Air pollution and type 1 diabetes in children

BACKGROUND: Over the past decade, there has been a worldwide largely unexplained increase in the incidence of type 1 diabetes in young children. This study explores the quantitative role of exposure to specific air pollutants in the development of type 1 diabetes in children. METHODS: A total of 402 children were retrospectively studied. Zip code-related, time-specific birth-to-diagnosis exposure to five ambient air pollutants was obtained for 102 children with type 1 diabetes and 300 healthy children receiving care at a single hospital. Pollution exposure levels were created by summing up zip code-specific pollution data and dividing by months of exposure from birth to diagnosis. Analysis employed chi2, two-tailed independent sample t-test and unconditional logistic regression. RESULTS: Odds ratio (OR) was significantly high for cumulative exposure to ambient ozone (O3) and sulfate (SO4) in cases compared with controls, OR = 2.89 [95% confidence interval (CI) = 1.80-4.62] and OR = 1.65 (CI = 1.20-2.28), respectively, even after adjustment for several potential confounders. Passive smoking was more frequent in children with diabetes (30 vs. 10%, p = 0.001). Attending day care and breast feeding in infancy were less frequent in children with diabetes (14 vs. 23%, p = 0.025; 59 vs. 78%, p = 0.001). Family history of diabetes, autoimmune disease and drug abuse was more frequent in cases (p < 0.01). CONCLUSION: Cumulative exposure to ozone and sulfate in ambient air may predispose to the development of type 1 diabetes in children. Early infant formula feeding and passive smoking in the household may precipitate or accelerate the onset of type 1 diabetes.     

Autoimmune characteristics in Japanese children diagnosed with type 1 diabetes before 5 years of age

Background:  Several studies have shown that the autoimmune features in young children with type 1 diabetes differ from those in older pediatric patients as well as adults. The purpose of the present study was to examine the prevalence of β-cell autoantibodies, glutamic acid decarboxylase antibodies (GADA), and antibodies to the protein tyrosine phosphatase-related molecule IA-2 (IA-2A), at the time of diagnosis in Japanese children with type 1 diabetes who were younger than 5 years at diagnosis.
Methods:  Subjects consisted of 23 Japanese children (nine boys, 14 girls), 3.1 ± 1.3 years of age at diagnosis (range, 1.1–4.8 years). The majority had severe metabolic decompensation accompanied by complete absence of β-cell function at diagnosis. We found 41.7% to have suffered viral infections before disease onset.
Results:  The prevalence of antibodies to GAD and IA-2 at diagnosis in these subjects was significantly lower than those in older patients diagnosed after 5 years of age (31.6 % vs 86.3% and 47.1% vs 82.5%, P  < 0.0001 and P  = 0.0064, respectively). Among 17 patients in whom both antibodies were measured, only two (11.8%) had both GADA and IA-2A, three (17.6%) had GADA alone, six (35.3%) had IA-2A alone, and six (35.3%) had neither GADA nor IA2-A.
Conclusions:  Non-autoimmune mechanisms or age-related differences in autoimmunity could be involved in the pathogenesis of diabetes in young patients.     

Neuropsychological profiles of young people with type 1 diabetes 12 yr after disease onset

