Derek G. Cook

Birth weight and risk of type 2 diabetes: A systematic review

CONTEXT Low birth weight is implicated as a risk factor for type 2 diabetes. However, the strength, consistency, independence, and shape of the association have not been systematically examined. OBJECTIVE To conduct a quantitative systematic review examining published evidence on the association of birth weight and type 2 diabetes in adults. DATA SOURCES AND STUDY SELECTION Relevant studies published by June 2008 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1950), and Web of Science (from 1980), with a combination of text words and Medical Subject Headings. Studies with either quantitative or qualitative estimates of the association between birth weight and type 2 diabetes were included. DATA EXTRACTION Estimates of association (odds ratio [OR] per kilogram of increase in birth weight) were obtained from authors or from published reports in models that allowed the effects of adjustment (for body mass index and socioeconomic status) and the effects of exclusion (for macrosomia and maternal diabetes) to be examined. Estimates were pooled using random-effects models, allowing for the possibility that true associations differed between populations. DATA SYNTHESIS Of 327 reports identified, 31 were found to be relevant. Data were obtained from 30 of these reports (31 populations; 6090 diabetes cases; 152 084 individuals). Inverse birth weight-type 2 diabetes associations were observed in 23 populations (9 of which were statistically significant) and positive associations were found in 8 (2 of which were statistically significant). Appreciable heterogeneity between populations (I(2) = 66%; 95% confidence interval [CI], 51%-77%) was largely explained by positive associations in 2 native North American populations with high prevalences of maternal diabetes and in 1 other population of young adults. In the remaining 28 populations, the pooled OR of type 2 diabetes, adjusted for age and sex, was 0.75 (95% CI, 0.70-0.81) per kilogram. The shape of the birth weight-type 2 diabetes association was strongly graded, particularly at birth weights of 3 kg or less. Adjustment for current body mass index slightly strengthened the association (OR, 0.76 [95% CI, 0.70-0.82] before adjustment and 0.70 [95% CI, 0.65-0.76] after adjustment). Adjustment for socioeconomic status did not materially affect the association (OR, 0.77 [95% CI, 0.70-0.84] before adjustment and 0.78 [95% CI, 0.72-0.84] after adjustment). There was no strong evidence of publication or small study bias. CONCLUSION In most populations studied, birth weight was inversely related to type 2 diabetes risk.

A Comparison of Questionnaire, Accelerometer, and Pedometer: Measures in Older People

PURPOSE To compare (i) the convergent validity of the self-report Zutphen Physical Activity Questionnaire with the 7-d objective physical activity (PA) measurement by accelerometers and pedometers and (ii) the construct validity of these measures by examining their associations with physical health and psychological and anthropometric variables. METHODS Five hundred and sixty community-dwelling people aged > or =65 yr were invited from a UK primary care practice and 238 (43%) participated (mean age = 74, 53% male). PA was assessed subjectively by the Zutphen questionnaire (modified to include housework questions) and objectively by the 7-d accelerometer monitoring: a random half also had a pedometer. A questionnaire assessed health, disability, and psychological factors, and anthropometric assessment was performed. RESULTS Mean daily PA levels were as follows: Zutphen = 9.1 kcal x kg(-1) x d(-1) (SD = 6.6 kcal x kg(-1) x d(-1)); accelerometer activity count = 226,648 (SD = 121,966); accelerometer step count = 6495 (SD = 3212); and pedometer step count = 6712 (SD = 3526). Zutphen score was moderately correlated with accelerometer activity count (R = 0.34, P < 0.001) and pedometer step count (R = 0.36, P < 0.001). Pedometer step count was highly correlated with accelerometer activity count (R = 0.82, P< 0.001) and accelerometer step count (R = 0.86, P < 0.001). Objective PA measures showed strong associations with health and anthropometric and psychological variables. Zutphen score was not significantly related to most health or anthropometric measures but was associated with psychological variables and provided information about activity type. CONCLUSIONS Convergent validity was strong between accelerometers and pedometers but weaker between these and self-report Zutphen. Pedometers may be preferred to accelerometers for simple studies due to their lower cost. Objective measures had better construct validity, being more strongly associated with established PA determinants, and thus offered better value to researchers than the questionnaire, but the latter provided useful detail on activity type, so a combined approach to PA assessment may be preferable.

