Juvenile-onset Insulin-dependent Diabetes Mellitus Research Articles

ALBUMINURIA IN DIABETIC CHILDREN

Sligth albuminuria has been induced by exercise in young adults with juvenile-onset insulin-dependent diabetes mellitus of short duration. We studied the influence of exercise on albuminuria in 46 diabetic and 38 healthy children using radioimmunoassay. The age of the children ranged from 9 to 18 years. The children worked on a bicycle ergometer for 16 minutes with increasing work load. In both groups, the pulse rate at the end of the exercise was 185±6/min.At rest the geometric mean of the albumin excretion rate of healthy children was 4.7 μg/min/m2, that of diabetics with a duration less than 5 years 6.0 μg/min/m2 and with a duration more than 5 years 9.1 μg/min/m2. During exercise the albumin excretion was 8.5, 10.0 and 19.5 μg/min/m2, respectively. During rest and exercise the albumin excretion was significantly increased in children with diabetes for more than 5 years.At rest the extent of albuminuria correlated with blood HbA1 concentration.During exercise there was a correlation between albuminuria and blood pressure rise in diabetic but not in healthy children. It is concluded that early signs of diabetic nephropathy can be detected with special techniques as soon as in childhood and the appearance of albuminuria is dependent on the metabolic balance of diabetes.

Immunopathology of Juvenile-onset Diabetes Mellitus: I. IgA Deficiency and Juvenile Diabetes

There is an increased prevalence (P less than 0.001) of IgA deficiency in children with juvenile-onset insulin-dependent diabetes mellitus (9/366) but not in adults with insulin-dependent diabetes (0/421). The juvenile diabetics with IgA deficiency have other immune-associated diseases, such as thyroiditis and chronic active hepatitis, and have a history of infections. Four of the nine IgA-deficient diabetics we studied have autoantibodies to endocrine organs. Seven of eight have the HLA-B8, a proportion significantly (P less than 0.05) greater than control populations. Based on the clinical findings of IgA deficiency and multiple autoantibodies in patients with ataxia-telangiectasia and chronic mucocutaneous candidiasis, diseases associated with thymus deficiency, we suspect that thymus deficiency and autoimmunity may play a role in the pathogenesis of some types of juvenile-onset diabetes mellitus. In addition, an excess morbidity of the IgA-deficient juvenile diabetic population may explain the lack of IgA deficiency in older insulin-dependent diabetic individuals.

HLA--Bw54 (Bw22-J, J-1) antigen in juvenile onset diabetes mellitus in Japan.

HLA--B8 and/or Bw15, associated with juvenile onset insulin-dependent diabetes mellitus (JDM) in Caucasians, have a very low frequency in the Japanese population. Thus, we were interested in investigating the association between JDM and HLA antigen in a Japanese population. Eighty-nine patients with JDM and 128 unrelated random controls were HLA-typed by the microlymphocytotoxicity test. The data revealed a significant, positive association between this type of diabetes mellitus and HLA--Bw54 (Bw22-J, J-1) antigen (Japanese-specific split antigen of HLA--Bw22).

Topical corticosteroid response and retinopathy in juvenile-onset diabetes mellitus.

In a prospective study, 64 patients with insulin-dependent juvenile-onset diabetes mellitus were followed for eight to 12 years to determine if those with higher spontaneous intraocular pressures (IOPs) would be protected from the development of retinopathy. The patients were also classified initially as high (GG), intermediate (NG), or low (NN), responders on the basis of their IOP response to corticosteroid eyedrops. High responders were found to be considerably in excess (25 per cent) of the proportion found in the general population (6 per cent). Retinopathy developed significantly less often and was less severe in the high (GG) corticosteroid responders. Although the GG diabetics had significantly higher mean baseline IOPs than the less responsive NN and NG groups in each corticosteroid response category, the mean IOP of the group with retinopathy was not significantly different from that without retinopathy. This suggested that factors associated with the GG response other than increased IOP might be important in the relative resistance to diabetic retinopathy.

Incidence, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus in Denmark.

The incidence, sex, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus (j.i.d.m.) were studied retrospectively on one third of the Danish population 1970-1974. The j.i.d.m. incidence remained fairly constant during the study period, the average being 13.2 per 100000 per year. The total number of boys exceeded the number of girls by 27%. A marked peak of incidence was found at 12-14 years, earlier for females than for males. A seasonal variation in onset (diagnosis) of j.i.d.m. was observed with the lowest number of new cases in May-July. The j.i.d.m. incidence seemed to show socioeconomic differences, being highest in those parts of the survey area with lower status.

HLA antigens in Japanese patients with diabetes mellitus.

Lymphocytes of 84 Japanese patients with diabetes mellitus and 150 normal controls were tested for HLA antigens by the microcytotoxicity test. HLA-B12 was found in 37.5 per cent of 32 patients with juvenile-onset diabetes mellitus, 13.5 per cent of 52 patients with late-onset diabetes, and 9.3 per cent of 150 normal controls. In the insulin-dependent juvenile form, HLA-B12 was associated with the disease more frequently and at a significant level (p less than 0.0005). In Japanese patients with juvenile-onset insulin-dependent diabetes mellitus the association is with HLA-B12, not with HLA-B8 and BW15, as in Caucasian patients. There was no significant increase of HLA-B12 in patients with insulin-indpendent diabetes mellitus.

HLA antigens and immunoresponsiveness to insulin in insulin-dependent diabetes mellitus.

HLA-A and B antigens were determined in 112 patients with insulin-dependent juvenile onset diabetes mellitus, who could be subdivided into "non" and "high responder" to insulin. The data revealed a trend of an association of these diabetes subgroups with only one of the diabetes-associated antigens HLA-B8 and HLA-BW15 and indicated the existence of at least two different genetic constellations for susceptibility to juvenile diabetes mellitus. One form with a strong immune-response to insulin seemed to be associated with HLA-BW 15 and the other form without humoral immunoreactivity to insulin seemed to be associated with the presence of HLA-B8 and the absence of HLA-B7.