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T J Wilkin

Publications and source records attributed to T J Wilkin.

At least 19 recordsLinked to original sources
PubMed2006

IOTF thresholds for overweight and obesity and their relation to metabolic risk in children (EarlyBird 20).

The International Obesity TaskForce has published paediatric cutoffs from the age of 2 years for overweight and obesity, based on adult thresholds. We question their rationale. The adult cutoffs were based on known health risk; the children's were not. Data from the EarlyBird Study show that BMI category for overweight and obesity in young children are poor markers of insulin resistance and, by implication, of metabolic risk and diabetes. Moreover, BMI is known to track poorly from early childhood to adulthood. We know even less about the tracking of insulin resistance and other indices of metabolic risk from the earliest years. Until we understand more about which children acquire such risk factors, any such thresholds for overweight and obesity should be used with caution in the very young, as they may unnecessarily stigmatise the heavier child.

Adult↗
PubMed2006

The gender insulin hypothesis: why girls are born lighter than boys, and the implications for insulin resistance.

Girls are born lighter than boys. The consistency of this observation across different populations is striking, suggesting that it may have fundamental significance for those conditions linked with lower birth weight, such as diabetes. Previous hypotheses relating low birth weight to subsequent diabetes have addressed differences in insulin resistance within the sexes, not between them. Here, we propose that gender-specific genes affecting insulin sensitivity are responsible for the gender difference in birth weight--the genetically more insulin resistant female fetus is less responsive to the trophic effects of insulin and is therefore smaller. These genes also render female subjects more susceptible to diabetes, explaining why reports of type 2 diabetes (T2D) in younger populations show a female preponderance. Consistent with our proposal, concentrations of insulin and/or its propeptides are higher at birth in female populations and they are intrinsically more insulin resistant throughout life, with attendant impact on their metabolism, and the regressions describing the relationship between insulin resistance and adiposity in female and male subjects have similar gradients, but different constants. These gender-specific genes have a demonstrable impact on fetal growth and insulin resistance. Diabetes and cardiovascular disease are thought to be driven by insulin resistance, and the observations reported here may help to focus the search for genes that control it.

Birth Weight↗
PubMed2006

Variation in physical activity lies with the child, not his environment: evidence for an 'activitystat' in young children (EarlyBird 16).

OBJECTIVE: There is currently wide interest in the physical activity of children, but little understanding of its control. Here, we use accelerometers to test the hypothesis that habitual activity in young children is centrally, rather than environmentally, regulated. By central regulation we mean a classic biological feedback loop, with a set-point individual to the child, which controls his/her activity independently of external factors. DESIGN: Non-intervention, observational and population-based, set in the home and at school. RESULTS: Girls were systematically less active than boys, and both weekday/weekend day and year-on-year activities were correlated (r=0.43-0.56). A fivefold variation in timetabled PE explained less than 1% of the total variation in physical activity. The activity cost of transport to school was only 2% of total activity, but over 90% of it was recovered elsewhere in the day. The weekly activity recorded by children in Plymouth was the same (to within <0.3%) as that recorded independently in Glasgow, 800 km away. Total daily activity was unrelated to time reportedly spent watching TV. INTERPRETATION: The correlations within groups and the similarities between them suggest that physical activity in children is under central biological regulation. There are implications both for public health planners and for the potentially novel signalling pathways involved.

Acceleration↗
PubMed2006

Increased urinary dopamine excretion in association with bilateral carotid body tumours-- clinical, biochemical and genetic findings.

This report describes a rare case of a patient with increased urinary dopamine excretion in association with bilateral carotid body tumours. Excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and 4-hydroxy-3-methoxymandelic acid (HMMA) were within the reference ranges, and an (123)I-meta-iodobenzylguanidine (MIBG) scan showed uptake in the neck masses, with no other abnormal uptake anywhere else in the body. The patient is being managed conservatively as the tumours are not amenable to resection on account of their size and vascularity. There are only four previous case reports of dopamine-secreting tumours of the carotid body described in the literature, all of whom were women. The tumours were unilateral in three cases and bilateral in the fourth case. Familial cases of carotid body tumours have a higher prevalence of bilateral tumours than non-familial cases. Recent reports in the literature have suggested that a significant number of patients with extra-adrenal catecholamine-secreting paragangliomas have a genetic mutation in one of the identified susceptibility genes for catecholamine-secreting tumours, despite having no other affected family members, and a mutation has been found in the succinate dehydrogenase gene for this patient.

3-Iodobenzylguanidine↗
PubMed2004

Anal intraepithelial neoplasia in heterosexual and homosexual HIV-positive men with access to antiretroviral therapy.

