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Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb + ) children and adults who are at risk of (confirmed single IAb + ) or living with (multiple IAb + ) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb + ; (2) when people who are IAb + are initially identified there is a need for confirmation using a second sample; (3) single IAb + individuals are at lower risk of progression than multiple IAb + individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care., (© 2024. American Diabetes Association and European Association for the Study of Diabetes.)

As children spend up to 9 h a day in kindergarten, the main purpose of our study was to evaluate the effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers (OSBs) in healthy children. In the randomized control trial with a follow-up, healthy 5-6-year-old children from six kindergartens were randomly divided into a prototype group (PG, n = 40) and a control group (CG, n = 17). PG followed a 2-week antioxidant-rich kindergarten meal plan (breakfast, lunch, and two snacks), and CG followed their standard kindergarten meal plans. Outside the kindergartens, participants ate as usual. We used a consecutive 7-day dietary record inside and outside the kindergarten and the national dietary assessment tool OPEN to assess the total dietary antioxidant capacity (dTAC) of the consumed foods. Malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and four F2-isoprostane were measured in fasting urine on days 1 and 15. We also measured total antioxidant power (PAT) and hydroperoxides (d-ROMs) in fasting serum on day 15 and obtained the value of the oxidative stress index (OSI). We used a Welch two-sample t-test and multiple regression analysis to compare the prototype and control groups and a nonparametric Wilcoxon signed rank exact test to compare pre- and post-intervention results in urine. Antioxidant-rich kindergarten meals contributed to a significantly (p < 0.05) higher intake of dTAC in PG participants compared to standard meals in CG participants (8.6 vs. 2.8 mmol/day). We detected a negative correlation between dTAC intake and d-ROMs and between dTAC intake and OSI (r =  - 0.29, p = 0.043 and r =  - 0.31, p = 0.032, respectively). A significant decrease in urinary 8-iso-15-prostaglandin-F-2 alpha was detected in PG participants between days 1 and 15; however, no other intra-individual significant differences in urinary OSBs were found.  Conclusion: Antioxidant-rich food in kindergarten is warranted due to its potential health-protective effect. Additionally, we present original data on the average levels of urinary and serum OSBs in healthy 5-6-year-old children.  Trial registration: The study was registered at ClinicalTrials.gov, on February 5, 2020 ( https://clinicaltrials.gov/ct2/show/NCT04252105 ). What is Known: • Kindergartens are recognized as promising environments for public health measures. • A diet rich in antioxidants can reduce OSBs and, consequently, the risk of developing NCDs. What is New: • Antioxidant-rich kindergarten diet can ensure a protective intake of dTAC in children. • Original data on serum oxidative stress biomarkers (d-ROMs, PAT, and OSI) and urinary oxidative stress biomarkers (MDA, 8-OHdG, and F2 isoprostanes) in healthy 5-6-year-old children., (© 2024. The Author(s).)

Aims/hypothesis: Type 1 diabetes is an heterogenous condition. Characterising factors explaining differences in an individual's clinical course and treatment response will have important clinical and research implications. Our aim was to explore type 1 diabetes heterogeneity, as assessed by clinical characteristics, autoantibodies, beta cell function and glycaemic outcomes, during the first 12 months from diagnosis, and how it relates to age at diagnosis., Methods: Data were collected from the large INNODIA cohort of individuals (aged 1.0-45.0 years) newly diagnosed with type 1 diabetes, followed 3 monthly, to assess clinical characteristics, C-peptide, HbA 1c and diabetes-associated antibodies, and their changes, during the first 12 months from diagnosis, across three age groups: <10 years; 10-17 years; and ≥18 years., Results: The study population included 649 individuals (57.3% male; age 12.1±8.3 years), 96.9% of whom were positive for one or more diabetes-related antibodies. Baseline (IQR) fasting C-peptide was 242.0 (139.0-382.0) pmol/l (AUC 749.3 [466.2-1106.1] pmol/l × min), with levels increasing with age (p<0.001). Over time, C-peptide remained lower in participants aged <10 years but it declined in all age groups. In parallel, glucose levels progressively increased. Lower baseline fasting C-peptide, BMI SD score and presence of diabetic ketoacidosis at diagnosis were associated with lower stimulated C-peptide over time. HbA 1c decreased during the first 3 months (p<0.001), whereas insulin requirement increased from 3 months post diagnosis (p<0.001)., Conclusions/interpretation: In this large cohort with newly diagnosed type 1 diabetes, we identified age-related differences in clinical and biochemical variables. Of note, C-peptide was lower in younger children but there were no main age differences in its rate of decline., (© 2024. The Author(s).)

