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.

Familial juvenile autoimmune hypothyroidism, pituitary enlargement, obesity, and insulin resistance.

The proband, a 9-year-old Hispanic female, presented with hair loss, strabismus, and weight gain. On magnetic resonance imaging (MRI) she was found to have severe primary hypothyroidism and a large pituitary mass. In addition, acanthosis nigricans, obesity, and hyperinsulinism were observed. Findings were similar in three of four siblings. Thyroid peroxidase antibodies were detected in the father and three of four siblings. Although all family members were obese, and hyperinsulinemia with high proinsulin and C-peptide was found in all except one sibling, only the mother and one child had overt type 2 diabetes mellitus. Because of the unusual association of autoimmune thyroid disease, insulin resistance and obesity rather than insulin deficiency, we searched for possible genetic abnormalities. The HLA haplotypes did not cosegregate with autoimmune thyroid disease or insulin resistance. Mutational analysis of known obesity genes was done. Leptin was not deficient, and sequencing of the proband's DNA showed no mutations in the perixisome proliferator activated receptor (PPAR)-gamma, PPAR-gamma(2), PPAR-alpha or melanocortin 4 receptor genes. Maternally inherited diabetes and deafness was ruled out since no mutations were found in mitochondria DNA. Insulin receptor antibodies were not detected. In conclusion, the remarkably high incidence of childhood autoimmune hypothyroidism, pituitary enlargement, insulin resistance and obesity in this family is not linked to known HLA types or known gene defects.

Effect of therapy with insulin glargine (lantus) on glycemic control in toddlers, children, and adolescents with diabetes.

To determine the effect of insulin glargine on glycemic control in pediatric type 1 and 2 diabetes, a retrospective repeated-measure analysis of variance was performed of hemoglobin A1C (HbA1C), frequency of hypoglycemia and hyperglycemia, mean blood glucose, body mass index (BMI), and daily weight-adjusted insulin dosage before and after institution of glargine therapy in 72 children and adolescents with diabetes. At glargine start, age range was 1.2-19.6 years, mean age was 12.5 +/- 4.6 years, BMI was 22.48 +/- 6.3 kg/m(2), and mean HbA1C was 9.7 +/- 1.9%. Mean duration of diabetes was 3.58 years, and mean baseline insulin dose was 0.93 U/kg/day. Gender breakdown was 60% female, and the majority (83%) had type 1 diabetes. Average HbA1C decreased from 9.5% pre-glargine to 8.6% post-glargine (p < 0.001). HbA1C decrease was significant in both types of diabetes without a concomitant increase in frequency of hypoglycemia, BMI, or weight-adjusted insulin dose. Hypoglycemia decreased significantly in type 1 diabetes. Thus, glargine therapy may decrease HbA1C and frequency of hypoglycemia in toddlers, children, and adolescents with diabetes, without an increase in BMI or insulin requirements.

Pediatric post-transplant diabetes: data from a large cohort of pediatric heart-transplant recipients.

A retrospective analysis of 381 pediatric heart-transplant recipients was performed to determine the frequency, characteristics, and risk factors for post-transplant diabetes. The rate of post-transplant diabetes was 1.8% with antithymocyte globulin, cyclosporine and azathioprine as primary immunosuppressive therapy. Time from transplant to diabetes was 0.25-13 years. Diabetes was characterized by reversibility, and lack of insulinopenia and autoimmunity. The post-transplant diabetes rate in tacrolimus-converted children (n = 45) was 8.8%. In tacrolimus-converted children, age at transplant, mean and maximum tacrolimus blood levels, and first-year rejection episodes were higher in the post-transplant diabetes group, which also consistently had DR-mismatched transplants and HLA DR3/DR4 haplotypes. Body mass index was not different between diabetic and control tacrolimus-converted children. In conclusion, pediatric post-transplant diabetes may be related to reversible insulin resistance. Tacrolimus levels, HLA DR mismatch, and older age at transplant may predispose to post-transplant diabetes.

Glycemic, auxologic, and seasonal aspects of continuous subcutaneous insulin infusion therapy in children and young adults with type 1 diabetes.

Use of continuous subcutaneous insulin infusion (CSII) therapy has increased among patients with type 1 diabetes. This study was performed: (1) to evaluate the effect of CSII on diabetes control in children and young adults, (2) to detect effects of CSII on weight, body mass index (BMI), and insulin requirements, (3) to investigate seasonal variation in diabetes control during CSII therapy, and (4) to investigate the effect of season of initiation of CSII on glycemic control. Thirty-nine patients, ranging in age from 10.1 to 20.5 years, with type 1 diabetes were studied. Quarterly data over 12 months preceding and following CSII initiation were obtained retrospectively. Variables were compared over similar time periods. SAS was used for descriptive and paired t test analysis. (1) Mean blood glucose level was significantly lower at 3 months but not different from baseline at 6, 9, and 12 months post-CSII. (2) Glycosylated hemoglobin (HbA1c) was significantly lower at 3 and 6 months but not at 9 and 12 months post-CSII. (3) There was no significant difference in the frequency of hypoglycemia or hyperglycemia at any of the time periods studied. (4) There was an initial but unsustained decrease in daily weight-adjusted insulin requirements after CSII. (5) There was a rapid, sustained increase in weight and BMI following CSII in females. (6) Frequency of ketoacidosis decreased in two patients. (7) There was no seasonal variation in weight change, HbA1c, or frequency of measured hypoglycemic episodes with CSII. (8) There was some effect of the season of initiation of CSII therapy on glycemic control. Thus, (1) CSII glycemic benefits may not be sustained, (2) weight gain is a significant effect of CSII in adolescent females, and (3) CSII may be a means of decreasing ketoacidosis episodes, and eliminating seasonal variability in diabetes control.