BACKGROUND: Studies of human immunodeficiency virus (HIV)-positive men have demonstrated high rates of anal intraepithelial neoplasia (AIN), a precursor to anal carcinoma, mostly in white homosexual men and men not receiving effective antiretroviral therapy (ART). METHODS: Ninety-two participants--53% Latino, 36% African American, and 40% without a history of receptive anal intercourse (RAI)--were evaluated with a behavioral questionnaire, liquid-based anal cytological testing, Hybrid Capture 2 human papillomavirus (HPV) DNA assay and polymerase chain reaction, and anal colposcopy with biopsy of lesions. RESULTS: High-risk HPV DNA was identified in 61%, and this was associated with a history of RAI (78% vs. 33%; P<.001); 47% had abnormal cytological results, and 40% had AIN on biopsy. In multivariate analysis, both were associated with a history of RAI (odds ratio [OR], 10 [P<.001] and OR, 3.6 [P=.02], respectively) and lower nadir CD4(+) cell counts (P=.06 and P=.01). Current ART use was protective (OR, 0.09; P<.01 and OR, 0.18; P=.02). CONCLUSIONS: Although anal infections with high-risk HPV and AIN in HIV-positive men are associated with a history of RAI, both conditions are commonly identified in HIV-positive men without this history. Both lower nadir CD4(+) cell counts and lack of current ART were associated with AIN but not with the detection of anal HPV.

Adult↗
PubMed2004

Metabolic risk in early childhood: the EarlyBird Study.

OBJECTIVE: For a decade or more, poor nutrition during gestation, expressed as low weight at birth, was held to be the factor responsible for insulin resistance later in life. Birth weights, however, are rising and insulin-resistant states, such as diabetes, faster still. Alternative explanations are needed for insulin resistance in contemporary society. This review cites data from the EarlyBird study on the relationships of insulin resistance and metabolic disturbance in early childhood. DESIGN: EarlyBird is a nonintervention prospective cohort study that asks the question 'Which children develop insulin resistance, and why?' It is unique in taking serial blood samples from a young age with which to monitor the behaviour of insulin resistance and its metabolic correlates, and in its comprehensive assessment of factors known or thought to influence insulin resistance SUBJECTS: In all, 307 randomly selected healthy school children at school entry (mean age 4.9 y) and at 12 and 24 months later. MEASUREMENTS: In the children: Birth weight and, at each time point height, weight, body mass index (BMI, kg/m(2)), skinfolds at five sites, circumferences, resting energy expenditure, physical activity, body composition, heart rate variability, diet, HOMA-IR and HOMA-ISC, blood pressure, full blood count, haemoglobin and haematocrit, HbA1C, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, uric acid, IGF-1, gonadotrophins and SHBG. In their parents: At baseline height, weight, BMI, waist circumference, HOMA-IR and HOMA-ISC, full blood count, haematocrit, HbA1C, total cholesterol, HDL cholesterol, calculated LDL cholesterol, triglycerides, uric acid, gonadotrophins and SHBG. RESULTS: Four observations are reported here: (1) There are clear correlations in contemporary children between insulin resistance and weight at 5 y, but none with birth weight. (2) Females throughout life are intrinsically more insulin resistant than males. (3) The substantial variation of physical activity among young children is attributable to the child, and not to his environment. (4) There is dissociation in young children between fatness and insulin resistance. CONCLUSION: There is much yet to be learned about the development of obesity and insulin resistance in children. The notions of overnutrition and underactivity alone are too simplistic.

Anthropometry↗
PubMed2004

Exploring the idiotypes of insulin antibodies as markers for remission in Type 1 diabetes.

AIMS: Complete or partial remission can occur in newly diagnosed Type 1 diabetes patients. We created idiotype-specific reagents to explore the idiotypes of insulin antibodies (IA) in a patient in remission, and to compare with a patient who was not. METHODS: Phage display was used to create a library of phagotopes specific to insulin binding in four sera. Sera from a Type 1 diabetes subject deemed to have undergone remission were taken at diagnosis and again during remission. Sera from a non-remitter were taken at diagnosis and after 3 months on insulin. Phagotopes from the four sera were randomly selected and tested for insulin specificity in a radiobinding assay by using sera from remitters and non-remitters. RESULTS: IA-binding phagotope selected from serum during remission displaced insulin binding in all nine IA(+) remitters and all 10 IA(+) non-remitters. IA-binding phagotope selected from the non-remission patient (3 months after insulin therapy) displaced insulin binding in 8/9 IA(+) remitters and 8/10 IA(+) non-remitters. The consensus peptide sequences adduced from the phages were identical for both these phagotopes. Phagotopes derived from insulin autoantibody-positive individuals at diagnosis were unable to displace insulin binding in the IA(+) sera 3 months later, whether in remission or not. CONCLUSIONS: We have established the principle of using phage display in the investigation of insulin antibodies during remission in Type 1 diabetes. The immunological characteristics of IA 3 months after the introduction of insulin treatment were different from those at diagnosis of Type 1 diabetes (IAA). Using phage display technology, it was not possible to distinguish insulin antibodies according to remission status.