The type 1 diabetes community is coalescing around the benefits and advantages of early screening for disease risk. To be accepted by healthcare providers, regulatory authorities and payers, screening programmes need to show that the testing variables allow accurate risk prediction and that individualised risk-informed monitoring plans are established, as well as operational feasibility, cost-effectiveness and acceptance at population level. Artificial intelligence (AI) has the potential to contribute to solving these issues, starting with the identification and stratification of at-risk individuals. ASSET (AI for Sustainable Prevention of Autoimmunity in the Society; www.asset.healthcare ) is a public/private consortium that was established to contribute to research around screening for type 1 diabetes and particularly to how AI can drive the implementation of a precision medicine approach to disease prevention. ASSET will additionally focus on issues pertaining to operational implementation of screening. The authors of this article, researchers and clinicians active in the field of type 1 diabetes, met in an open forum to independently debate key issues around screening for type 1 diabetes and to advise ASSET. The potential use of AI in the analysis of longitudinal data from observational cohort studies to inform the design of improved, more individualised screening programmes was also discussed. A key issue was whether AI would allow the research community and industry to capitalise on large publicly available data repositories to design screening programmes that allow the early detection of individuals at high risk and enable clinical evaluation of preventive therapies. Overall, AI has the potential to revolutionise type 1 diabetes screening, in particular to help identify individuals who are at increased risk of disease and aid in the design of appropriate follow-up plans. We hope that this initiative will stimulate further research on this very timely topic., (© 2024. The Author(s).)

Previous studies have suggested that clear HbA1c target setting by the diabetes team is associated with HbA1c outcomes in adolescents. The aim of this study was to evaluate whether this finding is consistent in a larger cohort of children from centers participating in the SWEET international diabetes registry. A questionnaire was sent out to 76 SWEET centers, of which responses from 53 pediatric centers were included (70%). Descriptive outcomes were presented as median with lower and upper quartile. The association between the centers' target HbA1c and mean outcome HbA1c was calculated using linear regression adjusted for age, diabetes duration, sex, and gross domestic product. Median age of the children in the studied centers (n = 35,483) was 13.3 [12.6-14.6] years (49% female). Of the 53 centers, 13.2% reported an HbA1c target between 6.0 and 6.5%, 32.1% had a target between ≥ 6.0 and 7.0%, 18.9% between ≥ 7.0 and 7.5%, and 3.8% between ≥ 7.5 and 8.5%. No specific target value was reported by 32.1% of all centers. Median HbA1c across all centers was 7.9 [7.6-8.3] %. Adjusted regression analysis showed a positive association between HbA1c outcome and target HbA1c (p = 0.005).Conclusions: This international study demonstrated that a lower target for HbA1c was associated with better metabolic control. It is unclear whether low target values result in better metabolic control, or lower HbA1c values actually result in more ambitious target values. This target setting could contribute to the differences in HbA1c values between centers and could be an approach for improving metabolic outcomes. What is Known: • Target setting of HbA1c is important in children and adolescents with type 1 diabetes. • The optimal therapeutic approach of children with type 1 diabetes requires a trained multidisciplinary team. What is New: • Lower HbA1c targets are associated with better metabolic control. • No associations between the composition of the diabetes teams and metabolic control could be demonstrated.

