Low-density lipoprotein cholesterol in adolescents and young adults with type 1 diabetes: Data from the Australasian Diabetes Data Network registry.

AIM: To determine low-density lipoprotein cholesterol (LDL-C) screening frequency and levels, and factors associated with elevated LDL-C, in Australasian youth with type 1 diabetes (T1D). METHODS: Data were extracted from the Australasian Diabetes Data Network (ADDN), a prospective clinical quality registry, on all T1D healthcare visits attended by young people aged 16-25 years (with T1D duration of >1 year) between January 2011 and December 2020. The primary outcomes were elevated LDL-C > 2.6 mmol/L (100 mg/dL) and threshold for treatment: >3.4 mmol/L (130 mg/dL), according to consensus guidelines. Multivariable Generalised Estimated Equations (GEE) were used to examine factors associated with elevated LDL-C across all visits. RESULTS: A cohort of 6338 young people (52.6% men) were identified, of whom 1603 (25.3%) had ≥1 LDL-C measurement documented. At last measurement, mean age, age at T1D diagnosis and T1D duration were 18.3 ± 2.4, 8.8 ± 4.5 and 8.9 ± 4.8 years, respectively. LDL-C was elevated in 737 (46.0%) and at the treatment threshold in 250 (15.6%). In multivariable GEE elevated LDL-C continuously was associated with older age (OR = 0.07; 0.01-0.13, p = 0.02), female sex (OR = 0.31; 0.18-0.43; p < 0.001), higher HbA1c (OR = 0.04; 0.01-0.08; p = 0.01) and having an elevated BMI (OR = 0.17, 0.06-0.39, p < 0.001). CONCLUSIONS: LDL-C screening and levels are suboptimal in this cohort, increasing future cardiovascular complication risk. There is an urgent need to understand how healthcare services can support improved screening and management of dyslipidaemia in this population.

Skin autofluorescence in people with type 1 diabetes and people without diabetes: An eight-decade cross-sectional study with evidence of accelerated aging and associations with complications.

AIM: To measure skin autofluorescence in youth (<18 y.o.) and adults (≥18 y.o.) and to assess its relationship with type 1 diabetes, chronic complications and smoking. METHODS: In a cross-sectional study (n = 383) skin autofluorescence was measured in 269 people with type 1 diabetes (67 with vascular complications) and 114 people without diabetes, covering eight decades of age. Associations of skin autofluorescence with demographics and traditional risk factors were assessed. RESULTS: Skin autofluorescence increased with age in people with diabetes: for those with complications it increased by a mean ± se of 0.029 ± 0.003 arbitrary units per year (r = 0.76) and, for those without complications, it increased by 0.028 ± 0.002 arbitrary units (r = 0.77). These increases were higher than for people without diabetes, whose skin autofluorescence increased by 0.022 ± 0.002 arbitrary units (r = 0.78) per year (p = 0.004). Mean ±se age-adjusted skin autofluorescence was higher in people with diabetes complications vs people without diabetes complications (1.85 ± 0.04 vs 1.66 ± 0.02 arbitrary units) and people without diabetes (1.48 ± 0.03 arbitrary units; all P < 0.0001). Age-adjusted skin autofluorescence was higher in current smokers and recent ex-smokers vs non-smokers and longer-term ex-smokers (1.86 ± 0.06 vs 1.63 ± 0.02 arbitrary units; P = 0.0005). Skin autofluorescence area under the receiver-operating characteristic curve was 0.89 (95% CI 0.85-0.94) for retinopathy and 0.56 (95% CI 0.47-0.65) for nephropathy. CONCLUSIONS: Skin autofluorescence increases with age, but faster in people with diabetes, particularly in those with complications and in smokers, consistent with accelerated aging. Skin autofluorescence may facilitate complication screening and prediction. Longitudinal studies are merited.

Early changes of arterial elasticity in Type 1 diabetes with microvascular complications - A cross-sectional study from childhood to adulthood.

