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Biomedical subjects

J P Shield

Publications and source records attributed to J P Shield.

At least 37 records · Page 2Linked to original sources
PubMed1997

A case-control study of environmental factors associated with diabetes in the under 5s.

In 1992 a national case-control study was conducted through the British Paediatric Association Surveillance Unit (BPASU) framework to evaluate both the incidence of IDDM in children under 5 in that year and the effects of various putative trigger factors in the disease pathogenesis. A total of 218 sets of matched case-control questionnaire data established that paternal IDDM (odds ratio (OR) = 16.11, 95% confidence interval (CI) 1.94-133.7, p < = 0.001) is independently associated with increased risk, and higher birth order (OR = 0.64, CI 0.44-0.94, p = 0.021) and paternal age greater than 25 years (age 25-39 OR = 0.52, CI 0.30-0.89; age 40 + OR = 0.23, CI 0.08-0.67, p = 0.009) with decreased risk of diabetes. Other factors previously implicated in the disease pathogenesis (birthweight, parental socio-economic status, infant feeding, and immunization record) showed no significant independent association with disease development.

Adult↗
PubMed1997

Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. The IMDIAB Group.

The IDDM2 type 1 diabetes susceptibility locus was mapped to and identified as allelic variation at the insulin gene (INS) VNTR regulatory polymorphism. In Caucasians, INS VNTR alleles divide into two discrete size classes. Class I alleles (26 to 63 repeats) predispose in a recessive way to type 1 diabetes, while class III alleles (140 to more than 200 repeats) are dominantly protective. The protective effect may be explained by higher levels of class III VNTR-associated INS mRNA in thymus such that elevated levels of preproinsulin protein enhance immune tolerance to preproinsulin, a key autoantigen in type 1 diabetes pathogenesis. The mode of action of IDDM2 is complicated, however, by parent-of-origin effects and possible allelic heterogeneity within the two defined allele classes. We have now analysed transmission of specific VNTR alleles in 1,316 families and demonstrate that a particular class I allele does not predispose to disease when paternally inherited, suggestive of polymorphic imprinting. But this paternal effect is observed only when the father's untransmitted allele is a class III. This allelic interaction is reminiscent of epigenetic phenomena observed in plants (for example, paramutation; ref. 17) and in yeast (for example, trans-inactivation; ref. 18). If untransmitted chromosomes can have functional effects on the biological properties of transmitted chromosomes, the implications for human genetics and disease are potentially considerable.

Alleles↗
PubMed1997

Audit of diabetes care by caseload.

OBJECTIVE: To investigate the relationship between clinic provision, consultant and nursing caseload, and processes and outcomes of diabetes care in children. DESIGN: Retrospective audit in the South Western region of England of 801 children and young people with diabetes; 701 were seen in a designated clinic. Seven of 21 consultants fulfilled the British Paediatric Association (BPA) criteria for a specialist in childhood diabetes. Seventeen nurses provided specialist care. MAIN OUTCOME MEASURES: Glycated haemoglobin, admissions to hospital clinic attendance rates, contacts with a dietitian, measurements of height and weight, and screening rates for hypertension, microalbuminuria, and retinopathy. RESULTS: Children under the care of 'non-specialists' had higher admission rates to hospital with all diabetes related problems and for hypoglycaemia and lower screening rates for microalbuminuria than those under 'specialists'. Children under the care of the two tertiary hospital consultants and lowest glycated haemoglobin results, spent least time in hospital at diagnosis, were most likely to have their heights and weights plotted, and to be screened for microalbuminuria and retinopathy, had higher admission rates, lower clinic attendance rates, and fewer dietitian consultations. Higher nursing caseloads were associated with longer periods of admission at diagnosis, better clinic attendance rates, reduced rates of admission after diagnosis, and less likelihood of having blood pressure measured and being screened for microalbuminuria. Children attending general paediatric clinics were less likely to be seen by a dietitian and to have their height and weight plotted. CONCLUSIONS: The results are consistent with the recommendation of a BPA working party in 1990 that children with diabetes should be cared for by specialist paediatricians with a caseload of more than 40 children, and that children should be seen in a designated diabetic clinic.

