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Biomedical subjects

A Mustonen

Publications and source records attributed to A Mustonen.

34 records · Page 2Linked to original sources

Evidence of delayed beta-cell destruction in type 1 (insulin-dependent) diabetic patients with persisting complement-fixing cytoplasmic islet cell antibodies.

Forty-four children with Type 1 (insulin-dependent) diabetes (aged 0.7-16.7 years) were observed from diagnosis for cytoplasmic islet cell antibodies and serum C-peptide concentrations. Islet cell antibodies were analysed by indirect immunofluorescence for both conventional IgG and complement-fixing antibodies. Thirty-seven children (84%) were found to be positive for conventional islet cell antibodies at diagnosis, and 21 (48%) remained positive over the observation period. Twenty-six patients (59%) were positive for complement-fixing antibodies at diagnosis and eight remained so during the follow-up period. The serum C-peptide concentrations increased significantly during the first 3 months after diagnosis, after which there was a gradual decrease in the levels. Those children who remained positive for complement-fixing antibodies over the observation period had significantly higher serum C-peptide concentrations on several occasions during the second year and had also a higher integrated serum C-peptide concentration over the initial 2 years than those who became negative for complement-fixing antibodies. These observations suggest that the continuous production of complement-fixing islet cell antibodies in those patients who are positive for these antibodies at diagnosis presupposes the preservation of a sufficient amount of functioning beta cells for antigenic stimulation. These results support the view that the complement-fixing islet cell antibodies reflect ongoing destructive processes in the beta cells.

Adolescent↗

Lymphocyte subpopulations at the onset of type 1 (insulin-dependent) diabetes.

Percentages of various T-lymphocyte subpopulations in the blood were studied at the onset of Type 1 (insulin-dependent) diabetes. The number of lymphocytes with OKT8 markers was higher in the diabetic patients than in control subjects (p less than 0.005) and the ratio between helper and suppressor/cytotoxic T-cells (OKT4/OKT8 ratio) was lower in the diabetic patients than in the control group (p less than 0.005). The values in the diabetic patients were, however, essentially within the normal range. When Ia-antigen-positive cells were analysed in T-cell enriched cell populations, Type 1 diabetic patients had higher percentages of these cells (p less than 0.01), suggesting T-cell activation. When patients with either of the two major HLA risk antigens (Dw3 or Dw4) were compared, there was a significant difference in the OKT4/OKT8 ratio (p less than 0.005), as Dw3-positive patients had higher and Dw4-positive patients lower ratios. This finding supports the concept of heterogeneity of the disease and can also explain the discrepant findings of earlier studies. When patients with complement-fixing islet cell antibodies were compared with patients without islet cell antibodies, there was no significant difference, although the OKT4/OKT8 ratio was slightly lower in the complement-fixing islet cell antibody-positive patients.

Antibodies↗

A 'new' DR4 associated D specificity 'JA' in type 1 (insulin-dependent) diabetes: A9, Bw16, DJA, DR4 haplotype.

The HLA antigen combination A9, Bw16 has been found to be associated with Type 1 (insulin-dependent) diabetes characterized by some special features in Northern Finland. This antigen combination has now been associated with a 'new' DR4-associated D antigen, provisionally called 'JA' or 'SN'. This 'new' D specificity was also associated with HLA-B18. Although the combination, Dw3/DJA, was common in Type 1 diabetic patients, the frequency of the combination Dw4/DJA was decreased compared with the expected value. This supports the hypothesis of two different risk factors associated with DR3 and DR4.

Diabetes Mellitus, Type 1↗

Defective erythrocyte C3b receptor function associated with low serum complement (C3, C4) concentrations in insulin-dependent diabetes mellitus.

An immune adherence haemagglutination (IAHA) method was used to measure erythrocyte C3b receptor (EC3bR) activity in 110 patients with insulin-dependent diabetes mellitus (IDDM) and 223 controls. Results obtained from IDDM were correlated with serum complement concentrations (C3, C4) as well as with HLA types of the patients. We observed an increased frequency of defective EC3bR in IDDM (26.4%) compared to controls (10.8%, P less than 0.0005). Those patients who had defective EC3bR (IAHA negative) also had lower serum C3 and C4 concentrations than those with normal EC3bR function (IAHA positive). HLA-Dw3 positive patients had lower C4 concentrations than HLA-Dw3 negative patients and more often had defective EC3bR activity, although this difference was statistically not significant. Our results may indicate the close relationship between the risk factors which predispose to both IDDM and systemic lupus erythematosus.

