Raija Puukka

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.

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.

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.

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.

Erythrocyte adenosine deaminase, purine nucleoside phosphorylase and phosphoribosyltransferase activity in patients with Down's syndrome.

The erythrocyte adenosine deaminase, nucleoside phosphorylase, hypoxanthineguanine phosphoribosyltransferase and adenine phosphoribosyltransferase activities and plasma urate concentrations were measured in 20 cases of Downs syndrome and in 20 age- and sex-matched control subjects. The mean erythrocyte adenosine deaminase and adenine phosphoribosyltransferase activities and plasma urate concentrations were significantly higher in Downs syndrome subjects than in controls (p less than 0.001, p less than 0.01 and p less than 0.001, respectively). In all subjects studied there was a positive correlation between the erythrocyte adenosine deaminase activity and plasma urate concentration (r = 0.488, p less than 0.005). The concentrations of the erythrocyte adenine nucleotides, AMP, ADP and ATP, did not differ in Downs syndrome (n = 10) from those of control subjects (n = 10). The results suggest that the increase of plasma urate concentrations is a consequence of the increase in adenosine deaminase activity in Downs syndrome patients.

Levels of some purine metabolizing enzymes in lymphocytes from patients with Down's syndrome

The activities of a number of purine metabolizing enzymes of erythrocytes and lymphocytes were determined in 18 subjects with Downs syndrome and in 18 age- and sex-matched control subjects. An increase of adenosine deaminase activity (adenosine or deoxyadenosine as substrates) was found in erythrocytes (P less than 0.001) as well as in lymphocytes (P less than 0.001) of Downs syndrome subjects compared to controls. The purine nucleoside phosphorylase activities in lymphocytes and plasma urate concentrations were also significantly higher in Downs syndrome subjects than in controls (P less than 0.001 and less than 0.02, respectively). Adenine phosphoribosyltransferase activities and hypoxanthine-guanine phosphoribosyltransferase activities in lymphocytes were identical in the two groups. In all subjects studied there were positive correlations between the erythrocyte adenosine deaminase activities, lymphocyte adenosine deaminase or deoxyadenosine activities, and plasma urate concentrations (P less than 0.05 in all cases), and between lymphocyte nucleoside phosphorylase and lymphocyte adenosine deaminase or deoxyadenosine deaminase activities (P less than 0.01 and less than 0.05, respectively). The results suggest that increased activities of some purine metabolizing enzymes found in both erythrocytes and lymphocytes may contribute to increased purine degradation and hyperuricemia in subjects with Downs syndrome. In addition, the increased adenosine deaminase and nucleoside phosphorylase activities may be related to the immunological dysfunction found in subjects with Downs syndrome.

Basal insulin secretion and erythrocyte insulin binding in preterm and term newborn infants.

To study the ontogeny of the insulin secretion and the erythrocyte insulin receptor we measured plasma immunoreactive insulin and C-peptide concentrations and the binding of [125I]-insulin to the erythrocytes in cord blood from 16 preterm and 16 term infants. 20 normal-weight adults were also studied. The C-peptide concentrations and the molar ratio of C-peptide to insulin were lower in the newborn infants than in the adults. The immunoreactive insulin correlated positively with birth weight in the term infants. The insulin binding to erythrocytes from the newborn infants was increased when compared to the adults. Erythrocytes from the preterm infants bound more insulin than the cells from the term infants. There was a strong negative correlation between insulin binding and gestational age. In the term infants, plasma C-peptide correlated negatively with the insulin binding. The increased binding to erythrocytes from the term infants was due to an increase in the receptor concentration. The high insulin binding in the preterm infants was a result of both an increased receptor concentration and affinity. These data suggest that the basal insulin secretion is similar in preterm and term infants and that the clearance of insulin is decreased in newborn infants. The increased insulin binding in newborn infants may be a mechanism by which the growth stimulatory effect of insulin in fetal life is mediated.

