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P W Franks

Publications and source records attributed to P W Franks.

10 recordsLinked to original sources
PubMed2007

PPARGC1A coding variation may initiate impaired NEFA clearance during glucose challenge.

AIMS/HYPOTHESIS: The peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein, encoded by the PPARGC1A gene, transcriptionally activates a complex pathway of lipid and glucose metabolism and is expressed primarily in tissues of high metabolic activity such as liver, heart and exercising oxidative skeletal muscle fibre. Ppargc1a-null mice develop systemic dyslipidaemia and hepatic steatosis. In humans, NEFAs downregulate PPARGC1A expression in skeletal muscle. Furthermore, a common non-synonymous coding variant at PPARGC1A (Gly482Ser, rs8192678) is associated with decreased PPARGC1A mRNA levels and increased type 2 diabetes risk. MATERIALS AND METHODS: In a population-based sample of 691 healthy middle-aged Europids we assessed whether Gly482Ser is associated with levels of NEFA when fasting and in response to an oral glucose challenge. We also assessed the potential effect-modifying role of adipose tissue mass on these phenotypes. RESULTS: After adjustment for age, sex, fat mass and fat-free mass, the Ser482 allele associated with higher NEFA at 30 min and 2 h and with NEFA AUC (all values p 0.6). CONCLUSIONS/INTERPRETATION: Our observations indicate that NEFA clearance is blunted following a glucose load in carriers of the PPARCG1A Ser482 allele. This association is augmented by obesity.

Adipose Tissue↗
PubMed2006

Sex-specific effect of the Val1483Ile polymorphism in the fatty acid synthase gene (FAS) on body mass index and lipid profile in Caucasian children.

OBJECTIVE: A Val1483Ile polymorphism in the human fatty acid sythase gene (FAS) has recently been shown to be associated with lower percentage of body fat and substrate oxidation rates in Pima Indians, but its role in other populations has not been described. Here, we investigate the effect of this variant on obesity in Caucasian children and adolescents. SUBJECTS AND METHODS: In total, 738 Caucasian children and adolescents aged 6-17 years of the Leipzig Schoolchildren cohort, which constitutes an unselected representative German population and 205 obese children (body mass index (BMI) 2.71+/-0.04 SDS) were genotyped for genotype-phenotype associations. RESULTS: The frequency of the Ile-allele was lower in German Caucasians compared with Pima Indians (0.03 compared to 0.10). Using generalized linear regression models, there was no effect of the polymorphism on BMI in the whole normal population. However, we identified a significant interaction effect between sex and genotype (P=0.004). Subsequent sex stratified analyses revealed a lower BMI SDS in boys with Ile/Val genotype compared to Val/Val (-0.36+/-0.29 vs 0.09+/-0.05, P<0.05), while an opposite effect was observed in girls (0.48+/-0.19 vs 0.09+/-0.05, P<0.05). In genotype-phenotype associations in obese children, the polymorphism did not affect parameters of insulin, glucose, or lipid metabolism in the whole population. Again, however, obese boys with Ile/Val genotype had significantly higher high-density lipoprotein (HDL) cholesterol levels (1.46+/-0.07 vs 1.23+/-0.03 mmol/l, P<0.05). CONCLUSION: In conclusion, our findings suggest a sex-specific protective effect of the Val1483Ile polymorphism in FAS for obesity in Caucasian boys. In addition, the polymorphism may be associated with a beneficial lipid profile in obese boys.

Adolescent↗
PubMed2006

Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes.

AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PPARGC1A) is a transcriptional co-activator with a central role in energy expenditure and glucose metabolism. Several studies have suggested that the common PPARGC1A polymorphism Gly482Ser may be associated with risk of type 2 diabetes, with conflicting results. To clarify the role of Gly482Ser in type 2 diabetes and related human metabolic phenotypes we genotyped this polymorphism in a case-control study and performed a meta-analysis of relevant published data. MATERIALS AND METHODS: Gly482Ser was genotyped in a type 2 diabetes case-control study (N=1,096) using MassArray technology. A literature search revealed publications that examined Gly482Ser for association with type 2 diabetes and related metabolic phenotypes. Meta-analysis of the current study and relevant published data was undertaken. RESULTS: In the pooled meta-analysis, including data from this study and seven published reports (3,718 cases, 4,818 controls), there was evidence of between-study heterogeneity (p<0.1). In the fixed-effects meta-analysis, the pooled odds ratio for risk of type 2 diabetes per Ser482 allele was 1.07 (95% CI 1.00-1.15, p=0.044). Elimination of one of the studies from the meta-analysis gave a summary odds ratio of 1.11 (95% CI 1.04-1.20, p=0.004), with no between-study heterogeneity (p=0.475). For quantitative metabolic traits in normoglycaemic subjects, we also found significant between-study heterogeneity. However, no significant association was observed between Gly482Ser and BMI, fasting glucose or fasting insulin. CONCLUSIONS/INTERPRETATION: This meta-analysis of data from the current and published studies supports a modest role for the Gly482Ser PPARGC1A variant in type 2 diabetes risk.

Blood Glucose↗
PubMed2005

Reliability and validity of the combined heart rate and movement sensor Actiheart.

UNLABELLED: Accurate quantification of physical activity energy expenditure is a key part of the effort to understand disorders of energy metabolism. The Actiheart, a combined heart rate (HR) and movement sensor, is designed to assess physical activity in populations. OBJECTIVE: To examine aspects of Actiheart reliability and validity in mechanical settings and during walking and running. METHODS: In eight Actiheart units, technical reliability (coefficients of variation, CV) and validity for movement were assessed with sinusoid accelerations (0.1-20 m/s(2)) and for HR by simulated R-wave impulses (25-250 bpm). Agreement between Actiheart and ECG was determined during rest and treadmill locomotion (3.2-12.1 km/h). Walking and running intensity (in J/min/kg) was assessed with indirect calorimetry in 11 men and nine women (26-50 y, 20-29 kg/m(2)) and modelled from movement, HR, and movement + HR by multiple linear regression, adjusting for sex. RESULTS: Median intrainstrument CV was 0.5 and 0.03% for movement and HR, respectively. Corresponding interinstrument CV values were 5.7 and 0.03% with some evidence of heteroscedasticity for movement. The linear relationship between movement and acceleration was strong (R(2) = 0.99, P < 0.001). Simulated R-waves were detected within 1 bpm from 30 to 250 bpm. The 95% limits of agreement between Actiheart and ECG were -4.2 to 4.3 bpm. Correlations with intensity were generally high (R(2) > 0.84, P < 0.001) but significantly highest when combining HR and movement (SEE < 1 MET). CONCLUSIONS: The Actiheart is technically reliable and valid. Walking and running intensity may be estimated accurately but further studies are needed to assess validity in other activities and during free-living. SPONSORSHIP: The study received financial support from the Wellcome Trust and SB was supported by a scholarship from Unilever, UK.

Adult↗
PubMed2004

Does peroxisome proliferator-activated receptor gamma genotype (Pro12ala) modify the association of physical activity and dietary fat with fasting insulin level?