Adolescent↗

Physical fitness of children and adolescents with insulin-dependent diabetes mellitus.

The physical working capacity (PWC170) of 84 children and adolescents with insulin-dependent diabetes mellitus (IDDM) and of 94 non-diabetic subjects was measured by a submaximal progressive exercise test. The age of the diabetic subjects ranged from 6.3 to 18.8 years and that of the control subjects from 8.5 to 18.8 years. The PWC170 of diabetic boys was lower than that of non-diabetic boys (p less than 0.01) while no difference was observed between diabetic and non-diabetic girls. PWC170 was inversely related to age (p less than 0.01) and concentration of hemoglobin A1 (p less than 0.025) in diabetic boys but not in diabetic girls. No relationship was observed between PWC170 and duration of diabetes in either boys or in girls. The results indicate that good physical fitness in boys is associated with a better metabolic control. Hence the study indirectly supports previous observations that physical activity improves the metabolic control of IDDM.

Adolescent↗

An association between complement-fixing cytoplasmic islet cell antibodies and endogenous insulin secretion in children with insulin-dependent diabetes mellitus.

Cytoplasmic islet cell antibodies and endogenous insulin secretion were studied in 184 children and adolescents having insulin-dependent diabetes mellitus (IDDM) in a cross-sectional study. The mean age of the subjects was 12.3 yr (range: 2.8-19.2 yr), and the mean duration of diabetes was 4.6 yr (range: 0.1-15.6 yr). Islet cell antibodies (ICA) were determined by both the indirect immunofluorescence (IF-ICA) and the complement-fixing (CF-ICA) methods. Forty-four patients (23.9%) were positive with respect to both IF- and CF-ICA, 54 patients (29.3%) had only IF-ICA, and 86 patients had no ICA. The patients having CF-ICA had a significantly higher endogenous insulin secretion in comparison with the patients who were only IF-ICA positive. The difference between the groups remained significant even when the age at onset of diabetes and the duration of the disease were taken into account. This finding, revealing an association between CF-ICA and endogenous insulin secretion, suggests that complement-fixing antibodies are seen only if the beta-cell mass is sufficiently preserved. The result contradicts the hypothesis, based on studies in vitro, that CF-ICA should be involved in the selective beta-cell damage in IDDM.

Adolescent↗

Organ-specific antibodies in healthy and diabetic children and young adults.

160 children and young adults (aged 7-21 years) and 84 diabetics (aged 2-19 years) were screened for thyroglobulin (TgA), thyroid microsomal (MsA), smooth muscle (SMA), parietal cell (PCA), reticulin (RA), glomerular (GIA) and mitochondrial (MA) antibodies. The diabetics were also screened for islet cell antibodies (ICA). The overall incidence of other antibodies than ICA at the lowest serum titre studied was 18.1 percent for healthy children and 30.9% for diabetic children. The elevation in diabetics is significant (p less than 0.01). Females were overrepresented in both groups and had the highest titres of antibodies. The age group 10-14 years was observed to be a special time at which antibody titres became positive. As compared with the controls, diabetics exhibited an increased incidence of MsA (4.4 and 11.9% respectively, p less than 0.001), PCA (5.0 and 10.7% respectively, p less than 0.05) and RA (3.8 and 9.5% respectively, p less than 0.05). The presence of ICA or the duration of diabetes showed no correlation with other autoantibodies. The results indicate that autoantibodies at a low titre are a common phenomenon. Diabetics seem to be susceptible to react against their own tissue, which is probably associated with their increased frequency of autoimmune diseases.

Adolescent↗

Postinitial remission in diabetic children--an analysis of 178 cases.

