Hyperglycemia, Insulin, and Insulin Resistance in Sepsis

Rivas, Ana Marcella; Nugent, Kenneth

doi:10.1016/j.amjms.2020.11.007

Cited by 21 publications

(10 citation statements)

References 40 publications

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“…This suggests a concordance of conditions that cause sepsis and hypophosphatemia. Overall, the distribution of underlying infections in our population of dogs with presumptive sepsis was similar to various previous studies (14,21,22,(41)(42)(43).…”

Section: Discussionsupporting

confidence: 89%

“…For instance, use of insulin has been established as a risk factor for hypophosphatemia in dogs and cats ( 8 , 9 ). In critically ill humans with sepsis, tight glucose regulation using insulin to manage disease-associated hyperglycemia has been commonly practiced ( 44 ). It is unknown how many of the dogs in the present study received insulin, but insulin is rarely used to manage hyperglycemia associated with critical illness in our institution and hence the percentage is likely small.…”

Section: Discussionmentioning

confidence: 99%

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Hypophosphatemia in Dogs With Presumptive Sepsis: A Retrospective Study (2008–2018)

et al. 2021

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Background: In humans with sepsis, hypophosphatemia is a marker of illness severity and a negative prognostic indicator. Hypophosphatemia has not been previously investigated in dogs with sepsis, however. This study aimed to estimate the prevalence of hypophosphatemia in dogs, the prevalence of presumptive sepsis in dogs with hypophosphatemia, the prevalence of hypophosphatemia in dogs with presumptive sepsis and the association between outcome and hypophosphatemia in dogs with presumptive sepsis.Methods: Electronic medical records of the Cornell University Hospital for Animals from 2008–2018 were queried to identify all dogs with hypophosphatemia and all dogs with presumptive sepsis. Hypophosphatemia was defined as a serum phosphate concentration <2.7 mg/dL. Sepsis was presumed where ≥2 of 4 systemic inflammatory response syndrome (SIRS) criteria were satisfied associated with a documented or highly suspected infection. Variables were assessed for normality using the D'Agostino-Pearson test. Continuous variables were compared between groups using the Mann-Whitney U test. Differences in frequency between categorical variables were analyzed using contingency tables, calculation of Fisher's exact test or Chi2 and estimation of odds ratios.Results: In the study period, 47,992 phosphate concentration measurements from 23,752 unique dogs were identified. After eliminating repeat analyses, the period prevalence of hypophosphatemia on a per dog basis over the 11-year study period was 10.6% (2,515/23,752). The prevalence of presumptive sepsis within dogs with hypophosphatemia was 10.7% (268/2,515). During the 11-year study period, 4,406 dogs with an infection were identified, of which 1,233 were diagnosed with presumptive sepsis and had a contemporaneous phosphate concentration. Hypophosphatemia was more prevalent in dogs with presumptive sepsis than in dogs without 21.7 vs. 10.2%; OR 2.44 [95% CI 2.12–2.81]; P < 0.0001. The mortality rate was greater in dogs with hypophosphatemia and presumptive sepsis than in dogs with hypophosphatemia without presumptive sepsis (15.3 vs. 3.1%; OR 5.70 [95% CI 3.76–8.52]; P < 0.0001), however hypophosphatemia was not associated with outcome in dogs with presumptive sepsis OR 0.87 [95% CI 0.60–1.26]; P = 0.518.Conclusions: In dogs with hypophosphatemia, a presumed diagnosis of sepsis was associated with increased mortality compared to other associated disease processes. In dogs with presumptive sepsis, hypophosphatemia was not associated with outcome.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Hypophosphatemia in Dogs With Presumptive Sepsis: A Retrospective Study (2008–2018)

et al. 2021

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“…Decreased insulin sensitivity may occur due to disruption of various molecular pathways. The exact underlying cause of insulin resistance remains unclear, with a number of key mechanisms proposed, including oxidative stress, inflammation, insulin receptor mutations, endoplasmic reticulum stress, and mitochondrial dysfunction [8,9]. Therefore, we make the assumption that the development of insulin resistance in patients with tuberculosis was associated with the severe course of the disease.…”