Peroxisome proliferator-activated receptor gamma (PPARgamma) has a role in controlling adipogenesis and insulin sensitivity. Previous studies have suggested that a common polymorphism (Pro12Ala) in the PPARgamma-2 isoform of this gene may be associated with markers of insulin resistance. We have previously shown that in combination, the relationships with fasting insulin of dietary polyunsaturated to saturated fatty acid ratio (P:S ratio) and physical activity are additive. We have also demonstrated that the association between P:S ratio and fasting insulin level is modified by the Pro12Ala genotype. The purpose of the present study was to investigate whether the Pro12Ala genotype modified the combined relationships of P:S ratio and physical activity level (PAL) on fasting insulin concentration. A population-based cohort of 506 Caucasian men and women aged 31 to 71 years was genotyped for the Pro12Ala polymorphism. P:S ratio was assessed by food-frequency questionnaire (FFQ) and PAL was estimated from 4 days of free-living heart rate monitoring following individual calibration of heart rate against energy expenditure during an exercise stress test. The combined associations of PAL and P:S ratio on fasting insulin level were examined stratified by Pro12Ala genotypes in a dominant model for the Ala allele. Among Pro allele homozygotes, there was no interaction between PAL and P:S ratio on fasting insulin (P =.929). However, in carriers of the Ala allele the association of P:S ratio with fasting insulin was modified by activity level (interaction P = 0.038). In those who were inactive and carried the Ala allele, the age-, sex-, and body mass-adjusted relationship between P:S ratio and log insulin was not significant (beta = -0.03, P =.93). In contrast, in physically active Ala carriers, the association of P:S ratio with log fasting insulin was highly significant (beta = -0.93, P =.004). In conclusion, this study examined the modification by PPARgamma genotype of the association between energy expenditure, P:S ratio, and fasting insulin level, a measure of insulin resistance. These data show that in Pro allele homozygotes the combined associations of P:S ratio and PAL are additive. In contrast, in Ala allele carriers, PAL modifies the association between P:S ratio and fasting insulin level in a multiplicative manner.

Adult↗
PubMed2004

Objectively measured physical activity correlates with indices of insulin resistance in Danish children. The European Youth Heart Study (EYHS).

OBJECTIVE: To explore the association between measures of insulin resistance with objectively assessed physical activity. DESIGN: School-based, cross-sectional study. SUBJECTS: A randomly selected sample of 589 children (310 girls, 279 boys, mean (standard deviations, s.d.) age=9.7 (0.44) y, weight=33.6 (6.4) kg, height=1.39 (0.06) m) from Denmark. METHODS: Fasting blood samples were analysed for serum insulin and glucose. Physical activity was measured with the uniaxial Computer Science and Applications (CSA) model 7164 accelerometer, worn for at least 3 days (>/=10 h day(-1)). Adiposity was assessed by the sum of four skinfolds. Multiple linear regression were performed to model insulin and glucose from average CSA output, adjusted for age, gender, puberty, ethnicity, birth weight, parental smoking, socioeconomic group, and CSA unit. In addition, we adjusted for skinfold thickness. RESULTS: Mean fasting serum glucose ranged from 4.1 to 6.5 mmol l(-1) with a mean (s.d.) of 5.1 (0.37) mmol l(-1). Fasting insulin was negatively correlated with CSA output on levels of adjustment. Fasting glucose was not significantly associated with physical activity. However, in girls both indices of insulin resistance were significantly related to activity, whereas in boys none of the associations were significant. CONCLUSION: Physical activity is inversely associated with fasting insulin in the nondiabetic range of fasting glucose. The relationship was stronger for insulin than for glucose, indicating compensatory action by the beta cells. Our data emphasise the importance of physical activity in children for the maintenance of metabolic control.

Biomarkers↗
PubMed1979

The use of ionising radiation for the treatment of injuries to flexor tendons and supporting ligaments in horses.

A technique was developed using radioactive isotopes as a source of radiation for the treatment of injuries to the superficial and deep flexor tendons and the associated ligaments in the horse. The treatment area was sub-divided so that different dosages could be applied over the limb as necessary. A plaster of Paris impression was taken of the whole area to be treated. In the isotope laboratory a plaster negative was made and loaded with the dose of radioactive isotope. The loaded cast was then strapped to the horse's limb for the calculated time, usually about three days. A total of 42 horses were treated and follow up information was obtained from 28. Twenty-five animals raced again; two relapsed before racing and one was destroyed with navicular disease. Ten of the 42 horses had been treated by firing before irradiation. Five of these returned to racing but the history of four of them was not known.

Animals↗