We studied 178 diabetic children and adolescents diagnosed during the period 1962-79 to find out the occurrence and duration of the postinitial remission, factors favoring a remission and the prognostic value of the remission. A postinitial remission occurred in 113 children (64%) being complete in only three boys (2%). The duration ranged from one month to 4.8 years, the mean being 8.4 months. The boys had a remission more often and of longer duration than the girls. The duration of diabetes was longer in the children without remission. The children with remission had lower blood glucose, milder hyperketonemia and ketonuria, higher pH and PCO2 at onset than those without remission. Hemoglobin A1 (HbA1) during 1979 were lower in the children with a positive remission history. The children with a remission lasting more than one year had a subsequently higher glucosuria index, lower HbA1 and higher C-peptide when compared to those without remission or to those with a short remission. The remission frequency increased from 1962 to 1979. Male sex and mild metabolic derangement at onset favor a postinitial remission, which results in a persisting residual beta-cell function and better metabolic control beyond the remission.

Adolescent↗

An islet cell antibody negative form of insulin-dependent diabetes mellitus (IDD) associated with HLA antigens A9 and Bw16.

One hundred and sixty-six unrelated children and adolescents having growth-onset, insulin-dependent diabetes mellitus (IDD) were studied for pancreatic-cytoplasmic islet cell antibodies (ICA) at various times from the diagnosis of the disease. A strong association between HLA antigens A9 and Bw16 and an absence of ICA early in the course of disease was seen. On the other hand B8/Dw3 or B15/Dw4 antigens were not significantly associated with the occurrence of ICA although both these antigens are greatly increased among pediatric IDD patients in northern Finland. The finding of the association of the HLA antigens A9 and Bw16 with ICA-negativity contributes to the evidence for the heterogeneity in the genetic susceptibility to IDD.

Adolescent↗

HLA genetics of insulin-dependent juvenile-onset diabetes mellitus in northern Finland.

HLA--A, B and C antigens were determined from 63 cases of juvenile-onset, insulin-dependent diabetes mellitus (IDDM) in northern Finland. There was a very strong association between IDDM and HLA--B8 and B15 antigens in this area where the incidence of IDDM is also high. Relative risks for B8 and B15 were 4.8 and 3.8, respectively. In a small group of subjects typed for HLA--D antigens Dw3 and Dw4 appeared to be stronger risk factors than associated B antigens, whereas Dw2 was almost totally absent in the patients. The effect of combinations of B8 and B15 antigens in unrelated patients and in diabetic families was analyzed. B8, B15 was found in 11 out of 63 unrelated diabetics; however, this did not differ significantly from the expected value. In diabetic families there was no increased rate of intra-HLA recombinations.

Diabetes Mellitus, Type 1↗

Is there bacteremia after suprapubic aspiration in children with urinary tract infections?

It has been shown that bacteremia may occur after bladder puncture in animals. Whether this also happens in man is not known. Thirty-three patients who were suspected to have urinary tract infection were examined for bacteremia after suprapubic bladder puncture. Of these children 19 had infection. There was no positive blood culture in any of these cases after suprapubic bladder puncture.

Adolescent↗

Increase of HLA haplotype A9-Bw16 in familial insulin-dependent diabetes mellitus in northern-Finland.

Twenty-one families, each with two diabetic children, from North Finland were HLA typed. The grade of HLA identity between diabetic siblings was evaluated, and frequencies of various HLA antigens in familial cases were compared to those of non-familial cases from the same area. Ten pairs of diabetic children were HLA-identical and eleven haploidentical; two of the latter were identical for the HLA-D locus. These figures emphasize the significance of HLA-region associated genetic factors in the susceptibility to the disease, but do not support a simple dominant/recessive gene theory. There was a significant difference between familial and non-familial IDDM cases in the frequencies of B15, Bw16, B40 and Cw3 antigens. Bw16 was greatly increased and B15, B40 and Cw3 decreased among familial cases. The haplotype A9, Bw16 was common in familial cases, but, compared to healthy controls, the frequencies of the two antigens were also slightly increased among non-familial cases. Neither Dw3 nor Dw4 was associated with Bw16 antigen. The differences between familial and non-familial IDDM cases and the significance of the A9, Bw16 combination in the patients emphasize the heterogeneity of IDDM.

Diabetes Mellitus↗