PANCREATIC ISLET CELL FUNCTION AND METABOLIC CONTROL IN AN INFANT WITH PERMANENT NEONATAL DIABETES

ABSTRACT. A girl with typical clinical manifestations of neonatal diabetes was observed for 16 months with consecutive evaluations of pancreatic beta and alpha‐cell function and metabolic control. At the diagnosis both the plasma immunoreactive insulin (IRI) and C‐peptide concentrations were inappropriate for the contemporaneous hyperglycemia. During the follow‐up, the C‐peptide fell twice below the detection limit but the beta‐cell function recovered partially on both occasions. Based on 24‐hour urinary C‐peptide excretion, the endogenous insulin secretion was less than 10% of that in non‐diabetic infants. When diagnosed the patient had plasma immunoreactive glucagon (IRG) and glucagon‐like immunoreactivity (GLI) concentrations below the reference range for normal neonates. The IRG normalised within the first month, while the GLI increased to a level exceeding the reference range. Hemoglobin A1 had already risen at the time of diagnosis and subsequently rose to a level indicating poor metabolic control. The findings indicate an immature function of both beta‐ and alpha‐cells at the diagnosis with the alpha‐cells maturing within the first month. The recovery of the beta‐cell function, after two failures in this patient with permanent neonatal diabetes, suggests that the beta‐cell damage was at least partially reversible.

Electrophoretically Determined Haemoglobin A1 Concentrations during Short-Term Changes in Glucose Concentration

In our experience, electrophoresis on agar gel is a very satisfactory alternative to the more widely used chromatographic methods for the determination of haemoglobin A1 (HbA1). Like the chromatographic method, the electrophoretic method is unable to detect any difference between the labile intermediate form of HbA1, which changes rapidly with acute changes in blood glucose level, and the more stable end-product, which reflects long-term glucose levels. In vitro at 37°C the electrophoretically determined HbA1 concentration increases with increasing glucose concentration and with time in both normal and diabetic erythrocytes, but decreases to the preincubation concentration during further incubation of the erythrocytes in a glucose-free medium at 37°C. Similarly, if normal or diabetic erythrocytes are incubated with isotonic saline before the HbA1 assay, the labile fraction is eliminated. In diabetics, the decrease in HbA1 concentration correlates with both the blood glucose level and the preincubation HbA1 concentration. Thus for HbA1 to be an accurate indicator of long-term glucose control in diabetic patients saline incubation of the erythrocytes may be necessary before HbA1 assay by the electrophoretic method, otherwise the assay results will also reflect recent changes in the blood glucose level.

Clinical characteristics and circulating collagen and laminin metabolites in insulin-dependent diabetic children with joint and skin manifestations

ABSTRACT: One hundred seventy-four children and adolescents with insulin-dependent diabetes mellitus were examined for joint contractures and skin manifestations in their hands. Joint contractures were found in 52 (29.8%) and skin manifestations in 29 (16.6%) patients. To eliminate the possible confounding effects of age and duration of diabetes on the variables to be studied, patients younger than 7 y and with a duration of diabetes shorter than 3 y were excluded from the subsequent analyses. Of the remaining 108 children, those with joint contractures had lower serum concentrations of the 7-S domain of type IV collagen and the P1 fragment of laminin than the other patients (p = 0.033) but higher mean glycated Hb levels (p = 0.048). A clear association was noted between the occurrence of joint contractures and skin changes (p = 0.007). Background retinopathy was found in six patients (5.6%), three of whom had stage II joint contractures (p = 0.064). The children with skin changes and those with combined joint and skin manifestations more often had insulin-dependent diabetes mellitus in their first-degree relatives (p = 0.038 and p = 0.043, respectively). No difference in relative height was found between the groups. No association could be seen between disease susceptibility antigens in the HLA-D locus and joint or skin manifestations. The lower levels of circulating collagen and laminin metabolites in the diabetic children with joint contractures suggest that these patients are characterized by a reduced turnover of basement membranes in tissues. In addition, our data suggest that the development of joint contractures is associated with impaired metabolic control but not necessarily with growth retardation.