Albuminuria↗
PubMed1997

Aetiopathology and genetic basis of neonatal diabetes.

A British Paediatric Association Surveillance Unit* study of neonatal diabetes determined a national incidence of 1 in 400,000 live births. Additional cases of transient neonatal diabetes were collected retrospectively. Most cases were of low birthweight at term: none had evidence of an autoimmune aetiopathogenesis. The median requirement for exogenous insulin treatment was three months. A significant number of cases developed type 2 diabetes in later life. Three of the 11 cases were found to have paternal uniparental isodisomy of chromosome 6. A further patient carried an unbalanced duplication of 6q 22-23, inherited from the father, which localised a potentially imprinted gene for diabetes to this region. The fact that low birthweight predisposes to type 2 diabetes in later life is well established, but a genetic defect that may relate both to intrauterine growth failure and the development of type 2 diabetes in later life has now been identified.

Aneuploidy↗
PubMed1996

Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23.

Transient neonatal diabetes mellitus (TNDM) is a rare form of childhood diabetes which usually resolves in the first 6 months of life but which predisposes to type 2 diabetes of adult onset. We recently reported paternal uniparental isodisomy of chromosome 6 (UPD6) in two children with TNDM and proposed that there may be an imprinted gene important in the aetiology of diabetes on chromosome 6. We now describe two unrelated families which independently suggest that the gene is imprinted, is paternally expressed and maps to 6q22-q23. One family has a duplication while the other, with familial TNDM, shows linkage to a marker in this region.

Adult↗
PubMed1995

The genetic contribution to disease pathogenesis in childhood diabetes is greatest in the very young.

Epidemiological data are presented to support the hypothesis that the genetic contribution to disease pathogenesis in childhood onset diabetes is greatest in those presenting at a very early age. Analysis of family data from two national surveys of childhood onset Type 1 (insulin-dependent) diabetes (1988 in under 15s: 1992 in under 5s) reveals that children developing diabetes between the ages 1 and 2 years are significantly more likely to have a parental history of Type 1 diabetes than older children. It is proposed that compared with other children, those with very early onset diabetes have either a greater genetic and smaller environmental contribution to the initiation of the autoimmune process leading to Type 1 diabetes: or inherited HLA alleles associated with a more fulminant autoimmune mediated Beta-cell destruction once the process is initiated.

Adolescent↗
PubMed1995

Are frozen urine samples acceptable for estimating albumin excretion in research?

Timed urine collections from diabetic children and adolescents were assessed for urinary albumin excretion rate (microgram min-1) before and after freezing at -20 degrees C. Freezing had the effect of changing the estimation such that frozen values could differ from that of the fresh, by as much as one half to twice as much. The variation depended on the concentration defining the initial albumin excretion rate but was not influenced by the length of storage when frozen. We conclude that researchers should be aware that freezing and storing of urine samples prior to albumin concentration assessments can affect the absolute values obtained. It would appear more appropriate to analyse samples prior to freezing to be certain of obtaining true prevalence estimates of microalbuminuria.

Adolescent↗
PubMed1995

Transient neonatal diabetes and later onset diabetes: a case of inherited insulin resistance.

A 13 year old girl who had had transient neonatal diabetes developed permanent diabetes. She had raised fasting insulin concentrations suggestive of insulin resistance with a suboptimal insulin response to glucose loading. Both her mother and sister had profound insulin resistance; neither had clinical diabetes. This is the first time inherited insulin resistance has been implicated in the pathogenesis of permanent diabetes developing after transient neonatal diabetes.

Adolescent↗
PubMed1995

Dermatoglyphics, fetal growth, and insulin dependent diabetes in children under 5 years.

