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C F Verge

Publications and source records attributed to C F Verge.

At least 19 recordsLinked to original sources

Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study.

AIMS: To determine whether the risk of hyponatraemia in children with gastroenteritis receiving intravenous (IV) fluids is decreased by the use of 0.9% saline. METHODS: A prospective randomised study was carried out in a tertiary paediatric hospital. A total of 102 children with gastroenteritis were randomised to receive either 0.9% saline + 2.5% dextrose (NS) or 0.45% saline + 2.5% dextrose (N/2) at a rate determined by their treating physician according to hospital guidelines and clinical judgement. Plasma electrolytes, osmolality, and plasma glucose were measured before (T(0)) and 4 hours after (T(4)) starting IV fluids, and subsequently if clinically indicated. Electrolytes and osmolality were measured in urine samples. Results were analysed according to whether children were hyponatraemic (plasma sodium <135 mmol/l) or normonatraemic at T(0). RESULTS: At T(0), mean (SD) plasma sodium was 135 (3.3) mmol/l (range 124-142), with 37/102 (36%) hyponatraemic. At T(4), mean plasma sodium in children receiving N/2 remained unchanged in those initially hyponatraemic (n = 16), but fell 2.3 (2.2) mmol/l in the normonatraemic group. In contrast, among children receiving NS, mean plasma sodium was 2.4 (2.0) mmol/l higher in those hyponatraemic at baseline (n = 21) and unchanged in the initially normonatraemic children. In 16 children who were still receiving IV fluids at 24 hours, 3/8 receiving N/2 were hyponatraemic compared with 0/8 receiving NS. No child became hypernatraemic. CONCLUSIONS: In gastroenteritis treated with intravenous fluids, normal saline is preferable to hypotonic saline because it protects against hyponatraemia without causing hypernatraemia.

Anthropometry↗

The re-emerging burden of rickets: a decade of experience from Sydney.

AIM: To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. METHODS: Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. RESULTS: A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. CONCLUSIONS: This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies.

Child, Preschool↗

Prevalence of diabetes complications 6 years after diagnosis in an incident cohort of childhood diabetes.

AIMS: To examine the prevalence of early diabetes complications 6 years after diagnosis of diabetes. The hypothesis that initial contact with a multidisciplinary team would be associated with a reduced risk of microvascular complications was tested in this cohort. METHODS: Participants were recruited from an incident cohort of children aged < 15 years diagnosed between 1990 and 1992 in NSW, Australia. Initial management at a teaching hospital was documented at case notification. At 6 years, health care questionnaires and complications were assessed: retinopathy by 7-field stereoscopic retinal photography and elevated albumin excretion rate (AER) defined as the median of three overnight urine collections > or = 7.5 microg/min. Case attainment was 58% (209/361) with participants younger than non-participants and more likely living in an urban than rural location. RESULTS: Retinopathy was present in 24%, median AER > or = 7.5 microg/min in 18%, and median AER > or = 20 microg/min in 2%. In multivariate analysis, initial management at a teaching hospital or consultation with all three allied health professionals combined with pubertal staging and cholesterol or HbA1c were all determinants of risk for retinopathy. CONCLUSIONS: Early retinopathy and elevated AER are common in children 6 years after diagnosis. Initial allied health contact and management at a teaching hospital were associated with a reduced risk of microvascular complications in this cohort.

Adolescent↗

Hyperinsulinism and overgrowth without obesity.

We report a 5 year old girl with postnatal overgrowth (height velocity >97th centile), hyperinsulinaemia, and increased insulin-like growth factor 1 for age, without evidence of bioactive or immunoreactive growth hormone excess or pituitary abnormality. Although her overgrowth may be a result of hyperinsulinism, her serum contains a factor (neither insulin nor IGF-1) which is able to stimulate the proliferation of lymphocyte precursors, and this could also account for the overgrowth. Over the course of two years observation she has developed acanthosis nigricans and diabetes mellitus.

