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Martin Silink

Publications and source records attributed to Martin Silink.

At least 19 recordsLinked to original sources
PubMed2007

Autonomic nerve testing predicts the development of complications: a 12-year follow-up study.

OBJECTIVE: Cardiac autonomic nerve tests have predicted increased mortality in adults with diabetes, predominantly due to nephropathy, cardiac disease, and hypoglycemia. The significance of subclinical autonomic nerve test abnormalities has not been systematically studied in adolescents. We aimed to reassess an adolescent cohort, whose autonomic nervous system had been tested 12 years earlier by both pupillometry and cardiovascular tests. RESEARCH DESIGN AND METHODS: From 1990 to 1993, adolescents with type 1 diabetes (n = 335) were assessed for autonomic neuropathy (median age 14.7 years [interquartile range 13.0-16.8], duration of diabetes 6.3 years [4.0-9.6], and A1C 8.3% [7.5-9.4]). Between 2003 and 2005, contact was made with 59% of the original group. Individual assessment 12 years later included completion of a validated hypoglycemia unawareness questionnaire (n = 123) and urinary albumin-to-creatinine ratio (n = 99) and retinal (n = 102) screening, as well as analysis of reports from external doctors (n = 35). RESULTS: At baseline, there was no difference in age, duration of diabetes, or complications between those who participated in the follow-up phase (n = 137) and those who did not participate (n = 196). However, baseline A1C was lower in the follow-up participants (8.2 vs. 8.5% for participants vs. nonparticipants, respectively, P = 0.031). At 12 years of follow-up, 93% were aware and 7% were unaware that they had hypoglycemia; 32 (31%) had no retinopathy, but 10% required laser therapy, and 80 (81%) had no microalbuminuria. Small pupil size at baseline was independently associated with the development of microalbuminuria (odds ratio 4.36 [95% CI 1.32-14.42], P = 0.016) and retinopathy (4.83 [1.3-17.98], P = 0.019) but not with the development of hypoglycemia unawareness. There was no association with baseline cardiovascular tests and the development of complications 12 years later. CONCLUSIONS: In this study, we found an association between baseline pupillometry tests and the presence of microalbuminuria and retinopathy at 12 years of follow-up. This suggests that pupillometry abnormalities may be early indicators of patients who are at high risk of future microvascular disease.

Adolescent↗
PubMed2006

Fludrocortisone therapy in cerebral salt wasting.

Cerebral salt wasting is an increasingly recognized condition in pediatrics and is characterized by inappropriate natriuresis and volume contraction in the presence of cerebral pathology. Diagnosis can be difficult and therapy challenging. A few single case reports of the successful use of fludrocortisone exist. We report 4 patients with cerebral salt wasting, all of whom presented with hyponatremia in the presence of known intracerebral pathology. All had clinically significant hyponatremia, and 3 had hyponatremic seizures. Two of the patients also satisfied clinical criteria for diabetes insipidus. They all were treated with regimens using increased sodium and fluid administration but experienced ongoing salt wasting. Fludrocortisone was instituted in all 4 patients and in 3 resulted in rapid improvement in net sodium balance, enabling the weaning of hypertonic fluids and stabilization of serum electrolytes. In 3 patients, fludrocortisone treatment was complicated by hypokalemia, and in 1 patient by hypertension, which necessitated a dose reduction or brief cessation of therapy. Duration of therapy was 4 to 125 days. Cerebral salt wasting presents considerable management challenges; however, fludrocortisone therapy can be an effective adjunct to treatment.

Brain Diseases↗
PubMed2006

Type 2 diabetes in youth from the Western Pacific region: glycaemic control, diabetes care and complications.

