Marja-Liisa Käär

Effect of Once-a-Week Training Program on Physical Fitness and Metabolic Control in Children With IDDM

To examine whether a physical activity program could improve physical fitness and glycemic control, 32 children and adolescents with insulin-dependent diabetes mellitus (IDDM) were examined before the program and 3 mo later. Fifty percent of the subjects (n = 16) participated in the training for 1 h/wk (exercise group), whereas the remaining subjects were engaged in nonphysical activities for an equal amount of time (nonexercise group). Age of the subjects ranged from 8.2 to 16.9 yr, (mean 11.9 yr), with mean duration of diabetes 0.6-13.1 yr (5.2 yr). During the 3-mo program peak oxygen consumption (Vo2) rose from 40.0 to 43.8 ml · min-1 · m-2 (P < .01) in the exercise group but only by 1.3 ml · min-1 · m-2 in the nonexercise group (NS). Metabolic control did not improve in either group, with glycosylated hemoglobin level rising from 9.8 to 10.5% (P < .01) in the exercise group and from 9.4 to 9.7% (NS) in the control group. When subjects were stratified according to their participation, metabolic control was significantly better among diabetic subjects participating frequently (5:11 of 13 sessions) than among those participating infrequently (<11 of 13 sessions), regardless of the type of activity. It was concluded that a training program of 1 h/wk for 3 mo does improve physical fitness but not the metabolic control of diabetes. On the other hand, glycemic control appears to be best among diabetic subjects who are motivated to participate in any kind of program related to the treatment of their disease.

POSTINITIAL REMISSION IN DIABETIC CHILDREN– AN ANALYSIS OF 178 CASES

ABSTRACT. 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.

Exercise-induced proteinuria in children and adolescents with Type 1 (insulin dependent) diabetes

SummaryThe urinary excretion of albumin and β-2microglubulin was measured by radioimmunoassay in 64 children and adolescents with Type 1 (insulin dependent) diabetes and in 68 non-diabetic subjects aged from 9 to 19 years. At rest the albumin excretion of the diabetic subjects did not differ from that of the non-diabetic children and adolescents but during exercise the albumin excretion was significantly higher in children and adolescents with Type 1 diabetes (p<0.02). The excretion rate of β2-microglobulin in diabetic subjects did not differ from that of the healthy subjects. Both at rest and during exercise the albumin excretion rate was highest in those diabetics with poorest metabolic control of their disease.

Relationship between serum insulin autoantibodies, islet cell antibodies and Coxsackie-B4 and mumps virus-specific antibodies at the clinical manifestation of Type 1 (insulin-dependent) diabetes

SummaryIn order to elucidate the possible relationship between insulin autoantibodies (IAA), conventional (ICA-IgG) and complement-fixing (CF-ICA) islet cell antibodies and Coxsackie-B4 and mumps virus-specific antibodies (IgG, IgM and IgA classes), we studied 194 children and adolescents with newly diagnosed Type 1 (insulin-dependent) diabetes. Sixty-one (31.4%) of the subjects were IAA-positive at diagnosis and 73.8% (45/61) of these also had ICA-IgG compared to 51.1% (68/113, p<0.01) of IAA-negative children. CF-ICA showed no significant association with IAA. The levels of IAA were significantly higher in the patients with ICA-IgG compared to those without [5.9±1.6% (SEM) vs 2.5±0.3%, p<0.01]. The patients positive for IAA were younger at diagnosis than the IAA-negative ones; (7.1±0.5 vs 9.3±0.3 years, p<0.001) and this was also true for ICA-IgG-positive children (8.1±0.4 vs 9.4±0.5 years, p<0.05) in comparison to ICA-IgG-negative subjects. No significant associations were found between IAA or ICA on the one hand and a positive family history of Type 1 diabetes or metabolic derangements at diagnosis on the other. Subjects negative for ICA were more frequently positive for mumps virus specific IgG antibodies than the ICA-positive patients (50/80 vs 53/111, p<0.05), and Coxsackie-B4 virus-specific IgA antibodies were more common in the CF-ICA-negative than the CF-ICA-positive children (53/111 vs 29/80, p<0.05). There was no association between the IAA levels and Coxsackie-B4 or mumps virus specific antibodies. However, patients with serological evidence of a recent mumps infection (n=13) had higher IAA levels than the other children (4.4±7.7% vs 2.8±1.4%, p<0.02). Our data suggest a positive association between IAA and ICA-IgG, supporting the view that IAA are like ICA serological markers of autoimmune B cell damage. The inverse associations between autoantibodies and age and between ICA and viral antibodies support the hypothesis that autoimmune mechanisms may play a more crucial role in younger patients contracting Type 1 diabetes while environmental factors may be more important in older ones.

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

SummaryForty-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 β cells for antigenic stimulation. These results support the view that the complement-fixing islet cell antibodies reflect ongoing destructive processes in the β cells.

