Month of birth and the risk of developing type 1 diabetes among children in the Swedish national Better Diabetes Diagnosis Study.

AIM: Previous studies have reported an association between month of birth and incidence of type 1 diabetes. Using population-based data, including almost all newly diagnosed children with type 1 diabetes in Sweden, we tested whether month of birth influences the risk of type 1 diabetes. METHODS: For 8761 children diagnosed with type 1 diabetes between May 2005 and December 2016 in the Better Diabetes Diagnosis study, month of birth, sex and age were compared. Human leucocyte antigen (HLA) genotype and autoantibodies at diagnosis were analysed for a subset of the cohort (n = 3647). Comparisons with the general population used data from Statistics Sweden. RESULTS: We found no association between month of birth or season and the incidence of type 1 diabetes in the cohort as a whole. However, boys diagnosed before 5 years were more often born in May (p = 0.004). We found no correlation between month of birth and HLA or antibodies. CONCLUSION: In this large nationwide study, the impact of month of birth on type 1 diabetes diagnosis was weak, except for boys diagnosed before 5 years of age, who were more likely born in May. This may suggest different triggers for different subgroups of patients with type 1 diabetes.

Size for gestational age affects the risk for type 1 diabetes in children and adolescents: a Swedish national case-control study.

AIM/HYPOTHESIS: Environmental factors are believed to contribute to the risk of developing type 1 diabetes. The aim of this study was to investigate how size for gestational age affects the risk of developing childhood type 1 diabetes. METHODS: Using the Swedish paediatric diabetes quality register and the Swedish medical birth register, children with type 1 diabetes diagnosed between 2000 and 2012 (n = 9376) were matched with four control children (n = 37,504). Small for gestational age (SGA) and large for gestational age (LGA) were defined according to Swedish national standards. Data were initially analysed using Pearson's χ2 and thereafter by single and multiple logistic regression models. RESULTS: An equal proportion of children were born appropriate for gestational age, but children with type 1 diabetes were more often born LGA and less often born SGA than control children (4.7% vs 3.5% and 2.0% vs 2.6%, respectively, p < 0.001). In the multiple logistic regression analysis, being born LGA increased (adjusted OR 1.16 [95% CI 1.02, 1.32]) and SGA decreased (adjusted OR 0.76 [95% CI 0.63, 0.92]) the risk for type 1 diabetes, regardless of maternal BMI and diabetes. CONCLUSIONS/INTERPRETATION: Size for gestational age of Swedish children affects the risk of type 1 diabetes, with increased risk if the child is born LGA and decreased risk if the child is born SGA. Being born LGA is an independent risk factor for type 1 diabetes irrespective of maternal BMI and diabetes. Thus, reducing the risk for a child being born LGA might to some extent reduce the risk for type 1 diabetes.

Combined Etanercept, GAD-alum and vitamin D treatment: an open pilot trial to preserve beta cell function in recent onset type 1 diabetes.

AIM: We aimed to study the feasibility and tolerability of a combination therapy consisting of glutamic acid decarboxylase (GAD-alum), Etanercept and vitamin D in children and adolescents with newly diagnosed with type 1 diabetes (T1D), and evaluate preservation of beta cell function. MATERIAL AND METHODS: Etanercept Diamyd Combination Regimen is an open-labelled multi-centre study pilot trial which enrolled 20 GAD antibodies positive T1D patients (7 girls and 13 boys), aged (mean ±SD): 12.4 ± 2.3 (8.3-16.1) years, with a diabetes duration of 81.4 ± 22.1 days. Baseline fasting C-peptide was 0.24 ± 0.1 (0.10-0.35) nmol/l. The patients received Day 1-450 Vitamin D (Calciferol) 2000 U/d per os, Etanercept sc Day 1-90 0.8 mg/kg once a week and GAD-alum sc injections (20 µg, Diamyd™) Day 30 and 60. They were followed for 30 months. RESULTS: No treatment related serious adverse events were observed. After 6 months 90-min stimulated C-peptide had improved in 8/20 patients and C-peptide area under the curve (AUC) after Mixed Meal Tolerance Test in 5 patients, but declined thereafter, while HbA1c and insulin requirement remained close to baseline. Administration of Etanercept did not reduce tumour necrosis factor (TNF) spontaneous secretion from peripheral blood mononuclear cells, but rather GAD65-induced TNF-α increased. Spontaneous interleukin-17a secretion increased after the administration of Etanercept, and GAD65-induced cytokines and chemokines were also enhanced following 1 month of Etanercept administration. CONCLUSIONS: Combination therapy with parallel treatment with GAD-alum, Etanercept and vitamin D in children and adolescents with type 1 diabetes was feasible and tolerable but had no beneficial effects on the autoimmune process or beta cell function.

