Immunologic Effects of Acute Hyperglycemia in Nondiabetic Rats

Kwoun, Moon; Ling, Pei-Ra; Lydon, Erin; Imrich, Amy; Qu, Zhensheng; Palombo, John D.; Bistrian, Bruce R.

doi:10.1177/014860719702100291

Cited by 111 publications

(57 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is ample evidence from studies in diabetes that prolonged hyperglycemia is associated with leukocyte dysfunction (42)(43)(44)(45). In contrast, acute hyperglycemia in nondiabetic animals has been shown to improve leukocyte function (46). However, in this acute in vivo experiment in healthy animals, to achieve hyperglycemia, glucose was infused, which, unlike in our study, evoked a substantial rise of plasma insulin.…”

Section: Discussioncontrasting

confidence: 55%

Survival Benefits of Intensive Insulin Therapy in Critical Illness

Ellger

Debaveye²,

Vanhorebeek³

et al. 2006

Diabetes

203

121

View full text Add to dashboard Cite

Tight blood glucose control with insulin reduces morbidity and mortality of critically ill patients. However, the relative impact of maintaining normoglycemia and of glycemiaindependent actions of insulin remains unknown. We therefore independently manipulated blood glucose and plasma insulin levels in burn-injured, parentally fed rabbits over 7 days to obtain four study groups: two normoglycemic groups with either normal or elevated insulin levels and two hyperglycemic groups with either normal or elevated insulin levels. We studied the relative impact of glycemia and glycemia-independent effects of insulin on survival; myocardial contractility in an open chest preparation; endothelial function in isolated aortic rings; and liver, kidney, and leukocyte function in a rabbit model of critical illness. Mortality was significantly lower in the two normoglycemic groups independent of insulin levels. Maintaining normoglycemia, independent of insulin levels, prevented endothelial dysfunction as well as liver and kidney injury. To increase myocardial systolic function, elevated insulin levels and prevention of hyperglycemia were required concomitantly. Leukocyte dysfunction was present in the two hyperglycemic groups, which could in part be rescued by insulin. The results suggest that the observed benefits of intensive insulin therapy required mainly maintenance of normoglycemia; whereas glycemia-independent actions of insulin exerted only minor, organ-specific impact. Diabetes 55:1096 -1105, 2006 H yperglycemia in critically ill patients is brought about by hepatic and peripheral insulin resistance and by concomitant relative insulin deficiency due to limited compensatory ability of pancreatic ␤-cells, largely independent of the underlying disease (1). Hyperglycemia during critical illness has long been considered essential to provide fuel for vital organ systems and hence was interpreted as a beneficial adaptation. Evidence is now growing against this notion as hyperglycemia is identified as an independent risk factor for adverse outcome of numerous surgical and medical conditions (2-4), and avoiding hyperglycemia with intensive insulin therapy has been shown to improve outcome (5,6). The risks of hyperglycemia comprise increased vulnerability to infectious complications, impaired recovery of organ failure, myocardial dysfunction, and neuromuscular weakness (7-12). The cardiovascular and immune systems thus emerge as two important target systems of glycemic control in the critically ill (7,10,13).It remains unclear, however, to what extent maintaining normoglycemia and glycemia-independent actions of insulin account for the different clinical benefits of intensive insulin therapy in the critically ill. A post hoc analysis of the randomized controlled study of intensive insulin therapy in surgical intensive care patients suggested that blood glucose control best explains the clinical benefits of the intervention (14). In contrast, insulin-induced promotion of glycolysis in cardiomyocytes and a diversion of fatty acids...

show abstract

Section: Discussioncontrasting

confidence: 55%

Survival Benefits of Intensive Insulin Therapy in Critical Illness

Ellger

Debaveye²,

Vanhorebeek³

et al. 2006

Diabetes

203

121

View full text Add to dashboard Cite

show abstract

“…Así entonces, este estado de inmunoparálisis puede contribuir a la adquisición de infecciones fúngicas en pacientes sin otras condiciones predisponentes más que una disfunción orgánica múltiple 21,22 . Por otra parte, la existencia de hiperglicemia es conocida como deletérea para la función inmune de los neutrófilos periféricos 23 . Otro factor predisponerte habitualmente señalado en diversas comunicaciones es el uso de corticoesteroides 7,24 .…”

Section: Discussionunclassified

Aspergilosis invasora multisistémica en un niño inmunocompetente: Comunicación de un caso

et al. 2006

Rev. chil. infectol.

