Diabetes In Young Children Research Articles

Incidence of Type 1 Diabetes in Relation to Exposure to Rotavirus Infections in Pre- and Postvaccine Birth Cohorts in Finland.

To explore the incidence of type 1 diabetes in children in relation to exposure to rotavirus infections. A nationwide register-based ecological study on the 1995-2015 birth cohorts in Finland compared those born before and after the national implementation of the rotavirus vaccine in 2009. When the prevaccine 2001-2005 birth cohorts were compared with the postvaccine birth cohorts, the number of children exposed to rotavirus infection by the age of 5 years decreased from 2,522 per 100,000 children (2.5%) to 171 per 100,000 children (0.2%), while the incidence of type 1 diabetes in those aged <5 years decreased from 71.5 to 54.4 per 100,000 person-years (incidence rate ratio 0.79, 95% CI 0.71-0.86). At the population level, a decrease in exposure to rotavirus infections was associated with a decrease in the incidence of type 1 diabetes in young children.

Twelve-month psychosocial outcomes of continuous glucose monitoring with behavioural support in parents of young children with type 1 diabetes.

Managing type 1 diabetes in young children can cause significant stress for parents. Continuous glucose monitoring (CGM) may reduce parental burden. The Strategies to Enhance CGM Use in Early Childhood (SENCE) trial randomized parents of children (ages 2 to <8 years) with type 1 diabetes to CGM with family behavioural intervention (CGM + FBI), CGM alone (Standard-CGM) or blood glucose monitoring for 26 weeks before receiving CGM + FBI (BGM-Crossover). This report assesses changes in psychosocial outcomes for all groups over 52 weeks. CGM + FBI (n = 45), Standard-CGM (n = 42) and BGM-Crossover (n = 44) participants completed psychosocial assessments at baseline, 26 weeks and 52 weeks. Repeated measures linear regression models evaluated change within and between treatment groups. The BGM-Crossover group reported improved diabetes burden (Δ -6.9, 95% CI [-11.3, -2.6], p = 0.003), fear of hypoglycaemia (Δ -6.4, CI [-10.1, -2.6], p = 0.002) and technology satisfaction (Δ 7.3, CI [2.4, 12.2], p = 0.005) from 26 to 52 weeks, similar to published findings in the CGM + FBI group over the first 26 weeks. The Standard-CGM group reported increased technology satisfaction (Δ 7.3, CI [0.6, 14.0], p = 0.027) from baseline to 52 weeks. The CGM + FBI group reported less diabetes burden and fear of hypoglycaemia from baseline to 52 weeks, but changes were not statistically significant. Scores from 26 to 52 weeks did not deteriorate. Parents demonstrated psychosocial benefits following FBI that appeared to maintain without additional intervention. CGM-focused education with behavioural support likely helps parents of young children with type 1 diabetes reduce burden and worry in the short- and long-term.

Predictors of the Initiation of Islet Autoimmunity and Progression to Multiple Autoantibodies and Clinical Diabetes: The TEDDY Study.

To distinguish among predictors of seroconversion, progression to multiple autoantibodies and from multiple autoantibodies to type 1 diabetes in young children. Genetically high-risk newborns (n = 8,502) were followed for a median of 11.2 years (interquartile range 9.3-12.6); 835 (9.8%) developed islet autoantibodies and 283 (3.3%) were diagnosed with type 1 diabetes. Predictors were examined using Cox proportional hazards models. Predictors of seroconversion and progression differed, depending on the type of first appearing autoantibody. Male sex, Finnish residence, having a sibling with type 1 diabetes, the HLA DR4 allele, probiotic use before age 28 days, and single nucleotide polymorphism (SNP) rs689_A (INS) predicted seroconversion to IAA-first (having islet autoantibody to insulin as the first appearing autoantibody). Increased weight at 12 months and SNPs rs12708716_G (CLEC16A) and rs2292239_T (ERBB3) predicted GADA-first (autoantibody to GAD as the first appearing). For those having a father with type 1 diabetes, the SNPs rs2476601_A (PTPN22) and rs3184504_T (SH2B3) predicted both. Younger age at seroconversion predicted progression from single to multiple autoantibodies as well as progression to diabetes, except for those presenting with GADA-first. Family history of type 1 diabetes and the HLA DR4 allele predicted progression to multiple autoantibodies but not diabetes. Sex did not predict progression to multiple autoantibodies, but males progressed more slowly than females from multiple autoantibodies to diabetes. SKAP2 and MIR3681HG SNPs are newly reported to be significantly associated with progression from multiple autoantibodies to type 1 diabetes. Predictors of IAA-first versus GADA-first autoimmunity differ from each other and from the predictors of progression to diabetes.

