c-peptide and Burns

Metabolic alterations after burn injury have been well described in children; however, in adult patients, glucose metabolism and insulin sensitivity are essentially unknown. We sought to characterize metabolic alterations and insulin resistance after burn injury and determine their magnitude and persistence at discharge.. Prospective, cohort study.. Tertiary burn centre.. Nondiabetic adults with an acute burn involving greater than or equal to 20% total body surface area.. An oral glucose tolerance test was administered at discharge.. Glucose, insulin, and C-peptide levels were measured to derive surrogate measures of insulin resistance and β-cell function, including quantitative insulin sensitivity check index, homeostasis model assessment of β-cell function, homeostasis model assessment of insulin sensitivity, homeostasis model assessment of insulin resistance, and the composite whole-body insulin sensitivity index. Patients were grouped according to the degree of glucose tolerance: normal glucose tolerance, impaired fasting glucose/impaired glucose tolerance, or diabetes. Forty-five adults, 44 ± 15 years old and with 38% ± 14% total body surface area burned, underwent an oral glucose tolerance test at discharge. Median quantitative insulin sensitivity check index (0.348 [0.332-0.375]) and median homeostasis model assessment of insulin resistance (1.13 [0.69-1.45]) were abnormal, indicating insulin resistance and impaired insulin production at discharge. Two-thirds of patients (n = 28) met criteria for impaired fasting glucose/impaired glucose tolerance or diabetes.. We have demonstrated that burn-injured adults remain hyperglycemic, are insulin resistant, and express defects in insulin secretion at discharge. Patients with lower burn severity (total body surface area, 20-30%) express similar metabolic alterations as patients with larger burns (total body surface area, ≥ 30%). Glucose tolerance testing at discharge offers an opportunity for early identification of burn patients who may be at high risk of prediabetes and diabetes. Our findings demonstrated that two-thirds of burn patients had some degree of glucose intolerance. With this in mind, surveillance of glucose intolerance post discharge should be considered. As hyperglycemia and insulin resistance are associated with poor outcomes, studies should focus on how long these profound alterations persist.

Topics: Adult; Aged; Blood Glucose; Body Surface Area; Burns; C-Peptide; Female; Glucose; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Patient Discharge; Prospective Studies; Young Adult

Mammalian target of rapamycin (mTOR) is an important mediator for cross talk between nutritional signals and metabolic signals of insulin by downregulating insulin receptor substrate proteins. Therefore, mTOR inhibition could become a therapeutic strategy in insulin-resistant states, including insulin resistance induced by burn. We tested this hypothesis in the rat model of 30% TBSA full thickness burn, using the mTOR inhibitor rapamycin. Rapamycin (0.4 mg/kg, i.p.) was injected 2 h before euglycemic-hyperinsulinemic glucose clamps at 4 days after burn. IRS-1, phospho-serine³⁰⁷, phospho-tyrosine of IRS-1 and phospho-mTOR in muscle tissue were determined by immunoprecipitation and Western blot analysis or immunohistochemistry. Plasma TNF-α, insulin and C-peptide were determined before and after euglycemic-hyperinsulinemic glucose clamps. Our data showed that TNF-α, insulin and C-peptide significantly increased in the early stage after burn (P < 0.01). The infused rates of total 10% glucose (GIR, mg/kg min) significantly decreased at 4 days after burn. The level of IRS-1 serine³⁰⁷ phosphorylation in muscle in vivo significantly increased after burn (P < 0.01), while insulin-induced tyrosine phosphorylation of IRS-1 significantly decreased (P < 0.01). Inhibition of mTOR by rapamycin inhibited the phosphorylation of mTOR, reduced serine³⁰⁷ phosphorylation, elevated tyrosine phosphorylation and partly prevented the decrease of GIR after burn. However, TNF-α, insulin and C-peptide were not decreased by rapamycin treatment postburn. Taken together, these results indicate that the mTOR pathway is an important modulator of the signals involved in the acute regulation of insulin-stimulated glucose metabolism, and at least, partly contributes to burn-induced insulin resistance. mTOR inhibition may become a therapeutic strategy in insulin-resistant states after burn.

Topics: Animals; Anti-Bacterial Agents; Blotting, Western; Burns; C-Peptide; Disease Models, Animal; Glucose Clamp Technique; Immunohistochemistry; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Muscle, Skeletal; Phosphorylation; Phosphoserine; Phosphotyrosine; Rats; Rats, Sprague-Dawley; Serine; Sirolimus; TOR Serine-Threonine Kinases; Tumor Necrosis Factor-alpha

The acute hypermetabolic response post-burn is associated with insulin resistance and hyperglycemia, significantly contributing to adverse outcome of these patients.. The aim of the study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree of insulin resistance in severely burned children for up to 3 yr after the burn injury.. A total of 194 severely burned pediatric patients, admitted to our institute between 2002 and 2007, were enrolled in this prospective study and compared to a cohort of 95 nonburned, noninjured children.. Urinary cortisol, epinephrine, and norepinephrine, serum cytokines, and resting energy requirements were determined at admission and 1, 2, 6, 9, 12, 18, 24, and 36 months post-burn. A 75-g oral glucose tolerance test was performed at similar time points; serum glucose, insulin, and C-peptide were measured; and insulin sensitivity indices, such as ISI Matsuda, homeostasis model assessment, quantitative insulin sensitivity check index, and ISI Cederholm, were calculated. Statistical analysis was performed by ANOVA with Bonferroni correction with significance accepted at P < 0.05.. Urinary cortisol and catecholamines, serum IL-7, IL-10, IL-12, macrophage inflammatory protein-1b, monocyte chemoattractant protein-1, and resting energy requirements were significantly increased for up to 36 months post-burn (P < 0.05). Glucose values were significantly augmented for 6 months post-burn (P < 0.05), associated with significant increases in serum C-peptide and insulin that remained significantly increased for 36 months compared to nonburned children (P < 0.05). Insulin sensitivity indices, ISI Matsuda, ISI quantitative insulin sensitivity check index, and homeostasis model assessment were abnormal throughout the whole study period, indicating peripheral and whole body insulin resistance. The insulinogenic index displayed physiological values, indicating normal pancreatic beta-cell function.. A severe burn is associated with stress-induced insulin resistance that persists not only during the acute phase but also for up to 3 yr post-burn.