Acromegaly↗

Complete molecular scanning of the human Fas gene: mutational analysis and linkage studies in families with type I diabetes mellitus. The Danish Study Group of Diabetes in Childhood and The Danish IDDM Epidemiology and Genetics Group.

AIMS/HYPOTHESIS: The human Fas gene (FAS) on chromosome 10q24.1 encoding a cell surface receptor involved in apoptosis was evaluated as a candidate susceptibility gene for Type I (insulin-dependent) diabetes mellitus. Apoptosis mediated by Fas is important in maintaining peripheral self-tolerance and in down-regulating the immune response and could have a role in immune-mediated beta-cell destruction. METHODS: We did a molecular scan of the entire human FAS (promoter, exons 1-9 including exon-intron boundaries and the 3'UTR) using single strand conformational polymorphism-heteroduplex analysis. RESULTS: We identified 15 mutations, of which 11 are new. Of these a g-1194A-->T and a g-295Ains give rise to alterations of transcription-factor-binding consensus sequences for c-Myb, SP-1 and NF-kappa B, respectively. A total of 1068 people from a Danish family collection comprising 138 Type I diabetic sib-pair families (289 affected and 121 unaffected offspring) and 103 Type I diabetic parent-offspring multiplex families (103 affected and 112 unaffected offspring) were typed for the three most frequent polymorphisms with high heterozygosity indices and for a FAS microsatellite. Haplotypes were established and data analysed using the extended transmission disequilibrium test, ETDT. CONCLUSION/INTERPRETATION: We found no overall evidence for linkage of the FAS polymorphisms to Type I diabetes. We conclude that it is unlikely that the Fas gene does contribute to genetic susceptibility for Type I diabetes.

Adult↗

True hermaphroditism.

OBJECTIVE: True hermaphroditism is a rare cause of atypical genitalia which presents significant diagnostic and management challenges. We present the clinical and laboratory findings and management of four patients with true hermaphroditism. METHODOLOGY: Case studies from a teaching hospital and literature review. RESULTS: All four patients had atypical genitalia identified at birth. All had a palpable gonad, only one of which was palpable at birth. Three patients were 46XX (SRY -ve) and one 46XY (SRY +ve). Three patients were raised as females (two 46XX and one 46XY) and one as a male. All four patients were found to have an ovotestis present. CONCLUSIONS: The management of true hermaphroditism is controversial and requires a multidisciplinary approach. It has many implications for both the parent and child. We discuss the issues involved for the patients and their parents.

Disorders of Sex Development↗

Evidence for oligogenic inheritance of type 1 diabetes in a large Bedouin Arab family.

Based on a genomic search for linkage, a locus contributing to type 1 diabetes in a large Bedouin Arab family (19 affected relatives) maps to the long arm of chromosome 10 (10q25; nonparametric linkage = 4.99; P = 0.00004). All affected relatives carry one or two high-risk HLA-DR3 haplotypes that are rarely found in other family members. One chromosome 10 haplotype, the B haplotype, was transmitted from a heterozygous parent to 13 of 13 affected offspring compared to 10 of 23 unaffected siblings. Recombination events occurring on this haplotype place the susceptibility locus in an 8-cM interval between markers D10S1750 and D10S1773. Two adjacent markers, D10S592 and D10S554, showed evidence of linkage disequilibrium with the disease locus. A 273-bp allele at D10S592 was transmitted to 8 of 10 affected offspring compared to 3 of 14 unaffected siblings, and a 151-bp allele at D10S554 was transmitted to 15 of 15 affected offspring compared with 10 of 24 unaffected siblings. D10S554 and D10S592 and the closest flanking markers are contained in a 1,240-kb yeast artificial chromosome, a region small enough to proceed with positional cloning.

Arabs↗

Combined use of autoantibodies (IA-2 autoantibody, GAD autoantibody, insulin autoantibody, cytoplasmic islet cell antibodies) in type 1 diabetes: Combinatorial Islet Autoantibody Workshop.