OBJECTIVE: To describe the glycaemic control, diabetes care and prevalence of complications in youth with type 2 diabetes from the Western Pacific Region. RESEARCH DESIGN AND METHODS: Cross-sectional, clinic-based audit of 331 patients aged < 18 years from 56 centres in Australia, China-Beijing, China-Shanghai, China-Hong Kong, Indonesia, Japan, South Korea, Malaysia, Philippines, Singapore, Taiwan and Thailand. Clinical and management data were recorded along with glycated haemoglobin (HbA(1c)), lipids and complication rates. MAIN OUTCOME MEASURES: Glycaemic control, complications, diabetes management. RESULTS: Median age was 14.9 years (interquartile range 13.2-16.4 years) and median diabetes duration 2.3 years (1.4-3.6 years). Median HbA(1c) was 7% (5.9-9.9%) and HbA(1c) was > 7.5% in 40% of patients. In multiple regression analysis, glycaemic control varied significantly between countries (p = 0.02); higher HbA(1c) was associated with fewer home blood glucose measurements (p = 0.005) and higher insulin dose/kg (p < 0.0001). Blood glucose monitoring was performed by 65% of patients (range 33-96% by country). In 25% of patients, management consisted of diet alone or no treatment (range 0-53% by country); oral anti-diabetic drugs alone were used in 49%, insulin alone in 11% and both in 15%. Microalbuminuria was found in 8% and hypertension in 24%. The risk of hypertension increased with higher BMI (OR 1.16, 95% CI 1.09-1.24, p < 0.0001); antihypertensive agents were used in 4% of patients. CONCLUSIONS: The management of type 2 diabetes in youth from the Western Pacific Region varies widely. Hypertension and microalbuminuria were frequent, but not commonly treated. Further investigation into the natural history and risk factors for complications in youth with type 2 diabetes is required to assist in developing evidence based management guidelines.

Adolescent↗
PubMed2006

Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes.

OBJECTIVE: To compare the prevalence of diabetes complications and their risk factors in youth with type 1 versus type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a comparative clinic-based study of 1,433 patients with type 1 diabetes and 68 patients with type 2 diabetes aged <18 years from New South Wales, Australia. Retinopathy was assessed by seven-field stereoscopic retinal photography; albumin excretion rate from three consecutive, timed, overnight urine collections; peripheral neuropathy by thermal and vibration threshold; and autonomic neuropathy by pupillometry. HbA(1c) (A1C) and lipids were measured in all patients and C-peptide in patients with type 2 diabetes. RESULTS: In patients with type 1 versus type 2 diabetes, median (interquartile range) age was 15.7 years (13.9-17.0) and 15.3 years (13.6-16.4), respectively (P = 0.2), whereas median diabetes duration was 6.8 years (4.7-9.6) and 1.3 years (0.6-3.1), respectively (P < 0.0001). Retinopathy was significantly more common in patients with type 1 diabetes (20 vs. 4%, P = 0.04), while microalbuminuria and hypertension were significantly less common (6 and 16% in type 1 diabetes vs. 28 and 36% in type 2 diabetes). Rates of peripheral and autonomic neuropathy were similar (27 and 61% in type 1 diabetes vs. 21 and 57% in type 2 diabetes). In multivariate analyses, microalbuminuria was significantly associated with older age (odds ratio 1.3 [95% CI 1.2-1.5], P < 0.001) and systolic hypertension (3.63 [2.0-6.3], P < 0.001) in type 1 diabetes, while only higher A1C (1.7 [1.3-2.9], P = 0.002) was significant in patients with type 2 diabetes. CONCLUSIONS: Youth with type 2 diabetes have significantly higher rates of microalbuminuria and hypertension than their peers with type 1 diabetes, despite shorter diabetes duration and lower A1C. The results of this study support recommendations for early complications screening and aggressive targeting of glycemic control in patients with type 2 diabetes.

Adolescent↗
PubMed2006

Decline in neurophysiological function after 7 years in an adolescent diabetic cohort and the role of aldose reductase gene polymorphisms.