Lin A, Northam EA, Rankins D, Werther GA, Cameron FJ. Neuropsychological profiles of young people with type 1 diabetes 12 yr after disease onset. Background: Lowered neuropsychological performance is evident in youth with type 1 diabetes, although evidence for associations with specific illness variables is inconsistent. This study examined the neuropsychological profiles of a cohort of youth with type 1 diabetes studied prospectively from diagnosis 12 yr previously. Methods: A total of 106 youth with type 1 diabetes and 75 healthy controls participated. There were no significant group differences on Full‐scale IQ assessed on study entry 12 yr previously, current socioeconomic status, gender distribution, or age. Neuropsychological tests assessed eight cognitive domains: verbal abilities, perceptual reasoning, new learning, working memory, non‐verbal processing speed, mental efficiency, divided attention, and sustained attention. Episodes of serious hypoglycemia and HbA_1c levels were recorded from diagnosis. Results: Youth with type 1 diabetes performed more poorly than controls on working memory (p < .05). Early onset diabetes was related to poorer sustained (p < .001) and divided attention (p = .001), new learning, and mental efficiency (both p < .05). Hypoglycemia was found to adversely effect verbal abilities, working memory, and non‐verbal processing speed (all p < .05). Poorer working memory was associated with hyperglycemia (p < .05). Youth with any combination of two or three illness risk factors (i.e., early onset diabetes, hypo‐, hyperglycemia), performed more poorly than controls and youth with no or one risk on verbal abilities, working memory, and mental efficiency. Conclusions: This study documents poorer neuropsychological performance and its association with illness risk factors in youth with type 1 diabetes. Findings suggest that early disease onset and hypoglycemia impact on the developing central nervous system, with hyperglycemia playing a lesser role.     

Role of the gastrointestinal ecosystem in the development of type 1 diabetes

A new emphasis has been put on the role of the gastrointestinal (GI) ecosystem in autoimmune diseases; however, there is limited knowledge about its role in type 1 diabetes (T1D). Distinct differences have been observed in intestinal permeability, epithelial barrier function, commensal microbiota, and mucosal innate and adaptive immunity of patients and animals with T1D, when compared with healthy controls. The non‐obese diabetic (NOD) mouse and the BioBreeding diabetes prone (BBdp) rat are the most commonly used models to study T1D pathogenesis. With the increasing awareness of the importance of the GI ecosystem in systemic disease, it is critical to understand the basics, as well as the similarities and differences between rat and mouse models and human patients. This review examines the current knowledge of the role of the GI ecosystem in T1D and indicates the extensive opportunities for further investigation that could lead to biomarkers and therapeutic interventions for disease prevention and/or modulation.     

Predicting metabolic control in the first 5 yr after diagnosis for youths with type 1 diabetes: the role of ethnicity and family structure

The primary purpose of this study was to determine if there were differences in trajectories of metabolic control between African American and White youth with type 1 diabetes in the first 5 yr after diagnosis. A secondary purpose was to investigate other sociodemographic variables that often covary with race/ethnicity such as number of parents in the home and family income to determine if they predicted trajectories of metabolic control in youth with diabetes over and above the effects of ethnicity. A convenience sample of 71 youth was recruited. Multilevel modeling was used to estimate the population trajectory and to investigate the contribution of other variables. Differences in metabolic control between African American and White youth began shortly after diagnosis and continued to accelerate well beyond the point of diagnosis. However, subsequent analysis showed that deterioration in metabolic control could equally well be explained by living in a single-parent household. At 24 months postdiagnosis, the metabolic control in youth from single-parent families worsened almost three times as fast as that in youth from two-parent families (0.11 vs. 0.04%/month). The difference in hemoglobin A1c level at 24 months was 1.34% (p = .007). Neither family income nor clinical variables such as child's age, Tanner stage, or body mass index was significant predictor of metabolic control. Diabetes care providers should consider developing targeted interventions such as parent social support resources or school-based youth monitoring programs for youth in single-parent families.     

Young children (<5 yr) and adolescents (>12 yr) with type 1 diabetes mellitus have low rate of partial remission: diabetic ketoacidosis is an important risk factor