Adolescent↗
PubMed2003

The use of phage display to distinguish insulin autoantibody (IAA) from insulin antibody (IA) idiotypes.

AIM/HYPOTHESIS: Radiobinding assays (RBA) are unable to differentiate insulin autoantibodies (IAA) from insulin antibodies (IA). We sought to establish whether random peptide phage display might generate reagents with which to distinguish IAA idiotopes from IA idiotopes. METHODS: Two insulin-binding sera were used to select phagotopes from a phage library. The first, designated IAS, came from an insulin-treated patient with the insulin autoimmune syndrome, and was known to contain both IA and a high titre of human insulin specific (B30 threonine dependent) IAA. The second, designated IDD, was taken from a newly-diagnosed IAA(+) Type 1 diabetic patient. Phage colonies selected by insulin-purified IgG extracts of IAS and IDD were selected at random for DNA sequencing, and tested for their reactivity with insulin antibodies and ability to distinguish disease-associated idiotopes. RESULTS: Seven phagotopes bound IAS and the phagotope designated IAS-9, corresponding to sequence KRSRLDV, gave the highest binding standard deviation (SD) score. Seven phagotopes bound IDD and the phagotope designated IDD-10, corresponding to sequence LGRGGSK, bound most strongly. IAS-9 was able to displace insulin binding in IAS and all of ten insulin-treated Type 2 diabetic patients, but not the IAA present in any of the eight patients with newly-diagnosed Type 1 diabetes. IDD-10, on the other hand, could displace insulin binding detected in the sera of eight patients with untreated Type 1 diabetes (IAA), but not in IAS or sera of the insulin-treated Type 2 diabetics. CONCLUSION: Phagotopes provide reagents which between them can distinguish positively as well as negatively diabetes-associated IAA from non-diabetes associated IAA and from IA.

Amino Acid Sequence↗
PubMed2003

Testing the accelerator hypothesis: the relationship between body mass and age at diagnosis of type 1 diabetes.

OBJECTIVE: Previous reports have predicted greater risk of type 1 diabetes among people who were heavier as young children. The Accelerator Hypothesis predicts earlier onset in heavier people, without necessarily a change in risk, and views type 1 and type 2 diabetes as the same disorder of insulin resistance, set against different genetic backgrounds. Insulin resistance is a function of fat mass, and increasing body weight in the industrialized world has been accompanied by earlier presentation (i.e., acceleration) of type 2 diabetes. We wanted to establish whether increasing body weight was also associated with the earlier presentation of type 1 diabetes, as the Accelerator Hypothesis would predict. RESEARCH DESIGN AND METHODS: The relationships between fatness and age at diagnosis were examined in context of birth weight, weight change since birth, weight at diagnosis, BMI at diagnosis, and BMI 12 months later in 94 children aged 1-16 years (49 boys and 45 girls) presenting for management of acute-onset type 1 diabetes. RESULTS: BMI standard deviation score (SDS) at diagnosis, weight SDS change since birth, and BMI SDS 12 months later were all inversely related to age at presentation (r = -0.39 to -0.40, P < 0.001). The boys were significantly fatter than the girls (BMI SDS 0.56 vs. -0.08, respectively; P = 0.006) and presented with diabetes at a significantly younger age (6.74 vs. 8.32 years, respectively; P < 0.05). The sex difference in age at diagnosis, however, disappeared when corrected for BMI (P = 0.31), suggesting that fatness or something related to it was the responsible factor. CONCLUSIONS: The data are consistent with the hypothesis that the age at presentation of type 1 diabetes is associated with fatness. The implications for prevention of type 1 diabetes may be important.

Adolescent↗
PubMed2002

Accelerometers identify inactive and potentially obese children (EarlyBird 3).

Accelerometers revealed a fivefold variation in physical activity among healthy 5 year old children. They singled out habitually inactive children, most of them girls, who did little, whether at school or over the weekend. Accelerometers are of potential value in identifying, from an early age, children at risk of becoming obese.

Biomechanical Phenomena↗