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (i.e. before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes. Graphical abstract.

Aims/hypothesis: Hypoglycaemia during and after exercise remains a challenge. The present study evaluated the safety and efficacy of closed-loop insulin delivery during unannounced (to the closed-loop algorithm) afternoon physical activity and during the following night in young people with type 1 diabetes., Methods: A randomised, two-arm, open-label, in-hospital, crossover clinical trial was performed at a single site in Slovenia. The order was randomly determined using an automated web-based programme with randomly permuted blocks of four. Allocation assignment was not masked. Children and adolescents with type 1 diabetes who were experienced insulin pump users were eligible for the trial. During four separate in-hospital visits, the participants performed two unannounced exercise protocols: moderate intensity (55% of [Formula: see text]) and moderate intensity with integrated high-intensity sprints (55/80% of [Formula: see text]), using the same study device either for closed-loop or open-loop insulin delivery. We investigated glycaemic control during the exercise period and the following night. The closed-loop insulin delivery was applied from 15:00 h on the day of the exercise to 13:00 h on the following day., Results: Between 20 January and 16 June 2016, 20 eligible participants (9 female, mean age 14.2 ± 2.0 years, HbA 1c 7.7 ± 0.6% [60.0 ± 6.6 mmol/mol]) were included in the trial and performed all trial-mandated activities. The median proportion of time spent in hypoglycaemia below 3.3 mmol/l was 0.00% for both treatment modalities (p = 0.7910). Use of the closed-loop insulin delivery system increased the proportion of time spent within the target glucose range of 3.9-10 mmol/l when compared with open-loop delivery: 84.1% (interquartile range 70.0-85.5) vs 68.7% (59.0-77.7), respectively (p = 0.0057), over the entire study period. This was achieved with significantly less insulin delivered via the closed-loop (p = 0.0123)., Conclusions/interpretation: Closed-loop insulin delivery was safe both during and after unannounced exercise protocols in the in-hospital environment, maintaining glucose values mostly within the target range without an increased risk of hypoglycaemia., Trial Registration: Clinicaltrials.gov NCT02657083 FUNDING: University Medical Centre Ljubljana, Slovenian National Research Agency, and ISPAD Research Fellowship.

Aims: To demonstrate whether young people with T1D using modern insulin treatment and CGM could successfully participate in extreme sport activity while maintaining good glycemic control., Methods: The challenge took place in Crete/Greece over 4 days combining a long-distance trek of different levels of severity with final destination the summit of the White Mountains at 2080 m. Eleven participants (5/6 female/male, age 18.2 ± 1.3 years, T1D duration 7.9 ± 3.5 years, HbA1c 7.3 ± .7% (56 ± 16 mmol/mol); mean ± SD) from 11 SWEET centers in Belgium, Brazil, Canada, Germany, Greece, France, India, Italy, Portugal, Slovenia and Sweden participated to the challenge. Five participants were on CSII, six on MDI; all were wearing a continuous glucose monitoring system. The glycemic targets during trekking were defined as 80-180 mg/dl (4.4-10 mmol/l)., Results: All participants completed the challenge. In total, the group walked 54.5 km under varying climate conditions (temperature 14-35 °C). During the challenge, insulin requirements decreased significantly compared to baseline: total daily insulin by 31.1 ± 16.7% (p < .001), basal by 30.8 ± 14.9% (p < .001), and prandial by 32.5 ± 28.0% (p = .023), with no differences between participants with CSII or MDI. No episode of severe hypoglycemia or DKA occurred. Mean glucose levels were 170.7 ± 60.1 mg/dl with 61.5 ± 18.7% of CGM values in the target range, 5.4 ± 5.4% under 80 mg/dl and 32.8 ± 16.6% above 180 mg/dl., Conclusions: The results of this SWEET Initiative activity demonstrated that well-educated adolescents and young adults with T1D using modern insulin treatments are able to perform successfully even extraordinary physical challenges while maintaining good glycemic control without diabetes-related acute complications.