The aim of this workshop was to assess the ability of individual autoantibody (ab) assays and their use in combination to discriminate between type 1 diabetic and control sera. Coded aliquots of sera were measured in a total of 119 assays by 49 participating laboratories in 17 countries. The sera were from 51 patients with new onset type 1 diabetes and 101 healthy control subjects with no family history of diabetes. In the final analysis, data on diabetic sera were restricted to 43 subjects younger than age 30 years. The laboratories were asked to report results for these sera using their currently available anti-islet autoantibody assays. In addition, they were asked to combine information from their assays to classify sera as having high, moderate, or low probability of originating from a patient with type 1 diabetes. Actual strategies for combining assays were determined by each laboratory. There were no significant differences in sensitivity among 19 radioimmunoassays (RIAs) for IA-2 autoantibodies (cytoplasmic islet cell antibody [ICA] 512) using different constructs that included the intracellular portion of the molecule (mean sensitivity 73%). However, an enzyme-linked immunosorbent assay (ELISA) using the extracellular portion of the IA-2 molecule did not discriminate between diabetic and control sera. Among GAD autoantibody assays that achieved sensitivity >70%, 26 were RIAs and one was an ELISA. When the sera were ranked according to their autoantibody levels, the concordance for insulin autoantibodies (IAAs) in different laboratories was markedly less than for IA-2ab and GADab. Using a combination of autoantibody assays, several laboratories achieved excellent discrimination between diabetic and control sera (sensitivity up to 80% with false-positive rate of 0%). A variety of strategies for combining information from different assays were successful (e.g., those including and excluding ICA), and no one strategy emerged as clearly superior. In conclusion, IA-2/ICA512 autoantibodies are a marker of type 1 diabetes and can be measured consistently by most assays. Several different strategies for combining assays achieved high sensitivity with a low false-positive rate.

Adolescent↗

Evaluation of islet cell antigen (ICA) 512/IA-2 autoantibody radioassays using overlapping ICA512/IA-2 constructs.

Islet cell antigen (ICA) 512 also termed IA-2 is a novel autoantigen of type 1 diabetes, which has a tyrosine phosphatase-like domain. We have assessed autoantibody RIAs using a series of ICA512/IA-2 constructs to produce in vitro synthesized 35S-methionine-labeled proteins. Levels of ICA512/IA-2 (256-979, truncated aminoterminus) autoantibodies were strongly correlated with those of the full-length ICA512/IA-2 (1-979) autoantibodies (r = 0.96, P < 0.0001) and ICA512/IA-2 (687-979) autoantibodies (r = 0.98, P < 0.0001). RIAs using these 3 constructs had increased sensitivity relative to our initially reported ICA512 autoantibody RIA (amino acids 389-948, truncated carboxy- and aminoterminus). Only 2 of 38 sera examined in this study reacted with an aminoterminus ICA512/IA-2 (1-577) construct. The mean SD score (SD score = (index of unknown sample-mean index of controls)/SD of controls) using the ICA512/IA-2 (256-979) construct was significantly higher than the SD score obtained with other ICA512/IA-2 constructs (P < 0.001). Amongst patients with new-onset diabetes and prediabetic relatives, using RIAs for autoantibodies reacting with ICA512/IA-2 (256-979), insulin, and glutamic acid decarboxylase 65, 98% expressed one or more of these autoantibodies and 78% expressed two or more, whereas no control (n = 208) expressed more than a single autoantibody. A combined ICA512/IA-2 (256-979), glutamic acid decarboxylase 65 autoantibody RIA with differential autoantigen labeling (35S-methionine, 3H-leucine) has been developed that uses 96-well plate membrane filtration and Top Counter beta counting. Concordance between results of dual and single RIAs was greater than 90%. This simple combined autoantibody assay should facilitate large-scale autoantibody screening.

Adolescent↗

Evaluation of ICA512As in combination with other islet cell autoantibodies at the onset of IDDM.