Age and Gender Variations in Age-related Macular Degeneration Prevalence in Populations of European Ancestry: A Meta-analysis

OBJECTIVE To obtain prevalence estimates of age-related macular degeneration (AMD; late, geographic atrophy, neovascular) by age and gender amongst populations of European ancestry taking into account study design and time trends. DESIGN Systematic review of population-based studies published by September 2010 with quantitative estimates of geographic atrophy (GA), neovascular (NV), and late AMD prevalence. Studies were identified by a literature search of MEDLINE (from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases. PARTICIPANTS Data from 25 published studies (57 173 subjects: 455 with GA, 464 with NVAMD, and 1571 with late AMD). METHODS Bayesian meta-regression of the log odds of AMD with age, gender, and year of study allowing for differences in study design characteristics, to estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals (CrI). MAIN OUTCOME MEASURES Log odds and prevalence of AMD. RESULTS There was considerable heterogeneity in prevalence rates between studies; for late AMD, 20% of the variability in prevalence rates was explained by differences in age and 50% by study characteristics. The prevalence of AMD increased exponentially with age (odds ratio [OR], 4.2 per decade; 95% CrI, 3.8-4.6), which did not differ by gender. There was some evidence to suggest higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0-1.5). Compared with studies using fundus imaging and international classification systems, studies using fundus imaging with alternative classifications were more likely (OR, 2.7; 95% CrI, 1.1-2.8), and studies using alternative classifications without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI, 1.3-7.8). There was no good evidence of trends in AMD prevalence over time. Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%-2.0%) at 70 years of age, rising to 5.6% (95% CrI, 3.9%-7.7%) at age 80 and 20% (95% CrI, 14%-27%) at age 90. CONCLUSIONS Studies using recognized classifications systems with fundus photography reported the lowest prevalences of AMD taking account of age and gender, and were stable over time, with a potentially higher risk of NVAMD for women. These prevalence estimates can be used to guide health service provision in populations of European ancestry.

Ethnic and gender differences in physical activity levels among 9–10-year-old children of white European, South Asian and African–Caribbean origin: the Child Heart Health Study in England (CHASE Study)

BACKGROUND Ethnic differences in physical activity in children in the UK have not been accurately assessed. We made objective measurements of physical activity in 9-10-year-old British children of South Asian, black African-Caribbean and white European origin. METHODS Cross-sectional study of urban primary school children (2006-07). Actigraph-GT1M activity monitors were worn by 2071 children during waking hours on at least 1 full day. Ethnic differences in mean daily activity [counts, counts per minute of registered time (CPM) and steps] were adjusted for age, gender, day of week and month. Multilevel modelling allowed for repeated days within individual and clustering within school. RESULTS In white Europeans, mean daily counts, CPM and mean daily steps were 394,785, 498 and 10,220, respectively. South Asian and black Caribbean children recorded more registered time per day than white Europeans (34 and 36 min, respectively). Compared with white Europeans, South Asians recorded 18 789 fewer counts [95% confidence interval (CI) 6390-31 187], 41 fewer CPM 95% CI 26-57) and 905 fewer steps (95% CI 624-1187). Black African-Caribbeans recorded 25 359 more counts (95% CI 14 273-36 445), and similar CPM, but fewer steps than white Europeans. Girls recorded less activity than boys in all ethnic groups, with 74 782 fewer counts (95% CI 66 665-82 899), 84 fewer CPM (95% CI 74-95) and 1484 fewer steps (95% CI 1301-1668). CONCLUSION British South Asian children have lower objectively measured physical activity levels than European whites and black African-Caribbeans.

Early emergence of ethnic differences in type 2 diabetes precursors in the UK: the Child Heart and Health Study in England (CHASE Study).

Peter Whincup and colleagues carry out a cross-sectional study examining ethnic differences in precursors of of type 2 diabetes among children aged 9–10 living in three UK cities.

Multiple regression in geographical mortality studies, with allowance for spatially correlated errors

In order to provide clues to the aetiology of a disease, mortality indices for different areas are often related to explanatory variables by using multiple regression. However, mortality in nearby areas may be similar for reasons not attributable to the covariates, so the errors will not be independent. This paper suggests a way of finding a parameterized form for the correlated error structure by examining the residuals from an ordinary least squares regression. Such a model is then fitted by using maximum likelihood. An example based on cardiovascular mortality in British towns is used to illustrate the problem and our solution.

Mortality Associations with Long-Term Exposure to Outdoor Air Pollution in a National English Cohort