AIM: To examine the trajectory of small artery elasticity (SAE) and pulse pressure (PP) in people with Type 1 diabetes and non-diabetic controls across the lifespan, and explore associations with microvascular complications (CX+). METHODS: This cross-sectional study included 477 Type 1 diabetes patients (188 with CX+, 289 without CX-) and 515 controls. Relationships between SAE and PP and age were evaluated using segmented linear regression. Logistic regression was used to assess the associations between microvascular complications (retinopathy and/or nephropathy) and SAE and PP. RESULTS: SAE peaked significantly later among controls than diabetic patients CX- vs. CX+ (21.2 vs. 20.4 vs. 17.6 years respectively, p < 0.001). In adults, mean SAE was significantly lower in CX+ vs. CX- vs. controls (6.8 vs. 7.8 vs. 8.0 ml/mm Hg × 10; p < 0.0001), and mean PP was significantly higher in CX+ vs CX- and controls (60 vs. 55 vs. 53 mm Hg; p < 0.0001). CONCLUSION: Type 1 diabetes CX+ subjects have an earlier peak and decline in SAE relative to CX- and controls, who did not differ. Lower SAE and higher PP were associated with increased odds of Type 1 diabetes complications in adults. These clinically applicable techniques demonstrate an association between accelerated vascular aging and vascular complications in diabetes.

Higher skin autofluorescence in young people with Type 1 diabetes and microvascular complications.

AIM: To test the hypothesis that non-invasive skin autofluorescence, a measure of advanced glycation end products, would provide a surrogate measure of long-term glycaemia and be associated with early markers of microvascular complications in adolescents with Type 1 diabetes. METHODS: Forearm skin autofluorescence (arbitrary units) was measured in a cross-sectional study of 135 adolescents with Type 1 diabetes [mean ± sd age 15.6 ± 2.1 years, diabetes duration 8.7 ± 3.5 years, HbA1c 72 ± 16 mmol/mol (8.7 ± 1.5%)]. Retinopathy, assessed using seven-field stereoscopic fundal photography, was defined as ≥1 microaneurysm or haemorrhage. Cardiac autonomic function was measured by standard deviation of consecutive RR intervals on a 10-min continuous electrocardiogram recording, as a measure of heart rate variability. RESULTS: Skin autofluorescence was significantly associated with age (R2 = 0.15; P < 0.001). Age- and gender-adjusted skin autofluorescence was associated with concurrent HbA1c (R2 = 0.32; P < 0.001) and HbA1c over the previous 2.5-10 years (R2 = 0.34-0.43; P < 0.002). Age- and gender-adjusted mean skin autofluorescence was higher in adolescents with retinopathy vs those without retinopathy [mean 1.38 (95% CI 1.29, 1.48) vs 1.22 (95% CI 1.17, 1.26) arbitrary units; P = 0.002]. In multivariable analysis, retinopathy was significantly associated with skin autofluorescence, adjusted for duration (R2 = 0.19; P = 0.03). Cardiac autonomic dysfunction was also independently associated with skin autofluorescence (R2 = 0.11; P = 0.006). CONCLUSIONS: Higher skin autofluorescence is associated with retinopathy and cardiac autonomic dysfunction in adolescents with Type 1 diabetes. The relationship between skin autofluorescence and previous glycaemia may provide insight into metabolic memory. Longitudinal studies will determine the utility of skin autofluorescence as a non-invasive screening tool to predict future microvascular complications.

QT interval, corrected for heart rate, is associated with HbA1c concentration and autonomic function in diabetes.