OBJECTIVE: The ICA512 pancreatic islet autoantigen is a putative tyrosine phosphatase that is co-identified with the earlier described 40-kDa autoantigen. We report the frequency of autoantibodies to islet cell antigen 512 (ICA512As) in recent-onset IDDM and compare this with other islet cell autoantibodies, including those to GAD (GADAs), insulin (IAAs), and islet cell cytoplasm (ICAs) identified by immunofluorescence. RESEARCH DESIGN AND METHODS: Sera from 232 children aged between 9 months and 14.9 years collected within 14 days of diagnosis were tested for ICA512As by a radioimmunoprecipitation assay. The results were compared with previously reported data for GADAs (n = 232), IAAs (n = 167), and ICAs (n = 230). RESULTS: The frequency of a positive result for ICA512As in children with newly diagnosed IDDM was 60%. The frequency was greater for children with an age of onset between 5 and 10 years (69%) than for children aged < 5 years (49%) and aged between 10 and 15 years (56%). The frequencies for other autoantibody reactivities were 69% for GADAs, 65% for IAAs, and 70% for ICAs. A combination of positive results for ICA512As, GADAs, and IAAs gave a sensitivity for the diagnosis of childhood IDDM of 95%, which was not significantly increased by a positive result for ICAs (96%). CONCLUSIONS: Our results further establish that positivity in a combination of tests is more valuable for the prediction of IDDM than a result for any single autoantibody and that the age of the patient should be considered when selecting the combination of tests to use.

Adolescent↗

Number of autoantibodies (against insulin, GAD or ICA512/IA2) rather than particular autoantibody specificities determines risk of type I diabetes.

We previously evaluated radioassays for insulin autoantibodies (IAA), glutamate decarboxylase autoantibodies (GAA) and ICA512bdc autoantibodies (ICA512bdcAA) in the prediction of type I diabetes. Among first degree relatives, the five year risk of diabetes was 0% if no autoantibody was positive, 15% if only one was positive, 44% if two were positive and 100% if all three were positive. We measured IAA, GAA and ICA512bdcAA in 45 patients with new onset type I diabetes (sampled within 7 days of insulin therapy), 882 first degree relatives of patients with type I diabetes, and 217 control subjects. ICA512bdc is a construct of the ICA512/IA2 molecule (amino acid residues 256-979), including the intracellular domain. Based on receiver-operating characteristic plots, there was no significant difference between the three assays in their ability to discriminate between disease and control subjects. The upper limits of normal for the assays were determined as the 99th percentile of levels in the control subjects or higher. Using these cut-offs, 76% of new onset patients were positive for two or more autoantibodies, and 98% were positive for one or more. In comparison, none of 198 control subjects tested for all three assays were positive for more than one autoantibody. In relatives with a single autoantibody, or exactly two autoantibodies, there was no difference in diabetes-free survival according to which one of the autoantibodies was present (P = 0.70, logrank test), or which particular combination of autoantibodies was present (P = 0.56, logrank test) respectively. Our conclusions were as follows: the number of autoantibodies (counting IAA, GAA and ICA512bdcAA) is important in prediction, rather than the particular autoantibody specificities present. Among patients with new onset insulin-dependent diabetes, the absence of any of these autoantibodies justifies the consideration of non-autoimmune forms of diabetes in the differential diagnosis.

Adolescent↗

Limited loss of tolerance to islet autoantigens in ICA+ first degree relatives of patients with type I diabetes expressing the HLA dqb1*0602 allele.

The DQB1*0602 allele confers dominant protection from Type I diabetes even among islet cell antibody positive (ICA+) first degree relatives of affected individuals. Lack of progression to diabetes in these subjects, despite ICA positivity, could be explained by a loss of tolerance limited to fewer islet autoantigens than in ICA+ relatives progressing to the disease. To test this hypothesis we have determined autoantibodies by radioassay to three islet autoantigens, glutamic acid decarboxylase (GAD), insulin and the novel neuroendocrine antigen ICA512/IA-2 in 84 HLA-typed ICA+ first degree relatives of patients with Type I diabetes. Among the eleven relatives expressing the 0602 allele (0602+) only two were positive for more than one antibody as determined by radioassay. In contrast, 55/73 ICA+ relatives lacking this allele (non-0602) expressed more than one autoantibody (P < 0.01). The prevalence of antibodies to GAD (GAA) was not significantly different in ICA+ relatives with and without the 0602 allele (7/11 in 0602+ versus 60/73 in non-0602). In contrast, anti-insulin antibodies (IAA) were present in only 2/11 0602+ ICA+ relatives versus 47/70 in non-0602 ICA+ relatives (P < 0.01). Similarly, only one individual carrying the 0602 allele was positive for ICA512 autoantibodies versus 33/70 in the non-0602 group (P < 0.01). These data indicate that even among ICA+ relatives the 0602 allele is associated with a limited immune response to islet antigens and amongst 0602+ relatives this response is mostly directed against GAD.