To investigate the impact of continuous glucose monitoring (CGM) on health-related quality of life (HRQOL), treatment satisfaction (TS) medical resource use, and indirect costs in the SWITCH study. SWITCH was a multicentre, randomized, crossover study. Patients with type 1 diabetes (n = 153) using continuous subcutaneous insulin infusion (CSII) were randomized to a 12 month sensor-On/Off or sensor-Off/On sequence (6 months each treatment), with a 4-month washout between periods. HRQOL in children and TS in adults were measured using validated questionnaires. Medical resource utilization data were collected. In adults, TS was significantly higher in the sensor-On arm, and there were significant improvements in ratings for treatment convenience and flexibility. There were no clinically significant differences in children's HRQOL or parents' proxy ratings. The incidence of severe hypoglycaemia, unscheduled visits, or diabetes-related hospitalizations did not differ significantly between the two arms. Adult patients made fewer telephone consultations during the sensor-On arm; children's caregivers made similar numbers of telephone consultations during both arms, and calls were on average only 3 min longer during the sensor-On arm. Regarding indirect costs, children with >70 % sensor usage missed fewer school days, compared with the sensor-Off arm (P = 0.0046) but there was no significant difference in the adults days of work off. The addition of CGM to CSII resulted in better metabolic control without imposing an additional burden on the patient or increased medical resource use, and offered the potential for cost offsets.

Unlabelled: Donohue syndrome (leprechaunism; OMIM *246200) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene (INSR) causing either defects in insulin binding or receptor autophosphorylation and tyrosine kinase activity. We report a patient with pronounced clinical picture of leprechaunism who developed severe progressive hypertrophic obstructive cardiomyopathy (HOCM) and renal tubular dysfunction which improved on continuous subcutaneous infusion of recombinant human insulin-like growth factor-1 (rhIGF-I). INSR gene molecular analysis and insulin receptor (IR) autophosphorylation on cultured fibroblasts were performed. A novel homozygous missense mutation p.Leu795Pro was found, located in the extracellular portion of the β subunit of the insulin receptor. The post-binding defect of the insulin receptor signaling in cultured fibroblasts demonstrated decreased insulin receptor autophosphorylation., Conclusion: Treatment with rhIGF-I partially reversed severe progressive HOCM and renal tubular dysfunction in a patient with Donohue syndrome associated with a novel p.Leu795Pro INSR gene mutation causing a severe decrease in IR autophosphorylation.

Aims/hypothesis: Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes., Methods: The beta cell function of 118 patients with type 1 diabetes of duration of 0.75-4.97 years was tested using a standardised liquid mixed meal test (MMT). Serum samples obtained at -5 to 120 min were analysed by multiplex bead-based technology for proinflammatory (IL-6, TNF-α), anti-inflammatory (IL-1 receptor antagonist [IL-1RA]) and regulatory (IL-10, TGF-β1-3) cytokines, and by standard procedures for C-peptide. Differences in beta cell function between patient groups were assessed using stepwise multiple regression analysis adjusting for sex, age, duration of diabetes, BMI, HbA1c and fasting blood glucose., Results: High fasting systemic concentrations of the proinflammatory cytokines IL-6 and TNF-α were associated with increased fasting and stimulated C-peptide concentrations even after adjustment for confounders (p < 0.03). Interestingly, increased concentrations of anti-inflammatory/regulatory IL-1RA, IL-10, TGF-β1 and TGF-β2 were associated with lower fasting and stimulated C-peptide levels (p < 0.04), losing significance on adjustment for anthropometric variables. During the MMT, circulating concentrations of IL-6 and TNF-α increased (p < 0.001) while those of IL-10 and TGF-β1 decreased (p < 0.02) and IL-1RA and TGF-β2 remained unchanged., Conclusions/interpretation: The association between better preserved beta cell function in longer term type 1 diabetes and increased systemic proinflammatory cytokines and decreased anti-inflammatory and regulatory cytokines is suggestive of ongoing inflammatory disease activity that might be perpetuated by the remaining beta cells. These findings should be considered when designing immune intervention studies aimed at patients with longer term type 1 diabetes and residual beta cell function.