OBJECTIVE: This 7-year longitudinal study examines the potential impact of aldose reductase gene (AKR1B1) polymorphisms on the decline of nerve function in an adolescent diabetic cohort. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes (n = 262) were assessed with three cardiovascular autonomic tests (heart rate variation during deep breathing, Valsalva maneuver, and during standing from a lying position) and pupillometry (resting pupil diameter, constriction velocity, and reflex amplitude), thermal, and vibration thresholds on the foot. Genotyping was performed for promoters (C-106T and C-12G), (CA)(n) dinucleotide repeats, and intragenic BamH1 polymorphism. RESULTS: Median time between first and last assessment was 7.0 years (interquartile range 5.1-11.1), with a median of five assessments (four to seven) per individual. At first assessment, median age was 12.7 years (11.7-13.9), median duration was 5.3 years (3.4-8.0), and median HbA(1c) was 8.5% (7.8-9.3). All tests declined over time except for two cardiovascular autonomic tests and vibration discrimination. Faster decline in maximum constriction velocity was found to associate with the Z-2 allele (P = 0.045), Z-2/Z-2 (P = 0.026). Slower decline in hot thermal threshold discrimination associated with Z+2 (P = 0.044), Z+2/Z+2 (P < 0.0005), Z+2/T (P = 0.038), and bb (P = 0.0001). CONCLUSIONS: Most autonomic and quantitative sensory nerve testings declined over time. AKR1B1 polymorphisms were strongly associated with the rate of decline of these complications.

Adolescent↗
PubMed2005

The rising incidence of childhood type 1 diabetes in New South Wales, 1990-2002.

OBJECTIVES: To determine the incidence of childhood type 1 diabetes mellitus (T1DM) in New South Wales from 1997 to 2002; to compare with previously published rates (1990-1996); and to analyse trends in incidence from 1990 to 2002. DESIGN, SETTING AND PARTICIPANTS: Prospective population-based incidence study. Primary ascertainment of incident cases aged < 15 years was from the Australasian Paediatric Endocrine Group NSW children's diabetes register. Secondary ascertainment was from the National Diabetes Supply Scheme until 1999 and from the Australian Institute of Health and Welfare thereafter. Childhood population data were obtained from the Australian Bureau of Statistics. MAIN OUTCOME MEASURES: Age-standardised incidence; trends in incidence by calendar year, and sex and age at diagnosis. RESULTS: There were 3260 incident cases (1629 boys, 1631 girls) in the 13 years. Case ascertainment was 99.7% complete using the capture-recapture method. Mean age-standardised incidence per 100 000 person-years was 20.9 (95% CI, 19.9 to 21.9) from 1997 to 2002 compared with 17.8 (95% CI, 17.0 to 18.7) from 1990 to 1996; there was a plateau in incidence between 1997 and 2002. Overall, the incidence increased on average by 2.8% per year (95% CI, 1.9% to 3.8%, P < 0.001) and increased with age, being 12.2 (95% CI, 11.3 to 13.1) in 0-4 year olds; 18.9 (95% CI, 17.8 to 20.0) in 5-9 year olds and 26.7 (95% CI, 25.4 to 28.1) in 10-14 year olds. The increase per year in 0-4 year olds (3.9%) was not significantly higher than in older children. The mean incidence of T1DM was 19.8 (95% CI, 18.8 to 20.7) in girls and 18.8 (95% CI, 17.9 to 19.7) in boys (P = 0.02). CONCLUSIONS: The incidence of childhood-onset T1DM has increased significantly in all age groups in NSW since 1990. Resource planning in the management of childhood diabetes in NSW should take these findings into account.

Adolescent↗
PubMed2005

The case for biennial retinopathy screening in children and adolescents.