Comparing continuous subcutaneous insulin infusion and multiple daily injections in children with Type 1 diabetes in Sweden from 2011 to 2016-A longitudinal study from the Swedish National Quality Register (SWEDIABKIDS).

OBJECTIVE: This study aimed to compare metabolic control measured as hemoglobin A1c (HbA1c), the risk of severe hypoglycemia, and body composition measured as body mass index standard deviation scores (BMI-SDS) in a nationwide sample of children and adolescents with Type 1 diabetes with continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI), respectively. RESEARCH DESIGN AND METHODS: Longitudinal data from 2011 to 2016 were extracted from the Swedish National Quality Register (SWEDIABKIDS) with both cross-sectional (6 years) and longitudinal (4 years) comparisons. Main end points were changes in HbA1c, BMI-SDS, and incidence of severe hypoglycemia. RESULTS: Data were available from 35,624 patient-years (54% boys). In general, HbA1c decreased approximately 0.5% (2-5 mmol/mol) from 2011 to 2016 (ptrend < 0.001) and the use of CSII increased in both sexes and all age groups. Mean HbA1c was 0.1% (0.7-1.5 mmol/mol) lower in the CSII treated group. Teenagers, especially girls, using CSII tended to have higher BMI-SDS. There was no difference in the number of hypoglycemias between CSII and MDI over the years 2011-2016. CONCLUSIONS: There was a small decrease in HbA1c with CSII treatment but of little clinical relevance. Overall, mean HbA1c decreased in both sexes and all age groups without increasing the episodes of severe hypoglycemia, indicating that other factors than insulin method contributed to a better metabolic control.

Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes.

OBJECTIVES: Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were ≥ 10 times the upper limit of normal (10× ULN) predicted CD in T1D. METHODS: Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhüber classification. RESULTS: All of the 60 children with anti-tTG ≥10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. CONCLUSIONS: As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.

The importance of low HbA1c during childhood on glycaemic control in adulthood and the risk of late complications.

AIM: To evaluate whether a very low glycated haemoglobin A (HbA1c) (<48 mmol/mol, 6.5%) during childhood compared to higher HbA1c values further decreases the risk for microvascular complications. METHODS: Data were included from the 5116 patients with type 1 diabetes transferred from the Swedish paediatric diabetes quality registry to the Swedish National Diabetes Register (NDR), until 2014. All HbA1c values ever registered in the paediatric registry were used to divide patients into six groups based on the mean HbA1c. Values were compared with HbA1c registered in 2013 and 2014 in NDR, together with data on retinopathy, micro- and macroalbuminuria, age at onset and duration of diabetes. RESULTS: The group with lowest mean-HbA1c during childhood had also the lowest mean as young adults during 2013 and 2014. The most common complication as young adults was retinopathy. The proportion with macroalbuminuria was 3% in the lowest HbA1c group during childhood and 3.9% in the highest group, and lower in the groups in between. Microalbuminuria had the same pattern. Retinopathy increased with each HbA1c group. CONCLUSION: Children with the lowest HbA1c values had the lowest HbA1c values as adults. HbA1c was associated with retinopathy but the relationship with albuminuria was not obvious.

Poor metabolic control in childhood strongly correlates to diabetes-related premature death in persons <30 years of age-A population-based cohort study.

