c-peptide and Acute-Phase-Reaction

Patients with type 2 diabetes (DM) demonstrate inadequate insulin release, elevated gluconeogenesis, and diminished nonoxidative glucose disposal. Similar metabolic changes occur during systemic injury caused by infection, trauma, or cancer. Described here are metabolic changes occurring in 16 DM and 11 lung cancer patients (CA) and 13 normal volunteers (NV). After a 10-h overnight fast, all subjects had fasting hormone and substrate concentrations determined, along with rates of glucose production, leucine appearance (LA), and leucine oxidation (LO). Fasting insulin (data not shown) and C-peptide concentrations were elevated in DM and CA compared with weight-matched NV (0.72 +/- 0.09 and 0.64 +/- 0.08 vs. 0.51 +/- 0.03 mg/l, P < 0.05). C-reactive protein concentration was elevated in CA compared with DM and NV (23.3 +/- 6.0 vs. 4.2 +/- 1.4 and 2.1 +/- 0.5 mg/l, P < 0.01). All counterregulatory hormones were normal except for serum cortisol (11.4 +/- 1.0 and 12.1 +/- 1.0 vs. 8.9 +/- 0.7 microg/dl, DM and CA vs. NL, respectively, P < 0.05). Glucose production was increased in DM and CA compared with NV (4.22 +/- 0.6 and 3.53 +/- 0.3 vs. 2.76 +/- 0.2 mg x kg lean body wt(-1) x min(-1), P < 0.01). LO and LA were increased in DM and CA compared with NV (LO: 27.3 +/- 1.5 and 19.7 +/- 1.5 vs. 12.5 +/- 1.1 mmol x kg lean body wt(-1) x min(-1), P < 0.05; LA: 91.9 +/- 6.6 and 90.7 +/- 7.0 vs. 79.1 +/- 6.0 mmol. kg lean body wt(-1) x min(-1), P < 0.01). DM share similar metabolic derangements with CA. The increase in LA may be secondary to an increased glucose production where amino acids are mobilized to provide the liver with adequate substrate to make glucose. The increase in glucose production may also be part of the injury response, or it may represent a form of insulin resistance that exists in both the DM and (non-DM) CA patients.

Topics: Acute-Phase Reaction; Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluconeogenesis; Humans; Hydrocortisone; Insulin; Interleukin-6; Leucine; Lung Neoplasms; Middle Aged; Triiodothyronine; Tumor Necrosis Factor-alpha

Topics: Acute-Phase Reaction; Adaptation, Physiological; C-Peptide; Dinoprostone; Energy Metabolism; Humans; Hydrocortisone; Insulin; Insulin Resistance; Insulin Secretion; Muscle Proteins; Muscle, Skeletal; Receptor, Insulin; Space Flight; Stress, Physiological

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