Longitudinal relation between limited joint mobility, height, insulin-like growth factor 1 levels, and risk of developing microalbuminuria: the Oxford Regional Prospective Study

Amin, Rakesh; Bahu, T Konopelska; Widmer, Barry; Dalton, R. Neil; Dunger, David B.

doi:10.1136/adc.2004.067272

Cited by 46 publications

(45 citation statements)

References 37 publications

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“…Those with mild LJM had four times the excess below the 25th percentile (72%), with no important difference for those with moderate to severe limitation (77% below the 25th percentile) (12). The Oxford study also found an association of LJM with growth limitation (13).…”

Section: Effects On Growthmentioning

confidence: 52%

“…Although cross-sectional studies suggested that duration of diabetes was the most important variable in the appearance of LJM, when the time of development of joint changes could be determined, attained age was of greater importance (12), an observation confirmed later by the large longitudinal Oxford Regional Prospective Study (13). The progression from detection of mild limitation to moderate or severe changes varied from 3 months to 4 years, with a mean of 2 years.…”

Section: Natural Historymentioning

confidence: 79%

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Limited Joint Mobility in Childhood Diabetes: Discovery, Description, and Decline

Rosenbloom

2013

The Journal of Clinical Endocrinology & Metabolism

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Context:The discovery of limited joint mobility (LJM) as the earliest clinically apparent complication of diabetes in children and adolescents nearly 40 years ago provided insights into the mechanism of diabetes complications.Results: LJM, due to periarticular connective tissue thickening and stiffness, varied from single joint involvement bilaterally to obvious hand deformity and limitation of movement of the spine. Thick, tight, waxy skin was apparent with more severe changes; biopsy indicated thickening of the dermis and epidermis with accumulation of collagen and loss of skin appendages. Substantial growth impairment was associated with all levels of LJM. Risk for microvascular disease over a 16-year period was actuarially increased nearly 4-fold by the presence of LJM. Long-term glycemic control influenced the onset of LJM; for every unit increase in average glycated hemoglobin from onset there was a 46% increase in the risk of LJM. Between 1976 -78 and 1998, the prevalence of LJM decreased from 30 to 7%, and the portion with moderate to severe changes decreased from 33 to 14%, with the disappearance of severely affected individuals. Furthermore, growth data markedly improved for those with and without LJM; 30% without LJM and 77% with LJM had been less than the 25th percentile for height, whereas the more contemporary group had 22% without LJM and 33% with LJM in this quartile. Conclusions:The elucidation of LJM as a novel and informative early complication of pediatric diabetes has provided insights into the evolution of the severe long-term complications of diabetes. The marked decrease in the frequency of LJM and statural deficit in children and youth with diabetes in the 20 years between the late 1970s and 1990s can be attributed to improved metabolic control of children and adolescents. The prevalence of LJM in a population may serve as a measure of quality of diabetes control. Discovery In the early 1970s, 3 older teenagers who had long-standing type 1 diabetes (T1D) were referred to the University of Florida pediatric diabetes clinic with striking limitation of extension and flexion of the interphalangeal (IP), metacarpophalangeal (MCP), wrist, elbow, and ankle joints-and in 2 of them, the spine-in association with short stature, thick, tight, waxy skin; delayed sexual maturation; and early microvascular complications (Figure 1) (1). Limitation appeared to be due to periarticular thickening and stiffness; radiography revealed normal joints and confirmed thickening of the periarticular tissues. These observations were followed by the description of milder manifestations in 28% of 229 campers with diabetes aged 7-18 years (2, 3). It is remarkable that these findings, particularly the more advanced changes, would not be described until more than half a century after the rescue and survival of children with T1D by insulin. DescriptionChanges were seen to begin in the MCP and proximal IP (PIP) joints of the little finger and extend radially; and in

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Section: Effects On Growthmentioning

confidence: 52%

Section: Natural Historymentioning

confidence: 79%

Limited Joint Mobility in Childhood Diabetes: Discovery, Description, and Decline

Rosenbloom

2013

The Journal of Clinical Endocrinology & Metabolism

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“…The Diabetes Control and Complications Trial showed that intensive glycaemic control in adolescents with type 1 diabetes mellitus is associated with a decreased risk of microvascular complications [1], and there is increasing evidence that control of diabetes during the prepubertal and pubertal years can also have a marked impact on the risk of such complications [2,3]. As a result, current guidelines recommend that the aim of treatment in children and adolescents with type 1 diabetes should be to achieve nearnormal glycaemic control as early as possible in the course of the disease [4,5].…”

