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ABSTRACT: OBJECTIVES: Although a diagnosis of coeliac disease (CD) may be confronting to children with type 1 diabetes and their families, we hypothesize that children with CD have lower urinary albumin excretion, a marker of renal dysfunction. RESEARCH DESIGN: Twenty-four children with type 1 diabetes and biopsy-proven CD, on a gluten-free diet for at least 1 yr, were recruited from a single paediatric diabetes clinic alongside 55 children with type 1 diabetes but without CD matched for age, gender, duration of diabetes, and glycaemic control. RESULTS: Despite comparable diabetes exposure, glycaemic control and nutritional status, children with type 1 diabetes and CD had a lower urinary albumin creatinine ratio than in diabetic subjects without CD (0.9 ± 0.3 mg/mmol vs. 1.6 ± 0.3 mg/mmol; p = 0.01). Participants with CD also showed slower progression in albuminuria over 5-yr of follow-up while a small but significant increase was observed in the children with diabetes alone (1.6 ± 0.3 mg/mmol; follow-up 2.4 ± 0.5 mg/mmol; p = 0.02). CONCLUSIONS: As urinary albumin excretion is continuously associated with the risk of kidney disease, it is possible to speculate that CD or its management confers a degree of renoprotection. Larger studies are required to test this hypothesis.
Pediatric Diabetes 06/2013; · 2.16 Impact Factor
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ABSTRACT: Few qualitative studies have examined the views of adolescents with type 1 diabetes mellitus (T1DM) regarding psychosocial programme development and content. We conducted focus groups with 13 adolescents with T1DM to explore stressors and gain feedback on adapting a generic coping skills programme. The following prevalent stressors were identified: parental/adolescent conflict, balancing self-management and daily life, and health concerns. Prevalent views on programme adaptation included enhancing social support and adding diabetes-specific information and skills. Based on these data, the programme was adapted to address stressors and support self-management, thus better meeting the needs of, and appeal to, adolescents with T1DM.
Journal of Health Psychology 08/2011; 17(3):313-23. · 1.22 Impact Factor
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ABSTRACT: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) were recently shown to confer a pituitary adenoma predisposition in patients with familial isolated pituitary adenomas (FIPA). We report a large Samoan FIPA kindred from Australia/New Zealand with an R271W mutation that was associated with aggressive pituitary tumors.
Case series with germline screening of AIP and haplotype analyses among R271W families.
This previously unreported kindred consisted of three affected individuals that either presented with or had first symptoms of a pituitary macroadenoma in late childhood or adolescence. The index case, a 15-year-old male with incipient gigantism and his maternal aunt, had somatotropinomas, and the maternal uncle of the index case had a prolactinoma. All tumors were large (15, 40, and 60 mm maximum diameter) and two required transcranial surgery and radiotherapy. All three affected subjects and ten other unaffected relatives were found to be positive for a germline R271W AIP mutation. Comparison of the single nucleotide polymorphism patterns among this family and two previously reported European FIPA families with the same R271W mutation demonstrated no common ancestry.
This kindred exemplifies the aggressive features of pituitary adenomas associated with AIP mutations, while genetic analyses among three R271W FIPA families indicate that R271W represents a mutational hotspot that should be studied further in functional studies.
European Journal of Endocrinology 09/2009; 161(5):799-804. · 3.42 Impact Factor
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ABSTRACT: Fair skin pigmentation has been associated with a higher risk of type 1 diabetes mellitus (T1DM). The aim is to compare children with T1DM directly to a sibling in relation to their skin pigmentation in sun-exposed and unexposed sites, past sun exposure and methylation of the VDR gene promoter. The sample consisted of children with T1DM attending a diabetes outpatient clinic and siblings (total n=42). Cutaneous melanin density was estimated using a spectrophotometer. Parental report on past sun exposure was obtained. DNA methylation analysis of the VDR gene promoter was conducted. Matched data analysis was performed comparing each case directly to their sibling. Cases were significantly more likely to have lighter skin pigmentation at the upper arm (AOR 0.69 [95% CI: 0.52, 0.90]; P=0.01). Low infant sun exposure was imprecisely associated with a two-fold increase in T1DM risk (AOR 2.43 [95% CI: 0.91, 6.51]; P=0.08 for under 1 h of winter sun exposure per leisure day). The VDR gene promoter was completely unmethylated in both cases and siblings. The previously demonstrated association between light skin pigmentation and T1DM risk was evident even in this comparison across sibling pairs. Further work on past UVR exposure and related factors such as skin pigmentation is required.
Photochemistry and Photobiology 05/2009; 85(5):1267-70. · 2.41 Impact Factor
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ABSTRACT: Despite a high incidence of nocturnal hypoglycemia documented by the use of continuous glucose monitoring (CGM), there are no reports in the literature of nocturnal hypoglycemic seizures while a patient is wearing a CGM device.
