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Biomedical subjects

M Silink

Publications and source records attributed to M Silink.

At least 19 recordsLinked to original sources
PubMed2005

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↗
PubMed2005

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.

Adolescent↗
PubMed2003

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.

Adolescent↗
PubMed2002

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.

Adolescent↗
PubMed2002

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.

Adolescent↗
PubMed2001

Ten years' experience of persistent hyperinsulinaemic hypoglycaemia of infancy.

OBJECTIVE: To review the presentation, management and outcome of persistent hyperinsulinaemic hypoglycaemia of infancy seen at the Royal Alexandra Hospital for Children over a 10 year period. METHODOLOGY: A retrospective review of 20 subjects was performed. As well as laboratory data, data were collected on clinical presentation, medical and surgical management and developmental outcome. RESULTS: Twenty subjects (11 male) were identified with presentation at a median age of 1.5 months (range 0-10 months), with 10 (50%) presenting in the first week of life. Only 20% of patients were large for gestational age. Diagnosis was made on the basis of high glucose requirements and inappropriately high insulin levels at the time of hypoglycaemia. Eight (40%) responded well to diazoxide treatment alone, seven (35%) received diazoxide in combination with other short-term medical therapy initially and five (25%) required pancreatectomy (repeat surgery in three). Those who required surgery had a higher mean birth weight. Infants presenting in the first week of life were less likely to respond to diazoxide. At the time of last review, eight (40%) of those treated medically had ceased all treatment. Two of the five cases requiring pancreatectomy now require insulin treatment. Neurodevelopmental assessment was normal in 11 (55%), mild delay was found in six (30%) and moderate or severe delay was found in three (15%). CONCLUSIONS: Persistent hyperinsulinaemic hypoglycaemia of infancy remains a major diagnostic and management challenge. Early suspicion and recognition is critical with definitive investigation and medical therapy to avoid hypoglycaemia, with pancreatectomy in medically unresponsive cases. Normal neurodevelopmental outcome was found in only 55% of cases.

Adolescent↗
PubMed2001

Comparison of Dinamap 8100 with sphygmomanometer blood pressure measurement in a prepubertal diabetes cohort.

OBJECTIVE: To compare the conventional sphygmomanometer with the semiautomated Dinamap 8100 (Critikon, Tampa, FL, USA) for the measurement of blood pressure in prepubertal children with insulin-dependent diabetes mellitus. METHODOLOGY: Blood pressure was measured using both methods in 61 prepubertal children (aged 8-13 years) on 189 occasions over 4 years. The measurements were compared using the Bland-Altman plot. Tracking correlations of blood pressure centiles over time were analyzed by the general estimating equation. RESULTS: Accuracy criteria of the Association for the Advancement of Medical Instrumentation were met and a British Hypertensive Society 'B' grading was reached. Differences in systolic and diastolic blood pressure were found between the two methods (P < 0.01). For systolic blood pressure, common correlations were 0.54 (Dinamap) and 0.51 (sphygmomanometer) and for diastolic blood pressure were 0.33 and 0.42, respectively. CONCLUSION: The Dinamap 8100 is an acceptable alternative in clinic practice and research for prepubertal children.

Australia↗
PubMed2001

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.

Adolescent↗
PubMed2000

Beneficial effects of increasing monounsaturated fat intake in adolescents with type 1 diabetes.

This study aimed to increase the monounsaturated fat content in the diet of outpatient adolescents with type 1 diabetes and to examine the metabolic effects after 12 weeks. Twenty-three adolescents were randomly allocated to either a high monounsaturated fat diet or a control diet. Their mean age was 16.9 (S.D. 2.1) years and median HbA(1c) was 9.1% [IQR 7.9-10.4%]. Dietary targets were not reached judged by their 4-day food diaries. However, the whole study group had a significant increase in monounsaturated fat as indexed by red cell phospholipid fatty acids (RCFAs), with an increase of n-9 RCFAs from 14.9% [IQR: 14.5-21.7%] to 21.7% [IQR: 18.8-25.6%] (P=0.002). Changes in n-9 RCFAs were inversely related to changes in HbA(1c) (R(2)=0.26, P=0.02), such that a 10% increase in n-9 RCFAs corresponded to a 0.64% improvement (decrease) in HbA(1c). Changes in n-9 RCFAs were also inversely related to changes in plasma total cholesterol (R(2)=0.38, P=0.002) and plasma LDL cholesterol (R(2)=0. 21, P=0.03). These changes were not associated with changes in insulin dose, body weight or physical activity. Overall, the results demonstrate that a modest increase in the monounsaturated fat content of an adolescent diet has the potential to improve glycaemic control and lipid profile.

Adolescent↗
PubMed2000

Insulin lispro versus regular insulin in children with type 1 diabetes on twice daily insulin.

OBJECTIVE: The aim of this study was to compare the clinical efficacy and safety of insulin lispro with regular insulin in 5- to 10-yr-old prepubertal children on twice daily insulin. RESEARCH DESIGN AND METHODS: Thirty-five children (16 M, 19 F) completed an open-label randomised crossover study, with each child receiving insulin lispro for 3 months and regular insulin for 3 months in addition to their intermediate-acting insulin. Families were instructed to give regular insulin 30 min before meals and insulin lispro immediately before meals. Glycaemic control was monitored by eight-point blood glucose profiles and six weekly hemoglobin A1cs (HbA1cs) and the frequency and severity of hypoglycaemia was documented. RESULTS: The endpoint HbA1c after 3 months on insulin lispro (8.33%, SD+/-0.89) was not significantly different to that on regular insulin (8.14%, SD+/-0.77). No significant differences were found in blood glucose levels before or after meals, 2-h postprandial glucose excursions or in blood glucose levels before bed between the treatments. However, blood glucose levels at 3 am were significantly lower on regular insulin than on insulin lispro (mean difference -2.35 mmol/L (95%CI: -3.98, -0.72, p=0.01). There was no significant difference in the frequency of hypoglycaemic episodes between the groups. CONCLUSIONS: The main advantage of insulin lispro in children on twice daily insulin was found to be its greater convenience, this being achieved without a deterioration in glycaemic control. The higher 3 am blood glucose levels in those on insulin lispro could translate to reduced nocturnal hypoglycaemia in some individuals.

