The Functional State of the Beta Cells in the Pathogenesis of Insulin-Dependent Diabetes Mellitus

Autoimmunity ◽  
1991 ◽  
Vol 10 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Karsten Buschard
1995 ◽  
Vol 41 (1) ◽  
pp. 4-6
Author(s):  
I. V. Osokina ◽  
L. N. Scherbacheva ◽  
N. B. Lebedev ◽  
I. M. Belovalova ◽  
A. P. Knyazeva ◽  
...  

The level of C-peptide is a marker determining the clinical course of insulin-dependent diabetes mellitus (IDDM). The factors influencing the volume of residual endogenous secretion of insulin in IDDM patients are not yet well known. In order to elucidate the effect of HLA-phenotype on the residual function .of pancreatic beta-cells and the course of diabetes, 114 children, 55 boys and 59 girls aged 8 months to 6.5 years, suffering from IDDM, were examined. HLA phenotype was detected by the standard microlymphocytotoxic test. Fifty-nine HLA antigens of classes I and II, locuses A, B, DR, DQ were taken into consideration. Basal and radial C-peptide was assessed by radioimmunoassay. The pancreatic insulin-secretory function was found reduced in young patients with IDDM. The mean values of C- peptide were 0.13 ± 0.01 nmol/liter. Residual secretion of insulin was revealed in 56.2% of children. HLA markers of high risk of IDDM development in the first yeais of life were revealed: DQw3. DR3/4. DR4, DR3, B8 antigens. The markers of high risk of diabetes DR3 and DR4, and moreover, DR3/4. as well as the age by the disease onset and duration of IDDM were found to influence the size and duration of functioning of beta-cells.


1995 ◽  
Vol 41 (1) ◽  
pp. 4-6
Author(s):  
I. V. Osokina ◽  
L. N. Scherbacheva ◽  
N. B. Lebedev ◽  
I. M. Belovalova ◽  
A. P. Knyazeva ◽  
...  

RESULTS:The level of C-peptide is a marker determining the clinical course of insulin-dependent diabetes mellitus (IDDM). The factors influencing the volume of residual endogenous secretion of insulin in IDDM patients are not yet well known. In order to elucidate the effect of HLA-phenotype on the residual function .of pancreatic beta-cells and the course of diabetes, 114 children, 55 boys and 59 girls aged 8 months to 6.5 years, suffering from IDDM, were examined. HLA phenotype was detected by the standard microlymphocytotoxic test. Fifty-nine HLA antigens of classes I and II, locuses A, B, DR, DQ were taken into consideration. Basal and radial C-peptide was assessed by radioimmunoassay. The pancreatic insulin-secretory function was found reduced in young patients with IDDM. The mean values of C- peptide were 0.13 ± 0.01 nmol/liter. Residual secretion of insulin was revealed in 56.2% of children. HLA markers of high risk of IDDM development in the first yeais of life were revealed: DQw3. DR3/4. DR4, DR3, B8 antigens. The markers of high risk of diabetes DR3 and DR4, and moreover, DR3/4. as well as the age by the disease onset and duration of IDDM were found to influence the size and duration of functioning of beta-cells.


1995 ◽  
Vol 41 (4) ◽  
pp. 43-48
Author(s):  
I. I. Dedov ◽  
I. A. Abugova ◽  
M. Sh. Shamhalova ◽  
P. I. Shishko

The autoimmune nature of insulin-dependent diabetes mellitus (IDDM) is currently undeniable. In the 80s, some features of its pathogenesis were determined: on beta cells of patients with newly diagnosed IDDM, overexpression of class I HLA antigens was detected; on beta and alpha cells of isolated islets of Langerhans, expression of class II HLA antigens in combination with tumor necrosis factor (TNF-alpha) and gamma-interferon (gamma-IF) was detected; the presence or absence of Asp-57 in the N-end of the beta1 domain of the HLADQ beta chain has been shown to be positively associated with IDDM in humans and NOD mice; it was revealed that macrophage interleukin-1 (IL-1) and TNF-alpha have a damaging effect on beta cells: IL-1 exhibits selective beta-cell cytotoxicity in low molar concentrations, and the effect of IL-1 is potentiated by TNF-alpha; it was determined that early infiltration during the development of inflammation of pancreas in BB rats is caused by macrophages and monocytes; destruction of beta cells is performed by T-helpers and natural killers. Thus, the autoimmune concept of the disease necessitates the use of immunotherapy to slow the development of IDDM.


1996 ◽  
Vol 76 (03) ◽  
pp. 328-332 ◽  
Author(s):  
Bernd Jilma ◽  
Peter Fasching ◽  
Christine Ruthner ◽  
Anna Rumplmayr ◽  
Sabine Ruzicka ◽  
...  

SummaryBased on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients.The aim of this study was to compare the plasma levels of cP-selec-tin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays.Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p ώ0.05).In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.


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