The course of diabetes in children, adolescents and young adults: does the autoimmunity status matter?

BACKGROUND: Initial classification of diabetes of young may require revision to improve diagnostic accuracy of different forms of diabetes. The aim of our study was to examine markers of beta-cell autoimmunity in a cohort of young (0-25 years) patients with type 1 diabetes and compare the presentation and course of the disease according to the presence of pancreatic antibodies. METHODS: Cross-sectional population-based study was performed covering 100% of pediatric (n = 860) and 70% of 18-25 years old adult patients (n = 349) with type 1 diabetes in Lithuania. RESULTS: No antibodies (GAD65, IA-2, IAA and ICA) were found in 87 (7.5%) cases. Familial history of diabetes was more frequent in those with antibodies-negative diabetes (24.1 vs. 9.4%, p < 0.001). Gestational age, birth weight and age at diagnosis was similar in both groups. Ketosis at presentation was more frequent in patients with autoimmune diabetes (88.1 vs. 73.5%, p < 0.05). HbA1c at the moment of investigation was 8.6 (3) vs. 8.7 (2.2)% in antibodies-negative and antibodies-positive diabetes groups, respectively, p > 0.05. In the whole cohort, neuropathy was found in 8.8% and nephropathy - in 8.1% of cases, not depending on autoimmunity status. Adjusted for age at onset, disease duration and HbA1c, retinopathy was more frequent in antibodies-negative subjects (13.8 vs. 7.8%, p < 0.05). CONCLUSION: Antibodies-negative pediatric and young adult patients with type 1 diabetes in this study had higher incidence of family history of diabetes, higher frequency of retinopathy, less frequent ketosis at presentation, but similar age at onset, HbA1c, incidence of nephropathy and neuropathy compared to antibodies-positive patients.

Breast-feeding and childhood-onset type 1 diabetes: a pooled analysis of individual participant data from 43 observational studies.

OBJECTIVE: To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN AND METHODS: Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. RESULTS: Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I(2) = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I(2) = 0%). Adjustments for potential confounders altered these estimates very little. CONCLUSIONS: The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

Interbirth interval is associated with childhood type 1 diabetes risk.

Short interbirth interval has been associated with maternal complications and childhood autism and leukemia, possibly due to deficiencies in maternal micronutrients at conception or increased exposure to sibling infections. A possible association between interbirth interval and subsequent risk of childhood type 1 diabetes has not been investigated. A secondary analysis of 14 published observational studies of perinatal risk factors for type 1 diabetes was conducted. Risk estimates of diabetes by category of interbirth interval were calculated for each study. Random effects models were used to calculate pooled odds ratios (ORs) and investigate heterogeneity between studies. Overall, 2,787 children with type 1 diabetes were included. There was a reduction in the risk of childhood type 1 diabetes in children born to mothers after interbirth intervals <3 years compared with longer interbirth intervals (OR 0.82 [95% CI 0.72-0.93]). Adjustments for various potential confounders little altered this estimate. In conclusion, there was evidence of a 20% reduction in the risk of childhood diabetes in children born to mothers after interbirth intervals <3 years.

Birth order and childhood type 1 diabetes risk: a pooled analysis of 31 observational studies.

BACKGROUND: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. METHODS: Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. RESULTS: Data were available for 6 cohort and 25 case-control studies, including 11,955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second- or later born children became apparent [fully adjusted OR = 0.90 95% confidence interval (CI) 0.83-0.98; P = 0.02] but this association varied markedly between studies (I² = 67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children < 5 years of age (n = 25 studies, maternal age adjusted OR = 0.84 95% CI 0.75, 0.93; I² = 23%). CONCLUSION: Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged < 5 years. This finding could reflect increased exposure to infections in early life in later born children.

Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies.

OBJECTIVE: The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. RESEARCH DESIGN AND METHODS: Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. RESULTS: Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I(2) = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS: There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.

Incidence of type 1 diabetes in Lithuanians aged 0-39 years varies by the urban-rural setting, and the time change differs for men and women during 1991-2000.

OBJECTIVE: Type 1 diabetes has been associated with factors related to welfare and social class. During the past decade, Lithuania has experienced a transition period, leading to dramatic changes in the socioeconomic structure of the society. RESEARCH DESIGN AND METHODS: Incidence in the group aged 0-39 years by urban-rural setting (cities >100000 inhabitants, towns, and rural areas), period (1991-1995 and 1996-2000), age, and sex were studied using Poisson regression. RESULTS: The age- and sex-standardized incidence per 100000 inhabitants per year was higher in men aged 0-39 years than in women (9.5 and 6.9, respectively, incidence rate ratio [IRR] = 1.39, P < 0.001). Incidence was lower in rural areas than in towns and cities (7.1, 9.0, and 8.8, respectively, P < 0.001). The urban-rural differences in incidence were most marked among children aged 0-9 years. From 1991-1995 to 1996-2000, the overall incidence increased from 8.7 to 10.5 (IRR = 1.22, P = 0.001) in men and from 6.2 to 7.8 (IRR = 1.25, P = 0.002) in women. For men, the increase over time occurred predominantly in the cities, from 8.4 to 11.8 (IRR = 1.40, P < 0.001), and in the older age-groups. In contrast, for women, the incidence increased more in small towns and rural areas, from 5.8 to 7.7 (IRR = 1.33, P = 0.003), and in the younger age-groups. CONCLUSIONS: The incidence of type 1 diabetes in Lithuania differs depending on the urban-rural setting, and the pattern of change over time differs between the sexes, both by urban-rural setting and age-group. The findings support the theory that lifestyle-related factors connected to socioeconomic status are important for the occurrence of type 1 diabetes.

Incidence, prevalence, and mortality of insulin-dependent (type 1) diabetes mellitus in Lithuanian children during 1983-98.

AIMS/HYPOTHESIS: Our purpose is to analyze interrelations of the incidence, prevalence and mortality of childhood-onset insulin-dependent diabetes mellitus (type 1) in Lithuania. METHODS: Incidence and prevalence rates were based on the national type 1 diabetes register during 1983-98. The cohort study was performed to evaluate the standardized mortality ratios. RESULTS: The average incidence of type 1 diabetes during the 16-yr study period was 7.36 per 100,000/yr. For both males and females the highest incidence of type 1 diabetes was recorded in the 10-14 yr age group. The regression-based linear trends of the increase in incidence in various age groups and the annual percentage change for both genders was 2.05 (p = 0.0039) and the greatest regression slope is observed for both genders in the 10-14 yr age group. Regression-based linear trends in type 1 diabetes prevalence indicate an even growth in all age groups (3.47; p = 0.001), although the annual percentage change is most prominent in the 5-9 yr age group for girls (4.95%/yr) and in the 10-14 yr age group for boys (4.06%/yr). The standardized mortality ratio of all-cause mortality in people with diabetes is higher than in the common population 7.71 (p < 0.0001). The standard mortality ratio for all causes increases with longer diabetes duration. CONCLUSION/INTERPRETATION: The significant increasing trend of incidence and prevalence during 1983-98 is observed. The annual percentage change is similar. The young patients with type 1 diabetes have a higher mortality risk.