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Biomedical subjects

N J Wareham

Publications and source records attributed to N J Wareham.

At least 19 recordsLinked to original sources
PubMed2007

Adiponectin receptor genes: mutation screening in syndromes of insulin resistance and association studies for type 2 diabetes and metabolic traits in UK populations.

AIMS/HYPOTHESIS: Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. Several reports suggest that genetic variants in the adiponectin gene are associated with circulating levels of adiponectin, insulin sensitivity and type 2 diabetes risk. Recently two receptors for adiponectin have been cloned. Genetic studies have yielded conflicting results on the role of these genes and type 2 diabetes predisposition. In this study we aimed to evaluate the potential role of genetic variation in these genes in syndromes of severe insulin resistance, type 2 diabetes and in related metabolic traits in UK Europid populations. MATERIALS AND METHODS: Exons and splice junctions of the adiponectin receptor 1 and 2 genes (ADIPOR1; ADIPOR2) were sequenced in patients from our severe insulin resistance cohort (n=129). Subsequently, 24 polymorphisms were tested for association with type 2 diabetes in population-based type 2 diabetes case-control studies (n=2,127) and with quantitative traits in a population-based longitudinal study (n=1,721). RESULTS: No missense or nonsense mutations in ADIPOR1 and ADIPOR2 were detected in the cohort of patients with severe insulin resistance. None of the 24 polymorphisms (allele frequency 2.3-48.3%) tested was associated with type 2 diabetes in the case-control study. Similarly, none of the polymorphisms was associated with fasting plasma insulin, fasting and 2-h post-load plasma glucose, 30-min insulin increment or BMI. CONCLUSIONS/INTERPRETATION: Genetic variation in ADIPOR1 and ADIPOR2 is not a major cause of extreme insulin resistance in humans, nor does it contribute in a significant manner to type 2 diabetes risk and related traits in UK Europid populations.

Diabetes Mellitus, Type 2↗
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

PARL Leu262Val is not associated with fasting insulin levels in UK populations.

AIMS/HYPOTHESIS: PARL, the gene encoding presenilins-associated rhomboid-like protein, maps to chromosome 3q27 within a quantitative trait locus that influences components of the metabolic syndrome. Recently, an amino acid substitution (Leu262Val, rs3732581) in PARL was associated with fasting plasma insulin levels in a US white population (N=1031). This variant was also found to modify the positive association between age and fasting insulin. The aim of this study was to test whether these findings could be replicated in two UK population-based cohorts. METHODS: Participants from the Medical Research Council Ely and Hertfordshire cohort studies were genotyped for this variant using a SNaPshot primer extension assay and Taqman assay respectively. Full phenotypic and genotypic data were available for 3,666 study participants. RESULTS: Based on a dominant model, we found no association between the Leu262Val polymorphism and fasting insulin levels (p=0.79) or BMI (p=0.98). We did not observe the previously reported interaction between age and genotype on fasting insulin (p=0.14). CONCLUSIONS/INTERPRETATION: Despite having greater statistical power, our data do not support the previously reported association between PARL Leu262Val and fasting plasma insulin levels, a measure of insulin resistance. Our findings indicate that this variant is unlikely to be an important contributor to insulin resistance in UK populations.

Aged↗
PubMed2006

Polymorphisms in the gene encoding sterol regulatory element-binding factor-1c are associated with type 2 diabetes.

AIMS/HYPOTHESIS: The sterol regulatory element-binding factor (SREBF)-1c is a transcription factor involved in the regulation of lipid and glucose metabolism. We have previously found evidence that a common SREBF1c single-nucleotide polymorphism (SNP), located between exons 18c and 19c, is associated with an increased risk of type 2 diabetes. The present study aimed to replicate our previously reported association in a larger case-control study and to examine an additional five SREBF1c SNPs for their association with diabetes risk and plasma glucose concentrations. METHODS: We genotyped six SREBF1c SNPs in two case-control studies (n=1,938) and in a large cohort study (n=1,721) and tested for association with type 2 diabetes and with plasma glucose concentrations (fasting and 120-min post-glucose load), respectively. RESULTS: In the case-control studies, carriers of the minor allele of the previously reported SNP (rs11868035) had a significantly increased diabetes risk (odds ratio [OR]=1.20 [95% CI 1.04-1.38], p=0.015). Also, three other SNPs (rs2236513, rs6502618 and rs1889018), located in the 5' region, were significantly associated with diabetes risk (OR > or =1.21, p< or =0.006). Furthermore, two SNPs (rs2236513 and rs1889018) in the 5' region were weakly (p<0.09) associated with plasma glucose concentrations in the cohort study. Rare homozygotes had increased (p< or =0.05) 120-min post-load glucose concentrations compared with carriers of the wild-type allele. Haplotype analyses showed significant (p=0.04) association with diabetes risk and confirmed the single SNP analyses. CONCLUSIONS/INTERPRETATION: In summary, we replicated our previous finding and found evidence for SNPs in the 5' region of the SREBF1c gene to be associated with the risk of type 2 diabetes and plasma glucose concentration.