View full text Add to dashboard Cite

Invasive aspergillosis is a severe disease, with an increased incidence in last decades. It occurs mainly in immunocompromised patients and rarely affects immunocompetent hosts. We describe a previously healthy 8 -year-old boy who acquired an invasive aspergillosis of abdominal origin associated with an opened laparotomy; within three weeks the patient progressed to a multiple organic failure syndrome and died despite amphotericin B deoxycolate plus voriconazole treatment and aggressive surgical debridement. Necropsy revealed multiple parenchyma involvement with characteristic findings of angioinvasive aspergillosis. Invasive aspergillosis must be considered an emergent infection in critical pediatric patients, including previously immunocompetent hosts; it is associated with high mortality despite adequate and opportune therapy.Key words: immunocompetent, invasive aspergillosis, Aspergillus fumigatus, pediatrics. Palabras claves: inmunocompetente, aspergillosis invasora, Aspergillus fumigatus, pediatría. Caso ClínicoHospital Padre Hurtado.Área de Cuidados Críticos.Unidad de Gestión Clínica del Niño (ADF, JCA). Laboratorio Microbiología (PAL)Universidad del DesarrolloClínica Alemana Programa de Medicina IntensivaInfantil (PCR). Recibido: 28-06-05Aceptado: 24-11-05Correspondencia a:Alejandro Donoso Fuentes adonoso@hurtadohosp.cl Caso clínicoPaciente de 8 años, sexo masculino, operado de peritonitis apendicular seis meses antes, cuya histología mostró un apéndice de aspecto isquémico con perforación puntiforme en su tercio distal; sin otros antecedentes mórbidos de importancia. Consultó a su hospital de origen por dolor periumbilical progresivo y 3 días de evolución, vómitos biliosos, fiebre 39ºC, anorexia y compromiso del estado general, cuadro interpretado como una obstrucción intestinal complicada y shock séptico secundario. Durante el acto quirúrgico se demostró obstrucción por bridas, con perforación y necrosis de ileon distal y peritonitis secundaria, realizándose una resección ileal de 20 cm y laparotomía contenida. Al tercer día post operatorio fue derivado a nuestro centro por persistir en anuria y necesitar de terapia de reemplazo renal. Al ingreso estaba en shock séptico descompensado, por lo que requirió soporte vasoactivo con epinefrina. Se inició inmediatamente hemofiltración veno-venosa continua y monitorización invasora, antibioterapia con ampicilina, cefotaxima y metronidazol, y nutricional parenteral total. A las 24 horas se realizó laparotomía exploradora, aseo, quedando nuevamente con laparotomía contenida. En una re-exploración al día siguiente se efectuó resección de 10 cm de ileon necrótico. Requirió terapia con infusión de insulina Introducción spergillus es un hongo filamentoso hialino de amplia distribución. Existen aproximadamente doscientas especies conocidas, pero sólo unas pocas son patógenas para el ser humano, siendo la más común Aspergillus fumigatus. La infección habitualmente ocurre por inhalación del conidio, causando una variedad de síndromes clínicos, desde un aspergiloma hast...

show abstract

“…Basic science research indicates that nondiabetic hospitalized patients who receive dextrose solutions at rates >4 g=kg=min (e.g., total parenteral nutrition [TPN] solutions) have a 50% chance of developing hyperglycemia [32]. There were 20 patients of the 356 who received TPN during their admissions.…”

Section: Mowery Et Almentioning

confidence: 99%

Insulin Resistance Heralds Positive Cultures after Severe Injury

Mowery

Carnevale

Gunter

et al. 2009

Surgical Infections

View full text Add to dashboard Cite

"Insulin resistance heralds positive cultures after severe injury." Surgical infections. 10,6. 503-509. (2009 Background: Insulin resistance and hyperglycemia are common in acutely injured patients, and associated with poor outcomes. In the era of tight glucose control, measures of insulin responsiveness (IR) may provide a better indicator of patient status than does the serum glucose concentration. We hypothesized that measures of IR during tight glycemic control protocols are associated with infection and may be more predictive than the serum glucose concentration.Methods: All critically injured, mechanically ventilated patients undergo protocolized tight glycemic control with the aid of a computer-based system that calculates the insulin dose using an adapting multiplier (insulin dose ¼ [blood glucose -60)ÂM). Consecutive patients on protocol were studied to identify the incidence of positive sterile-site or quantitative bronchoalveolar lavage cultures (>10 4 colony-forming units=mL). Patients were stratified by presence and number of positive cultures and analyzed by both serum glucose measures and measures of IR (average multiplier and average insulin infusion rate). Results: During the six-month study period, 356 patients were placed on the tight glycemic control protocol. Of these, 101 patients had 192 positive cultures. Patients with positive cultures required significantly more hourly insulin than those without a positive culture (3.7 vs. 2.8 units=h; p ¼ <0.001). Logistic regression showed the insulin dose (odds ratio 2.1; 95% confidence interval 1.6, 3.0; p ¼ <0.001) and the adapting multiplier to be independent predictors of the patient having a positive culture among other factors associated with nosocomial infection. Conclusions: Insulin resistance, quantified by hourly insulin dose and median multiplier, confers a higher risk of systemic nosocomial infection. Patients with positive cultures actually had lower admission and median blood glucose values over their intensive care unit stays, highlighting the decreased value of this measure as a predictor of outcome in the setting of tight glucose control. A greater insulin requirement suggesting resistance may be used as a marker of a higher risk of nosocomial infection.

show abstract

Immunologic Effects of Acute Hyperglycemia in Nondiabetic Rats

Abstract: We conclude that hyperglycemia itself can influence immune function in some phagocytic cells, which may be an important factor in postsurgical infection.

Cited by 111 publications

References 24 publications

Survival Benefits of Intensive Insulin Therapy in Critical Illness

Survival Benefits of Intensive Insulin Therapy in Critical Illness

Aspergilosis invasora multisistémica en un niño inmunocompetente: Comunicación de un caso

Insulin Resistance Heralds Positive Cultures after Severe Injury

Contact Info

Product

Resources

About