Adolescent↗

Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies.

Islet cell antibodies (ICAs) are predictive of type I diabetes in first-degree relatives, but this immunohistochemical assay has proven difficult to standardize. As an alternative, we assessed the use of radioassays for antibodies against three molecularly characterized islet autoantigens, including ICA512bdc (amino acid residues 256-979 of the IA-2 molecule, incorporating the intracellular domain). We measured insulin autoantibodies (IAAs), GAD autoantibodies (GAAs), and ICA512bdc autoantibodies (ICA512bdcAAs) by radioassay, in addition to ICAs, in 882 first-degree relatives of patients with type I diabetes, 50 of whom later developed diabetes with a median follow-up of 2.0 years (maximum 11.3 years). The cutoff for each radioassay was determined by testing >200 control subjects. When autoantibody frequencies among the relatives were analyzed according to relationship to the proband, the offspring of diabetic fathers had a higher frequency of ICA5I2bdcAAs (P = 0.008), IAAs (P = 0.0001) and GAAs (P = 0.0001) than the offspring of diabetic mothers. ICA512bdcAAs and IAAs both showed a significant association with HLA-DR4-DQ8 (P = 0.0005). Among relatives developing diabetes, 98% had one or more of IAAs, GAAs, or ICA512bdcAAs, and 80% had two or more of these autoantibodies, compared with none of the control subjects. Using survival analysis to allow for different lengths of follow-up, there was a significant increase in the risk of diabetes with the number of these autoantibodies present, comparing zero, one, two, and three autoantibodies (P < 0.0001, log-rank test), and by Cox regression analysis, this was independent of ICAs and age. For relatives with two or more of these autoantibodies, the risk of diabetes within 3 years was 39% (95% CI, 27-52) and the risk within 5 years was 68% (95% CI, 52-84). Relatives with all three autoantibodies had a risk within 5 years estimated to be 100%. The presence of low first-phase insulin release further increased the risk for relatives with one or two autoantibodies. We conclude that the presence of two or more autoantibodies (out of IAAs, GAAs, and ICA512bdcAAs) is highly predictive of the development of type I diabetes among relatives.

Adolescent↗

Strategies for preventing type I diabetes mellitus.

Type I diabetes mellitus is a chronic autoimmune disease in which there is T cell-mediated destruction of the pancreatic beta cells. Susceptibility to the disease is determined by several genes, with HLA genes having the strongest effect. The onset of the disease is predictable, at least in the relatives of affected persons, using a combination of autoantibody measurements, intravenous glucose tolerance testing, and genetic typing. The disease may be preventable, and several large clinical trials are now underway to test whether interventions such as administering low-dose insulin or the use of nicotinamide can prevent the onset of diabetes in at-risk relatives.

Animals↗

Late progression to diabetes and evidence for chronic beta-cell autoimmunity in identical twins of patients with type I diabetes.