In this article, we describe four such cases and assess the duration of nocturnal hypoglycemia before the seizure.
In the cases where patients had a nocturnal hypoglycemic seizure while wearing a CGM device, sensor hypoglycemia (<60 mg/dl) was documented on the CGM record for 2.25-4 h before seizure activity.
Even with a subcutaneous glucose lag of 18 min when compared with blood glucose measurements, glucose sensors have time to provide clinically meaningful alarms. Current nocturnal hypoglycemic alarms need to be improved, however, since patients can sleep through the current alarm systems.
Diabetes care 08/2008; 31(11):2110-2. · 8.09 Impact Factor
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ABSTRACT: Vitamin D receptor (VDR) gene polymorphisms may be associated with risk of developing type 1 diabetes mellitus (T1DM), but reports have been conflicting. The authors reexamined population-based case-control studies on selected VDR polymorphisms and T1DM to investigate whether variation in reported associations could be partly explained by differences in ambient winter ultraviolet radiation (UVR) levels. A meta-analysis of 16 studies from 19 regions (midwinter UVR range, 1.0-133.8 mW/m(2)) was conducted. The association between winter UVR and the log odds ratio was examined by meta-regression. For FokI and BsmI, the log odds ratio for the association between the F and B alleles and T1DM increased as regional winter UVR increased (p = 0.039 and p = 0.036, respectively). The association between the TaqI T allele and T1DM was reduced with increasing winter UVR (p = 0.040). Low winter regional UVR was associated with a higher proportion of controls carrying BsmI and ApaI uppercase alleles and a lower proportion of controls carrying TaqI uppercase alleles. These findings strengthen the case that VDR variants are involved in the etiology of T1DM. They suggest that environmental UVR may influence the association between VDR genotype and T1DM risk. Further work on VDR polymorphisms and T1DM should concomitantly examine the roles of past UVR exposure and vitamin D status.
American journal of epidemiology 07/2008; 168(4):358-65. · 5.59 Impact Factor
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Fergus Cameron
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ABSTRACT: During adolescence major hormonal, neuro-maturational, emotional and psychosocial changes occur within a relatively short time interval. The additional burden of living with a chronic disease such as type 1 diabetes can further add to the potential for instability.
This article discusses the specific management issues facing diabetic patients and their doctors in the teenage years.
Deteriorating metabolic control of diabetes during adolescence is a relatively common event. Increasing insulin resistance during adolescence is usual for both sexes. Adolescents may increasingly resent parental supervision of their diabetes care, and also rebel against the restrictive nature of diabetes treatment regimens with acceptance of medical advice and adherence to treatment regimens diminishing. Diabetes may interfere with conformity to a peer group and increase the likelihood of risk taking behaviours and fluctuating glycaemia may increase the likelihood of an adverse outcome. Physical risk taking, binge drinking, recreational drug use and unplanned sexual activity all present particular problems for adolescents with diabetes. Subthreshold eating disorders are more common in adolescent females with type 1 diabetes than in their nondiabetic peers. The most helpful thing for a health care professional to do is to maintain a mutually respectful relationship with an adolescent who is struggling to control their diabetes, encourage family support, and praise.
Australian family physician 07/2006; 35(6):386-90. · 0.73 Impact Factor
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Diabetes Care 12/2005; 28(11):2771-3. · 8.09 Impact Factor
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ABSTRACT: Vitamin K is essential for development of normal bone density and achieving adequate peak bone mass in childhood and is thought to be important in preventing the development of osteoporosis in later life. Warfarin, a vitamin K antagonist, is being used with greater frequency in children. The long-term effect of warfarin on bone density of children is not known. We performed a case control study survey of bone density in children on long-term warfarin (n=17, average duration of warfarin treatment 8.2 y) compared with randomly selected controls (n=321). There was a marked reduction in bone mineral apparent density of lumbar spine between patients and controls [patients 0.10 g/cm3; 95% confidence interval (CI), 0.93-0.11 g/cm3, controls 0.12 g/cm3; 95% CI, 0.11-0.12 g/cm3, p<0.001). The lumbar spine areal bone mineral density Z-score of patients was reduced compared with controls [patients, -1.96 (95% CI, -2.52 to -1.40). This difference persisted after adjustment for age and body size. The etiology for the reduced bone density is likely to be multifactorial, however, screening of children on long-term warfarin for reduced bone density should be considered.
Pediatric Research 04/2005; 57(4):578-81. · 2.70 Impact Factor
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ABSTRACT: Children with severe hemophilia are at risk for reduced bone mineral density (BMD) because of reduced weight-bearing exercise and hepatitis C infection. Reduced bone density in childhood is a risk factor for osteoporosis in later life.
We performed a cross-sectional survey of bone density among 19 children with severe hemophilia, at the Royal Children's Hospital. Results were correlated with findings of blinded objective evaluations of the joints of the lower limb and with hepatitis C status.