Examination of dermatoglyphic patterns in 112 diabetic children under 5 years and matched controls found no difference between the groups. Either those developing diabetes under 5 do not experience the same genetic and environmental conditions that influence its development in later life or the dermatoglyphic abnormalities described in later onset insulin dependent diabetes mellitus reflect the vast number of pattern formations available for study, which has inevitably led to some statistically significant associations.

Age Factors↗
PubMed1995

Screening for diabetic microalbuminuria in routine clinical care: which method?

The measurement of albumin/creatinine ratios and simple albumin concentrations in early morning urine specimens were evaluated to establish which was the best screening test for those likely to have microalbuminuria by the reference standard analysis of timed overnight urine specimens. The measurement of an albumin/creatinine ratio with a cut off of > or = 2.0 mg/mmol was found to be suitable with a specificity of 93% and sensitivity of 97%.

Adolescent↗
PubMed1995

Foot pathology in insulin dependent diabetes.

OBJECTIVES: Foot pathology is a major source of morbidity in adults with diabetes. The aim of this study was to determine if children with insulin dependent diabetes have an increased incidence of foot pathology compared with non-diabetic children. DESIGN: Questionnaire, clinical examination, and biomechanical assessment. SUBJECTS: 67 diabetic children and a comparison group matched for age, sex, and social class. RESULTS: We found significantly more foot pathology in the children with diabetes (52 children) than the comparison group (28 children); with more biomechanical anomalies (58 children with diabetes, 34 comparison group); and a higher incidence of abnormal skin conditions (53 children with diabetes, 27 comparison group). Forty two children with diabetes had received foot health education compared with 27 in the comparison group, but the study revealed ignorance and misconceptions among the diabetic group, and previous contact with a podiatrist was minimal. CONCLUSIONS: The survey suggests that children with diabetes have an increased incidence of foot pathology justifying greater input of podiatric care in the hope of preventing later problems.

Adolescent↗
PubMed1995

Is microalbuminuria progressive?

In 1990, 81 children and adolescents with insulin dependent diabetes were studied for early signs of diabetic nephropathy. Nine patients were identified as having microalbuminuria (incipient nephropathy). These subjects were re-examined three years later. In five of these cases, the second examination revealed normal albumin excretion; in three of the four cases in whom microalbuminuria persisted, the rate of albumin excretion had decreased. The general improvement in albumin excretion rates in the initially microalbuminuric group could not be explained by improved glycaemic control nor interventional drug treatment. The lack of progression in this microalbuminuric group from the original prevalence study suggests that this method of identifying early nephropathy in childhood may not be valid or that the progression of incipient nephropathy in childhood is more irregular or slower than in later life.

Adolescent↗
PubMed1995

Urinary heparan sulphate proteoglycan excretion is abnormal in insulin dependent diabetes.

Urinary excretion of heparan sulphate proteoglycan (HSPG), the main anionic component of the glomerular basement membrane (GBM), was estimated in 30 adolescents and young adults with insulin dependent diabetes (IDDM), 10 with microalbuminuria and 20 sex matched, diabetic controls of similar age without evidence of microalbuminuria. A further 10 non-diabetic control subjects were also examined. Both groups of patients with diabetes had significantly elevated excretion of HSPG when compared to normal individuals. There was no difference in HSPG excretion between diabetic subjects with and without microalbuminuria.

Adolescent↗
PubMed1994

Fructosamine and glycated haemoglobin in the assessment of long term glycaemic control in diabetes.

Fructosamine and glycated haemoglobin were measured simultaneously in 147 children with diabetes. If glycated haemoglobin is considered as the 'gold standard' for long term glycaemic control, then fructosamine is a poor indicator of actual glycated haemoglobin values, with wide 95% confidence (fiducial) limits. This shows that it is impossible to accurately predict glycated haemoglobin concentrations and therefore, by implication, longer term glycaemic control, from measurements of fructosamine. As the major studies on the prevention of microvascular complications in diabetes have used glycated haemoglobin levels to assess glycaemic control, it is suggested that this measurement should be used in all children with diabetes in preference to the measurement of fructosamine.

Adolescent↗