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A The possibility of other types of diabetes should be considered in the child who has negative diabetes-associated autoantibodies and: B an autosomal dominant family history of diabetes (maturity onset diabetes of the young [MODY]) age less than 12 months and especially in first 6 months of life (neonatal diabetes mellitus [NDM]) mild-fasting hyperglycemia (5.5–8.5 mmol/L [100–150 mg/dl]), especially if young, non-obese, and asymptomatic (MODY) a prolonged honeymoon period lasting more than 1 year or an unusually low requirement for insulin of ≤0.5 U/kg/day after 1 year of diabetes (MODY) associated conditions such as deafness, optic atrophy, or syndromic features (mitochondrial disease) a history of exposure to drugs known to be toxic to β-cells or cause insulin resistance (e.g., immunosuppressive drugs such as tacrolimus or cyclosporin; glucocorticoids or some antidepressants). Impaired insulin secretion and deficient insulin action may coexist in the same individual.2,3 While the etiology of diabetes is heterogeneous, most cases of diabetes can be classified into two broad etiopathogenetic categories (discussed later in further detail): T1D, characterized by the destruction of the ß-cells, usually by an autoimmune process, resulting in loss of endogenous insulin production, or T2D, characterized by the lack of an adequate insulin response in the presence of increasing insulin resistance. [...]it is now recognized that people with monogenic diabetes, an autosomal dominant diabetes pattern first termed MODY, may make up 1%–6% of autoantibody negative individuals who may, initially, be considered to have either T1D or T2D with decreased insulin secretion.6,7 DIAGNOSTIC CRITERIA FOR DIABETES IN CHILDHOOD AND ADOLESCENCE Diagnostic criteria for diabetes are based on BGL measurements and the presence or absence of symptoms.1–3 Different strategies can be used to measure BGL, including using a fasting plasma glucose (FPG) value, the 2-h plasma glucose (2-h PG) value during an OGTT, or hemoglobin A1c (HbA1c) criteria (Table 1) and in the absence of unequivocal hyperglycemia, diagnosis must be confirmed by repeat testing. HbA1c can be used as a diagnostic test for diabetes, in particular to test for prediabetes or T2D in youth4; providing that stringent quality assurance tests are in place and assays are standardized to criteria aligned to the international

Open-source automated insulin delivery (AID) systems are used by many patients with type 1 diabetes. Data are needed on the efficacy and safety of an open-source AID system. In this multicenter, open-label, randomized, controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio to use an open-source AID system or a sensor-augmented insulin pump (control). The patients included both children (defined as 7 to 15 years of age) and adults (defined as 16 to 70 years of age). The AID system was a modified version of AndroidAPS 2.8 (with a standard OpenAPS 0.7.0 algorithm) paired with a preproduction DANA-i insulin pump and Dexcom G6 CGM, which has an Android smartphone application as the user interface. The primary outcome was the percentage of time in the target glucose range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) between days 155 and 168 (the final 2 weeks of the trial). A total of 97 patients (48 children and 49 adults) underwent randomization (44 to open-source AID and 53 to the control group). At 24 weeks, the mean (±SD) time in the target range increased from 61.2±12.3% to 71.2±12.1% in the AID group and decreased from 57.7±14.3% to 54.5±16.0% in the control group (adjusted difference, 14 percentage points; 95% confidence interval, 9.2 to 18.8; P<0.001), with no treatment effect according to age (P = 0.56). Patients in the AID group spent 3 hours 21 minutes more in the target range per day than those in the control group. No severe hypoglycemia or diabetic ketoacidosis occurred in either group. Two patients in the AID group withdrew from the trial owing to connectivity issues. In children and adults with type 1 diabetes, the use of an open-source AID system resulted in a significantly higher percentage of time in the target glucose range than the use of a sensor-augmented insulin pump at 24 weeks. (Supported by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12620000034932.).