OBJECTIVE: Current guidelines recommend annual retinopathy screening 2 years after onset (for pubertal-onset type 1 diabetes) and after 5 years (or age 11, whichever is earlier) for prepubertal onset. Our aim was to describe the natural history of retinopathy and to explore optimal retinal screening intervals for children and adolescents (aged <20 years) screened according to these guidelines. RESEARCH DESIGN AND METHODS: More than 1,000 children and adolescents, followed longitudinally, were screened for retinopathy using seven-field stereoscopic fundus photography through dilated pupils. Of these, 668 had baseline and follow-up retinal screening. Using generalized estimating equations, we compared the risk of retinopathy with baselines at yearly intervals, in older and younger groups, in higher risk groups (diabetes duration >10 years or HbA(1c) >10% at any screening), and after stratification </=10 and <10 years in duration. RESULTS: After 1 year, retinopathy did not increase significantly in the older group (n = 618, median HbA(1c) 8.7%, range 8.0-9.5), younger group (n = 50, median HbA(1c) 8.5%, range 8.0-9.2), or the higher-risk groups. Retinopathy increased significantly after 2 years in the older group (P = 0.003) but not until 6 years in the younger group (P = 0.01). In the group with HbA(1c) >10% recorded at any visit, retinopathy increased significantly after 2 years (P = 0.001) but not until 3 years in the group whose HbA(1c) was always </=10% (P = 0.003). After the second eye assessment, retinopathy did not increase significantly until 3 and 6 years later in the older and younger groups, respectively (P = 0.028 and 0.014). CONCLUSIONS: These results suggest that adolescents (in reasonable metabolic control) could safely be screened every 2 years rather than the currently recommended 1-year interval. In younger children, the next screening interval could be >2 years later. Individuals with especially poor control, duration >10 years, or significant retinopathy should be screened more frequently.

Adolescent↗
PubMed2005

Discordant trends in microvascular complications in adolescents with type 1 diabetes from 1990 to 2002.

OBJECTIVE: Since the Diabetes Control and Complications Trial, diabetes management goals have changed. The aims of the present study were to assess complication rates, including nerve abnormalities, in adolescents from 1990 to 2002 and to investigate associated risk factors. RESEARCH DESIGN AND METHODS: Cross-sectional analysis of complications was assessed in three study periods (1990-1994 [T1], 1995-1998 [T2], and 1999-2002 [T3]) in adolescents matched for age and diabetes duration (n = 878, median age 14.6 years, median duration 7.5 years). Retinopathy was assessed by seven-field stereoscopic fundal photography, albumin excretion rate (AER) from three consecutive timed overnight urine collections, peripheral nerve function by thermal and vibration thresholds, and autonomic nerve function by cardiovascular reflexes. RESULTS: Retinopathy declined significantly (T1, 49%; T2, 31%; and T3, 24%; P < 0.0001), early elevation of AER (> or = 7.5 microg/min) declined (38, 30, and 25%, respectively, P = 0.022), and microalbuminuria (AER > or = 20 microg/min) declined (7, 3, and 3%, respectively; P = 0.017, T1 vs. T2 and T3). Autonomic nerve abnormalities were unchanged (18, 21, and 18%, respectively; P = 0.60), but peripheral nerve abnormalities increased (12, 19, and 24%, respectively; P = 0.0017). More patients were treated with three or more injections per day (12, 46, and 67%, respectively; P < 0.0001) and insulin dose increased (1.08, 1.17, and 1.22 units x kg(-1) x day(-1), respectively; P < 0.0001), but median HbA(1c) (A1C) was unchanged (8.5, 8.5, and 8.4%, respectively). BMI and height SD score increased: BMI 0.46, 0.67, and 0.79, respectively (P < 0.0001), and height -0.09, 0.05, and 0.27, respectively (P < 0.0001). CONCLUSIONS: Retinopathy and microalbuminuria declined over time in this cohort, but the increased rate of peripheral nerve abnormalities is of concern. Despite intensified management (higher insulin dose and more injections), A1C has not changed and remains well above the recommended targets for adolescents.

Adolescent↗
PubMed2004

Prophylactic bilateral nephrectomies in two paediatric patients with missense mutations in the WT1 gene.