BACKGROUND/OBJECTIVE: The importance of metabolic control in childhood regarding excess risk of death in young persons has not been well studied. This registry-based study aimed to investigate mortality rates and cause of death related to metabolic control in young persons (≤29 years) in Sweden with type 1 diabetes. METHODS: All 12 652 subjects registered in the Swedish pediatric diabetes quality register, from 2006 to 2014, were included. Data were merged with the Swedish Cause of Death Register. Standardized mortality rates were calculated using the official Swedish population register. RESULTS: Of 68 deaths identified, 38.2% of the deaths were registered as being due to diabetes whereof the major cause of death was acute complications. Overall standardized mortality ratio was 2.7 (2.1-3.4, 95% CI). Subjects who died from diabetes had a mean HbA1c of 74 ± 19 mmol/mol (8.9 ± 1.7%) during childhood vs 62 ± 12 mmol/mol (7.8 ± 1.1%) in those still alive (P < .001). CONCLUSIONS: In this nationwide cohort of young subjects with type 1 diabetes, there was a high mortality rate compared to the general population. Mean HbA1c in childhood was significantly higher in those who died from diabetes, compared to subjects who were still alive. To decrease mortality in young persons with type 1 diabetes it is essential not only to achieve but also to maintain a good metabolic control during childhood and adolescence.

Microalbuminuria and retinopathy in adolescents and young adults with type 1 and type 2 diabetes.

AIM: To estimate the occurrence of complications related to early-onset type 2 diabetes compared with type 1 diabetes. METHODS: All individuals registered in the Swedish Pediatric Quality Diabetes Register and the Swedish National Diabetes Register with type 2 diabetes diagnosis at 10 to 25 years of age between 1996 and 2014 (n = 1413) were included. As controls, individuals with type 1 diabetes were randomly selected from the same registers and were matched for age, sex, and year-of-onset (n = 3748). RESULTS: Of the adolescents with type 2 diabetes in the pediatric register, 7.7% had microalbuminuria and 24.6% had signs of retinopathy 5 years after diagnosis, whereas the adolescents with type 1 diabetes 3.8% had microalbuminuria and 19.2% had retinopathy. Among the young adults with type 2 diabetes from the adult diabetes register 10 years after diagnosis 15.2% had microalbuminuria and 39.7% retinopathy, whereas the young adults with type 1 diabetes 4.8% had microalbuminuria and 43.8% retinopathy. After adjustment for established risk factors measured over time in the whole combined cohort, individuals with type 2 diabetes had significantly higher risk of microalbuminuria with a hazard ratio (HR) of 3.32 (95% confidence interval, CI 2.86-3.85, P < .001), and retinopathy with a HR of 1.17 (95% CI 1.06-1.30, P 0.04). CONCLUSIONS: The prevalence of complications and comorbidities was higher among those with type 2 diabetes compared with type 1 diabetes, although prevalent in both groups. Early monitoring and more active treatment of type 2 diabetes in young individuals is required.

Geographical variation in the incidence of type 1 diabetes in the Nordic countries: A study within NordicDiabKids.

BACKGROUND: The incidence of type 1 diabetes (T1D) is high in the Nordic countries with geographic differences between as well as within countries. OBJECTIVE: To describe the geographical distribution of the incidence of T1D among children in four Nordic countries, an area where the population is considered genetically similar. METHODS: Data on children 0 to 14 years of age and diagnosed with T1D 2006 to 2011 was collected from four Nordic national pediatric quality diabetes registries. Data included year of diagnosis (2006-2011), sex, and age at diagnosis. Figures for number of children at risk during 2006 to 2011-as well as total population, proportion with foreign background and size of populated areas of geographic regions-were collected from official statistics. RESULTS: The total incidence during the study period for all four countries was 35.7/100 000 person years but differed between the countries (range 18.2-44.1; P < .001). The incidence difference between the countries was most obvious in the highest age group, 10 to 14 years of age, whereas there was no difference in the youngest age group 0 to 5 years of age. Iceland had similar incidence in the entire country, whereas the other countries had areas with different incidence. Densely populated areas, such as major cities, had the lowest incidence. CONCLUSION: The incidence of T1D differed between the Nordic countries and also between the neighboring countries and generally decreased with population density. This indicates that environmental factors may contribute to the level of incidence of T1D.

International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study.

OBJECTIVES: To identify differences and similarities in HbA1c levels and patterns regarding age and gender in eight high-income countries. SUBJECTS: 66 071 children and adolescents below18 years of age with type 1 diabetes for at least 3 months and at least one HbA1c measurement during the study period. METHODS: Pediatric Diabetes Quality Registry data from Austria, Denmark, England, Germany, Norway, Sweden, the United States, and Wales were collected between 2013 and 2014. HbA1c, gender, age, and duration were used in the analysis. RESULTS: Distribution of gender and age groups was similar in the eight participating countries. The mean HbA1c varied from 60 to 73 mmol/mol (7.6%-8.8%) between the countries. The increase in HbA1c between the youngest (0-9 years) to the oldest (15-17 years) age group was close to 8 mmol/mol (0.7%) in all countries (P < .001). Females had a 1 mmol/mol (0.1%) higher mean HbA1c than boys (P < .001) in seven out of eight countries. CONCLUSIONS: In spite of large differences in the mean HbA1c between countries, a remarkable similarity in the increase of HbA1c from childhood to adolescence was found.