Aims/hypothesis: The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes., Methods: Children and adults (n = 153) on CSII with HbA(1c) 7.5-9.5% (58.5-80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months' washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA(1c) levels between arms after 6 months., Results: Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA(1c) was -0.43% (-4.74 mmol/mol) in favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol]; 95% CI -0.32%, -0.55% [-3.50, -6.01 mmol/mol]; p < 0.001). Following cessation of glucose sensing, HbA(1c) reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day; p = 0.009). The mean number of daily boluses increased in the Sensor On arm (6.8 ± 2.5 vs 5.8 ± 1.9, p < 0.0001), together with the frequency of use of the temporary basal rate (0.75 ± 1.11 vs 0.26 ± 0.47, p < 0.0001) and manual insulin suspend (0.91 ± 1.25 vs 0.70 ± 0.75, p < 0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p = 0.40)., Conclusions/interpretation: Continuous glucose monitoring was associated with decreased HbA(1c) levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.

Septo-optic dysplasia (SOD) is a heterogeneous brain midline anomaly associated with ophthalmological, endocrinological, and/or neurodevelopmental symptoms. The clinical phenotype correlates with abnormal brain magnetic resonance imaging (MRI) findings. However, variations of the septum pellucidum (SP) appearance and their clinical impact have not been studied in depth. Sixty-eight patients with optic nerve hypoplasia (ONH) were investigated for the presence of associated SP anomalies and correlations between clinical findings and their MRI abnormalities established. Thirty patients had either complete (n = 22) or partial (n = 8) absence of the SP. Pituitary hormone deficiencies were present in 64% or 25% of the cases, respectively. Neurological symptoms did not occur in patients with SP remnants or unilateral ONH. Hippocampus abnormalities (43%) that have not been described before in SOD and falx abnormalities (17%) correlated significantly with neurological symptoms and developmental delay (p < 0.05 and p < 0.01, respectively). Maternal age at birth was low (21.2 years) and drug abuse during pregnancy was reported in 27% of the patients. Twelve patients with pituitary anomaly and ONH but normal SP showed similar clinical and MRI features, and were classified as SOD-like. The remaining 26 patients were not assigned to SOD. We conclude that unilateral ONH and SP remnants are associated with a milder SOD phenotype. Hippocampus abnormalities and falx abnormalities seem to constitute important features of severe clinical disease, irrespective of SP appearance. Our anamnestic data support the hypothesis of vascular disruption during embryogenesis.

Aims/hypothesis: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome., Methods: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally., Results: A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA(1c) level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively., Conclusions/interpretation: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).

Nocturnal hypoglycemia is reported in 13%-56% of adolescents with type 1 diabetes mellitus. It may be asymptomatic in more than 50% of patients. No noninvasive method for detecting asymptomatic nocturnal hypoglycemia (ANH) has so far proven successful. The aim of the present study was to evaluate quantitative changes of motor activity by actigraphy during episodes of ANH in adolescents with type 1 diabetes mellitus. A total of 18 patients aged 10-16 years with a history of ANH were investigated. Blood was sampled at half-hourly intervals between 22.30 and 06.00 hours with a micropump, and an actigraph was fastened to the right wrist. Blood glucose concentrations were measured and compared to motor activity. Nocturnal hypoglycemia was recorded in 10 patients (55%), with blood glucose during periods of hypoglycemia of 3.00+0.17 mmol/l (range, 1.2-3.4 mmol/l), and duration of hypoglycemia of 1.95+1.34 hours (range, 0.5-5.0 hours). All periods of hypoglycemia were clinically asymptomatic. Regression analysis revealed a statistically significant linear correlation ( p=0.03) between blood glucose concentration and the respective 30-min activity counts. Activity counts in patients with nocturnal hypoglycemia were significantly (ANOVA, p<0.02) higher than in patients with normoglycemia. We conclude that low blood glucose was significantly correlated with an increase in motor activity as detected by actigraphy. This implies the possibility of noninvasive screening of asymptomatic nocturnal hypoglycemia.