BACKGROUND: Denys-Drash syndrome (DDS) is associated with mutations of the Wilms' tumour 1 (WT1) gene, and is characterized by pseudohermaphroditism, a progressive glomerulopathy, and the development of Wilms' tumour. More than 90% of patients with DDS who carry constitutional intragenic WT1 mutations are at high risk (90%) for the development of Wilms' tumour. WT1 is a signalling protein with 90% of WT1 mutations occurring in the WT1 zinc finger region as single nucleotide polymorphisms, the majority of which are missense mutations. METHODS: Constitutional DNA was extracted from peripheral blood. Direct sequencing and restriction enzymes were employed to analyse mutations. RESULTS: Two children, 46XY males who had evidence of pseudohermaphroditism, hypogonadism and renal failure with a glomerulopathy atypical for DDS, but no Wilms' tumour or nephroblastomatosis, on investigation, prior to transplant, were identified with missense mutations in the WT1 gene, in exons 8 and 9, respectively. The decision to do prophylactic nephrectomies was based on the genetic identification of WT1 mutations supporting a diagnosis of incomplete DDS, with the potential for increased risk of malignancy with the development of Wilms' tumour. The nephrectomy specimens demonstrated nephrogenic rests (nephroblastomatosis), which have a potential for malignant transformation. CONCLUSIONS: WT1 missense mutations in exons 8 and 9 can be regarded as having the potential for malignant change supporting prophylactic nephrectomy in apparent incomplete DDS patients with end-stage renal disease.

Child↗
PubMed2003

Reduced frequency of HLA DRB1*03-DQB1*02 in children with type 1 diabetes associated with enterovirus RNA.

Enteroviruses have been associated with type 1 diabetes mellitus (T1DM), but it is unclear whether there is a distinct disease subtype. Plasma and stool samples from 206 consecutively diagnosed children and 160 healthy control children were analyzed by reverse-transcription polymerase chain reaction for the RNA of 60 enteroviruses. More children with diabetes tested positive for enterovirus RNA (30% vs. 4%; odds ratio, 11.1; 95% confidence interval, 4.7-25.7; P<.001). Enterovirus 71 was detected in 25% of children; these were temporally associated with outbreaks in Southeast Asia and Australia. Fewer children with the diabetes-associated human leukocyte antigen DRB1*03-DQB1*02 genotype tested positive for enterovirus RNA (P=.02). More children presenting with severe diabetic ketoacidosis (pH, <7.1) tested positive for enterovirus RNA (P=.04). These results suggest that there is a subgroup of patients with T1DM, who are at low genetic risk, in whom enteroviruses contribute to diabetes onset.

Adolescent↗
PubMed2003

Diagnosis of enterovirus infection by genus-specific PCR and enzyme-linked immunosorbent assays.

PCR for the diagnosis of enterovirus infections is resource intensive but is increasingly used due to wide availability. Enzyme-linked immunosorbent assays (ELISAs) that detect heterotypical antibodies against enterovirus immunoglobulin M (IgM), IgA, and IgG were compared with reverse transcription-PCR by using primers specific to the 5' untranslated regions of 60 enterovirus species. The ELISAs were less sensitive than the PCR, and only the ELISA for IgM was highly specific. When retrospective diagnosis is important or when specimens are unsuitable for PCR, the ELISA has a limited role if PCR is not available.

Enterovirus↗
PubMed2003

Do all prepubertal years of diabetes duration contribute equally to diabetes complications?