Clinical, autoimmune, and HLA characteristics of children diagnosed with type 1 diabetes before 5 years of age.

BACKGROUND: Little is known about auxologic, autoimmune, and HLA characteristics specific to children with early-onset diabetes (EOD). HLA subtypes have been shown to play an important part in the determination of islet-cell autoimmunity and in the pace and intensity of the beta-cell destructive process. OBJECTIVES: Our goals were to: 1) outline auxologic, autoimmune, and HLA class II characteristics of children diagnosed with type 1 diabetes before 5 years of age (EOD); 2) evaluate differences between EOD and later-onset or non-age-stratified type 1 diabetes; and 3) investigate the relation between type 1 diabetes-related HLA subtypes and markers of diabetic autoimmunity in EOD. METHODS: Forty children with EOD were studied. Auxologic and antibody radioimmunoassay data were obtained by retrospective analysis of records. HLA diabetes-related class II alleles were typed by polymerase chain reaction using sequence-specific primers. RESULTS: At diagnosis, the average age of the EOD study patients was 2.6 years, body mass index was 16.9 kg/m2, and weight was 106% of average weight for height. When compared with a matched subgroup of children with later-onset type 1 diabetes, preschoolers did not significantly differ in terms of birth weight or body mass index. The frequency of positive islet cell antibodies 512 and glutamic acid decarboxylase 65 antibodies was significantly less in EOD (28.6% and 31.6%, respectively). There were significant differences in the frequencies of some diabetes-related HLA alleles and haplotypes between the early-onset group and a large non-age-stratified type 1 diabetes group. None of the patients with EOD had either of the protective DRB1*1501 or DQB1*0602 alleles. There was a negative correlation between glutamic acid decarboxylase and the predisposing haplotype DR3/DQ2. CONCLUSIONS: Children diagnosed with type 1 diabetes before 5 years of age may have different diabetes-related autoimmune and genetic characteristics from those diagnosed at a later age.

Role of exposure to air pollutants in the development of type 1 diabetes before and after 5 yr of age.

OBJECTIVE: To assess the role of ambient air pollutants in type 1 diabetes in children. DESIGN AND METHODS: Prediagnosis exposure to five air pollutants was studied in two subgroups with onset of type 1 diabetes before and after 5 yr of age, and two matched subgroups of healthy children. Zip codes and dates of residence from birth to diagnosis were used to obtain geographic- and time-specific air concentrations of SO(2), NO(2), ozone (O(3)), SO(4), and particulate matter < 10 micro m in diameter (PM(10)). Prediagnosis time-adjusted pollutant exposure levels were created by summing up zip code-specific pollution data and dividing by months of exposure from birth to diagnosis. Two-tailed t-test and logistic regression were used to evaluate relative effects and test data between cases and controls. RESULTS: Prediagnosis average O(3) exposure was significantly higher in children with type 1 diabetes than in healthy controls. Prediagnosis PM(10) exposure was significantly higher in children diagnosed before 5 yr of age, when compared with healthy controls. SO(2) exposure was significantly higher in children with later-onset diabetes compared with those with early-onset diabetes (EOD). NO(2), SO(2) and SO(4) exposure was significantly lower in children diagnosed after 5 yr of age, when compared with healthy controls. O(3), NO(2), SO(4) and PM(10) levels did not significantly differ between the two diabetic subgroups. CONCLUSION: Increased ozone exposure may be a contributory factor to the increased incidence of type 1 diabetes. PM(10) may be a specific contributory factor to the development of type 1 diabetes before 5 yr of age.

Use of the GlucoWatch biographer in children and adolescents with diabetes.

OBJECTIVE: This study was done to evaluate the accuracy and safety of measuring glucose with the GlucoWatch biographer in children and adolescents with diabetes. METHODS: Accuracy was assessed by comparing biographer glucose measurements with hourly blood glucose measurements using the HemoCue (Aktiebolaget Leo, Helsingborg, Sweden) Photometer for up to 12 h of monitoring. Safety was evaluated by examining the biographer application sites immediately upon removal of the devices, and then at regular intervals. RESULTS: Sixty-six subjects each wore three biographers at sites including the forearm, upper arm, leg, and torso. For forearm biographers, the mean absolute relative difference between biographer readings and blood glucose was 21%. Ninety-five per cent of biographer readings fell into the A or B regions of the Clarke error grid, and 97.3% into the A or B regions of the consensus error grid. Data from biographers worn at the alternative sites were similar to data from the forearm biographers. Two strong reactions to the adhesive pad of the biographer AutoSensor were observed. Most skin reactions were mild. CONCLUSIONS: The GlucoWatch biographer is well tolerated by children and adolescents with diabetes. Performance is similar when the device is worn at different anatomical sites, and is similar to the performance on the forearm, previously reported in adults.