Abnormalities within CD4 and CD8 T lymphocyte subsets in type 1 (insulin-dependent) diabetes

Abnormalities in the proportions of various T lymphocyte subpopulations have been found in a number of autoimmune diseases. Monoclonal antibodies labelled with various fluorochromes were used here to define the percentages of subsets, and especially to divide CD4+ (helper/inducer) and CD8+ (suppressor/cytotoxic) cells into phenotypic subgroups. Blood samples were analysed from 25 patients (age 10.1±3.7 years) with recently diagnosed insulin‐dependent diabetes mellitus (IDDM) and 25 age‐ and sex‐matched control subjects. The percentages of CD4+ cells and CD4+CD45RA+ cells described as naive T helper cells or suppressor/inducers were increased in the IDDM patients (P<0.05 and P<0.05, Students t‐test, respectively), whereas the percentage of CD4+CD45RA‐cells (memory T‐helper cells, helper/inducers) was similar in the patients and controls. The percentage of CD8+CD11b+ cells containing suppressor/effector lymphocytes was decreased in the IDDM patients as compared with the controls (P<0.01) but no significant difference was seen in total CD8+ cells. The percentages of CD3+ cells and the proportions of these simultaneously positive for HLA‐DR antigen (activated T cells) were also increased in the recent IDDM patients (P<0.001 and P<0.05, respectively), while the proportion of CD20+ B cells was decreased (P<0.05). The findings support the view that disturbed immune regulation occurs in IDDM and indicate that further division of T cell subpopulations may clarify our understanding of the disease process.

PERIPHERAL NEUROPATHY IN DIABETIC CHILDREN AND ADOLESCENTS.: A Cross-sectional Study

ABSTRACT. In order to establish the general prevalence of peripheral neuropathy in diabetic children and adolescents, median motor and sensory conduction velocities and the peroneal motor conduction velocity were registered in 161 unselected diabetic children and adolescents and 55 healthy controls. The influence of the duration and the balance of diabetes on the results was analysed in the diabetic group. In the controls the age correlated positively with the median motor and sensory conduction velocity, but not with peroneal motor conduction velocity. In diabetic children, the greatest impairment was found in the peroneal motor conduction velocity, 49 patients (30 %) had a value lower than ‐2SD below the mean normal value. There was a correlation between the balance of diabetes based on HbA1 and glucosuria, and median and peroneal motor conduction velocities. The median motor conduction velocity was independent of the duration of diabetes, but a correlation was found between the duration of diabetes and peroneal motor conduction velocity impairment. Motor conduction velocity determination of the peroneal nerve can be used both in revealing and following the abnormality in peripheral nervous function in diabetic children. Regular follow‐up of nervous function test results may help in assessing the importance of good metabolic control in preventing diabetic complications.

Defective Stimulation of Adipocyte Adenylate Cyclase, Blunted Lipolysis, and Obesity in Pseudohypoparathyroidism 1a

ABSTRACT: Adipocyte plasma membranes were isolated from four patients with type la pseudohypoparathyroidism, a disease in which deficiency of the stimulatory guanine nucleotide binding protein Gs has been reported, and from controls. Stimulation of adenylate cyclase by isoproterenol was defective, whereas inhibition of forskolin-stimulated cyclase activity by N6-(phenylisopropyl)adenosine was normal. The patients had low serum FFA concentrations and developed obesity in childhood. These results suggest that pseudohypoparathyroidism 1a is connected with a blunted stimulatory response of adenylate cyclase, possibly because of low Gs activity, and that this blunted response may lead to decreased lipolysis and to obesity.

Metabolic Control in Children and Adolescents with Insulin‐Dependent Diabetes Mellitus

ABSTRACT. The metabolic control, assessed from the mean daily glucosuria, mean daily glucosuria index based on home tests, and mean haemoglobin A1 (HbA1) concentrations during 1980, and the influence of various factors on the control were analysed in 177 diabetic children and adolescents. The mean daily glucosuria was 21 % of the carbohydrates in the subscribed diet, and the mean glucosuria index 55 %. The mean HbA] was 14.0 %. Boys had better metabolic control than girls. Good motivation towards treatment was associated with better metabolic control. There was a negative correlation between metabolic control and both the age of the child and the duration of diabetes. Prepubertal children were better controlled than those in puberty. Adherence to the dietary regimen was related to better control, as was the patients endogenous insulin secretion, measured by serum C‐peptide concentration. There was also an association between the season and the metabolic control, the control being better in the spring than during the other seasons. On the basis of these results male sex, a good motivation towards treatment, residual beta‐cell function and adherence to the prescribed diet favor good metabolic control, while a long duration of the disease, the presence of puberty and relatively high age in childhood are factors impairing the metabolic control.

Remission phase, endogenous insulin secretion and metabolic control in diabetic children

SummaryThe occurrence and duration of clinical remission were analyzed in 173 diabetic children. One hundred and twelve (65%) children experienced a remission, which was complete in only five (3%) cases. Duration varied from one month to three years, the mean being 8.5 months. Boys showed a more frequent and longer remission phase (p<0.01) than girls. Children with a negative remission history were younger (p<0.05) at the onset of diabetes than children having remission periods. Duration of remission correlated positively with age at onset (rs=0.19; p<0.01) and with non-fasting serum C-peptide concentration (rs=0.31; p<0.001). There was a negative correlation between duration of remission and daily insulin dose (rs=−0.23; p<0.005). We found no correlation between duration of remission and duration of diabetes or hemoglobin A1 (HbA1) concentrations beyond the remission period. Serum C-peptide concentrations correlated negatively with HbA1 levels (rs=−0.23; p<0.001) indicating that residual B-cell function favors good metabolic control. There was a negative correlation between HbA1 concentration and duration of diabetes (r=−0.30; p<0.001). Clinical remission of long duration is associated with persisting endogenous insulin secretion, and reduced daily insulin requirement, but its favorable effect on metabolic control beyond the remission period is questionable.