Pediatric Diabetes

Context. Insulin sensitivity and secretion indices can be useful tools in understanding insulin homeostasis in children at risk for diabetes. There have been few studies examining the reproducibility of these measures in pediatrics. Objective. To determine whether fasting or oral glucose tolerance test (OGTT)-derived insulin measures would be more reproducible and whether there would be differences based on weight, sex, race, and pubertal status. Design. Observational study. Setting. Clinical research unit. Patients or Other Participants. Two hundred fifty-seven overweight/obese (BMI ≥ 85th%, n = 186) and normal weight (BMI < 85th%, n = 71) children without diabetes between ages of 8 and 17 were included in the study. Methods. OGTT tests performed in study participants at two separate visits within a 3-week period. We performed two formal oral glucose tolerance tests within a 3-week period. The reproducibility of fasting measures was compared with OGTT-derived measures by weight categories and compared by weight, sex, race, and pubertal status. Comparisons were made between the correlation coefficients of fasting vs. OGTT-derived measures and between normal weight vs. obese/overweight participants, male vs. female, White vs. Black, and pre- vs. post-midpubertal. Intraclass correlation coefficients were calculated for each comparison as well. Results. For insulin sensitivity, the OGTT-derived measure was more reproducible than the fasting measures. There were no significant differences in reproducibility in the overweight/obese population compared to the normal weight population nor by sex, race, or pubertal status. Conclusions. Nonfasting insulin sensitivity measures are more reproducible than fasting insulin sensitivity measures, regardless of weight category. Insulin secretion measures have poor reproducibility overall. Weight status, sex, race, and midpubertal stage do not impact the reproducibility of insulin sensitivity and secretion measures.

Introduction. Cardiovascular disease (CVD) is highly prevalent in patients with type 1 diabetes (T1DM) and is responsible for a significant reduction in life expectancy. Objective. To compare the arterial stiffness indices, arterial compliance and vascular resistance assessed centrally and peripherally between healthy adolescents and young adults (CTRL group) and those with T1DM. Methods. This is an observational cross-sectional study involving 90 adolescents and young adults, with half of them being considered healthy (n = 45) and the other half with T1DM (n = 45), matched by age and sex. Cardiovascular parameters were evaluated using the oscillometric method of brachial artery pressure assessment for a noninvasive estimation of central arterial pressures. Results. Weight and body mass index were significantly higher in the T1DM group. AIx@75 was significantly higher in the T1DM group (24.96% ± 8.88%) compared to the CTRL (20.16% ± 9.95%). Peripheral and central arterial compliance were significantly lower in the T1DM group (0.79 ± 0.21; 1.16 ± 0.27 ml/m²/mmHg) compared to the CTRL (0.98 ± 0.32; 1.47 ± 0.61 ml/m²/mmHg). Peripheral and central vascular resistance were significantly higher in the T1DM group (1.32 ± 0.32; 0.91 ± 0.21 mmHg/ml/m²) compared to the CTRL (1.11 ± 0.30; 0.75 ± 0.22 mmHg/ml/m²). Conclusion. Our data confirm premature aging of the vascular system in adolescents and young adults with T1DM and extend our knowledge by showing important changes in central and peripheral hemodynamics indices.

Objective. Microvascular complications increase the risk of cardiovascular disease and premature death in adults with type 1 diabetes. We examined the association between microvascular complications during adolescence, including cardiac autonomic nerve dysfunction and subsequent mortality. Research Design and Methods. We undertook data linkage with the Australian National Death Index in a cohort of 409 adolescents (diagnosed between 1973 and 1993), 48% male, median age at final complications assessment 17.4 years (interquartile range: 16.0–18.9), followed longitudinally for median 22.3 years (21.0–23.4) from diagnosis. Generalized estimating equations (GEE) were used to examine associations between mortality and adolescent complications. Mortality risk was calculated as standardized mortality ratio (SMR). Results. At final adolescent visit, 20% had CAN abnormality, 30% abnormal pupillary response, 20% albuminuria, 40% early elevation of albumin excretion rate (AER) and 45% retinopathy. Data linkage 8–13 years later showed 14 were deceased (3% of cohort), 57% male, median age 28.3 years (24.8–32.9). Acute or chronic diabetes complications accounted for 25% of deaths. In multivariable GEE, elevated AER (OR 4.54, 1.23–16.80, ), pupillary abnormality (OR 4.27, 1.20–15.22, ), systolic blood pressure SDS (OR 2.17, 1.26–3.74, ) and CAN (OR 4.65, 1.03–21.0, ) predicted mortality. HbA1c was not significant. SMR was 2.5 (1.4–4.2) and was higher in females (SMR 3.5, 1.3–7.8) but not in males (SMR 2.1, 0.9–4.0). Conclusion. Mortality in young adults with type 1 diabetes is predicted by subclinical markers of autonomic neuropathy and elevated AER during adolescence, but not glycemia. Mortality was over twice that of the background population in females but not in males.