Section: Introductionmentioning

confidence: 99%

Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries

et al. 2008

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Aims/hypothesis To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome.Methods Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA 1c was measured centrally.Electronic supplementary material The online version of this article

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“…A study on type 2 diabetes progression suggests that TCF7L2 may be associated with insulin secretion [6]. [7]) and 7,596 geographically matched White control subjects (from the 1958 British Birth Cohort [8]) using TaqMan® 5′ nuclease assay (Applied Biosystems, Warrington, UK). All type 1 diabetic subjects were diagnosed under the age of 17 years.…”

mentioning

confidence: 99%

Analysis of the type 2 diabetes gene, TCF7L2, in 13,795 type 1 diabetes cases and control subjects

et al. 2006

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The two most common forms of diabetes that have been classified are type 1 diabetes and type 2 diabetes. Type 1 diabetes is characterised by infiltration of the pancreas by autoreactive T cells and autoimmune destruction of pancreatic beta cells, leading to a complete loss of insulin production, whereas type 2 diabetes is associated with the gradual increase of insulin insensitivity in tissues leading to hyperglycaemia and beta-cell failure. However, it has been suggested that type 1 diabetes and type 2 diabetes may share a common genetic aetiology [1]. For example, the accelerator hypothesis suggests that type 1 diabetes and type 2 diabetes are the same disease of hyperglycaemia-induced beta-cell damage but that type 1 diabetes has the added affect of autoimmunity [1].One way of testing the hypothesis that there is a common causal pathway between type 1 and type 2 diabetes is to analyse a type 2 diabetes gene with a large effect in a large type 1 diabetes sample. Until very recently [2], this has not been possible since no such locus has emerged from type 2 diabetes genetics studies. However, recently the transcription factor 7 like-2 (TCF7L2) gene region on chromosome 10q25.2 has been found to contribute substantially to the risk of type 2 diabetes with convincing statistical support (relative risk (RR) = 0.67; P = 2.1 × 10 −9 for the 0 allele of the microsatellite marker DG10S478) [2].This study was carried out in three different populations: Icelandic, Danish and WhiteAmerican. Two single nucleotide polymorphisms (SNPs) were also genotyped in this study: rs12255372 (G>T, minor allele frequency (MAF) 0.36 in control subjects) and rs7903146 (C>T, MAF = 0.28 in control subjects) rs12255372 was found to be in high linkage disequilibrium (LD) with DG10S478 (r 2 = 0.95 for the major G allele of the SNP with the 0 allele of the microsatellite marker). rs7903146 is in lower LD with the DG10S478 (r 2 = 0.75), for the minor allele (T) of this SNP they obtained odds ratios (ORs) of 1.41-1.71 in the three populations and P values from 0.0018 -1.6 × 10 −9 [2]. These results were independently replicated in 2,158 White UK type 2 diabetic subjects, 2,574 geographically matched White control subjects and 388 parent-offspring trios [3]. In this population it was found that the T allele of rs7903146 was the most associated with type 2 diabetes susceptibility (OR = 1.36, 95% CI = 1.24-1.48 and P = 3.6 × 10 −10 , MAF = 0.31 in control ) our study has 80% power to detect an effect with an OR as low as 1.12 at α = 10 −3 . This α level can be considered appropriate assuming that the prior information about common genetic and mechanistic pathways in type 2 diabetes and type 1 diabetes is true. Alternatively, assuming no prior information, on a genome wide level, α = 10 −8 , our study has 80% power to detect an effect with an OR as low as 1.19. In this sample set we obtained a MAF = 0.29 for the T alleles of both rs12255372 and rs7903146. The genotype distributions for both of these SNPs were consistent with Hardy-Weinberg equilibri...

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Longitudinal relation between limited joint mobility, height, insulin-like growth factor 1 levels, and risk of developing microalbuminuria: the Oxford Regional Prospective Study

Cited by 46 publications

References 37 publications

Limited Joint Mobility in Childhood Diabetes: Discovery, Description, and Decline

Limited Joint Mobility in Childhood Diabetes: Discovery, Description, and Decline

Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries

Analysis of the type 2 diabetes gene, TCF7L2, in 13,795 type 1 diabetes cases and control subjects

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