Topics: Adolescent; Area Under Curve; Blood Glucose; Body Height; Burns; C-Peptide; Calorimetry, Indirect; Catecholamines; Child; Child, Preschool; Cohort Studies; Cytokines; Female; Glucose Tolerance Test; Glycated Hemoglobin; Growth; Hormones; Humans; Hydrocortisone; Infant; Infant, Newborn; Insulin; Insulin Resistance; Male; Prospective Studies

Several of the possible molecular mechanisms that contribute to the insulin resistance associated with burn injury were examined in a rat model of thermal injury. Rats were subjected to full thickness scald injury (25% total body surface area, 10 sec burn) and resuscitated with saline. After 1, 2 and 3 weeks, urinary C-peptide excretion was measured in burned and sham-treated control animals. At 3 weeks after injury, glucose production by the liver and utilization by skeletal muscle was measured under insulin clamp conditions, insulin receptor binding was measured in skeletal muscle, liver and adipose tissue membranes and IRS-1 expression was measured by Western blot methods. Urinary C-peptide excretion was significantly elevated at 1, 2 and 3 weeks after injury. At 3 weeks after injury, several key metabolic processes were blunted, including the ability of insulin infusion to stimulate glucose uptake by skeletal muscle, the potency of insulin infusion for inhibiting hepatic glucose production, and the ability of a bolus injection of insulin to simulate phosphorylation of IRS-1 in liver, skeletal muscle or adipose tissue. In contrast, there were no apparent alterations in the binding of insulin to membranes from liver, skeletal muscle or adipose tissue. These findings support the concept that the burn injury stimulates insulin production 3 weeks after burn injury, and produces insulin resistance in skeletal muscle, adipose tissue and liver by processes that are associated with post-receptor alterations in the absence of changes in insulin receptor binding.

Topics: Adipose Tissue; Animals; Burns; C-Peptide; Glucose; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Liver; Male; Membranes; Muscle, Skeletal; Phosphoproteins; Phosphotyrosine; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Temperature

Animal experiments demonstrate that interleukin-1 beta (IL-1 beta) is beta-cell cytotoxic in vitro and inhibits insulin secretion in vivo. However, it is unknown if IL-1 beta affects beta-cell function in man. Since IL-1 beta and other cytokines are main mediators of the acute phase response, the objectives of the present study were to examine beta-cell function in patients with major burn injuries, and to test if changes in beta-cell function correlated to systemic levels of IL-1 beta and tumour necrosis factor alpha (TNF alpha). We established and validated an IL-1 beta assay measuring free and protein bound IL-1 beta; protein bound IL-1 beta was detached from the IL-1 beta specific binding protein by acidification, rendering it accessible for the employed antibody. The IL-1 beta specific binding protein (43-60 kDa) was found in serum and plasma from all tested patients and normal subjects. Survivors of burn injuries had a stimulated beta-cell function, whereas non-survivors had an impaired beta-cell function as indicated by an increased plasma concentration of proinsulin, and an increased proinsulin/insulin ratio. In addition, non-survivors had significantly increased plasma levels of IL-1 beta. However, we could not demonstrate any correlation between C-peptide, proinsulin, insulin or proinsulin/insulin ratio and plasma concentration of IL-1 beta. In conclusion, beta-cell function abnormalities are evident in patients with major burn injuries, and a high plasma level of IL-1 beta correlates with a fatal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute-Phase Reaction; Adult; Burns; C-Peptide; Carrier Proteins; Female; Humans; Insulin; Insulin Secretion; Interleukin-1; Islets of Langerhans; Male; Middle Aged; Prognosis; Proinsulin; Tumor Necrosis Factor-alpha

Plasma concentrations of glucose, insulin, C-peptide, glucagon, cortisol and hGH were measured in burn patients (mean burn surface area 21 per cent) treated or not with ornithine alpha-ketoglutarate (OKG). An increase in basal values of glucose, insulin, C-peptide and cortisol was demonstrated in both groups, whereas hGH values diminished. OKG modified neither insulin nor hGH values 24 h after its enteral administration nor insulin levels within the first 4 h after intake. On the other hand, 60 min after enteral nutrition was restarted the hyperglycaemia observed in untreated subjects was reduced by OKG whereas a hyperinsulinism was observed in both groups. These results suggest that: (i) the anticatabolic/anabolic action of OKG in burn patients is not mediated by insulin or hGH, (ii) OKG probably induces an increase in glucose tolerance in burn patients, in whom there is a state of insulin resistance. The mechanism of this action requires further study.

Topics: Adolescent; Adult; Blood Glucose; Burns; C-Peptide; Female; Glucagon; Growth Hormone; Humans; Hydrocortisone; Insulin; Kinetics; Male; Middle Aged; Ornithine