AIMS: To examine QT intervals corrected for heart rate (QTc) in adolescents with Type 1 diabetes compared with control subjects, and to determine associations with metabolic control and autonomic function. METHODS: Resting electrocardiogram recordings of 142 adolescents with Type 1 diabetes [mean (sd) age 15.3 (2.0) years, diabetes duration 9.0 (3.5) years, HbA1c 71 (17) mmol/mol or 8.7 (1.6)%] and 125 control subjects [mean (sd) age 15.7 (2.5) years] were used to calculate QTc duration and derive mean heart rate and heart rate variability (HRV) values. Linear and logistic regression models were used to examine the associations between QTc, metabolic control and autonomic function (HRV and pupillary function). RESULTS: QTc duration was not significantly different between subjects with Type 1 diabetes and control subjects (mean duration 392 vs 391 ms; P = 0.65). In the Type 1 diabetes group, QTc was positively associated with HbA1c [ß = 4 (95% CI 2, 6); P < 0.001] and inversely associated with severe hypoglycaemic events [ß = -10 (95% CI -20,-2); P = 0.01], less insulin/kg [ß = -12 (95% CI -22, -2); P = 0.024] and less HRV. In the Type 1 diabetes group, QTc in the highest quintile (≥409 ms) vs quintiles 1-4 had more pupillary abnormalities (83 vs 56%; P = 0.03), lower pupillary maximum constriction velocity (4.8 vs 5.3 mm/s; P = 0.04), higher heart rate (78 vs 72 beats per min; P = 0.02) and lower HRV (standard deviation of mean NN intervals 4.0 vs 4.3 ms, P = 0.004 and root-mean-square difference of successive NN intervals 3.7 vs 4.1 ms; P = 0.004). CONCLUSIONS: Although there are concerns about hypoglycaemia in general in people with Type 1 diabetes, chronic hyperglycaemia, rather than intermittent hypoglycaemia, appears to be more deleterious to autonomic cardiac function, even in adolescence. Longer QTc was associated with higher HbA1c concentration, lower risk of hypoglycaemia and autonomic dysfunction. Longitudinal studies are warranted.

Plateau of adiposity in Australian children diagnosed with Type 1 diabetes: a 20-year study.

AIMS: To examine temporal trends in anthropometry in children with Type 1 diabetes from Sydney, Australia. METHODS: We conducted a retrospective study in a total of 1975 children with Type 1 diabetes, aged <16 years, between 1990 and 2009. Trends in height, weight and BMI standard deviation score after initial stabilization were examined by age group (<5 years, 5 to <10 years, 10 to 16 years) and time period of diagnosis (T1: 1990-1994, T2: 1995-1999; T3: 2000-2004 and T4: 2005-2009). Factors associated with BMI standard deviation score (time period, age group, gender and socio-economic status) were examined using multivariable linear regression. RESULTS: The mean BMI standard deviation score (±sd) increased between T1 and T2 (0.54 ± 1.14 vs 0.81 ± 1.14, P = 0.002), but remained steady thereafter (T3: 0.85 ± 1.11, T4: 0.87 ± 1.09; T2 to T4: P = 0.40). Similarly, the prevalence of overweight and obesity increased from T1 to T2 (26 to 35%, P = 0.01), but was unchanged thereafter (T3: 34%, T4: 34%; T2 to T4: P = 0.90). On multivariable regression analysis, a higher BMI standard deviation score was associated with younger age (≥5 years vs <5 years, ß=-0.40, 95% CI -0.51 to -0.28, P < 0.001), later time period (T2 to T4 vs T1, ß=0.30, 95% CI 0.16-0.45, P < 0.001) and male gender (ß=0.25, 95% CI 0.15-0.34, P < 0.001). CONCLUSION: The prevalence of overweight and obesity has remained unchanged in children at diagnosis of Type 1 diabetes over 15 years. These findings suggest that higher adiposity alone cannot account for the continued rising incidence of Type 1 diabetes in recent years.

Early elevation of albumin excretion rate is associated with poor gluten-free diet adherence in young people with coeliac disease and diabetes.