Section: Resultsmentioning

confidence: 99%

Pro-atherogenic lipid profile in pulmonary tuberculosis patients with concurrent insulin resistance

Shvets

Шевченко

Piskur

et al. 2021

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Background. The problem of studying lipid metabolism in patients with tuberculosis is of interest to scientists around the world. The purpose of the study - to investigate lipid profile in pulmonary tuberculosis patients with concurrent insulin resistance. Materials and methods. Forty-one patients with pulmonary tuberculosis were examined. Insulin resistance index (HOMA-IR), total cholesterol level (TC), triglycerides (TG) level, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol and atherogenic index (AI) were measured. Results. Group 1 - 26 patients with tuberculosis and insulin resistance (HOMA-IR ˃ 2.7); Group 2 – 15 patients with tuberculosis without insulin resistance (HOMA-IR ˂ 2.7). Group 1 patients had severe course of TB with fever, severe fatigue and weakness, profuse sweating, weight loss, cough and shortness of breath. Median TC indices differed at significant level (p = 0.012): group 1 - 4.82 mmol/l, group 2 - 4.25 mmol/l. TG level was higher in group 1 patients - 1.32 mmol/l than in group 2 patients - 1.28 mmol/l. LDL cholesterol values were higher in group 1 patients - 3.2 mmol/l vs 2.5 mmol/l in group 2. The AI was higher in group1 (p = 0.005): 3.9 units against 2.8 units in group 2 patients. Conclusions. Insulin resistance in pulmonary tuberculosis patients was associated with severe course of the disease, severe clinical manifestations and impaired external respiration. Pro-atherogenic disorders of lipid metabolism in pulmonary tuberculosis patients with concurrent insulin resistance can be considered as the degree of endogenous intoxication.

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“…Based on the results from the KEGG analysis regarding the upregulated acetylome, the acetylation increased in four proteins-ALDOA, PGK1, ENO1, and PKM2-in the glycolysis pathways. The sepsis metabolism is associated with various metabolic changes, including insulin resistance, hyperlactatemia, hypoglutaminemia, hypercatabolism, and muscle wasting [33][34][35][36]. In particular, an increase in lactate concentration, a diagnostic marker in the early stages of sepsis, is thought to be a sign of acute organ dysfunction [37].…”

Section: Discussionmentioning

confidence: 99%

Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis

Paudel

Choi

et al. 2021

IJMS

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Sepsis-induced liver dysfunction (SILD) is a common event and is strongly associated with mortality. Establishing a causative link between protein post-translational modification and diseases is challenging. We studied the relationship among lysine acetylation (Kac), sirtuin (SIRTs), and the factors involved in SILD, which was induced in LPS-stimulated HepG2 cells. Protein hyperacetylation was observed according to SIRTs reduction after LPS treatment for 24 h. We identified 1449 Kac sites based on comparative acetylome analysis and quantified 1086 Kac sites on 410 proteins for acetylation. Interestingly, the upregulated Kac proteins are enriched in glycolysis/gluconeogenesis pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) category. Among the proteins in the glycolysis pathway, hyperacetylation, a key regulator of lactate level in sepsis, was observed at three pyruvate kinase M2 (PKM2) sites. Hyperacetylation of PKM2 induced an increase in its activity, consequently increasing the lactate concentration. In conclusion, this study is the first to conduct global profiling of Kac, suggesting that the Kac mechanism of PKM2 in glycolysis is associated with sepsis. Moreover, it helps to further understand the systematic information regarding hyperacetylation during the sepsis process.

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Hyperglycemia, Insulin, and Insulin Resistance in Sepsis

Cited by 21 publications

References 40 publications

Hypophosphatemia in Dogs With Presumptive Sepsis: A Retrospective Study (2008–2018)

Hypophosphatemia in Dogs With Presumptive Sepsis: A Retrospective Study (2008–2018)

Pro-atherogenic lipid profile in pulmonary tuberculosis patients with concurrent insulin resistance

Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis

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