Down’s syndrome in diabetic patients aged &lt;20 years: an analysis of metabolic status, glycaemic control and autoimmunity in comparison with type 1 diabetes

Rohrer, Tilman; Hennes, Pia; Thon, A.; Dost, Axel; Grabert, M.; Rami, Birgit; Wiegand, Susanna; Holl, Reinhard W.

doi:10.1007/s00125-010-1686-z

Cited by 39 publications

(44 citation statements)

References 13 publications

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“…A recent study of 159 DS children diagnosed with type 1 diabetes (DSD) demonstrated two peaks in diabetes incidence, one occurring before 2 years of age and the other in early adolescence. The mean age at onset in the 41,983 control subjects with type 1 diabetes was 8.42 years (8). These data suggest that diabetes occurring before 2 years of age in DS children may be etiologically different from type 1 diabetes.…”

mentioning

confidence: 76%

Early-Onset, Coexisting Autoimmunity and Decreased HLA-Mediated Susceptibility Are the Characteristics of Diabetes in Down Syndrome

et al. 2013

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OBJECTIVEdDown syndrome (DS) is associated with an increased risk of diabetes, particularly in young children. HLA-mediated risk is however decreased in children with DS and diabetes (DSD). We hypothesized that early-onset diabetes in children with DS is etiologically different from autoimmune diabetes.RESEARCH DESIGN AND METHODSdClinical and immunogenetic markers of autoimmune diabetes were studied in 136 individuals with DSD and compared with 194 age-and sex-matched individuals with type 1 diabetes, 222 with DS, and 671 healthy controls. HLA class II was analyzed by sequence-specific primed PCR. Islet autoantibodies were measured by radioimmunoassay.RESULTSdAge at onset of diabetes was biphasic, with 22% of DS children diagnosed before 2 years of age, compared with only 4% in this age-group with type 1 diabetes in the general population (P , 0.0001). The frequency of the highest-risk type 1 diabetes-associated HLA genotype, DR3-DQ2/DR4-DQ8, was decreased in both early-and later-onset DSD compared with age-matched children with type 1 diabetes (P , 0.0001), although HLA DR3-DQ2 genotypes were increased (P = 0.004). Antibodies to GAD were observed in all five samples tested from children diagnosed at #2 years of age, and persistent islet autoantibodies were detected in 72% of DSD cases. Thyroid and celiac disease were diagnosed in 74 and 14%, respectively, of the DSD cohort.CONCLUSIONSdEarly-onset diabetes in children with DS is unlikely to be etiologically different from autoimmune diabetes occurring in older DS children. Overall, these studies demonstrate more extreme autoimmunity in DSD typified by early-onset diabetes with multiple autoimmunity, persistent islet autoantibodies, and decreased HLA-mediated susceptibility.

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confidence: 76%

Early-Onset, Coexisting Autoimmunity and Decreased HLA-Mediated Susceptibility Are the Characteristics of Diabetes in Down Syndrome

et al. 2013

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“…The trisomy of chromosome 21 in individuals with Down syndrome provides a unique genetic landscape to assess gene function in organs other than the brain. The increased incidence of diabetes in Down syndrome individuals is indicative that a gene, or genes, on chromosome 21 could be essential to the maintenance of whole body glucose homeostasis and pancreatic β‐cell function. To this end β‐cell morphology and function were examined in fetal tissue from normal and Down syndrome donors .…”

Section: Endocrine Functionmentioning

confidence: 99%

The neuronal and endocrine roles of RCAN1 in health and disease

Peiris

Keating

2017

Clin Exp Pharma Physio

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The regulator of calcineurin 1 (RCAN1) was first discovered as a gene located on human chromosome 21, expressed in neurons and overexpressed in the brains of Down syndrome individuals. Increased expression of RCAN1 has been linked with not only Down syndrome-associated pathology but also an associated neurological disorder, Alzheimer's Disease, in which neuronal RCAN1 expression is also increased. RCAN1 has additionally been demonstrated to affect other cell types including endocrine cells, with links to the pathogenesis of β-cell dysfunction in type 2 diabetes. The primary functions of RCAN1 relate to the inhibition of the phosphatase calcineurin, and to the regulation of mitochondrial function. Various forms of cellular stress such as reactive oxygen species and hyperglycaemia cause transient increases in RCAN1 expression. The short term (hours to days) induction of RCAN1 expression is generally thought to have a protective effect by regulating the expression of pro-survival genes in multiple cell types, many of which are mediated via the calcineurin/NFAT transcriptional pathway. However, strong evidence also supports the notion that chronic (weeks-years) overexpression of RCAN1 has a detrimental effect on cells and that this may drive pathophysiological changes in neurons and endocrine cells linked to Down syndrome, Alzheimer's Disease and type 2 diabetes. Here we review the evidence related to these roles of RCAN1 in neurons and endocrine cells and their relationship to these human health disorders.

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“…We also thank Katharina Molz, Esther Molz, Andreas Hungele, and Martin de Souza (Epidemiology, University of Ulm) for help with data collection, integration, and analysis. In addition, we thank all pediatricians and family doctors in Germany for participation in the BABYDIAB study and Munich Family Study, as well as the patients, families, and physicians participating in the DPV initiative (for list of participating centers, see Rohrer et al ).…”

Section: Acknowledgementsmentioning

confidence: 99%

Markedly reduced rate of diabetic ketoacidosis at onset of type 1 diabetes in relatives screened for islet autoantibodies

Winkler¹,

Schober

Ziegler³

et al. 2011

Pediatr Diabetes

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Down’s syndrome in diabetic patients aged <20 years: an analysis of metabolic status, glycaemic control and autoimmunity in comparison with type 1 diabetes

Cited by 39 publications

References 13 publications

Early-Onset, Coexisting Autoimmunity and Decreased HLA-Mediated Susceptibility Are the Characteristics of Diabetes in Down Syndrome

Early-Onset, Coexisting Autoimmunity and Decreased HLA-Mediated Susceptibility Are the Characteristics of Diabetes in Down Syndrome

The neuronal and endocrine roles of RCAN1 in health and disease

Markedly reduced rate of diabetic ketoacidosis at onset of type 1 diabetes in relatives screened for islet autoantibodies

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