Aged↗
PubMed2006

Tissue factor serum levels and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study.

INTRODUCTION: Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS: We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS: In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION: High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals.

Aged↗
PubMed2006

Studies of the SIM1 gene in relation to human obesity and obesity-related traits.

OBJECTIVE: The single-minded 1 (SIM1) is a basic helix-loop-helix transcription factor, which plays a critical role in the development of the paraventricular nucleus (PVN) of the hypothalamus. SIM1-deficient mice have a hypocellular PVN and are severely obese with increased food intake. DESIGN: We examined whether variants in the SIM1 gene might be associated with severe early-onset obesity in humans. Two hundred and seventy-seven subjects with hyperphagia and severe, early-onset obesity were screened. Association studies with common single-nucleotide polymorphisms (SNPs) in the SIM1 gene were performed in two population-based cohorts. RESULTS: One novel missense mutation, I128T, was found in one obese subject and not in 192 controls. However, the variant did not co-segregate with obesity in the family. Four SNPs, IVS4+83GA, P352T, A371V and T653T, were also identified. The two common SNPs, P352T and A371V, which are in complete linkage disequilibrium, were genotyped in 981 subjects from a population-based cohort, the Ely Study. An allele frequency of 0.13 was observed. Male subjects carrying the P352T/A371V haplotype were found to have a slightly higher body mass index (BMI; P=0.038). Female subjects homozygous for the haplotype gained more weight over a period of 4.5 and 10 years (P=0.003 and P=0.02, respectively). The association studies were repeated in another population-based cohort, the European Prospective Investigation into Cancer and Nutrition (EPIC) - Norfolk Study with 4869 subjects successfully genotyped. Male subjects homozygous for the P352T/A371V haplotype had slightly higher BMI (P=0.04). CONCLUSION: Mutations in SIM1 are not commonly found in humans with severe early-onset obesity. The relationship between the common variants in SIM1 with BMI and body weight gain deserves further exploration in other populations.

Basic Helix-Loop-Helix Proteins↗
PubMed2006

Fibrinogen plasma levels modify the association between the factor XIII Val34Leu variant and risk of coronary artery disease: the EPIC-Norfolk prospective population study.

BACKGROUND: The factor (F) XIII Val34Leu variant has been implicated in coronary artery disease (CAD). In vitro evidence suggests an interaction between this variant and fibrinogen concentrations in determining thrombus structure. OBJECTIVES: To test whether this interaction is relevant in influencing coronary risk in apparently healthy individuals. METHODS: In an 8-year prospective population study of 25 663 men and women, we compared 898 apparently healthy men and women developing incident CAD with 1580 matched controls. RESULTS: Overall, the FXIII Val34Leu variant was not associated with the risk of future CAD. However, a significant interaction existed between the Val34Leu variant and fibrinogen levels for the risk of future CAD (P = 0.004). Among people in the lowest tertile of fibrinogen concentrations, LeuLeu carriers had an odds ratio (OR) of 2.88 (95% confidence interval; CI 1.24-6.74) compared to wild-type individuals (P for linearity = 0.003). By contrast, among those in the highest fibrinogen tertile, LeuLeu carriers were had a lower risk than wild-type individuals (OR 0.47, 95% CI 0.18-1.17, P for linearity = 0.1). CONCLUSIONS: Our results suggest that a significant gene-covariate interaction exists between the FXIII Val34Leu variant and fibrinogen levels. Relationships between genotype and disease risk may be altered by biological covariates. Simplistic paradigms of gene or biomarker associations are unlikely to fully characterize disease risk in populations.

Adult↗
PubMed2006

Elevated plasma adiponectin in humans with genetically defective insulin receptors.