Closed‐loop control of type 1 diabetes in young children

Journal of Paediatrics and Child HealthVolume 58, Issue 4 p. 734-734 Heads UpFree Access Closed-loop control of type 1 diabetes in young children First published: 26 February 2022 https://doi.org/10.1111/jpc.15929 edited by Craig Mellis (craig.mellis@sydney.edu.au) AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Management of type 1 diabetes in young children is difficult because of their unpredictable eating habits, variable insulin requirements and parents' fear of hypoglycaemia. Sensor-augmented pump therapy decreases hypoglycaemia and ketoacidosis in this age-group but has not been shown to improve glycaemic control. Hybrid closed-loop systems (i.e. artificial pancreas) in which an algorithm adjusts insulin delivery based on real-time sensor glucose levels have been used in adolescents. European researchers randomised 74 children aged 1–7 years, mean 5.6 (standard deviation = 1.6) years, to receive insulin via either a closed-loop system or sensor-augmented pump therapy (control) for 16 weeks; they then crossed over to the other treatment for 16 weeks in a multicentre, randomised, cross-over trial.1 The closed-loop period was significantly superior to standard pump therapy in terms of time with glucose levels in the target range (72 vs. 63%, P < 0.001, which equated to a clinically significant 125 min/day), time spent in a hyperglycaemic state, difference in glycated haemoglobin level and difference in mean sensor glucose level (Fig. 1). The time spent in a hypoglycaemic state was similar between treatments, but one child had a severe hypoglycaemic episode during the closed-loop period. A hybrid closed-loop system significantly improved glycaemic control in young children with type 1 diabetes. Fig. 1Open in figure viewerPowerPoint Sensor glucose levels. (), Closed-loop insulin delivery (), interquartile range (IQR)); (), sensor-augmented pump therapy (), IQR); (), target glucose range (N.B. 70 mg/dL = 3.9 mmol/L; 180 mg/dL = 10 mmol/L). Reference 1Ware J, Allen JM, Boughton CK et al. Randomized trial of closed-loop control in very young children with type 1 diabetes. N. Engl. J. Med. 2022; 386: 209– 19. CrossrefCASPubMedWeb of Science®Google Scholar Reviewers: David Isaacs, david.isaacs@health.nsw.gov.au, Children's Hospital at Westmead, Sydney; Lara Graves, lara.graves@health.nsw.gov.au, Children's Hospital at Westmead, Sydney Volume58, Issue4April 2022Pages 734-734 FiguresReferencesRelatedInformation

Psychological Well-Being of Parents of Very Young Children With Type 1 Diabetes - Baseline Assessment.

BackgroundType 1 diabetes in young children is a heavy parental burden. As part of pilot phase of the KIDSAP01 study, we conducted a baseline assessment in parents to study the association between hypoglycemia fear, parental well-being and child behavior.MethodsAll parents were invited to fill in baseline questionnaires: hypoglycemia fear survey (HFS), WHO-5, Epworth Sleepiness Scale and Strength and Difficulties Questionnaire (SDQ).Results24 children (median age: 5-year, range 1-7 years, 63% male, mean diabetes duration: 3 ± 1.7 years) participated. 23/24 parents filled out the questionnaires. We found a higher score for the hypoglycemia fear behavior 33.9 ± 5.6 compared to hypoglycemia worry 34.6 ± 12.2. Median WHO-5 score was 16 (8 - 22) with poor well-being in two parents. Median daytime sleepiness score was high in five parents (>10). For six children a high total behavioral difficulty score (>16) was reported. Pro social behavior score was lower than normal in six children (<6). Parental well-being was negatively associated with HFS total (r = - 0.50, p <.05) and subscale scores (r = - 0.44, p <.05 for HFS-Worry and HFS-Behavior), child behavior (r = - 0.45, p = .05) and positively with child age and diabetes duration (r = 0.58, p <.01, r = 0.6, p <.01). HFS, parental well-being nor daytime sleepiness are associated with the HbA1c.ConclusionRegular screening of parental well-being, hypoglycemia fear and child behavior should be part of routine care to target early intervention.