Aims/hypothesis: The incidence rate of childhood-onset Type I (insulin-dependent) diabetes mellitus in Slovenian children during the period 1990-1998 was studied and compared to that of children from the Tuzla region (Bosnia and Herzegovina). The secular trend for a 25-year period in Slovenia was also investigated., Methods: The incidence data were obtained from the national Slovenian Type I diabetes register and from the local Type I diabetes register held in Tuzla. The ascertainment was based on the capture-recapture method and was estimated to be 100%., Results: The age-standardized incidence of Type I diabetes mellitus for the age group 0-14 years for Slovenia was 8.54 per 100,000 (95 %-C.I. 7.5-9.5) person-years for both sexes. The incidence for boys was 8.03 per 100,000 (95 %-C.I. 6.7-9.4) and 9.12 per 100,000 (95% -C.I. 7.6-10.6) for girls. The age-standardized incidence in the Tuzla region was much lower: 3.03 per 100,000 (95 %-C.I. 2.0-4.1) for the whole group, 3.44 per 100 000 (95 %-C.I. 1.8-5.0) for boys and 3.21 per 100,000 (95 %-C.I. 1.6-4.7) for girls. A very low incidence of 0.8 per 100,000 in the youngest age group (0-4 years) was observed in the Tuzla region. The linear trend of the Type I diabetes incidence rate in Slovenia has been steadily increasing by 3.6% per year for the last 25 years. The incidence rate in the period 1974-1985 was significantly lower than that in the period 1986-1998 (p < 0.00026)., Conclusions/interpretation: Although the incidence rate in Slovenia slightly increased during the period 1990-1998, the incidence rate in the Tuzla region remained at the pre-war level.

The incidence of type 1 diabetes mellitus in Slovenian children aged 0-14 years was studied between 1 January 1988 and 31 December 1995. The crude annual incidence rate of the disease (per 100000) over this 8-year period was 8.00 (95% C. I. 6.98-9.02) for both sexes (7.18 for boys and 8.87 for girls). Thus, the incidence standardized to the world population was 7.59 (95% C. I. 6.57 - 8.61). Male/female ratios were 1.33 in the age group 0-4 years, 0.66 in the age group 5-9 years, and 0.83 in the age group 10-14 years. The study has proven that the incidence of type 1 diabetes in Slovenia is similar to that in other central European countries where the population is of different ethnic origin. However, a remarkably higher incidence of the disease in girls than boys except in the age group below 5 years of age was found which needs further investigation.

A total of 1419 children with type 1 diabetes mellitus was investigated in order to assess the true frequency of Hashimoto's thyroiditis (HT), diagnosed by microsomal and/or thyroglobulin autoantibodies, by ultrasound and in many cases also by fine needle biopsy. According to these criteria, 55 cases (3.9%) of HT were identified, a number significantly higher (P < 0.0001) than the distribution reported in the normal paediatric population. No typical antibody pattern was seen prior to the onset of HT, nor was an antibody threshold level found which could have been diagnostic for this disease. Patients with subclinical hypothyroidism were treated with L-thyroxine and were investigated regarding the behaviour of anti-thyroid autoantibodies; however, no significant changes were seen. The data showed a high frequency of HT in diabetic children, and therefore we recommend that children with type 1 diabetes mellitus should be screened for thyroid autoantibodies and those positive should undergo periodic thyroid function testing.