The determinants of the degree of metabolic decompensation at the diagnosis of type 1 (insulin dependent) diabetes mellitus (IDDM) and the possible role of diabetic ketoacidosis in the preservation and recovery of residual P cell function were examined in 745 Finnish children and adolescents. Children younger than 2 years or older than 10 years of age were found to be more susceptible to diabetic ketoacidosis than children between 2 and 10 years of age (<2 It is well known that the capacity of residual 5 cells to secrete insulin is decreased at the time of diagnosis of IDDM, often improving in a few weeks after the initiation of exogenous insulin treatment.8'-`The extent of improvement in insulin secretory capacity has been observed to be associated with age at diagnosis,' degree of metabolic decompensation,9 mild clinical symptoms at diagnosis,2910 and strict initial blood glucose control.2 13 Diabetic ketoacidosis is a serious consequence of insufficient insulin secretion.'4 In addition to possible acute complications, it may also influence the later outcome of diabetes.To study the effect of age, sex, and socioeconomic factors on the clinical condition of the patient at the diagnosis of IDDM, and to find out whether metabolic decompensation at diagnosis is related to subsequent endogenous insulin secretion and impaired metabolic control, 745 Finnish children and adolescents, aged 0.8-14.9 years, were evaluated at the time of diagnosis of IDDM and then observed for two years. Methods PATIENTSAs a part of the Finnish nationwide 'Childhood diabetes in Finland' study,'5 801 probands younger than 15 years, diagnosed as having IDDM during the recruitment period from 1 September 1986 to 30 April 1989, were offered the possibility of participating in the study. Of these 745 had analyses of blood pH, serum C peptide concentrations, and blood glycated haemoglobin levels at the time of hospital admission. At the time of admission, a clinical examination including assessment of consciousness and dehydration was performed, and the parents were asked to fill out a questionnaire concerning the socioeconomic status of the family. The subjects were then followed up in their own outpatient clinics (n = 31) for two years. At six month intervals, the recommended amount of insulin was recorded, blood specimens werc taken for glycated haemoglobin and serum C peptide concentrations, and a clinical examination including height and weight recording was performed.The mean age of the probands was 8.4 years (range 0.8 to 14.9 years). The majority of them were males (n = 412; 55.3%). The subjects were divided into two groups: those with and without diabetic ketoacidosis at diagnosis. In the longitudinal study the groups were compared at the time of diagnosis and at six, 12, 18, and 24 months after diagnosis. LABORATORY MEASUREMENTSCapillary or venous blood pH was measured at the time of hospital admission. Diabetic

The objective of this study was to test whether levels of proinsulin immunoreactivity (PIM) relative to those of insulin immunoreactivity (IRI) or C-peptide are changed and related to subclinical beta-cell dysfunction in siblings of insulin-dependent diabetes mellitus (IDDM) patients. Twenty-three siblings, previously found positive for islet cell antibodies and/or insulin autoantibodies, were divided into 2 groups according to their first phase insulin response (FPIR) to i.v. glucose tolerance tests (IVGTTs) sequentially performed during an observation period of 2 yr. Eleven siblings had diminished FPIR on at least 1 occasion (group 1), whereas 12 siblings had a normal FPIR on all occasions studied (group 2). All underwent a further IVGTT (0.5 g glucose/kg BW), and serum samples were taken at 0, 1, 3, 6, 10, 20, 30, 40, 50, and 60 min. The 2 groups had comparable median age, female/male ratio, weight, height, fasting blood glucose, immunoreactive insulin, C-peptide, and insulin autoantibodies levels, but group 1 had significantly higher islet cell antibodies levels. Fasting median PIM/IRI and PIM/C-peptide ratios were 2- to 3-fold higher in group 1 [10.5% (range, 1.8-93.8%) vs. 5.2% (range, 1.9-14.3%) and 3.3% (range, 0.4-23.1%) vs. 1.3% (range, 0.7-2.6%; P < 0.05]. Fasting PIM/C-peptide ratios correlated inversely with FPIRs (rs = -0.68; P < 0.01). During glucose stimulation, maximal responses of IRI and C-peptide were 4-fold lower in group 1, and the time of maximal responses of IRI and C-peptide occurred later in group 1 than in group 2. In contrast, no difference in maximal responses of PIM was found, but the time of maximal responses of PIM occurred later in group 1. Nine of 11 siblings in group 1 presented with IDDM 1-28 months after the test, compared to none in group 2. In group 1 a paradoxical inhibitory response of PIM was observed during the first 6 min of the IVGTT. These data indicate that fasting PIM/IRI and/or PIM/C-peptide ratio reflects subclinical beta-cell dysfunction in prediabetic subjects with evidence of immunological beta-cell assault and suggests that an elevated ratio may be an additional marker for later development of IDDM.

Diabetologia (2005) 48:829-837In the print and pdf versions of this paper, the last six authors were omitted. The complete list of authors should have been as above. The typesetters apologise for this mistake.The online version of the original article can be found at http://dx

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.

Summary. 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/~ cells for antigenic stimulation. These results support the view that the complement-fixing islet cell antibodies reflect ongoing destructive processes in the/3 cells.