Source-specific social support and psychosocial stress among mothers and fathers during initial diagnosis of type 1 diabetes in young children.

Background: Given parents' elevated stress following children's diagnoses of type I diabetes (T1D), more information about protective factors is needed. The current study examined social support from various sources (e.g., partner, family, general) in relation to stress among mothers and fathers of young children shortly following T1D diagnosis. Methods: Participants included 157 children ages 1-6 recently diagnosed with T1D and their parents (152 mothers and 59 fathers) who were enrolled in a behavioral randomized controlled trial (RCT). Mothers and fathers self-reported on their demographic background, social support and stress; T1D data were parent report and/or gathered from medical records. Results: Maternal and paternal stress were examined in two separate regression models. Higher general social support predicted less stress for both mothers and fathers. For mothers, higher family support predicted less stress, while college educations status predicted more stress. For fathers, more partner support predicted less stress. Discussion: Findings contribute to the literature on gender differences in source-specific social support and psychosocial functioning in a pediatric health population. Sample characteristics limit generalizability of results, and future studies should aim to include diverse samples. Results have both scientific and clinical implications for supporting families following T1D diagnosis. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

First-appearing islet autoantibodies for type 1 diabetes in young children: maternal life events during pregnancy and the child's genetic risk.

Psychological stress has long been considered a possible trigger of type 1 diabetes, although prospective studies examining the link between psychological stress or life events during pregnancy and the child's type 1 diabetes risk are rare. The objective of this study was to examine the association between life events during pregnancy and first-appearing islet autoantibodies (IA) in young children, conditioned by the child's type 1 diabetes-related genetic risk. The IA status of 7317 genetically at-risk The Environmental Determinants of Diabetes in the Young (TEDDY) participants was assessed every 3months from 3months to 4years, and bi-annually thereafter. Reports of major life events during pregnancy were collected at study inception when the child was 3months of age and placed into one of six categories. Life events during pregnancy were examined for association with first-appearing insulin (IAA) (N = 222) or GAD (GADA) (N = 209) autoantibodies in the child until 6years of age using proportional hazard models. Relative excess risk due to interaction (RERI) by the child's HLA-DR and SNP profile was estimated. Overall, 65% of mothers reported a life event during pregnancy; disease/injury (25%), serious interpersonal (28%) and job-related (25%) life events were most common. The association of life events during pregnancy differed between IAA and GADA as the first-appearing autoantibody. Serious interpersonal life events correlated with increased risk of GADA-first only in HLA-DR3 children with the BACH2-T allele (HR 2.28, p < 0.0001), an additive interaction (RERI 1.87, p = 0.0004). Job-related life events were also associated with increased risk of GADA-first among HLA-DR3/4 children (HR 1.53, p = 0.04) independent of serious interpersonal life events (HR 1.90, p = 0.002), an additive interaction (RERI 1.19, p = 0.004). Job-related life events correlated with reduced risk of IAA-first (HR 0.55, p = 0.004), particularly in children with the BTNL2-GG allele (HR 0.48; 95% CI 0.31, 0.76). Specific life events during pregnancy are differentially related to IAA vs GADA as first-appearing IA and interact with different HLA and non-HLA genetic factors, supporting the concept of different endotypes underlying type 1 diabetes. However, the mechanisms underlying these associations remain to be discovered. Life events may be markers for other yet-to-be-identified factors important to the development of first-appearing IA.

Increasing incidence of type 1 diabetes mellitus in young children in Slovakia.

