultaneous C-peptide was 0.44 nmol/L, and HbA1c was 64 mmol/mol, and urine ketone was positive. However, antiglutamic acid decarboxylase, anti-insulin antibody, and islet cell antibody were negative. At the last outpatient visit, 22 months after the diagnosis, his insulin dose was still 0.4 IU/kg/day and HbA1c was 40 mmol/mol, and without prophylaxis, there was no ISCLS attack. Conclusion. Early recognition of ISCLS is important for therapeutic awareness, since it is very rare in childhood and occurs usually without any prior provoking factors in healthy children. With the increase in awareness of the disease, knowledge and experiences about pediatric patients may also increase. We think that our case will contribute to the literature since there have been no pediatric diabetic patients with ISCLS reported.

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Diabetic Hyperglycemia: A Facilitating Factor in Systemic Capillary Leak

Cited by 10 publications

References 18 publications

Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation

Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation

Priming of the neutrophil respiratory burst: role in host defense and inflammation

A Remarkable Coexistence of Systemic Capillary Leak Syndrome and Diabetes in an 11-Year-Old Boy: A Case Report and Review of the Literature

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