Before the COVID-19 pandemic, adolescents with type 1 diabetes (T1D) had already experienced far greater rates of psychological distress than their peers. With the pandemic further challenging mental health and increasing the barriers to maintaining optimal diabetes self-management, it is vital that this population has access to remotely deliverable, evidence-based interventions to improve psychological and diabetes outcomes. Chatbots, defined as digital conversational agents, offer these unique advantages, as well as the ability to engage in empathetic and personalized conversations 24-7. Building on previous work developing a self-compassion program for adolescents with T1D, a self-compassion chatbot (COMPASS) was developed for adolescents with T1D to address these concerns. However, the acceptability and potential clinical usability of a chatbot to deliver self-compassion coping tools to adolescents with T1D remained unknown. This qualitative study was designed to evaluate the acceptability and potential clinical utility of COMPASS among adolescents aged 12 to 16 years with T1D and diabetes health care professionals. Potential adolescent participants were recruited from previous participant lists, and on the web and in-clinic study flyers, whereas health care professionals were recruited via clinic emails and from diabetes research special interest groups. Qualitative Zoom (Zoom Video Communications, Inc) interviews exploring views on COMPASS were conducted with 19 adolescents (in 4 focus groups) and 11 diabetes health care professionals (in 2 focus groups and 6 individual interviews) from March 2022 to April 2022. Transcripts were analyzed using directed content analysis to examine the features and content of greatest importance to both groups. Adolescents were broadly representative of the youth population living with T1D in Aotearoa (11/19, 58% female; 13/19, 68% Aotearoa New Zealand European; and 2/19, 11% Māori). Health care professionals represented a range of disciplines, including diabetes nurse specialists (3/11, 27%), health psychologists (3/11, 27%), dieticians (3/11, 27%), and endocrinologists (2/11, 18%). The findings offer insight into what adolescents with T1D and their health care professionals see as the shared advantages of COMPASS and desired future additions, such as personalization (mentioned by all 19 adolescents), self-management support (mentioned by 13/19, 68% of adolescents), clinical utility (mentioned by all 11 health care professionals), and breadth and flexibility of tools (mentioned by 10/11, 91% of health care professionals). Early data suggest that COMPASS is acceptable, is relevant to common difficulties, and has clinical utility during the COVID-19 pandemic. However, shared desired features among both groups, including problem-solving and integration with diabetes technology to support self-management; creating a safe peer-to-peer sense of community; and broadening the representation of cultures, lived experience stories, and diabetes challenges, could further improve the potential of the chatbot. On the basis of these findings, COMPASS is currently being improved to be tested in a feasibility study.

There is evidence pointing towards shared etiological features between type 1 diabetes (T1D) and type 2 diabetes (T2D) despite both phenotypes being considered genetically distinct. However, the existence of shared genetic features for T1D and T2D remains complex and poorly defined. To better understand the link between T1D and T2D, we employed an integrated functional genomics approach involving extensive chromatin interaction data (Hi-C) and expression quantitative trait loci (eQTL) data to characterize the tissue-specific impacts of single nucleotide polymorphisms associated with T1D and T2D. We identified 195 pleiotropic genes that are modulated by tissue-specific spatial eQTLs associated with both T1D and T2D. The pleiotropic genes are enriched in inflammatory and metabolic pathways that include mitogen-activated protein kinase activity, pertussis toxin signaling, and the Parkinson’s disease pathway. We identified 8 regulatory elements within the TCF7L2 locus that modulate transcript levels of genes involved in immune regulation as well as genes important in the etiology of T2D. Despite the observed gene and pathway overlaps, there was no significant genetic correlation between variant effects on T1D and T2D risk using European ancestral summary data. Collectively, our findings support the hypothesis that T1D and T2D specific genetic variants act through genetic regulatory mechanisms to alter the regulation of common genes, and genes that co-locate in biological pathways, to mediate pleiotropic effects on disease development. Crucially, a high risk genetic profile for T1D alters biological pathways that increase the risk of developing both T1D and T2D. The same is not true for genetic profiles that increase the risk of developing T2D. The conversion of information on genetic susceptibility to the protein pathways that are altered provides an important resource for repurposing or designing novel therapies for the management of diabetes.