We aimed to study the prevalence of the early onset Type 1 diabetes in Slovakia during the years 1996-2017. Prevalence of Type 1 diabetes in young children is increasing worldwide. However, recent data from Slovakia are missing. All children with newly diagnosed Type 1 diabetes included in the study were diagnosed in the Children Diabetes Centre in Bratislava during the years 1996-2017. The incidence of T1D in children aged below 3 and below 5 years was calculated and compared to the T1D incidence in older children. Incidence trends were calculated with the Poissed regression. Gender-adjusted incidence of T1D annually increased by 5.4 % (CI: 3.9-6.8; p < 0.001) in children <3 years, and by 3.4 % (95 % CI 2.2-4.6; p<0.001) in children <5 years during the last two decades. Moreover, the proportion of young children <3 years of age among all newly diagnosed children and adolescents increased over time (4.2±2.8 % in years 1996-1998; 12.2±5.8 % in years 2004-2008, and 13.7±7.4 % during the years 2013-2017). We found a significant increase in the incidence and proportion of T1D in young children during the last two decades. Similar data were also found in other European countries. This could be explained by changing environmental conditions (Fig. 1, Ref. 32).

Monogenic Diabetes in Children and Adolescents: Recognition and Treatment Options.

We provide a review of monogenic diabetes in young children and adolescents with a focus on recognition, management, and pharmacological treatment. Monogenic forms of diabetes account for approximately 1-2% of diabetes in children and adolescents, and its incidence has increased in recent years due to greater awareness and wider availability of genetic testing. Monogenic diabetes is due to single gene defects that primarily affect beta cell function with more than 30 different genes reported. Children with antibody-negative, C-peptide-positive diabetes should be evaluated and genetically tested for monogenic diabetes. Accurate genetic diagnosis impacts treatment in the most common types of monogenic diabetes, including the use of sulfonylureas in place of insulin or other glucose-lowering agents or discontinuing pharmacologic treatment altogether. Diagnosis of monogenic diabetes can significantly improve patient care by enabling prediction of the disease course and guiding appropriate management and treatment.

Clinical characteristics of type 1 diabetes mellitus in Taiwanese children aged younger than 6 years: A single-center experience.

Cases of type 1 diabetes mellitus in children aged younger than 6 years in Taiwan has increased in the past 10 years. This retrospective study aimed to review the management experience of such patients in a single center. From January 2004 to June 2015, 52 newly diagnosed diabetic children younger than 6 years who had regular follow-up for >1 year were enrolled, as well as 94 older diabetic children for comparison. Their medical records were thoroughly reviewed. The most common symptoms and signs were polyuria, polydipsia, dry lips, weight loss, and nocturia. Among the children younger than 6 years, 87% had ketoacidosis upon diagnosis-significantly higher than that of the older age group-and 88% had at least one islet cellautoantibody detected. Their serum C-peptide levels were significantly lower and the frequency of insulin autoantibodies detected was significantly higher compared with the older age group (37% vs. 10%). The remission rate of the young diabetic patients was significantly lower than that of the older age group (40% vs. 59%), but there was no difference in time of onset and duration of remission between the two groups. Autoimmune destruction of pancreatic β-cells is an important cause of type 1 diabetes mellitus in Taiwanese children aged younger than 6 years. These patients usually have a low insulin reserve and severe ketoacidosis upon diagnosis. A high index of suspicion in the presence of classic symptoms of diabetes in young children is important to prevent complications.

Young children with type 1 diabetes: challenges, research, and future directions.

The incidence of type 1 diabetes (T1D) in young children (age <6 years) is rising. Diabetes management guidelines offered by the American Diabetes Association and health care teams understandably place a high burden of responsibility on caregivers to check young children's blood glucose levels, administer insulin, and monitor diet and physical activity with the ultimate goal of maintaining tight glycemic control. Unfortunately, this tight control is needed during a vulnerable developmental period when behavior is unpredictable, T1D can be physiologically difficult to control, parenting stress can be elevated, and caregivers are strained by normal child caretaking routines. Despite the potentially different management needs, specific education and clinical services for managing diabetes in young children are rarely offered, and behavioral research with this young child age group has been limited in scope and quantity. Research findings pertinent to young children with T1D are reviewed, and potential clinical implications, as well as areas for future research, are discussed.

Aberrant gut microbiota composition at the onset of type 1 diabetes in young children.