OBJECTIVE: This study was designed to explore the timeline of protection against complications in prepubertal children with diabetes, in particular the effects of diabetes duration before age 5 years. RESEARCH DESIGN AND METHODS: In this study, 193 adolescents with prepubertal diabetes onset were followed longitudinally for retinopathy (early background and clinical) and microalbuminuria (albumin excretion rate >7.5 micro g/min and >20 micro g/min). Multiple logistic regression analysis was used to compare the effect of pre- and postpubertal diabetes duration on the risk of each complication in 90 subjects reassessed as young adults. For the entire cohort, Kaplan-Meier estimates were used to determine time free of each complication, and survival was compared in those diagnosed before and after age 5 years. Accelerated failure time modeling was used to estimate the effect of covariates, including diabetes duration before puberty, on the risk of complications. RESULTS: Prepubertal duration improved the prediction for retinopathy over postpubertal duration alone in the young adults. The survival-free period of retinopathy and microalbuminuria was significantly longer (2-4 years) for those diagnosed before age 5 years compared with those diagnosed after age 5 years. Time to onset of all complications increased progressively with longer diabetes duration before gonadarche. Higher HbA(1c) during adolescence had an independent effect on the risk of retinopathy and microalbuminuria. CONCLUSIONS: Prepubertal diabetes duration remains a significant predictor of retinopathy in young adults. The effect of time on the risk of retinopathy and microalbuminuria is nonuniform, with an increasing delay in the onset of complications in those with longer prepubertal duration. These findings are of major clinical importance when setting targets of glycemic control in young children who are at greatest risk of hypoglycemia.

Adolescent↗
PubMed2002

Predictors of glycaemic control and hypoglycaemia in children and adolescents with type 1 diabetes from NSW and the ACT.

OBJECTIVES: To audit glycaemic control and incidence of severe hypoglycaemia in children and adolescents with type 1 diabetes in New South Wales (NSW) and the Australian Capital Territory (ACT). DESIGN: A multicentre, population-based, cross-sectional study from 1 September to 31 December, 1999. PARTICIPANTS: 1190 children and adolescents aged 1.2-15.8 years with type 1 diabetes, identified from three hospital-based paediatric diabetes units, four private city-based paediatric practices and 18 regional outreach clinics in NSW and the ACT. MAIN OUTCOME MEASURES: HbA(1c) level and incidence of severe hypoglycaemia (defined by unconsciousness or seizures). RESULTS: The response rate was 67% (1190 of a target group of 1765). The median HbA(1c) level was 8.2% (interquartile range, 7.6%-9.1%). Significant predictors of HbA1c level in a multiple regression model were duration (b = 0.05; 95% CI, 0.02-0.07) and insulin dose/kg (b = 0.46; 95% CI, 0.27-0.66). At least one episode of severe hypoglycaemia in the previous three months was reported in 6.7%, and the rate of severe hypoglycaemia was 36/100 patient-years. Significant predictors of hypoglycaemia in a Poisson regression model were younger age (P = 0.03), male sex (P = 0.04), longer diabetes duration (P = 0.02), and > 3 daily insulin injections (P = 0.02), but not HbA(1c) level. Children with diabetes had higher BMI standard deviation scores compared with population standards, and those in the highest quartile of BMI standard deviation score were younger, had shorter diabetes duration and had higher HbA(1c) level. CONCLUSIONS: Many children and adolescents with type 1 diabetes have suboptimal glycaemic control, placing them at high risk of developing microvascular complications. Those with longer diabetes duration are at increased risk of suboptimal glycaemic control and severe hypoglycaemia and should be targeted for interventional strategies.

Adolescent↗
PubMed2002

Childhood diabetes: a global perspective.

Diabetes is an evolving disease, with changing patterns seen in both type 1 and type 2 diabetes. A wide (over 400-fold) variation exists in worldwide incidence rates of type 1 diabetes, with the highest occurring in Finland (over 45 per 100,000 under the age of 15 years) and the lowest in parts of China. In many countries (e.g. in Europe, the Middle East, Australia) the incidence of autoimmune-mediated type 1 diabetes in children <15 years of age has risen by 2-5% per annum. Type 2 diabetes is also increasing rapidly globally and is occurring at a younger age, including in adolescence and childhood. In the USA, approximately one third of newly diagnosed in the adolescent age group is type 2, with up to 20% presenting with ketosis and ketoacidosis. The management of type 2 diabetes is especially difficult in the adolescent age group. Obesity is the single most obvious risk factor for type 2 diabetes. Lifestyle modification programmes starting in childhood are urgently needed and society needs to change its attitudes to childhood nutrition, play and exercise.

Child, Preschool↗