Previous studies suggest that after 6 years of discordance, identical twin pairs rarely become concordant for type I diabetes. With up to 39 years of follow-up from the onset of diabetes in the index twin, we determined how many discordant twins have evidence of beta-cell autoimmunity and how many develop overt diabetes. We longitudinally followed 23 pairs of identical twins (or triplets) that were selected from a total group of 30 pairs because they were discordant for type I diabetes when first ascertained. Seven developed diabetes after 3, 3, 7, 8, 9, 31 and 36 years of discordance. By survival analysis, the concordance after 10 years from the onset of diabetes in the index twin was estimated as 23% (95% confidence interval, 5-40%), increasing to 38% (95% confidence interval, 8-69%) after 31 years. Among 16 twins remaining nondiabetic at last follow-up (8-39 years of discordance), 12 were assessed with serial intravenous glucose tolerance tests and a total of 407 measurements by radioassay of antibodies against three defined autoantigens (glutamic acid decarboxylase, insulin, and the recently cloned molecule ICA512). Two-thirds (8 of 12) had evidence of beta-cell autoimmunity (persistently positive autoantibody levels) and/or first-phase insulin release less than the 1st percentile of control subjects. In summary, identical twins may develop diabetes after a prolonged period of discordance and approximately two-thirds of long-term discordant twins have evidence of persistent beta-cell autoimmunity and/or beta-cell damage. The concordance for beta-cell autoimmunity, therefore, is much higher than for overt diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

ICA512 autoantibody radioassay.

As part of a general program of screening islet expression libraries we have identified a clone from a lambda gt11 human islet expression library that reacts with human diabetic sera and, upon sequencing, was determined to be the neuroendocrine islet autoantigen ICA512 (islet cell antigen 512). In the current communication, we describe the development of a radioassay for autoantibodies to ICA512 (ICA512AA) using in vitro transcribed and translated protein for production of labeled antigen. Our initial results indicate that this radioassay is significantly more sensitive than the enzyme-linked immunosorbant assay, which uses a COOH-terminal fragment of ICA512. The ICA512AA radioassay uses a 96-well format with membrane separation of antibody bound from free antigen and should be readily adaptable to automated large-scale screening. Only 7 microliters of serum is required for triplicate determinations. In order to determine the specificity and sensitivity of this assay and estimate its positive predictive value, we have studied 42 new-onset diabetic patients, 33 first-degree relatives of diabetic patients followed to diabetes, 694 islet cell antibody-negative (ICA-) relatives, and 205 normal control subjects. Thirty-eight percent of new-onset patients and 48% of relatives followed to diabetes express autoantibodies to ICA512 exceeding the 99th percentile of the normal control subjects. In contrast, only 1.4% of ICA- first-degree relatives were positive for ICA512 autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Anti-glutamate decarboxylase and other antibodies at the onset of childhood IDDM: a population-based study.

Sera obtained at diagnosis from 273 children (0-14 years) with insulin-dependent diabetes mellitus (IDDM) were studied to compare different autoantibody levels. The subjects comprise 75% of all incident cases in New South Wales, Australia, for a 2-year period (ascertainment > 99% complete). Antibodies against glutamate decarboxylase were measured by radioimmunoprecipitation, insulin autoantibodies (on 176 sera collected within 4 days of initiation of insulin therapy) by radioimmunoassay, thyroid peroxidase and antigliadin IgA antibodies by enzyme-linked immunoassay, and anti-endomysial IgA and islet cell antibodies by indirect immunofluorescence. Reference ranges for anti-glutamate decarboxylase and insulin autoantibodies were determined in a group of non-diabetic children. Of the sera 69% were positive for anti-glutamate decarboxylase, 65% for insulin autoantibodies, 71% for islet cell antibodies (> or = 20 Juvenile Diabetes Foundation units), 10% for anti-thyroid peroxidase, 2.6% for antigliadin and 3.0% for anti-endomysial antibodies. Islet cell antibodies and insulin autoantibodies were both negative in 13.7% of the sera, while only 5.8% were negative for all three of islet cell antibodies, insulin autoantibodies and anti-glutamate decarboxylase. There was a higher frequency of anti-glutamate decarboxylase among girls than boys (75% vs 63%, p = 0.03) and a negative correlation between the level of insulin autoantibodies and age at diagnosis (r = -0.41, p < 0.0001). A higher frequency of antithyroid peroxidase was found with increasing age (p = 0.05). Higher titres of islet cell antibodies were associated with a higher frequency of both anti-glutamate decarboxylase (p < 0.0001) and insulin autoantibodies (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