Recent studies indicate that an aberrant gut microbiota is associated with the development of type 1 diabetes, yet little is known about the microbiota in children who have diabetes at an early age. To this end, the microbiota of children aged 1-5years with new-onset type 1 diabetes was compared with the microbiota of age-matched healthy controls. A deep global analysis of the gut microbiota composition was established by phylogenetic microarray analysis using a Human Intestinal Tract Chip (HITChip). Principal component analyses highlighted the importance of age when comparing age-matched pairs. In pairs younger than 2.9years, the combined abundance of the class Bacilli (notably streptococci) and the phylum Bacteroidetes was higher in diabetic children, whereas the combined abundance of members of Clostridium clusters IV and XIVa was higher in the healthy controls. Controls older than 2.9years were characterised by a higher fraction of butyrate-producing species within Clostridium clusters IV and XIVa than was seen in the corresponding diabetic children or in children from the younger age groups, while the diabetic children older than 2.9years could be differentiated by having an increased microbial diversity. The results from both age groups suggest that non-diabetic children have a more balanced microbiota in which butyrate-producing species appear to hold a pivotal position.

Extended 6-Month Follow-Up of A Randomized Clinical Trial to Assess the Efficacy and Safety of Real-Time Continuous Glucose Monitoring in the Management of Type 1 Diabetes in Young Children Aged 4 to &amp;lt;10 Years

In a 6-month randomized trial of continuous glucose monitoring (CGM) in children 4–9 years of age with type 1 diabetes (1), the DirecNet Study Group reported no difference in change in A1C between the CGM and usual care groups, although parents expressed high satisfaction with use of CGM. In a 6-month posttrial phase, the CGM group continued to use CGM and the control group was started on CGM. This observation provides a summary of the findings for both groups during this posttrial phase. Sixty-four of the 69 children in the CGM group who completed the trial participated in the extension phase; all 64 completed the 12-month visit. Baseline A1C was 7.9 ± 0.8 and 7.8 ± 0.8% at the beginning of the extension phase and 7.9 ± 0.8% at 12 months. During the extension phase, A1C decreased ≥0.5% in 14% and increased ≥0.5% in 25%. Sensor use dropped from a median of 92 h/week at 6 months to …

A Randomized Clinical Trial to Assess the Efficacy and Safety of Real-Time Continuous Glucose Monitoring in the Management of Type 1 Diabetes in Young Children Aged 4 to &amp;lt;10 Years

OBJECTIVEContinuous glucose monitoring (CGM) has been demonstrated to improve glycemic control in adults with type 1 diabetes but less so in children. We designed a study to assess CGM benefit in young children aged 4 to 9 years with type 1 diabetes.RESEARCH DESIGN AND METHODSAfter a run-in phase, 146 children with type 1 diabetes (mean age 7.5 ± 1.7 years, 64% on pumps, median diabetes duration 3.5 years) were randomly assigned to CGM or to usual care. The primary outcome was reduction in HbA1c at 26 weeks by ≥0.5% without the occurrence of severe hypoglycemia.RESULTSThe primary outcome was achieved by 19% in the CGM group and 28% in the control group (P = 0.17). Mean change in HbA1c was −0.1% in each group (P = 0.79). Severe hypoglycemia rates were similarly low in both groups. CGM wear decreased over time, with only 41% averaging at least 6 days/week at 26 weeks. There was no correlation between CGM use and change in HbA1c (rs = −0.09, P = 0.44). CGM wear was well tolerated, and parental satisfaction with CGM was high. However, parental fear of hypoglycemia was not reduced.CONCLUSIONSCGM in 4- to 9-year-olds did not improve glycemic control despite a high degree of parental satisfaction with CGM. We postulate that this finding may be related in part to limited use of the CGM glucose data in day-to-day management and to an unremitting fear of hypoglycemia. Overcoming the barriers that prevent integration of these critical glucose data into day-to-day management remains a challenge.

Reduced prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in young children participating in longitudinal follow-up.