Clinical Trial↗
PubMed2000

The rising incidence of childhood type 1 diabetes in New South Wales, Australia.

OBJECTIVES: 1. To determine the incidence of type 1 (insulin dependent) diabetes in children aged 0-14 years who were resident in the state of New South Wales, Australia over the period 1992-1996. 2. To analyse the trends in incidence over the period 1990-1996. METHODS: Primary ascertainment of patients was performed using a prospective incidence register established in 1990. The secondary source of ascertainment was the National Diabetes Supply Scheme, a government subsidised scheme for diabetic supplies. RESULTS: There were 1,230 patients identified over the five-year period. Using the capture-recapture method, ascertainment was estimated to be 99% complete. The lowest incidence occurred in 1992 (16.9 per 10(5) person years) and the highest incidence was in 1995 (21.7 per 10(5)). The crude incidence of IDDM from 1990-1996 was 17.8 per 10(5) and there was a statistically significant rise in the incidence of type 1 diabetes over this period (p=0.0003). The annual incidence has increased on average by 3.2% per year since 1990. CONCLUSION: The incidence of childhood type 1 diabetes in NSW has increased significantly since 1990.

Adolescent↗
PubMed1999

An aldose reductase intragenic polymorphism associated with diabetic retinopathy.

The polyol pathway has been considered important in the development of diabetes long-term complications. Diabetic patients with microvascular disease have increased gene expression and enzyme activity, which may be due to variants in the aldose reductase gene. An association of an intragenic BamHI polymorphic site with diabetic retinopathy and nephropathy has been suggested, but the BamHI site has not been confirmed. In the current study, long template PCR-RFLP and DNA sequencing were used to ascertain its existence. A single substitution of A to C at 95th nucleotide of intron 8 was identified. This polymorphism was investigated in 164 adolescents with type 1 diabetes in whom diabetic retinopathy was assessed by stereoscopic retinal photography. Both the wild haplotype B and homozygote BB were significantly more common in the adolescents with retinopathy than in those without retinopathy (P = 0.018 and 0.002, respectively). We also confirmed an association between a previously described (CA)n repeat sequence and retinopathy in these adolescents (P < 0.0005). However, there was no association between the two polymorphisms.

Adolescent↗
PubMed1999

Limited joint mobility in the hands and feet of adolescents with Type 1 diabetes mellitus.

AIMS: Limited joint mobility (LJM) in the foot has not been assessed in adolescents with Type 1 diabetes mellitus (DM) but is associated with neuropathic ulceration in adults. This study was designed to determine the presence of LJM in adolescents with Type 1 DM and its association with microvascular disease. METHODS: The hands, feet and hips were examined in 302 diabetic adolescents and 51 nondiabetic controls (aged 11.5-20 years). LJM was defined as less than the fifth percent reference for controls. RESULTS: Reduced motion was found in 35% of diabetic adolescents at the subtalar (ST) joint, 18% at the first metatarsophalangeal (MTP) joint, 26% at the fifth metacarpophalangeal (MCP) joint and 13% had limited passive extension of the interphalangeal (IP) joints of the hands. Limited passive IP joint extension of the hands was not present in the controls. Limited active IP joint extension, a positive 'prayer sign', occurred in 35% of diabetic adolescents and 14% of controls. Diabetic adolescents showing LJM in any of these areas, except the prayer sign, were more likely to have retinopathy (odds ratio 2.53, CI: 1.53-4.18). Those with LJM in the foot were more likely to have albumin excretion rates >7.5 microg/min (OR 2.06, CI: 1.16-3.68). CONCLUSION: LJM in the feet of adolescents with Type 1 DM is associated with microvascular disease and is a useful routine clinical measure.

Adolescent↗
PubMed1998

Practical management of diabetic ketoacidosis in childhood and adolescence.

Diabetic ketoacidosis results from insulin deficiency and insulin resistance and is marked by hyperglycaemia, ketoacidosis, dehydration and electrolyte losses. Management includes correction of shock, dehydration, electrolyte deficits, hyperglycaemia, acidosis and sepsis (if present). Warning signs include severe dehydration, shock, pH < 7.0, hypokalaemia, hypernatraemia, hyperosmolality, hyperlipidaemia, deterioration in consciousness and diabetic ketoacidosis in very young patients. The principles of treatment include (i) admission to a unit with paediatric experience, (ii) treatment of shock, (iii) rehydration over 24-36 h, or longer if the osmolality is >360 mmoll(-1), (iv) normal saline for rehydration unless the patient is hypernatraemic, (v) avoidance of bicarbonate unless acidosis is interfering with myocardial contractility, (vi) insulin infusion to achieve a fall in blood glucose levels of 5 mmol h(-1), (vi) potassium, (vii) use of 5% glucose when the blood glucose level falls <12mmoll(-1), (ix) treatment of any complications and (x) change to subcutaneous insulin when diabetic ketoacidosis is controlled.

Adolescent↗