AIMS: There are conflicting data on microvascular complications in coexisting Type 1 diabetes and coeliac disease. We compared complications rates in youth with or without coeliac disease and examined the association between gluten-free diet adherence and complications. METHODS: This was a comparative study of adolescents (2510 without coeliac disease, 129 with coeliac disease); 60 (47%) did not adhere to a gluten-free diet--defined as elevated anti-tissue transglutaminase or endomysial immunoglobulin A titres. Retinopathy was detected using 7-field fundal photography and albumin excretion rate by timed overnight urine collections, with early elevation defined as albumin excretion rate ≥ 7.5 µg/min. Logistic regression was used to examine the association between complications and explanatory variables, including coeliac disease vs. no coeliac disease, gluten-free diet adherence vs. non-adherence, diabetes duration and HbA1c . RESULTS: Median age at last assessment was 16.5 years. Those with coeliac disease vs. those without were younger at diabetes diagnosis (7.1 vs. 8.6 years, P < 0.001) and had longer diabetes duration (9.3 vs. 7.2 years, P < 0.001). HbA1c was lower in those with coeliac disease vs. those without (67 vs. 70 mmol/mol, 8.3 vs. 8.6%, P = 0.04) and adherence to a gluten-free diet vs. non-adherence (66 vs. 72 mmol/mol, 8.2 vs. 8.7%, P = 0.003). There were no differences in complication rates between those with coeliac disease vs. those without (retinopathy 22 vs. 23%, elevated albumin excretion rate 31 vs. 28%). Non-adherence to a gluten-free diet was associated with elevated albumin excretion rate (40 vs. 23%, P = 0.04). In multivariable logistic regression, elevated albumin excretion rate was associated with non-adherence to a gluten-free diet (odds ratio 2.37, 95% CI 1.04-5.40, P = 0.04) and diabetes duration (odds ratio 1.13, 95% CI 1.02-1.25, P = 0.03), but not HbA1c . CONCLUSIONS: While glycaemic control is better in patients with coeliac disease, non-adherence to a gluten-free diet is associated with elevated albumin excretion rate. The possible protection of a gluten-free diet on complications warrants further investigation.

Thyroid autoimmunity in Type 1 diabetes: systematic review and meta-analysis.

AIMS: To review the incidence and evidence for screening for thyroid autoimmunity and thyroid dysfunction in Type 1 diabetes. METHODS: Systematic review and meta-analysis. Inclusion criteria were prospective cohort studies screening for thyroid autoimmunity and/or dysfunction (defined as an abnormal thyroid-stimulating hormone level) in Type 1 diabetes. Exclusion criteria included pregnancy and thyroid dysfunction before diabetes onset. Outcomes examined were: incidence of thyroid autoimmunity and/or dysfunction; association between thyroid autoimmunity and dysfunction; and cost-effectiveness. Data sources were MEDLINE, EMBASE, the Cochrane Library, manual searching and contact with authors, with limitations to English language and human studies. Meta-analysis was performed using random effects models. RESULTS: We identified 14 eligible studies, involving 2972 young people and 789 adults with Type 1 diabetes. Follow-up ranged from 1-18 years. None of the studies were of good methodological quality (Newcastle Ottowa Scale score > 7). The incidence of thyroid dysfunction (11 studies) ranged from 27 (95% CI 15-45) to 246 (95% CI 118-453) per 10 000 patient-years and thyroid autoimmunity (four studies) from 13 (95% CI 0.3-71) to 326 (95% CI 194-510). The risk of thyroid dysfunction was higher in those with thyroid autoimmunity: summary risk ratio 25 (95% CI 9-71) and was higher in children (49, 95% CI 16-150) compared with adults (7, 95% CI 3-13). No studies examined cost-effectiveness of screening. CONCLUSIONS: There is a markedly increased risk of thyroid dysfunction in people with Type 1 diabetes and thyroid autoimmunity. The optimal method or frequency of screening could not be determined from available data. Future studies should examine whether screening improves clinical outcomes in this population.

Functional characterization of a heterozygous GLI2 missense mutation in patients with multiple pituitary hormone deficiency.

CONTEXT: The GLI2 transcription factor is a major effector protein of the sonic hedgehog pathway and suggested to play a key role in pituitary development. Genomic GLI2 aberrations that mainly result in truncated proteins have been reported to cause holoprosencephaly or holoprosencephaly-like features, sometimes associated with hypopituitarism. OBJECTIVE: Our objective was to determine the frequency of GLI2 mutations in patients with multiple pituitary hormone deficiency (MPHD). DESIGN: Patients were selected from participants in the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) program. Patients with mutations within established candidate genes were excluded. PATIENTS: A total of 165 patients with MPHD defined as GH deficiency and at least 1 additional pituitary hormone deficiency were studied regardless of the presence of extrapituitary clinical manifestations. MAIN OUTCOME MEASURES: Prevalence of GLI2 variations in MPHD patients was assessed and detailed phenotypic characterization is given. Transcriptional activity of identified GLI2 variants was evaluated by functional reporter assays. RESULTS: In 5 subjects, 4 heterozygous missense variants were identified, of which 2 are unpublished so far. One variant, p.R516P, results in vitro in a complete loss of protein function. In addition to GH deficiency, the carrier of the mutation demonstrates deficiency of thyrotrope and gonadotrope function, a maldescended posterior pituitary lobe, and polydactyly, but no midline defects. CONCLUSIONS: For the first time, we show that heterozygous amino acid substitutions within GLI2 may lead to MPHD with mild extrapituitary findings. The phenotype of GLI2 mutations is variable, and penetrance is incomplete. GLI2 mutations are associated with anterior pituitary hypoplasia, and frequently, ectopy of the posterior lobe occurs.