Objective:  To determine whether there are different rates of partial remission in preschool, school-age children, and adolescents with type 1 diabetes mellitus (T1DM) and to identify clinical characteristics that are associated with increased rate of partial remission.
Design/methods:  A total of 152 consecutive patients with newly diagnosed T1DM in 2004 were studied. Clinical characteristics at diagnosis, hemoglobin A1C (HbA1C), and total daily insulin dose (TDD) at 3-month interval follow-up for 1 yr were analyzed in each age-group (group 1, aged <5 yr; group 2, aged 5–12 yr; and group 3, aged >12 yr). Partial remission was defined as TDD <0.5 units/kg/d with HbA1C <8% assessed at 6 months after diagnosis.
Results:  Young children (group 1, 26.8%) and adolescents (group 3, 29%) had low rates of partial remission compared with school-age children (group 2, 56%, p = 0.002). There were no differences in the rates of diabetic ketoacidosis (DKA), autoantibody frequency, and HbA1C at diagnosis between age-groups. DKA at diagnosis was associated with less likelihood of having partial remission (p < 0.001). There were no associations between gender, autoantibodies, and HbA1C at diagnosis and the rate of partial remission.
Conclusions:  Young children and adolescent children with T1DM had a low rate of partial remission. Metabolic control was poorest in young children, whereas higher dose insulin in adolescents because of insulin resistance contributes to less likelihood of having partial remission. DKA at diagnosis was associated with low rate of partial remission. It is possible that the low frequency of honeymoon phase in young children reflects more aggressive beta-cell destruction in young children.     

Low risk of overt nephropathy after 24 yr of childhood-onset type 1 diabetes mellitus (T1DM) in Norway

AIM: To estimate the risk of diabetic nephropathy and associated risk factors in a nationwide cohort of childhood-onset type 1 diabetes mellitus (T1DM) and 19-30 yr of diabetes duration. METHODS: Patients diagnosed with childhood-onset T1DM (<15 yr) from 1973 through 1982, who previously (1989-1990) participated in a clinical examination to assess diabetic complications, were invited for a new examination in 2002-2003. Of 355 eligible patients, 299 participated (84.2%), and complete urine samples for evaluation of albuminuria were obtained from 295 patients, with a mean age of 33 yr (range 20.9-44.0) and mean diabetes duration of 24 yr (range 19.3-29.9). Persistent microalbuminuria and overt nephropathy [albumin excretion rate (AER) 15-200 microg/min and AER > 200 microg/min, respectively] in at least two out of three consecutive overnight urine samples were defined as diabetic nephropathy. RESULTS: Overt nephropathy was found in 7.8% [95% confidence interval (CI) 4.7-10.9] and persistent microalbuminuria in 14.9% (95% CI 10.8-19.0) of the subjects. Hemoglobin A1c (HbA1c) (p = 0.001), systolic blood pressure (BP) (p = 0.002), total cholesterol (p = 0.019), and C-reactive protein (CRP) (p = 0.019) were associated with diabetic nephropathy. Significant predictors in 1989-1990 for the development of diabetic nephropathy in 2002-2003 were HbA1c (p < 0.001), AER (p = 0.007), and cholesterol (p = 0.022). CONCLUSIONS: In a subgroup of patients diagnosed with childhood-onset T1DM in 1973-1982, 7.8% had overt nephropathy after 19-30 yr of diabetes duration, which is low compared with studies from other countries. HbA1c, systolic BP, total cholesterol, and CRP were each independently associated with diabetic nephropathy.     

Continuous glucose monitoring in children with type 1 diabetes: before and after insulin pump therapy

Abstract: Objective: The aim of continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM) is to mimic as closely as possible the normal physiologic pattern seen in individuals without diabetes. This study was undertaken to determine the specific areas of improved glycemic control in subjects after initiation of insulin pump therapy and times where further improvement is needed. Research design and methods: Eight patients with T1DM (age 7.5–17 yr) wore the Continuous Glucose Monitoring System (CGMS) (Medtronic MiniMed, Northridge, CA, USA) for 3 d before and 3 months after initiation of insulin pump therapy. The CGMS, which measures inter‐ stitial glucose concentrations every 5 min for a 72‐h period, was used to evaluate glucose profiles. Patients entered 4–5 fingerstick blood glucose measurements daily into the sensor for calibration. Detailed logs of food intake, exercise, and hypoglycemic symptoms were also recorded. Results: Hemoglobin A1c (HbA1C) was reduced (p < 0.007) following 3 months of insulin pump therapy. Post‐CSII continuous glucose profiles demonstrated an overall improvement in hourly mean glucose over a 24‐h period (p < 0.001) as well as a reduction in the area under the curve for glucose (27 ± 4 prepump vs. 8.6 ± 1.4 mg/dL/d postpump, p < 0.004). This improvement was a result of an attenuation of the maximal postprandial glycemic excursions. Postbreakfast 349 ± 24 vs. 267 ± 16 mg/dL, p < 0.003; lunch 340 ± 16 vs. 217 ± 20 mg/dL, p < 0.003. Postdinner average similarly decreased after 3 months of CSII by 22%, p < 0.04. Conclusions: Pump therapy specifically improved the postprandial glucose excursions in children.     

