DPV Scientific Initiative of Germany and Austria, The ‘accelerator hypothesis': relationship between weight, height, body mass index and age at diagnosis in a large cohort of 9,248 German and Austrian children with type 1 diabetes mellitus
We evaluated anthropometric measurements in a large cohort of 9,248 patients of European extraction who were diagnosed in the years 1990-2003 in 116 pediatric clinics throughout Germany and Austria.
Patients were divided into four groups according to age (0-4.9 years, 5-9.9 years, 10-14.9 years and 15-20 years). Significantly higher standard deviation scores (SDSs) for weight and BMI at diabetes onset were found for both boys and girls in the three younger age groups (up to 14.9 years of age) compared with the reference population (p<0.00001). In addition, the BMI SDS and the weight SDS were significantly higher in the 0-4.9-years age group than in all other groups (p<0.00001), and BMI SDS at onset gradually decreased with increasing age at manifestation (p<0.0001). Over the >10-year study period, there was a continuous rise in the weight-SDS and the BMI-SDS in the cohort (p<0.0001), especially in the 5-9.9-years and the 10-14.9-years age groups. Multivariate analysis revealed a significant influence of male sex and of year of manifestation on BMI SDS (p<0.0001) and demonstrated a negative association between the patients' BMI SDS and age at diagnosis, with a mean annual decrease in BMI SDS of -0.0248 (95% CI -0.0294 to -0.0202, p<0.0001).
A higher BMI was associated with a younger age at diabetes onset. Increased weight gain could therefore be a risk factor for the early manifestation of type 1 diabetes.
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Article: DPV Scientific Initiative of Germany and Austria, The ‘accelerator hypothesis': relationship between weight, height, body mass index and age at diagnosis in a large cohort of 9,248 German and Austrian children with type 1 diabetes mellitus
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- "However, children in the German BabyDiab cohort showed no effect of weight gain on risk of islet autoimmunity . Younger age of T1D onset is inconsistently associated with higher BMI at diagnosis [45,46]. Retrospective case control studies from Scandinavia link increased linear growth and weight gain in early childhood with T1D . "
ABSTRACT: The incidence of type 1 diabetes has increased worldwide, particularly in younger children and those with lower genetic susceptibility. These observations suggest factors in the modern environment promote pancreatic islet autoimmunity and destruction of insulin-producing beta cells. The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is investigating candidate environmental exposures and gene-environment interactions that may contribute to the development of islet autoimmunity and type 1 diabetes.Methods/design: ENDIA is the only prospective pregnancy/birth cohort study in the Southern Hemisphere investigating the determinants of type 1 diabetes in at-risk children. The study will recruit 1,400 unborn infants or infants less than six months of age with a first-degree relative (i.e. mother, father or sibling) with type 1 diabetes, across five Australian states. Pregnant mothers/infants will be followed prospectively from early pregnancy through childhood to investigate relationships between genotype, the development of islet autoimmunity (and subsequently type 1 diabetes), and prenatal and postnatal environmental factors. ENDIA will evaluate the microbiome, nutrition, bodyweight/composition, metabolome-lipidome, insulin resistance, innate and adaptive immune function and viral infections. A systems biology approach will be used to integrate these. Investigation will be by 3-monthly assessments of the mother during pregnancy, then 3-monthly assessments of the child until 24 months of age and 6-monthly thereafter. The primary outcome measure is persistent islet autoimmunity, defined as the presence of autoantibodies to one or more islet autoantigens on consecutive tests. Defining gene-environment interactions that initiate and/or promote destruction of the insulin-producing beta cells in early life will inform approaches to primary prevention of type 1 diabetes. The strength of ENDIA is the prospective, comprehensive and frequent systems-wide profiling from early pregnancy through to early childhood, to capture dynamic environmental exposures that may shape the development of islet autoimmunity.Trial registration: Australia New Zealand Clinical Trials Registry ACTRN12613000794707.
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- "The doubling in incidence of T1D in childhood in Australia over the last 20 years parallels the overweight/obesity epidemic in Western childhood populations. In addition, age of diagnosis of T1D has decreased over the last 20 years and younger age of T1D onset is associated in some populations with higher Body Mass Index (BMI) at diagnosis [8,9]. The T1D population is susceptible to the population shift in BMI, with 65% of adults in a US cohort with T1D in the overweight or obese BMI range . "
ABSTRACT: Cardiovascular disease is the leading cause of mortality in Type 1 diabetes (T1D). Vascular dysfunction is an early and critical event in the development of cardiovascular disease. Children with T1D have vascular dysfunction therefore early interventions to improve vascular health are essential to reduce cardiovascular mortality in T1D. Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes (T2D) and other individuals with insulin resistance. It has been used safely in children and adolescents with T2D for over 10 years. This study aims to assess the effect of metformin on vascular health in children with T1D.Methods/designThis study is a 12 month, double blind, randomised, placebo controlled trial to determine the effect of metformin on vascular health in children (age 8--18) with T1D. The sample size is 76 with 38 children in the metformin group and 38 children in the placebo group. Vascular health and biochemical markers will be measured at baseline, 3, 6 and 12 months. Vascular function will be measured using flow mediated dilatation and glyceryl trinitrate mediated dilatation of the brachial artery and vascular structure will be measured with carotid and aortic intima media thickness, using standardised protocols. This study will be the first to investigate the effect of metformin on vascular health in children with T1D. It will provide important information on a potential intervention to improve cardiovascular morbidity and mortality in this population at high risk from cardiovascular disease.Trial registrationAustralia New Zealand Clinical Trials Registry ACTRN12611000148976.
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- "This would be consistent with the ‘accelerator hypothesis’, which suggests that an increasing rate of obesity is a primary driver for an earlier age of diabetes onset . Studies have shown an association between higher BMI and younger age at diagnosis , , , indicating greater adiposity in childhood may hasten the onset of diabetes mellitus. The ‘accelerator hypothesis’ predicts an early onset rather than increased risk , and a Swedish study examining type 1 diabetes incidence on a nation-wide cohort 0–34 yr showed a shift in age of onset towards younger ages, rather than an increase in incidence per se across the whole population . "
ABSTRACT: We aimed to evaluate the incidence of type 1 diabetes mellitus in children <15 years of age (yr) in the Auckland region (New Zealand) over 20 years (1990-2009). We performed a retrospective review of all patients <15 yr diagnosed with type 1 diabetes, from an unselected complete regional cohort. There were 884 new cases of type 1 diabetes, and age at diagnosis rose from 7.6 yr in 1990/1 to 8.9 yr in 2008/9 (r(2) = 0.31, p = 0.009). There was a progressive increase in type 1 diabetes incidence among children <15 yr (p<0.0001), reaching 22.5 per 100,000 in 2009. However, the rise in incidence did not occur evenly among age groups, being 2.5-fold higher in older children (10-14 yr) than in the youngest group (0-4 yr). The incidence of new cases of type 1 diabetes was highest in New Zealand Europeans throughout the study period in all age groups (p<0.0001), but the rate of increase was similar in New Zealand Europeans and Non-Europeans. Type 1 diabetes incidence and average annual increase were similar in both sexes. There was no change in BMI SDS shortly after diagnosis, and no association between BMI SDS and age at diagnosis. There has been a steady increase in type 1 diabetes incidence among children <15 yr in Auckland over 20 years. Contrary to other studies, age at diagnosis has increased and the greatest rise in incidence occurred in children 10-14 yr. There was little change in BMI SDS in this population, providing no support for the 'accelerator hypothesis'.