Term infants who are small for gestational age are prone to the development of insulin resistance later in life. This study measured insulin sensitivity at the age of 4 to 10 years in children who had been born prematurely. An isolated reduction in insulin sensitivity was observed in both children who had been born prematurely but were appropriate for gestational age at birth and those who had been born prematurely but were small for gestational age, suggesting that premature infants may be at high risk for the metabolic syndrome and type 2 diabetes mellitus. This study measured insulin sensitivity at the age of 4 to 10 years in children who had been born prematurely. It suggests that premature infants may be at high risk for the metabolic syndrome and type 2 diabetes mellitus. The intrauterine environment and early postnatal life are now generally accepted as important determinants of the risk of disease in adulthood. Low birth weight, a marker of intrauterine adversity, has consistently been associated with a variety of adult-onset diseases, including type 2 diabetes mellitus, essential hypertension, dyslipidemia, coronary artery disease, and cerebrovascular accidents. 1 – 8 Attempts to establish the cause of these associations have led to the recognition that subjects with low birth weights have an early and consistent reduction in insulin sensitivity. 9 , 10 Insulin resistance (i.e., reduced insulin sensitivity) is a well-recognized, early metabolic abnormality in the pathogenesis of these . . .

Preterm birth is associated with abnormalities in growth, body composition, and metabolism during childhood, but adult data are scarce and none exist for their offspring. We therefore aimed to examine body composition and cardiovascular risk factors in adults born preterm and their children. A cohort of 52 adults (aged 35.7 years, 54% female, 31 born preterm) and their term-born children (n=61, aged 8.0 years, 54% female, 60% from a preterm parent) were studied. Auxology and body composition (whole-body dual-energy X-ray absorptiometry) were measured, and fasting blood samples taken for metabolic and hormonal assessments. Adults born preterm had greater abdominal adiposity, displaying more truncal fat (p=0.006) and higher android to gynoid fat ratio (p=0.004). Although women born preterm and at term were of similar weight and BMI, men born preterm (n=8) were on average 20 kg heavier (p=0.010) and of greater BMI (34.2 vs 28.4 kg/m(2); p=0.021) than men born at term (n=16). Adults born preterm also displayed a less favourable lipid profile, including lower HDL-C concentrations (p=0.007) and greater total cholesterol to HDL-C ratio (p=0.047). Children of parents born preterm tended to have more body fat than the children of parents born at term (21.3 vs 17.6%; p=0.055). Even after adjustment for mean parental BMI, children of parents born preterm had altered fat distribution, with more truncal fat (p=0.048) and greater android to gynoid fat ratio (p=0.009). Adults born preterm, particularly men, have markedly increased fat mass and altered fat distribution. A similar increase in abdominal adiposity was observed in the term born offspring of parents born preterm, indicating that adverse outcomes associated with preterm birth may extend to the next generation.

Objective To determine the incidence of new onset type 1 diabetes in children aged 0–14 years from 1977 to 2019 in Auckland, New Zealand. Research design and methods A cohort study of children with type 1 diabetes aged 0–14 years (n = 1688; 50.4% male) managed by the regional diabetes service between 1977 and 2019. Incidence rates were estimated using census data. Results The incidence of type 1 diabetes increased by 2.9%/year from 1977 to 2006 (95% confidence interval [CI] 2.13% – 3.48%). Although there was no significant change from 2006 to 2019 (−0.3%/year, 95% CI ‐1.62% – 1.08%), there was a dramatic fall from 1976 to 2018 in the proportion of New Zealand Europeans, from 69.9 to 33.9%. New Zealand Europeans had the highest incidence (23.3/100,000, 95% CI 20.6–26.1) compared to Māori (8.3/100,000, 95% CI 6.3–10.2), Pasifika (8.6/100,000, 95% CI 6.9–10.4) and other (6.4/100,000, 95% CI 4.7–8.0). All groups showed an overall increase in incidence over time, Māori 4.4%/year, Pasifika 3.7%, compared to New Zealand European 2.7%, and other 2.1%. Incidence increased consistently in 5–9 and 10–14 year olds (2.0% and 2.2%/year, respectively). By contrast, whereas 0–4 year olds showed an increase of 4.6%/year from 1977 to 2003 (p < 0.01), there was no change from 2003 to 2019 (p = 0.2). Conclusion There has been a plateau in the incidence of type 1 diabetes in children 0–4 years of age in the Auckland region since 2003, but not older children. The apparent plateau in the overall incidence of new onset type 1 diabetes in children 0–14 years since 2006 was mediated by substantial changes in the ethnic makeup of the Auckland region.