CONTEXT: Adiponectin has been suggested to play a role in the etiopathogenesis of at least some forms of insulin resistance, in part based on a strong correlation between plasma levels of adiponectin and measures of insulin sensitivity. OBJECTIVE: The objective of the study was to establish whether this relationship is maintained at extreme levels of insulin resistance. DESIGN/SETTING: This was a cross-sectional study in a university teaching hospital of subjects recruited from the United Kingdom and the United States. PARTICIPANTS: Participants included 75 subjects with a range of syndromes of severe insulin resistance and 872 nondiabetic controls. OUTCOME MEASURES: Fasting plasma insulin, adiponectin, and leptin were measured. RESULTS: Unexpectedly, subjects with mutations in the insulin receptor, despite having the most severe degree of insulin resistance, had elevated plasma adiponectin [median 24.4 mg/liter; range 6.6-36.6 (normal adult range for body mass index 20 kg/m(2) = 3-19 mg/liter)], whereas all other subjects had low adiponectin levels (median 2.0 mg/liter; range 0.12-11.2). Plasma leptin in all but one subject with an insulin receptoropathy was low or undetectable [median 0.5 ng/ml; range 0-16: normal adult range for body mass index of < 25 kg/m(2) = 2.4-24.4 (female) and 0.4-8.3 ng/ml (male)]. CONCLUSIONS: We conclude that the relationship between plasma adiponectin and insulin sensitivity is complex and dependent on the precise etiology of defective insulin action and that the combination of high plasma adiponectin with low leptin may have clinical utility in patients with severe insulin resistance as a marker of the presence of a genetic defect in the insulin receptor.

Adiponectin↗
PubMed2006

Does physical activity equally predict gain in fat mass among obese and nonobese young adults?

BACKGROUND: Differences in energy metabolism and physical activity (PA) may contribute to the long-term regulation of body weight (BW). OBJECTIVE: To examine the associations between metabolic determinants, energy expenditure and objectively measured components of PA with change in BW and fat mass (FM). DESIGN: Prospective (4 years.), case-control study in obese (n=13) and normal weight (n=15) young adults. MEASUREMENTS: At baseline, we measured resting metabolic rate, substrate oxidation, movement economy (ml O(2) kg(-1) min(-1)), aerobic fitness (VO(2max)), total and PA energy expenditure by doubly labelled water, and PA by accelerometry. Fat mass was measured by DXA. At follow-up we repeated our measurements of PA and FM. RESULTS: Fat mass increased significantly (P<0.001) in both groups. Physical activity did not change between baseline and 'follow up'. Change in overall PA (counts per minute) was inversely associated with change in BW and (beta=-0.0124, P=0.054) and FM (beta=-0.008, P=0.04). Post hoc analyses suggested that this association was explained by changes in the normal weight group only (beta=-0.01; P=0.008; and beta=-0.0097; P=0.009, for BW and FM, respectively). Metabolic determinants, energy expenditure estimates and subcomponents of PA (i.e. time spent at different intensity levels) were not significantly associated with change in BW or FM. CONCLUSION: Our results suggest an independent association between PA and FM. However, this association may differ depending on obesity status. The gain in FM, without any change in PA, may suggest that dietary intake is the major contributor to the positive energy balance.

Adipose Tissue↗
PubMed2006

What determines the cost-effectiveness of diabetes screening?

AIMS/HYPOTHESIS: The cost-effectiveness of screening for diabetes is unknown but has been modelled previously. None of these models has taken account of uncertainty. We aimed to describe these uncertainties in a model where the outcome was CHD risk. SUBJECTS AND METHODS: Our model used population data from the Danish Inter99 study, and simulations were run in a theoretical population of 1,000,000 individuals. CHD risk was estimated using the UK Prospective Diabetes Study (UKPDS) risk engine, and risk reduction from published randomised clinical trials. Probabilistic sensitivity analysis was used to provide confidence intervals for modelled outputs. Uncertain parameter values were independently simulated from distributions derived from existing literature and deterministic sensitivity analysis performed using multiple model runs under different strategy choices and using extreme parameter estimates. RESULTS: In the least conservative model (low costs and multiplicative risk reduction for combined treatments), the 95% confidence interval of the incremental cost-effectiveness ratio varied from pound23,300-82,000. The major contributors to this uncertainty were treatment risk reduction model parameters: the risk reduction for hypertension treatment and UKPDS risk model intercept. Overall cost-effectiveness ratio was not sensitive to decisions about which groups to screen, nor the costs of screening or treatment. It was strongly affected by assumptions about how treatments combine to reduce risk. CONCLUSIONS/INTERPRETATION: Our model suggests that there is considerable uncertainty about whether or not screening for diabetes would be cost-effective. The most important but uncertain parameter is the effect of treatment. In addition to directly influencing current policy decisions, health care modelling can identify important unknown or uncertain parameters that may be the target of future research.