Maternal obesity as a risk factor for early childhood type 1 diabetes: a nationwide, prospective, population-based case-control study.

AIMS/HYPOTHESIS: Genetic and environmental factors are believed to cause type 1 diabetes. The aim of this study was to investigate the influence of maternal BMI and gestational weight gain on the subsequent risk of childhood type 1 diabetes. METHODS: Children in the Swedish National Quality Register for Diabetes in Children were matched with control children from the Swedish Medical Birth Register. Children were included whose mothers had data available on BMI in early pregnancy and gestational weight gain, giving a total of 16,179 individuals: 3231 children with type 1 diabetes and 12,948 control children. RESULTS: Mothers of children with type 1 diabetes were more likely to be obese (9% [n = 292/3231] vs 7.7% [n = 991/12,948]; p = 0.02) and/or have diabetes themselves (2.8% [n = 90/3231] vs 0.8% [n = 108/12,948]; p < 0.001) compared with mothers of control children. Gestational weight gain did not differ significantly between the two groups of mothers. In mothers without diabetes, maternal obesity was a significant risk factor for type 1 diabetes in the offspring (p = 0.04). A child had an increased risk of developing type 1 diabetes if the mother had been obese in early pregnancy (crude OR 1.20; 95% CI 1.05, 1.38; adjusted OR 1.18; 95% CI 1.02, 1.36). Among children with type 1 diabetes (n = 3231) there was a difference (p < 0.001) in age at onset in relation to the mother's BMI. Among children in the oldest age group (15-19 years), there were more mothers who had been underweight during pregnancy, while in the youngest age group (0-4 years) the pattern was reversed. CONCLUSIONS/INTERPRETATION: Maternal obesity, in the absence of maternal diabetes, is a risk factor for type 1 diabetes in the offspring, and influences the age of onset of type 1 diabetes. This emphasises the importance of a normal maternal BMI to potentially decrease the incidence of type 1 diabetes.

Continued improvement of metabolic control in Swedish pediatric diabetes care.

BACKGROUND: To prospectively investigate if the grand mean HbA1c and the differences in mean HbA1c between centers in Sweden could be reduced, thereby improving care delivered by pediatric diabetes teams. METHODS: We used an 18-month quality improvement collaborative (QIC) together with the Swedish pediatric diabetes quality registry (SWEDIABKIDS). The first program (IQ-1), started in April 2011 and the second (IQ-2) in April 2012; together they encompassed 70% of Swedish children and adolescents with diabetes. RESULTS: The proportion of patients in IQ-1 with a mean HbA1c <7.4% (57 mmol/mol) increased from 26.4% before start to 35.9% at 36 months (P < .001), and from 30.2% to 37.2% (P < .001) for IQ-2. Mean HbA1c decreased in both participating and non-participating (NP) centers in Sweden, thereby indicating an improvement by a spatial spill over effect in NP centers. The grand mean HbA1c decreased by 0.45% (4.9 mmol/mol) during 36 months; at the end of 2014 it was 7.43% (57.7 mmol/mol) (P < .001). A linear regression model with the difference in HbA1c before start and second follow-up as dependent variable showed that QIC participation significantly decreased mean HbA1c both for IQ-1 and IQ-2. The proportion of patients with high HbA1c values (>8.7%, 72 mmol/mol) decreased significantly in both QICs, while it increased in the NP group. CONCLUSIONS: The grand mean HbA1c has decreased significantly in Sweden from 2010 to 2014, and QICs have contributed significantly to this decrease. There seems to be a spatial spill-over effect in NP centers.

Type 1 diabetes during adolescence: International comparison between Germany, Austria, and Sweden.