OBJECTIVEYoung children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type 1 diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged <2 and <5 years compared with population-based incidence studies and registries.RESEARCH DESIGN AND METHODSSymptoms and laboratory data collected on TEDDY participants diagnosed with type 1 diabetes between 2004 and 2010 were compared with data collected during the similar periods from studies and registries in all TEDDY-participating countries (U.S., SEARCH for Diabetes in Youth Study; Sweden, Swediabkids; Finland, Finnish Pediatric Diabetes Register; and Germany, Diabetes Patienten Verlaufsdokumenation [DPV] Register).RESULTSA total of 40 children younger than age 2 years and 79 children younger than age 5 years were diagnosed with type 1 diabetes in TEDDY as of December 2010. In children <2 years of age at onset, DKA prevalence in TEDDY participants was significantly lower than in all comparative registries (German DPV Register, P < 0.0001; Swediabkids, P = 0.02; SEARCH, P < 0.0001; Finnish Register, P < 0.0001). The prevalence of DKA in TEDDY children diagnosed at <5 years of age (13.1%) was significantly lower compared with SEARCH (36.4%) (P < 0.0001) and the German DPV Register (32.2%) (P < 0.0001) but not compared with Swediabkids or the Finnish Register.CONCLUSIONSParticipation in the TEDDY study is associated with reduced risk of DKA at diagnosis of type 1 diabetes in young children.

216 Reductions in Unwanted Behaviours in Children with Autism Spectrum Disorders Treated with ESDM in a Community Child Care Setting

Type 1 diabetes mellitus was previously referred to as insulin-dependent or juvenile-onset diabetes mellitus. It is a chronic disease caused by pancreatic insufficiency of insulin production. Type 1 diabetes is the major form of the disease in children and adolescents, making up 5%–10% of all diabetes cases. It is rare during the first 9 months of life, and is at its highest incidence at 12 years of age. When the patient is lacking insulin, glucose cannot enter the body cells that require insulin-mediated uptake of glucose. This can cause extremely high levels of blood glucose, and diabetic ketoacidosis, which may be life-threatening. This information suggests that a more vigorous autoimmune response occurs with type 1 diabetes in young children. Type 1 diabetes is an autoimmune disease, in which cytotoxic CD8-T lymphocytes attack and destroy the pancreatic islets.

The Feasibility of Detecting Neuropsychologic and Neuroanatomic Effects of Type 1 Diabetes in Young Children

OBJECTIVETo determine if frequent exposures to hypoglycemia and hyperglycemia during early childhood lead to neurocognitive deficits and changes in brain anatomy.RESEARCH DESIGN AND METHODSIn this feasibility, cross-sectional study, young children, aged 3 to 10 years, with type 1 diabetes and age- and sex-matched healthy control (HC) subjects completed neuropsychologic (NP) testing and magnetic resonance imaging (MRI) scans of the brain.RESULTSNP testing and MRI scanning was successfully completed in 98% of the type 1 diabetic and 93% of the HC children. A significant negative relationship between HbA1c and Wechsler Intelligence Scale for Children (WISC) verbal comprehension was observed. WISC index scores were significantly reduced in type 1 diabetic subjects who had experienced seizures. White matter volume did not show the expected increase with age in children with type 1 diabetes compared with HC children (diagnosis by age interaction, P = 0.005). A similar trend was detected for hippocampal volume. Children with type 1 diabetes who had experienced seizures showed significantly reduced gray matter and white matter volumes relative to children with type 1 diabetes who had not experienced seizures.CONCLUSIONSIt is feasible to perform MRI and NP testing in young children with type 1 diabetes. Further, early signs of neuroanatomic variation may be present in this population. Larger cross-sectional and longitudinal studies of neurocognitive function and neuroanatomy are needed to define the effect of type 1 diabetes on the developing brain.

Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children

The incidence of type 1 diabetes is rising worldwide, particularly in young children. Since type 1 diabetes is preceded by autoimmunity to islet antigens, there must be a consequent increase in the incidence of islet autoimmunity in young children or a more rapid rate of progression to diabetes once islet autoimmunity initiates. This study was to determine whether the incidence of islet autoimmunity or the rate of progression from autoimmunity to diabetes onset has changed over a 20-year period in children genetically predisposed to type 1 diabetes. Between 1989 and 2010, children who were first-degree relatives of patients with type 1 diabetes and who were born in Germany were prospectively followed from birth without intervention. A total of 324 children (BABYDIAB study) born between 1989 and 2000 and 216 children (TEDDY study) born between 2004 and 2010 with matched HLA genotypes were recruited before age 3 months and included for analysis. Children were followed for the development of autoantibodies to insulin, GAD, and IA-2, and for progression to diabetes. The cumulative frequency of diabetes by age 4 years was 2.5% (95% CI 0.8–4.2%) in BABYDIAB children and 6.2% (95% CI 2.3–10.1%) in TEDDY children ( p = 0.03). The cumulative frequency of islet autoantibodies by age 4 years was similar in the children from both studies (11.3% vs 13.9%). Progression to diabetes from the development of islet autoantibodies was markedly increased in autoantibody-positive children from the more recently recruited TEDDY cohort (50% progression within 85.2 months for BABYDIAB children vs 9.6 months for TEDDY children; p = 0.009), also if children were further selected on the basis of high-risk HLA genotypes or the development of autoantibodies to multiple islet antigens ( p = 0.01). The findings suggest that recent increasing incidence of type 1 diabetes in young children could be due to weakening of mechanisms that normally regulate autoimmune destruction of islet beta cells.

