c-peptide and Fever

Anti-CD3 mAbs may prolong beta cell function up to 2 years in patients with new onset Type 1 diabetes (T1DM). A randomized open label trial of anti-CD3 mAb, Teplizumab, in T1DM was stopped after 10 subjects because of increased adverse events than in a previous trial related with higher dosing of drug. Teplizumab caused transient reduction in circulating T cells, but the recovered cells were not new thymic emigrants because T cell receptor excision circles were not increased. There was a trend for reduced loss of C-peptide over 2 years with drug treatment (p=0.1), and insulin use was lower (p<0.001). In 4 drug-treated subjects followed up to 60 months, C-peptide responses were maintained. We conclude that increased doses of Teplizumab are associated with greater adverse events without improved efficacy. The drug may marginate rather than deplete T cells. C-peptide levels may remain detectable up to 5 years after treatment.

Topics: Adolescent; Antibodies, Monoclonal, Humanized; C-Peptide; CD3 Complex; Child; Diabetes Mellitus, Type 1; Exanthema; Female; Fever; Follow-Up Studies; Gastrointestinal Diseases; Humans; Hypoglycemic Agents; Insulin; Male; Muromonab-CD3; Nausea; Treatment Outcome; Vomiting

To study whether hyperthermia reproduces hormonal and metabolic responses seen in stress states such as mild infections, six normal male subjects underwent (i) a 3-h hot bath and (ii) a 3-h thermoneutral control period. During the hot bath body temperature rose by 1.2 +/- 0.03 degrees C (mean +/- SEM) and significant peaks of circulating growth hormone (56 +/- 9 vs 7 +/- 4 mU/l), adrenaline (310 +/- 34 vs 152 +/- 39 pmol/l), glucagon (19.2 +/- 4.3 vs 11.8 +/- 2.3 pmol/l) and cortisol were recorded together with slight hyperinsulinaemia (6.5 +/- 1.3 vs 5.3 +/- 1.0 mU/l, P less than 0.05). Hyperthermia was also accompanied by significant increases in circulating levels of free fatty acids (0.93 +/- 0.1 vs 0.46 +/- 0.1 mmol/l), 3-hydroxybutyrate (196 +/- 67 vs 50 +/- 18 mumol/l), glycerol (102 +/- 10 vs 48 +/- 5 mumol/l) and lactate. Blood alanine decreased and blood glucose remained constant. When an intravenous glucose tolerance test was performed during the last hour of hyperthermia signs of impaired first phase and enhanced second phase insulin responses were recorded. Calculated values for glucose disappearance also deteriorated (1.34 +/- 0.19 vs 2.04 +/- 0.50 %/min, P less than 0.05). We conclude that hyperthermia mimics most major metabolic and hormonal changes observed during mild infection and could provide a model to study these conditions.

Topics: Adult; Alanine; C-Peptide; Epinephrine; Fever; Glucagon; Glucose; Glucose Tolerance Test; Growth Hormone; Hormones; Hot Temperature; Humans; Immersion; Insulin; Lactates; Lactic Acid; Lipid Metabolism; Male