Young patients with both type 1 diabetes mellitus and asthma have a unique IL-12 and IL-18 secretory pattern.

BACKGROUND: The expression of the regulatory cytokines interleukin (IL)-12 and IL-18 in patients with both Th1- and Th2-mediated diseases, type 1 diabetes mellitus (T1DM) and asthma, is unknown. OBJECTIVE: To investigate the in vivo and in vitro IL-12 and IL-18 secretion patterns in patients with both T1DM and asthma. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 44 patients. Mean age 19.4 ± 4.7 yr (10.5-28 yr), divided into four paired groups: T1DM and asthma, asthma only, T1DM only, and healthy controls. T-cell proliferative response was assessed. IL-12 and IL-18 serum levels and expression by PBMC following in vitro stimulation by lipopolysaccharide (LPS) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with T1DM and asthma had higher serum levels of both IL-12 and IL-18 compared to controls: 146.2 ± 69.2 and 109.7 ± 34.6 pg/mL, p = 0.038 and 436.1 ± 117.9, 320.2 ± 99.1 pg/mL, p = 0.028, respectively. Stimulated IL-12 secretion was significantly lower in these patients compared to those with one disease only: 809 ± 426.4, 2111.6 ± 2214.3, 3188.1 ± 2692.9 pg/mL and after 48 h: 956.3 ± 489.3, 2429.8 ± 2394.6, 3874.5 ± 2820.3 pg/mL, respectively, p < 0.03 for all. The IL-18/IL-12 serum ratio was also significantly higher in patients with both diseases compared to those with asthma only, p = 0.017. CONCLUSION: Patients with both T1DM and asthma display a different pattern of IL-12 and IL-18 expression compared to patients with one disease only and controls.

Insulin pump therapy in youth with type 1 diabetes: a retrospective paired study.

OBJECTIVE: To compare by age and glycemic control continuous subcutaneous insulin infusion with multiple daily injections in youth with type 1 diabetes. METHODS: The files of 279 patients who had type 1 diabetes and switched from multiple daily injections to continuous subcutaneous insulin infusion between 1998 and 2003 were reviewed for glycemic control, body mass index standard deviation score, and adverse events. Patients were divided by age as follows: 23 prepubertal (median age: 5.4; range: 1.6-8.6 years), 127 adolescent (median age: 13.7; range 9-17 years), and 129 young adult (median age: 22.8; range: 17-40 years). The data were compared between the 12 months of multiple daily injections that preceded continuous subcutaneous insulin infusion and the period after the start of continuous subcutaneous insulin infusion for the whole cohort and by age group. RESULTS: A significant decrease in hemoglobin A1c was demonstrated after the start of continuous subcutaneous insulin infusion use for the entire cohort (-0.51%) and for the prepubertal (-0.48%), adolescent (-0.26%), and young adult (-0.76%) groups. There was a significant interaction between the change in hemoglobin A1c level and hemoglobin A1c value at initiation of pump therapy (-1.7% for patients with hemoglobin A1c > or = 10%; 0.2% for patients with hemoglobin A1c < or = 7%). The rate of severe hypoglycemic episodes decreased significantly in the adolescent group, from 36.5 to 11.1 events per 100 patient-years, and in the young adult group, from 58.1 to 23.3. There was no significant change in the rate of diabetic ketoacidosis between the 2 periods. The young adults showed a significant decrease in body mass index standard deviation scores (-0.08 +/- 0.37). CONCLUSIONS: Continuous subcutaneous insulin infusion improves glycemic control in youth with type 1 diabetes, especially in those with a history of poor glycemic control. This improvement is associated with a decrease in the rate of severe hypoglycemia in the absence of weight gain.

TH1/TH2 cytokine balance in patients with both type 1 diabetes mellitus and asthma.

BACKGROUND AND OBJECTIVE: T1DM and asthma are mediated by opposite arms of the cellular immune system namely T helper (Th)1 and Th2 CD4(+) cells, respectively. Our aim was to characterize the Th1/Th2 cytokine balance in patients with both T1DM and asthma. METHODS: Forty-four patients, mean age 19 years were matched by gender and age, to 4 paired groups: T1DM and asthma, asthma only, T1DM only and healthy controls. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with disease-specific recombinant antigens; glutamic acid decarboxylase and house dust mite (Der p1 antigen) for T1DM and asthma, respectively, and non-specific mitogens; phytohemaglutinin (PHA), tetanus toxin and anti-CD3 mAb. ELISPOT and ELISA technique were used to determine INF-gamma, IL-2, IL-4, IL-13 and IL-10 expression. RESULTS: Patients with T1DM and asthma demonstrated a similar cytokine pattern but lower Th1/Th2 ratio compared to patients with T1DM only. The Th2 cytokines response to Der p1 was enhanced in patients with both diseases compared to controls. The IL-10 overall secretion was higher in patients with both diseases compared to one disease only. CONCLUSION: The Th1 and Th2 secretory pattern of patients with T1DM and asthma combines features of both diseases suggesting a unique Th1/Th2 balance.