Adult↗
PubMed2006

The threshold for diagnosing impaired fasting glucose: a position statement by the European Diabetes Epidemiology Group.

The category of IFG was introduced in the late 1990s to denote a state of non-diabetic hyperglycaemia defined by a fasting plasma glucose (FPG) concentration between 6.1 and 6.9 mmol/l. In 2003 the American Diabetes Association recommended that this diagnostic threshold be lowered to 5.6 mmol/l. The justification for lowering the threshold has been questioned. This simple change in cut-off value creates a pandemic of IFG, with a two- to five-fold increase in the prevalence of IFG across the world. Such a change in threshold has far-reaching public health implications. The European Diabetes Epidemiology Group (EDEG) has reviewed the evidence for this lower cut-off point for the definition of IFG and concludes that the previous definition should not be altered. EDEG further recommends that the value of all categorical definitions of non-diabetic hyperglycaemia should be reconsidered.

Blood Glucose↗
PubMed2006

How much might achievement of diabetes prevention behaviour goals reduce the incidence of diabetes if implemented at the population level?

AIMS/HYPOTHESIS: Randomised trials targeting high-risk people with impaired glucose tolerance have halved progression to diabetes using behavioural interventions aimed at achieving five goals related to weight, diet and physical activity. The number of people currently meeting these goals in the general population is unknown. The potential impact on the incidence of diabetes of increasing the proportion of people who meet these goals is also unclear. We quantified the association between the achievement of behavioural goals for the prevention of diabetes and the incidence of diabetes in a population-based cohort study. SUBJECTS AND METHODS: European Prospective Investigation into Cancer (EPIC)-Norfolk is a prospective cohort of 24,155 participants aged 40-79 years who attended a baseline health check and completed validated diet and activity questionnaires. We assessed the association between achievement of five diabetes healthy behaviour prevention goals (BMI <25 kg/m(2), fat intake <30% of energy intake, saturated fat intake <10% of energy intake, fibre intake > or =15 g/4,184 kJ, physical activity >4 h/week) and risk of developing diabetes at follow-up (mean 4.6 years). RESULTS: Only 20% of EPIC participants met three or more diabetes prevention goals. Diabetes incidence was inversely related to the number of goals achieved (p<0.001). None of the participants who met all five goals developed diabetes, whereas diabetes incidence was highest in those who did not meet any goals. If the entire population were able to meet one more goal, the total incidence of diabetes would be predicted to fall by 20%. CONCLUSIONS/INTERPRETATION: In this population-based study, the risk of diabetes was inversely associated with the number of behaviour goals for diabetes prevention that were met. Interventions that promote achievement of these goals in the general population could significantly reduce the growing burden of diabetes-related morbidity and mortality.

Adult↗
PubMed2006

Dietary antioxidants and asthma in adults.

BACKGROUND: Several antioxidant nutrients have been reported to be inversely associated with asthma. A study was undertaken to assess the independent associations of these nutrients with asthma in adults. METHODS: A nested case-control study was performed in 515 adults with physician diagnosed asthma and 515 matched controls using dietary data obtained from 7 day food diaries. The main outcome measures were physician diagnosed asthma and current symptomatic asthma (diagnosed asthma and self-reported wheeze within the previous 12 months). RESULTS: Cases were similar to controls in age, sex, social class, and daily energy intake but had a lower median intake of fruit (132.1 v 149.1 g/day, p< or =0.05). 51.5% of the population reported zero consumption of citrus fruit; relative to these individuals, people who consumed >46.3 g/day had a reduced risk of diagnosed and symptomatic asthma (OR adjusted for potential confounders 0.59 (95% CI 0.43 to 0.82) and 0.51 (95% CI 0.33 to 0.79), respectively). In nutrient analysis, dietary vitamin C and manganese were inversely and independently associated with symptomatic asthma (adjusted OR per quintile increase 0.88 (95% CI 0.77 to 1.00) for vitamin C and 0.85 (95% CI 0.74 to 0.98) for manganese), but only manganese was independently associated with diagnosed asthma (OR 0.86 (95% CI 0.77 to 0.95)). Adjusted plasma levels of vitamin C were significantly lower in symptomatic cases than in controls (54.3 v 58.2 micromol/l, p = 0.003). CONCLUSIONS: Symptomatic asthma in adults is associated with a low dietary intake of fruit, the antioxidant nutrients vitamin C and manganese, and low plasma vitamin C levels. These findings suggest that diet may be a potentially modifiable risk factor for the development of asthma.