Type 2 diabetes in a 5‐year‐old and single center experience of type 2 diabetes in youth under 10

The worrisome rise in pediatric type 2 diabetes (T2DM) is most prevalent among minority ethnic/racial populations. Typically, T2DM occurs during puberty in high risk obese adolescents with evidence of insulin resistance. Screening for T2DM in obese youth can be a daunting task for pediatricians and differentiating between pediatric T1DM and T2DM in obese youth can be challenging for pediatric endocrinologists. There is very limited data regarding the prevalence of T2DM among youth < 10 years of age. Here we present the case of a 5‐year‐old Hispanic male diagnosed with T2DM after referral by his pediatrician for abnormal weight gain, acanthosis nigricans and an elevated HbgA1c. He subsequently became symptomatic for diabetes with confirmed hyperglycemia and HbgA1c of 9.7% (83 mmol/mol) at the time of formal diagnosis. Type 1 diabetes autoantibodies (GAD65, Islet, and ZincT8) and monogenic diabetes genetic tests were negative. Due to elevated liver enzymes and baseline HbgA1c, he received basal insulin as his initial therapy. In this paper, we will discuss this case and present an IRB approved retrospective review of the characteristics of the 20 T2DM patients <10 years of age identified to date in our pediatric diabetes center. This review highlights that while uncommon, the diagnosis of T2DM merits consideration even in prepubertal children. This is especially true when working with a high risk population, such as our Hispanic South Texas youth.     

Personnel costs and perceived benefit of telephone care in the management of children with type 1 diabetes

Intensive management of patients with type 1 diabetes improves control and reduces rates of long-term complications. Telephone care as an adjunct to office visits is important in the management of children with type 1 diabetes in pediatric endocrine practices in the USA. The goal of this project was to assess the personnel costs and patients' perceptions of telephone care in a moderately sized pediatric diabetes care center (301 patients with a diagnosis of type 1 diabetes). There were two parts to this study. First, telephone logs were kept by three pediatric endocrine nurses (2.2 full-time equivalents [FTEs]) and three pediatric endocrinologists (2.0 FTEs) for two 1-wk blocks. Computerized databases were used to determine the number of clinic visits in 1998. Second, a survey assessing the frequency, perceived value and consequences of phone contact with the diabetes team was distributed to 40 families at clinic visits. Mean nurse/certified diabetes educator (CDE) time spent on the phone was 12.1 h/wk, with an additional 9.7 h/wk spent preparing and documenting. Physicians spent 6.4 h/wk on the phone, and 6.1 h/wk preparing/supervising/documenting. For our 301 patients with diabetes, the weekly personnel cost for telephone care at our institution was 1367 US dollars or 236 US dollars/patient/yr. Of the families surveyed, 80% reported that they had used the phone to obtain care for their child with diabetes and 55% had paged the doctor on call in the previous 6 months. Seven patients reported that phone contact prevented a total of 13 emergency department (ED) visits and 35 office visits. Using a cost estimate of 550 US dollars per ED visit, and 103 US dollars per office visit, the cost of prevented visits was 232 US dollars/patient/yr in our center. These data indicate that telephone care is effective in reducing the cost of reimbursable care via the ED and office visits, as well as avoiding hospitalization. However, the cost of providing this telephone care is not reimbursable to providers.