Browsing by Subject "Type 1 diabetes"
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(2016)Aims/hypothesis To characterise rapid progressors to type 1 diabetes among children recruited from the general population based on HLA-conferred disease susceptibility. Methods We observed 7410 HLA-predisposed children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study from birth for development of beta cell autoimmunity and type 1 diabetes over a median follow-up time of 16.2 (range 0.9-21.1) years. Islet cell antibodies, and autoantibodies to insulin (IAA), GAD (GADA), and islet antigen 2 (IA-2A) were analysed as markers of beta cell autoimmunity. Rapid progression was defined as progression to clinical type 1 diabetes within 1.5 years after autoantibody seroconversion. We analysed the association between rapid progression and demographic and autoantibody characteristics as well as genetic markers including 25 non-HLA single nucleotide polymorphisms (SNPs) predisposing to type 1 diabetes. Results Altogether 1645 children (22%) tested positive for at least one diabetes-associated autoantibody, and 248 (15%) of the seroconverters progressed to type 1 diabetes by the end of 2015. The median time from seroconversion to diagnosis was 0.51 years in rapid progressors (n=42, 17%), and 5.4 years in slower progressors. Rapid progression was observed both among young and early pubertal children. Compared to slower progressors, rapid progressors had higher frequency of multipositivity, higher titres of ICA, IAA, and IA-2A at seroconversion, and higher prevalence of the secretor genotype in the FUT2 gene. Compared to autoantibody-positive non-progressors, rapid progressors were younger, carried more often the high-risk HLA genotype, the FUT2 secretor genotype, and a predisposing SNP in the PTPN22 gene, had higher frequency of ICA, IAA, GADA, IA-2A, and multipositivity, and higher titres of all four autoantibodies at seroconversion. Conclusions At seroconversion, individuals with rapid progression to type 1 diabetes are characterised by young age, higher autoantibody titres, positivity for multiple autoantibodies, and higher prevalence of a FUT2 SNP. The double-peak profile of seroconversion age among the rapid progressors demonstrates for the first time that rapid progression may take place not only in young children, but also in children in early puberty. Rapid progressors might benefit from careful clinical follow-up and early preventive measures.
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(2024)Background Sedentary behavior, such as excessive sitting, is associated with an increased risk of cardiovascular disease and premature mortality in the general population, but this has not been assessed in type 1 diabetes. Occupational sitting is increasingly ubiquitous and often composes the largest portion of individuals´ daily sitting time. Our aim was, therefore, to identify clinical factors associated with excessive occupational sitting in individuals with type 1 diabetes, and additionally, in a prospective setting, to explore the association between excessive occupational sitting and cardiovascular events and all-cause mortality, independently of leisure-time physical activity. Methods Observational follow-up study, including 1,704 individuals (mean age 38.9 ± 10.1 years) from the Finnish Diabetic Nephropathy Study. Baseline assessments of occupational sitting and leisure-time physical activity were conducted using a validated self-report questionnaire. Excessive occupational sitting was defined as ≥ 6 hours of daily workplace sitting. Data on cardiovascular events and mortality were retrieved from national registries. Multivariable logistic regression analysis was applied to determine independently associated factors. Kaplan-Meier curves and Cox proportional hazard models were performed regarding prospective analyses. Results Factors independently and positively associated with excessive occupational sitting included a high educational level [OR 6.53, 95% CI (4.09‒10.40)] and older age [1.02 (1.00‒1.03)], whereas negatively associated factors included current smoking [0.68 (0.50‒0.92)], moderate albuminuria [0.55 (0.38‒ 0.80)], and high amounts of leisure-time physical activity [0.52 (0.36‒0.74)]. During a median followup of 12.5 (6.5-16.4) years, 163 (9.6%) individuals suffered a cardiovascular event. Respectively, during a median follow-up of 13.7 (9.4-16.6) years, 108 (6.3%) deaths occurred. Excessive occupational sitting increased the risk of cardiovascular events (hazard ratio [HR] 1.43 [95% CI 1.02‒2.01]) after adjustment for confounders. In a stratified multivariable analysis among current smokers, excessive occupational 5 sitting increased the risk of cardiovascular events (1.93 [1.03‒3.62]) and all-cause mortality (2.16 [1.10‒ 4.21]). Conclusions Excessive occupational sitting is associated with an increased risk of cardiovascular events and all-cause mortality in individuals with type 1 diabetes, especially among current smokers, regardless of leisuretime physical activity. These findings highlight the importance of recommendations for reducing sedentary time, as part of the physical activity guidelines for individuals with type 1 diabetes.
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