Coeliac disease in Type 1 diabetes from 1990 to 2009: higher incidence in young children after longer diabetes duration.

AIMS: To determine the incidence of coeliac disease in young people with Type 1 diabetes and to examine the effect of age at diabetes onset and disease duration. METHODS: This was a clinic-based observational cohort study of 4379 people aged ≤ 18 years (49% male) between 1990 and 2009 from Sydney, Australia. Screening for coeliac disease was performed at diagnosis and 1-2 yearly using anti-endomysial and/or anti-tissue transglutaminase immunoglobulin A (IgA) antibodies. Coeliac disease was diagnosed by small bowel biopsy based on Marsh score ≥ III. RESULTS: Coeliac disease was confirmed by biopsy in 185; of these, 61 (33%) were endomysial or tissue transglutaminase IgA antibody-positive at diabetes diagnosis. Mean age at diabetes onset was 6.6 ± 4.0 vs. 8.4 ± 4.1 years in those without coeliac disease (P < 0.001). Mean incidence was 7.7 per 1000 person years (95% CI 6.6-8.9) over 20 years. Incidence was higher in children aged < 5 years at diabetes diagnosis (10.4 per 1000 person years) vs. ≥ 5 years (6.4 per 1000), incidence rate ratio 1.6 (95% CI 1.2-2.2, P = 0.002). Coeliac disease was diagnosed after 2, 5 and 10 years of diabetes in 45, 78 and 94% of cases, respectively. Median time to coeliac disease diagnosis was longer in children aged < 5 years at diabetes onset (3.3 years) compared with older children (0.7 years, P < 0.001). CONCLUSIONS: Coeliac disease is common in young people with Type 1 diabetes; the risk is greatest with diabetes onset < 5 years, but after longer diabetes duration. Screening for coeliac disease should be performed at diabetes diagnosis and for at least 10 years in young children.

The association of aldose reductase gene (AKR1B1) polymorphisms with diabetic neuropathy in adolescents.

AIMS: Variants in the aldose reductase gene (AKR1B1) have been implicated in the development of diabetic retinopathy and nephropathy, with the most convincing data identifying a (CA)(n) repeat microsatellite allele (Z-2), which has a functional role in gene expression. In this study the association between polymorphisms in the AKR1B1 gene and diabetic neuropathy was investigated. METHODS: The pupillary response to light was used as the major outcome in this study along with abnormal hot thermal threshold. Three hundred and sixty-three adolescents underwent genotyping of the AKR1B1 gene. The microsatellite (CA)(n) repeat was sequenced and two single nucleotide polymorphisms, -106C-->T and -12C-->G, were investigated by restriction fragment length polymorphism. RESULTS: Seventy-six percent of participants had pupillary abnormalities (45% with two, 15% with three abnormalities). Presence of the Z-2/Z-2 genotype increased the risk nearly three-fold for pupillary abnormalities [odds ratio (OR) 3.02, 95% confidence interval (CI) 1.14, 7.98). The susceptibility genotypes (Z-2/Z-2 with -106C/-106C, Z-2/Z with -106C/-106C or Z/Z with -106C/-106C) were associated with resting pupil diameter abnormalities when compared with the protective genotypes (Z+2/Z+2 or -106T/-106T) (OR 2.83, 95% CI 1.25, 6.41). The combination of Z+2/-106T reduced the risk of abnormal heat discrimination (OR 0.48, 95% CI 0.23, 0.99). CONCLUSIONS: In this study we have shown that Z-2/Z-2 genotype is significantly associated with the development of pupillary abnormality, an early indicator of diabetic autonomic neuropathy, in adolescent Australian patients with Type 1 diabetes.

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.

Secular trends in growth in diabetes: are we winning?