Role of insulin autoantibody affinity as a predictive marker for type 1 diabetes in young children with HLA‐conferred disease susceptibility

Insulin autoantibodies (IAA) are early markers of prediabetic autoimmunity. As transient and fluctuating IAA positivity are common among young children, distinguishing non-progressive IAA from destruction-related IAA is essential when preventive measures are considered. We tested whether children progressing rapidly to type 1 diabetes (progressors) are characterized by a higher prediabetic IAA affinity than IAA-positive children remaining unaffected or progressing more slowly to diabetes (non-progressors), and whether IAA affinity increases towards diagnosis. Finnish children with HLA-conferred diabetes susceptibility were observed from birth for diabetes-associated autoantibodies and progression to overt type 1 diabetes. IAA levels and affinities of the first IAA-positive prediabetic samples and samples obtained closest to the diagnosis in 64 progressors were compared with corresponding values in 64 matched IAA-positive non-progressors. The median age at diagnosis was 3.9 years in progressors and the median follow-up time 7.6 years among unaffected subjects. In the first samples the median IAA affinity was 1.4 x 10(10) L/mol in both groups (p = 0.33), while at the second sampling it was 1.1 x 10(10) L/mol in progressors and 1.2 x 10(10) L/mol in unaffected subjects (p = 0.46). No changes in affinity levels were observed (p = 0.33 and p = 0.84, respectively). IAA titers increased towards diagnosis among progressors (from a median of 13.6 to 20.1 relative units; p = 0.02). Among young IAA-positive children with HLA-conferred disease susceptibility IAA affinity failed to distinguish rapid progressors from slowly or non-progressing subjects. In relation to IAA affinity, no maturation of the humoral immune response was observed over time from seroconversion to diagnosis.

Dietary Glycemic Index, Development of Islet Autoimmunity, and Subsequent Progression to Type 1 Diabetes in Young Children

Dietary factors may trigger or exacerbate the autoimmune disease process. Our objective was to examine dietary glycemic index (GI) and glycemic load (GL) for association with islet autoimmunity (IA) development, and progression from IA to type 1 diabetes. The Diabetes Autoimmunity Study in the Young follows children at increased genetic type 1 diabetes risk. Diet is collected prospectively via a parent-reported food frequency questionnaire. This was an observational study of children in the Denver area. A total of 1776 Diabetes Autoimmunity Study in the Young children younger than 11.5 yr was included in the study. There were no interventions. IA, defined as the presence of autoantibodies to insulin, glutamic acid decarboxylase, or protein tyrosine phosphatase at two consecutive visits, or the presence of autoantibodies at one visit and diabetic on the next consecutive visit was determined. Type 1 diabetes was diagnosed by a physician. A total of 89 subjects developed IA, and 17 subsequently developed type 1 diabetes during follow-up. Our hypothesis was formulated after data collection. GI and GL were not associated with IA development. More rapid progression to type 1 diabetes in children with IA was associated with higher dietary GI (hazard ratio: 2.20; 95% confidence interval: 1.17-4.15) and marginally associated with GL (hazard ratio: 1.59; 95% confidence interval: 0.96-2.64) at the first IA-positive visit. Higher dietary GI and GL are not associated with IA development, but higher GI is associated with more rapid progression to type 1 diabetes in children with IA, perhaps due to increased demand on the beta-cell to release insulin. Further study is needed to confirm this finding and identify the underlying biological mechanism.