Aged↗
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

Derivation and validation of diabetes risk score for urban Asian Indians.

OBJECTIVE: Simple risk scores for identifying people with undiagnosed diabetes have been developed, mostly in Caucasian groups. This may not be suitable for Asian Indians, therefore this study was undertaken to develop and validate a simple diabetes risk score in an urban Asian Indian population with a high prevalence of diabetes. We also tested whether this score was applicable to South Asian migrants living in a different cultural context. RESEARCH DESIGN AND METHODS: A population based Cohort of 10,003 participants aged >or=20 years was divided into two equal halves (Cohorts 1 and 2), after excluding people with known diabetes. Cohort 1 (n=4993) was used to derive the risk score. Validation of the score was performed in the other half of the survey population (Cohort 2) (n=5010). The validation was also done in a separate survey population in Chennai, India (Cohort 3) (n=2002) (diagnosis of diabetes was based on OGTT) and in the South Asian Cohort of the 1999 Health Survey for England (n=676) (fasting glucose value>or=7 mmol/l and HbA1c>or=6.5% were used for diagnosis). A logistic regression model was used to compute the beta coefficients for risk factors. The risk score value was derived from a receiver operating characteristic curve. RESULTS: The significant risk factors included in the risk score were age, BMI, waist circumference, family history of diabetes and sedentary physical activity. A risk score value of >21 gave a sensitivity, specificity, positive predictive value and negative predictive value of 76.6%, 59.9%, 9.4% and 97.9% in Cohort 1, 72.4%, 59%, 8.3% and 97.6% in Cohort 2 and 73.7%, 61.0%, 12.2% and 96.9% in Cohort 3, respectively. The higher distribution of risk factors in the UK Cohort means that at the same cut point the score was much more sensitive but also less specific. (sensitivity 92.2%, specificity 25.7%, positive predictive value of 21.6% and negative predictive value of 93.7%). CONCLUSIONS: A diabetes risk score involving simple non-biochemical measurements was developed and validated in a native Asian Indian population. This easily applicable simple score could play an important role as the first step in the process of identifying individuals with an increased likelihood of having prevalent but undiagnosed diabetes. The different distribution of risk factors with the migrant Asian Indians living in England and the different relationship between sensitivity and specificity for the same score demonstrate that risk scores and cut-points developed and tested even within one ethnic group cannot be generalized to individuals of the same ethnic group living in a different cultural setting where the distribution of risk factors for diabetes is different.

Adult↗
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↗
PubMed2005

Are insulin resistance, impaired fasting glucose and impaired glucose tolerance all equally strongly related to age?

BACKGROUND: Insulin resistance (IR) has been considered an underlying cause of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Whether IR increases with age has been debated. We investigated the age-associated deterioration in the homeostasis model assessment (HOMA) of IR and in glucose metabolism. METHODS: Ten (nine including women) European studies contributed data on 6314 men and 6393 women aged 30-88 years. The cohort- and sex-specific top 25% of HOMA of IR in non-diabetic subjects was used to define HOMA-IR. RESULTS: Compared with subjects aged 50-59 years, the cohort- and body mass index-adjusted odds ratio (95% confidence interval) for HOMA-IR was 0.83 (0.64, 1.08), 0.87 (0.74, 1.03), 1.20 (1.02, 1.42) and 1.45 (1.10, 1.92) in men and 0.84 (0.62, 1.14), 0.91 (0.77, 1.09), 1.38 (1.19, 1.62) and 1.71 (1.35, 2.17) in women, respectively, aged 30-39, 40-49, 60-69 and > or = 70 years (P < 0.0001 for trend test). The same increasing trend was also observed for IFG. In contrast, the corresponding odds ratios for IGT increased linearly and more strongly with age, being 0.37 (0.22, 0.63), 0.67 (0.52, 0.87), 1.55 (1.24, 1.92) and 2.96 (2.13, 4.13) in men and 0.51 (0.31, 0.85), 0.66 (0.52, 0.86), 1.92 (1.57, 2.35) and 3.85 (2.89, 5.12) in women, respectively. CONCLUSIONS: Age is more strongly associated with IGT than with HOMA-IR or IFG in non-diabetic European populations.

Adult↗