AIM: To determine potential effects of modern treatment on growth in diabetic children. METHODS: Retrospective analysis of growth in diabetic children stratified by their year of diagnosis between 1974 and 1995. A total of 451 children and adolescents attending the Diabetes Outpatient and Outreach Clinics of Royal Alexandra Hospital for Children in Sydney and rural NSW, Australia were studied. Standard deviation scores (SDS) for height and body mass index (BMI) were assessed at diagnosis, five years later (n = 451), and 10 years later (n = 111). RESULTS: After five years of diabetes duration height SDS loss correlated with higher HbA(1c) and fewer injections. BMI SDS gain correlated with HbA(1c) and age at diagnosis. Although there was no significant difference in their height SDS or age at diagnosis, children diagnosed 1974-90 were significantly shorter than children diagnosed 1991-95 (height SDS 0.07 v 0.37) after five years diabetes duration. Furthermore, over 5 and 10 years, the 1979-90 group had lost significant height SDS (mean change -0.20 at 5 years, -0.29 at 10 years); this did not occur in the 1991-95 group (-0.01 at 5 years, -0.13 at 10 years). The BMI SDS increased significantly after 10 years in the 1974-90 group (mean change 0.37) but not in the 1991-95 group. There was no significant difference in the 174 females' age of menarche (13.0 v 12.8 years). CONCLUSIONS: Children with diabetes treated with modern regimens maintain their increased height from diagnosis better, and after five years diabetes duration, were taller than children diagnosed before 1991.

Paraoxonase gene cluster is a genetic marker for early microvascular complications in type 1 diabetes.

BACKGROUND: Paraoxonase is a serum enzyme, which prevents oxidation of low-density lipoprotein (LDL) by hydrolyzing lipid peroxides. Two polymorphisms in PON1 gene have been associated with cardiovascular and microvascular diseases in both diabetic and non-diabetic patients. AIMS: The current project was designed to investigate the association between the polymorphisms of two PON genes and diabetes microvascular diseases (retinopathy and microalbuminuria) and any potential linkage between Met54Leu of PON1 and Cys311Ser of PON2 gene. METHODS: Diabetic retinopathy and albumin excretion rate were assessed in 372 adolescents with Type 1 diabetes who were genotyped for the two polymorphisms. RESULTS: We confirmed the increased susceptibility for diabetic retinopathy for the Leu/Leu genotype (odds ratio (OR) 3.34 (confidence interval (CI) 1.95, 5.75), P < 0.0001). The Ser/Ser genotype was significantly more common in those patients with microalbuminuria (albumin excretion rate > or = 20 microg/min) compared with those with albumin excretion rate < 20 microg/min (OR 4.72 (CI 2.65, 8.41), P < 0.0001). The Ser311 of PON2 was in strong linkage disequilibrium with Leu54 of PON1 gene (Delta = 23 x 10(4), P < 0.001). The delta value was higher for those without complications (28 x 104, P < 0.001) compared with those with complications (15.5 x 10(4), P < 0.001). CONCLUSIONS: This study supports the hypothesis that diabetic microangiopathy is genetically heterogeneous. PON1 Leu/Leu increases the risk for retinopathy and PON2 Ser/Ser increases the risk for microalbuminuria.

Ultrasonography of plantar soft tissues thickness in young people with diabetes.

AIMS: The aims of this study were to examine soft tissue changes in the skin and plantar aponeurosis of young people with Type 1 diabetes mellitus (T1DM) and to evaluate any relationship between any soft tissue changes, arch length, limited joint mobility (LJM) and plantar pressure. METHODS: The thickness of the skin on the plantar surface of the foot and plantar aponeurosis were examined using ultrasound in 216 young people with diabetes and 57 controls. Foot length, arch length, joint mobility, peak pressure and pressure time integrals were evaluated. RESULTS: Skin was not significantly thicker in the diabetic subjects. The plantar aponeurosis was significantly thicker in the diabetic subjects and was associated with foot size, male gender and subtalar joint (ST) LJM (P < 0.01). Males were nearly three times more likely to have thickened plantar aponeurosis. CONCLUSION: Soft tissue thickening in young people with T1DM affects the deeper structures on the plantar surface of the foot rather than the skin. Thickening of the plantar aponeurosis was associated with LJM at the ST joint and male gender, but was not associated with plantar pressure or arch height changes. Plantar aponeurosis thickening does not appear to alter foot mechanics in young people with T1DM.