The mean lumbar bone mineral apparent density for patients was reduced (0.102 g/cm3), compared with that for control subjects (0.113 g/cm3). The mean areal BMD z score was -0.92, which was significantly reduced, compared with that for control subjects. The difference in bone density was independent of body size. There was a statistically significant relationship between the lumbar BMD z scores and the maximal single joint evaluation scores, but there was no difference based on hepatitis C status.
Our results suggest that children with severe hemophilia have reduced BMD. Patients at risk are those with signs of hemophilic arthropathy. Because osteoporosis may complicate the future treatment of patients with hemophilia, screening of young patients for reduced bone density is recommended.
PEDIATRICS 09/2004; 114(2):e177-81. · 4.47 Impact Factor
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ABSTRACT: Neonatal diabetes mellitus (hyperglycaemia within the first month of life, with an insulin requirement) may be transient or permanent. Management is complex, due to lack of subcutaneous fat and the need for small doses of insulin, and may be complicated by additional medical problems. Three cases are presented, the first of which was treated with conventional insulin therapy. The latter two were successfully treated with subcutaneous insulin pump therapy. We present suggested guidelines for treatment of neonatal diabetes, using this novel approach to management.
Journal of Paediatrics and Child Health 41(9-10):522-6. · 1.28 Impact Factor
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ABSTRACT: The interpretation of bone density measurement in children is difficult due to a number of factors including rapid change in body size and uncertain clinical significance of bone density in children. This study asked two questions. (1) Is there a preferred bone density measurement site or type for fracture risk in children? (2) What is the best way to interpret bone density in children? This population-based case control study included 321 upper limb fracture cases and 321 class- and sex- matched randomly selected controls. Bone density at the hip, spine, and total body (including the arm) was measured by a Hologic QDR2000 densitometer (Waltham, MA) and examined as bone area (BA), bone mineral content (BMC), bone mineral density (BMD), bone mineral apparent density (BMAD), and BMC/lean mass (BMCLM). The only dual-energy X-ray absorptiometry (DXA) variables that were consistently associated with fracture risk in both boys and girls were spine BMD and BMAD for total upper limb fractures, and spine and hip BMAD for wrist and forearm fractures. No significant associations were observed for BA and BMCLM and inconsistent associations for BMC and other BMD sites. Five-yr fracture risk varied from 15-24% depending on site and gender in a child with a Z-score of -3. In the controls, all DXA variables were associated with age, height, and weight, but the weakest associations were with BMAD. In conclusion, in this study the spine BMAD had the strongest and most consistent association with upper limb fracture risk in children. The associations with age and body size imply that age specific Z-scores will be the most convenient for interpretation of DXA measures in children. Five-yr wrist and forearm fracture risk has potential as a clinical endpoint of immediate relevance.
Journal of Clinical Densitometry 9(2):202-9. · 1.29 Impact Factor
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Paul Q Thomas,
Mehul T Dattani,
Joshua M Brickman,
David McNay,
Garry Warne,
Margaret Zacharin, Fergus Cameron,
Jane Hurst,
Katie Woods,
David Dunger,
Richard Stanhope,
Susan Forrest,
Iain C A F Robinson,
Rosa S P Beddington
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ABSTRACT: We have previously shown that familial septo-optic dysplasia (SOD), a syndromic form of congenital hypopituitarism involving optic nerve hypoplasia and agenesis of midline brain structures, is associated with homozygosity for an inactivating mutation in the homeobox gene HESX1 / Hesx1 in man and mouse. However, as most SOD/congenital hypopituitarism occurs sporadically, the possible contribution of HESX1 mutations to the aetiology of these cases is presently unclear. Interestingly, a small proportion of mice heterozygous for the Hesx1 null allele show a milder SOD phenocopy, implying that heterozygous mutations in human HESX1 could underlie some cases of congenital pituitary hypoplasia with or without midline defects. Accordingly, we have now scanned for HESX1 mutations in 228 patients with a broad spectrum of congenital pituitary defects, ranging in severity from isolated growth hormone deficiency to SOD with panhypopituitarism. Three different heterozygous missense mutations were detected in individuals with relatively mild pituitary hypoplasia or SOD, which display incomplete penetrance and variable phenotype amongst heterozygous family members. Gel shift analysis of the HESX1-S170L mutant protein, which is encoded by the C509T mutated allele, indicated that a significant reduction in relative DNA binding activity results from this mutation. Segregation analysis of a haplotype spanning 6.1 cM, which contains the HESX1 locus, indicated that only one HESX1 mutation was present in the families containing the C509T and A541G mutations. These results demonstrate that some sporadic cases of the more common mild forms of pituitary hypoplasia have a genetic basis, resulting from heterozygous mutation of the HESX1 gene.