Adolescents living with either type 1 diabetes (T1D) or type 2 diabetes (T2D) have an increased risk of psychological disorders due to the demands of managing a chronic illness and the challenges of adolescence. Psychological disorders during adolescence increase the risk of suboptimal glycemic outcomes and may lead to serious diabetes-related complications. Research shows that digital health interventions may increase access to psychological support for adolescents and improve physical and mental health outcomes for youth with diabetes. To our knowledge, there are no evidence-based, publicly available mental health apps with a focus on improving the psychological well-being of adolescents with diabetes. This study aimed to explore the acceptability and usability of our evidence-based well-being app for New Zealand adolescents, Whitu: 7 Ways in 7 Days (Whitu), to allow us to further tailor it for youth with diabetes. We interviewed adolescents with T1D and T2D, their parents, and health care professionals to explore their views on the Whitu app and suggestions for tailoring the app for adolescent with diabetes. We also explored the cultural acceptability of the Whitu app for Māori and Pacific adolescents. A total of 34 participants, comprising 13 adolescents aged 12-16 years (11 with T1D and 2 with T2D), 10 parents, and 11 health care professionals, were recruited from a specialist diabetes outpatient clinic and Facebook diabetes groups. Each participant attended one 1-hour focus group on Zoom, in person, or via phone. Researchers gathered general feedback on what makes an effective and engaging app for adolescents with diabetes, as well as specific feedback about Whitu. Transcribed audio recordings of the focus groups were analyzed using directed content analysis. Adolescents with T1D, their parents, and health care professionals found Whitu to be acceptable and usable. Adolescents with T1D and their parents signaled a preference for more diabetes-specific content. Health care professionals expressed less awareness and trust of digital health interventions and, as such, recommended that they be used with external support. Due to challenges in recruitment and retention, we were unable to include the views of adolescents with T2D in this qualitative study. There appears to be sufficient openness to the use of an app such as Whitu for supporting the well-being of adolescents with T1D, albeit with modifications to make its content more diabetes specific. Based on this qualitative study, we have recently developed a diabetes-specific version of Whitu (called LIFT: Thriving with Diabetes). We are also planning a qualitative study to explore the views of youth with T2D and their perspectives on the new LIFT app, where we are using alternative research approaches to recruit and engage adolescents with T2D and their families.

Aims . Diabetic retinopathy (DR) is the primary microvascular complication associated with diabetes. Evidence on DR prevalence among children in New Zealand is scarce. We examined DR rates and associated risk factors in youth with type 1 diabetes (T1D) aged <16 years receiving care from a regional diabetes service in January 2006–December 2020. Materials and Methods . DR diagnosis followed the International Society for Pediatric and Adolescent Diabetes guidelines. The study included 646 participants; mean age (±SD) at T1D diagnosis was 7.4 ± 3.6 years, 47% were female, and 69% identified as NZ Europeans. Results . The initial DR screening occurred at a mean age of 12.6 ± 2.4 years and 5.2 ± 2.2 years after T1D diagnosis. At the first DR screen, 23.5% of participants (152/646) were diagnosed with DR: 69.1% (105/152) with minimal, 30.3% (46/152) with mild, and one moderate case (0.7%). Older age at diagnosis ( p = 0.029) and longer diabetes duration ( p = 0.015) were predictors of DR at first screen. Patients with at least one positive DR screen had a higher average HbA1c at their first screen (+2.6 mmol/mol; p = 0.042). Overall, 55.6% (359/646) of patients had a positive DR screen, whose worst grade was mostly either minimal (58.2%) or mild (40.7%) DR, with only three moderate cases (0.8%) and one severe (0.3%). Children diagnosed with T1D before age 10 were 72% more likely to have DR than older children ( p < 0.0001), and DR risk was 32% and 41% higher among Pacific children than NZ European ( p = 0.008) and Māori ( p = 0.014) children. Lastly, the only predictor of DR at discharge from paediatric services was HbA1c at the first screen ( p < 0.0001). Conclusions . In this regional cohort of children with T1D, there was a high rate of low‐grade DR overall and at first retinal screen, with an increasing rate until transfer to adult services. Our findings underscore the importance of ongoing DR screening, reducing glycaemic levels, and supporting vulnerable high‐risk groups.

Purpose Advanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA 1c has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group. Methods A prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7–25 years with T1D, a current HbA 1c  ≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA 1c between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes. Conclusion This study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden. Trial registration This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452).