OBJECTIVES: By using pediatric diabetes quality registries in Austria, Germany, and Sweden treatment of type 1 diabetes and the outcome of care during the vulnerable adolescence period were compared. METHODS: Data in DPV, broadly used in Austria and Germany, and Swediabkids used in Sweden, from clinical visits in the year 2013 on 14 383 patients aged 11 to 16 years regarding hemoglobin A1c (HbA1c), insulin regimen, body mass index (BMI)-SD score (SDS), blood pressure, hypoglycemia, ketoacidosis, and smoking habits were analyzed. RESULTS: Patients in Sweden had fewer clinical visits per year (P < .05), lower insulin dose per kg (P < .001), and lower proportion of fast acting insulin compared with Germany and Austria (P < .001). The proportion of pump users was higher in Sweden (P < .001). Patients in Sweden had lower mean HbA1c levels (Austria: 64 mmol/mol, Germany: 63 mmol/mol, and Sweden: 61 mmol/mol [8.0%, 7.9%, and 7.7%, respectively]; P < .001). The frequency of severe hypoglycemia was higher in Sweden while it was lower for ketoacidosis (3.3% and 1.1%, respectively) than in Austria (1.1% and 5.3%) and Germany (2.0% and 4.4%) (P < .001). Girls in all 3 countries had higher HbA1c and BMI-SDS than boys. CONCLUSIONS: Sharing data between diabetes registries and nations enables us to better understand differences in diabetes outcome between countries. In this particular comparison, pediatric patients with diabetes in Sweden were more often treated with insulin pump, had lower HbA1c levels and a higher rate of severe hypoglycemia. Patients in Austria and Germany used rapid acting insulin analogs more often and had a lower rate of ketoacidosis.

Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes.

AIM: It is of interest to predict possible lifetime risk of type 1 diabetes (T1D) in young children for recruiting high-risk subjects into longitudinal studies of effective prevention strategies. METHODS: Utilizing a case-control study in Sweden, we applied a recently developed next generation targeted sequencing technology to genotype class II genes and applied an object-oriented regression to build and validate a prediction model for T1D. RESULTS: In the training set, estimated risk scores were significantly different between patients and controls (P = 8.12 × 10-92 ), and the area under the curve (AUC) from the receiver operating characteristic (ROC) analysis was 0.917. Using the validation data set, we validated the result with AUC of 0.886. Combining both training and validation data resulted in a predictive model with AUC of 0.903. Further, we performed a "biological validation" by correlating risk scores with 6 islet autoantibodies, and found that the risk score was significantly correlated with IA-2A (Z-score = 3.628, P < 0.001). When applying this prediction model to the Swedish population, where the lifetime T1D risk ranges from 0.5% to 2%, we anticipate identifying approximately 20 000 high-risk subjects after testing all newborns, and this calculation would identify approximately 80% of all patients expected to develop T1D in their lifetime. CONCLUSION: Through both empirical and biological validation, we have established a prediction model for estimating lifetime T1D risk, using class II HLA. This prediction model should prove useful for future investigations to identify high-risk subjects for prevention research in high-risk populations.

Adolescent life with diabetes-Gender matters for level of distress. Experiences from the national TODS study.

OBJECTIVE: To examine the relationship between diabetes distress and gender, and the association with glycemic control, social support, health behaviors, and socio-economic status. METHODS: All adolescents, aged 15 to 18 years, in the national, pediatric diabetes registry SWEDIABKIDS with type 1 diabetes were invited to complete an online questionnaire. A total of 2112 teenagers were identified. RESULTS: 453 complete responses were valid for analyses. Young women scored significantly higher on the distress-screening instrument DDS-2. Almost half of the female respondents exhibited moderate to severe diabetes distress-more than twice the proportion than among male respondents (44% vs 19%). Females reported twice as high scores on the fear of hypoglycemia scale (P < 0.0001) and had a higher HbA1c value than males (P < 0.0001). Gender was highly correlated with distress level even when controlling for multiple factors that may affect distress (parameterfemale = 0.4, P = 0.0003). Particular social problems were highly significant, that is, those who trust that their parents can handle their diabetes when necessary were significantly less distressed than others (P = 0.018). Higher HbA1c levels were associated with higher distress scores (P = 0.0005 [female], P = 0.0487 [male]). CONCLUSIONS: Diabetes-related distress is a great burden for adolescents living with diabetes. Actively involved family and friends may reduce diabetes distress, but female adolescents appear to be particularly vulnerable and may need extra focus and support. Our findings indicate that pediatric diabetes teams working with teenagers must intensify the care during this vulnerable period of life in order to reduce the risk of both psychological and vascular complications in young adults.