CCR5 genotyping in an Australian and New Zealand type 1 diabetes cohort.

Infiltration of pancreatic tissue by autoreactive T-cells involves secretion of multiple cytokines and chemokine receptor expression. Genetically determined variation in cell surface expression of the chemokine receptor CCR5 may result in differences in inflammatory cell migration in response to relevant chemokines. Adolescents with type 1 diabetes (T1D) from Australia and New Zealand were genotyped for CCR5-delta32 (n = 626). The allele frequency was compared with that of 253 non-diabetic Australian adolescents and with that of 92 adults with systemic lupus erythematosus. A reduced allele frequency was seen in T1D compared with controls (0.092 vs. 0.123, p = 0.05). This difference was not seen for the cohort of patients with SLE (freq = 0.114). A reduction in the number of CCR5-delta32/delta32 homozygotes, who lack CCR5, in the T1D cohort was also seen and while not statistically significant (2 observed compared to 5.25 expected; p = 0.12) is interesting. These results suggest a partial protection from T1D for CCR5-delta32 homozygous individuals is possible and that CCR5 has a potential role in the pathogenesis of T1D.

Modulation by blood glucose levels of activity and concentration of paraoxonase in young patients with type 1 diabetes mellitus.

Paraoxonase (PON) is a high-density lipoprotein (HDL)-associated esterase, which may prevent the transformation of low-density lipoproteins (LDL) into biologically active, atherogenic particles. PON concentration and activity are affected by PON1 gene polymorphisms and found to be altered in type 2 diabetes patients with retinopathy. We investigated serum PON concentration, in vitro activity and polymorphism at position 54 (L/M, Leu-Met54) in 193 Caucasian adolescents and young adults (88 males, 105 females) with type 1 diabetes mellitus, as well as its relationship to the presence of retinopathy. An inverse linear correlation was found between blood glucose levels and both serum PON concentration (r = -.20, P =.017) and its activity (r = -0.17, P =.037). Patients with elevated blood glucose values (> or =10 mmol/L) had significantly lower levels of both PON concentration (P =.003) and activity (P =.028) than those with lower glucose levels. After adjusting for blood glucose and diabetes duration, PON activity was significantly higher in patients with different stages of retinopathy compared with those without retinopathy (P =.003). The L/L genotype was closely associated with the presence of retinopathy (P <.0001). These data show that young people with type 1 diabetes and the L/L polymorphism at position 54 of PON1 gene are more susceptible to retinal complications. However, the role of serum PON concentration and activity as a possible marker for monitoring late microvascular complications in these patients has to be established.

Urinary selenium and iodine during pregnancy and lactation.

The New Zealand environment is low in selenium and iodine, and is therefore ideally suited for the study of these anionic trace elements. The aim of this study was to determine urinary excretion of selenium and iodine during pregnancy and postpartum as part of an investigation of the influence of pregnancy and lactation on selenium metabolism in women of low selenium status. In a double-blind placebo-controlled study, 35 women in the earliest stages of pregnancy and 17 non-pregnant women were recruited in Dunedin, New Zealand. Eighteen pregnant women received 50 microg selenium as L-selenomethionine, while the others received a placebo daily during pregnancy and 12 months postpartum. The non-pregnant women received the supplement, serving as a positive control. Blood samples and twenty-four hour urine samples were collected monthly during pregnancy and at 3, 6, and 12 months postpartum for analysis of selenium and iodine. Selenium content in plasma and urinary excretion of selenium fell during pregnancy; however, total excretion of selenium was greater during pregnancy than postpartum. Urinary iodine excretion was much lower than reported previously in New Zealand. Due to large intra- and inter-subject variability, no trends in iodide excretion were observed. Factors which influence urinary excretion of selenium include dietary intake, but more closely, plasma concentrations of selenium (which is probably related to total selenium pool), creatinine excretion and therefore lean body mass, and glomerular filtration rate. The exact mechanism and sequence of events remains unclear and future studies incorporating new speciation techniques are necessary.