Objective. Evaluate the mortality risk of childhood-onset type 1 diabetes compared to the general population. Research Design and Methods. The study population, identified from the Australasian Paediatric Endocrinology Group diabetes register, was diagnosed with type 1 diabetes at age < 16 in New South Wales (NSW), Australia, from 1990 to 2010. The register was linked to National Death Index registrations to ascertain timing and cause of death up to 31/12/2022. Risk factors for mortality were assessed using multivariable Cox regression models and observed mortality rate compared to “expected” rates in the Australian general population using indirect-standardized mortality ratios (SMR), overall and by sex and age at diagnosis. Diabetes-related cause of death categories were identified. Results. Of 5,417 children diagnosed with type 1 diabetes, 157 subsequently died, with all-cause mortality of 1.37/1,000 person years. Increased mortality risk was associated with living in most disadvantaged areas (aHR 1.81 (1.05, 3.11)) but not living in a rural area. Overall SMR was 2.83 (95% CI 2.40, 3.33) with females having higher SMR than males (4.18 vs. 2.19). Most common causes of death recorded were acute diabetes complications (26%), including diabetes ketoacidosis, accident/misadventure (21%), and chronic diabetes complications (15%). Alcohol and/or drug use contributed to 17% of deaths. Conclusion. Compared to the general population, higher risk of mortality in people with type 1 diabetes was associated with female sex and living in area of socioeconomic disadvantage. Education about minimizing risk-taking behaviors should be communicated to young adults with type 1 diabetes.

Background. Elevated serum IgA levels have been observed in various autoimmune conditions, including type 1 diabetes (T1D). However, whether children with T1D and elevated serum IgA have unique features has not been studied. We aimed to evaluate the prevalence and characteristics associated with elevated serum IgA at the onset of pediatric T1D. Materials and Methods. We analyzed demographic, clinical, and laboratory data retrospectively collected from 631 racially diverse children (6 months–18 years of age) with T1D who had serum IgA levels measured within 90 days of T1D diagnosis. Univariable and multivariable logistic regression models were used to identify characteristics that were significantly associated with elevated versus normal IgA. Results. Elevated serum IgA was present in 20.3% (128/631) of the children with newly diagnosed T1D. After adjusting for other variables, A1c level (), positive insulin autoantibodies (IAA) (), negative glutamic acid decarboxylase autoantibodies (GADA) () and Hispanic ethnicity () were significantly associated with elevated serum IgA. After adjustment for confounders, the odds of elevated serum IgA were significantly increased with positive IAA (OR 1.653, 95% CI 1.019–2.679), higher HbA1c (OR 1.132, 95% CI 1.014–1.268) and Hispanic ethnicity (OR 3.279, 95% CI 2.003–5.359) but decreased with GADA positivity (OR 0.474, 95% CI 0.281–0.805). Conclusions. Elevated serum IgA is present in 20.3% of the children at T1D onset and is associated with specific demographic and clinical characteristics, suggesting a unique pathogenesis in a subset of individuals. Further studies are warranted to investigate the IgA response, its role in T1D pathogenesis, and whether these associations persist over time.

This study aimed to investigate the level of fasting plasma glucose (FPG), the prevalence of impaired fasting glucose (IFG), and the associated factors among children and adolescents in urban China. Based on a cross-sectional study conducted in three Chinese metropolises during 2013–2014, this analysis included 7,143 participants aged 7–18 years. Information on demographics, family environment, diet, and physical activity was collected by questionnaires. Anthropometric parameters and blood biochemical indicators were measured. Logistic regression models were applied to assess risk factors of glucose level. Results revealed that the average FPG level was 4.81 ± 0.53 mmol/L, and the prevalence of IFG was 3.3%. Trends of these two variables varied significantly with age increasing (all ), reaching double peaks at 10–12 and 15–17 years. IFG was positively associated with the male sex, age increasing, obesity, higher triglyceride (TG) levels, and living in northern China. When stratified by sex, family history of diabetes, elevated total cholesterol levels, and higher intake of sugar-sweetened beverages were positively associated with IFG only in females, suggesting these parameters were female-specific risk factors of IFG. We concluded that the prevalence of IFG among children and adolescents aged 7–18 years in urban China was higher than that reported in previous regional studies and was associated with obesity and higher levels of TG. Therefore, sex-specific lifestyle interventions should be provided to promote healthy weight and lipids and stem the upward trend of IFG.