High HbA1c at onset cannot be used as a predictor for future metabolic control for the individual child with type 1 diabetes mellitus.

BACKGROUND: To study how metabolic control at onset of type 1 diabetes correlates to metabolic control and clinical parameters during childhood until transition from pediatric care to adult diabetes care. MATERIALS AND METHODS: Data at onset, three months, one, three, and five years after diagnosis and at transition, on HbA1c and clinical parameters, on 8084 patients in the Swedish pediatric quality registry, SWEDIABKIDS, were used. Of these patients, 26% had been referred to adult diabetes care by 2014. RESULTS: Children with HbA1c < 72 mmol/mol (8.7%) (20% of patients, low group) at diagnosis continued to have good metabolic control during childhood, in contrast to children with HbA1c > 114 mmol/mol (12.6%) (20% of patients, high group) at diagnosis, who continued to have high HbA1c at follow-up. For the individual, there was no significant correlation between high HbA1c at onset and during follow-up. During follow-up, children in the high group were more often smokers, less physically active, and more often had retinopathy than children in the low group (P < .01, .01, .03 respectively). CONCLUSION: High HbA1c at onset was associated with high HbA1c during follow-up on a group level, but it cannot be used as a predictor of future metabolic control on an individual level. These results emphasize the important work done by the diabetes team in the first years after diagnosis. It is important to continuously set high goals for the achievement of tight metabolic control, in order to decrease the risk of microvascular complications.

National Swedish study of immigrant children with type 1 diabetes showed impaired metabolic control after three years of treatment.

AIM: This study examined the clinical status and socio-demographic conditions of children with type 1 diabetes at baseline and after three years of treatment, comparing those born to immigrant parents and Swedish parents. METHODS: This observational nationwide population-based cohort study used prospectively collected registry data from Swediabkids, the National Quality Registry for Paediatric Diabetes in Sweden from 2000 to 2010. Of the 13 415 children with type 1 diabetes, there were 879 born to immigrant parents. We selected three children born to Swedish parents from the same registry for each immigrant child matching them by gender, age and year of diabetes onset (n = 2627; with 10 control children missing probably due to the matching procedure). RESULTS: Immigrant children had a higher median glycated haemoglobin level (HbA1c) than their Swedish peers, but there was no difference in the frequency of hypoglycaemia or ketoacidosis between the two cohorts. A linear regression model with HbA1c as a dependent variable showed that insulin units per kilogram of body weight were the main reason for inferior metabolic control. CONCLUSION: Children with type 1 diabetes born to immigrant parents had inferior metabolic control three years after disease onset compared to children with Swedish born parents. Social family support and educational coping programmes are needed to improve treatment outcomes in immigrants with diabetes.

Caesarean section per se does not increase the risk of offspring developing type 1 diabetes: a Swedish population-based study.

AIMS/HYPOTHESIS: Some studies have revealed a relationship between Caesarean section (CS) and type 1 diabetes, while other studies have not. By using the Swedish paediatric quality register we investigated whether birth by CS is related to the risk of developing type 1 diabetes during childhood. METHODS: All children diagnosed with type 1 diabetes from 2000 to 2012 and included in the register (n = 9,376) were matched with four controls by year, day of birth, sex and county of birth from the Swedish Medical Birth Register. RESULTS: Overall, 13.5% of deliveries were by CS. By group, 14.7% of children who developed type 1 diabetes were delivered by CS compared with 13.3% of control children (p < 0.001). Mothers with diabetes more often gave birth by CS than mothers without diabetes (78.8% vs 12.7%, p < 0.001). In a logistic regression model adjusting for maternal age, maternal diabetes and BMI in early pregnancy, the OR for CS was 1.0. A child who developed type 1 diabetes and had a mother with type 1 diabetes at the time of delivery had the highest OR to have been born by CS. Children of mothers without diabetes, delivered by CS, had no increased risk of developing type 1 diabetes. Maternal diabetes was the strongest predictor of childhood diabetes (OR 3.4), especially if the mother had type 1 diabetes (OR 7.54). CONCLUSIONS/INTERPRETATION: CS had no influence on the risk of type 1 diabetes during childhood or adolescence. However, maternal diabetes itself strongly increased the risk of offspring developing type 1 diabetes.

GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus.

BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences. CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.).