RATIONALE Cohort evidence linking long-term exposure to outdoor particulate air pollution and mortality has come largely from the United States. There is relatively little evidence from nationally representative cohorts in other countries. OBJECTIVES To investigate the relationship between long-term exposure to a range of pollutants and causes of death in a national English cohort. METHODS A total of 835,607 patients aged 40-89 years registered with 205 general practices were followed from 2003-2007. Annual average concentrations in 2002 for particulate matter with a median aerodynamic diameter less than 10 (PM(10)) and less than 2.5 μm (PM(2.5)), nitrogen dioxide (NO(2)), ozone, and sulfur dioxide (SO(2)) at 1 km(2) resolution, estimated from emission-based models, were linked to residential postcode. Deaths (n = 83,103) were ascertained from linkage to death certificates, and hazard ratios (HRs) for all- and cause-specific mortality for pollutants were estimated for interquartile pollutant changes from Cox models adjusting for age, sex, smoking, body mass index, and area-level socioeconomic status markers. MEASUREMENTS AND MAIN RESULTS Residential concentrations of all pollutants except ozone were positively associated with all-cause mortality (HR, 1.02, 1.03, and 1.04 for PM(2.5), NO(2), and SO(2), respectively). Associations for PM(2.5), NO(2), and SO(2) were larger for respiratory deaths (HR, 1.09 each) and lung cancer (HR, 1.02, 1.06, and 1.05) but nearer unity for cardiovascular deaths (1.00, 1.00, and 1.04). CONCLUSIONS These results strengthen the evidence linking long-term ambient air pollution exposure to increased all-cause mortality. However, the stronger associations with respiratory mortality are not consistent with most US studies in which associations with cardiovascular causes of death tend to predominate.

Long-term exposure to outdoor air pollution and incidence of cardiovascular diseases.

Background: Evidence based largely on US cohorts suggests that long-term exposure to fine particulate matter is associated with cardiovascular mortality. There is less evidence for other pollutants and for cardiovascular morbidity. By using a cohort of 836,557 patients age 40 to 89 years registered with 205 English general practices in 2003, we investigated relationships between ambient outdoor air pollution and incident myocardial infarction, stroke, arrhythmia, and heart failure over a 5-year period. Methods: Events were identified from primary care records, hospital admissions, and death certificates. Annual average concentrations in 2002 for particulate matter with a median aerodynamic diameter <10 (PM10) and <2.5 microns, nitrogen dioxide (NO2), ozone, and sulfur dioxide at a 1 × 1 km resolution were derived from emission-based models and linked to residential postcode. Analyses were performed using Cox proportional hazards models adjusting for relevant confounders, including social and economic deprivation and smoking. Results: While evidence was weak for relationships with myocardial infarction, stroke, or arrhythmia, we found consistent associations between pollutant concentrations and incident cases of heart failure. An interquartile range change in PM10 and in NO2 (3.0 and 10.7 µg/m3, respectively) both produced a hazard ratio of 1.06 (95% confidence interval = 1.01–1.11) after adjustment for confounders. There was some evidence that these effects were greater in more affluent areas. Conclusions: This study of an English national cohort found evidence linking long-term exposure to particulate matter and NO2 with the development of heart failure. We did not, however, replicate associations for other cardiovascular outcomes that have been reported elsewhere.

What Factors Predict Potentially Inappropriate Primary Care Prescribing in Older People? : Analysis of UK Primary Care Patient Record Database

BackgroundPotentially inappropriate prescribing (PIP) in older people has been identified as a substantial problem, but few large population-based studies have investigated the underlying factors that predict it.ObjectiveTo: (i) examine trends in PIP in UK older primary care patients; and (ii) assess factors associated with PIP.MethodsAn analysis of routine, anonymized, computerized patient records of 201 UK general practices providing data to the DIN-LINK database between 1996 and 2005, which included approximately 230 000 registered patients per year aged ≥65 years. The main outcome measures were the number of different drugs prescribed per patient annually and the percentage of patients prescribed a PIP drug (modified 2003 Beers criteria). These were assessed for all drugs, and then for selected sub-classes (analgesics, antidepressants and sedatives/anxiolytics).ResultsWhilst the number of drugs prescribed per patient increased, the percentage of subjects receiving a PIP drug declined from 32.2% in 1996 to 28.3% in 2005, largely due to a fall in co-proxamol (dextropropoxyphene/paracetamol [acetaminophen]) prescribing. In 2005, female gender, being older, more socioeconomically deprived or in a care home were strongly associated with PIP. However, the number of drugs prescribed was strongly associated with these variables and the strongest predictor of PIP; adjusting for number of drugs dramatically reduced the strength of all other associations except female gender with PIP. Factors predicting PIP in drug sub-groups were similarly reduced when adjusted for polypharmacy. However, some age trends remained: in the oldest group (aged ≥85 years), PIP of analgesics was less likely (odds ratio [OR] = 0.70, 95% CI 0.66, 0.75) while PIP of antidepressants was more likely (OR =1.39, 95% CI 1.28, 1.51).ConclusionPIP amongst older people in the UK, although declining, remains at a high level. The association of PIP with age, deprivation and care homes is largely explained by the higher overall prescribing rates in these groups. The overall rise in prescribing emphasizes that polypharmacy does not necessarily increase PIP and attempts to reduce PIP by focusing on polypharmacy have not been successful. Reductions in PIP have previously been achieved by introducing national guidelines (e.g. co-proxamol), but might also be achieved by alerting practitioners at the point of prescribing.

Retinal Arteriolar Tortuosity and Cardiovascular Risk Factors in a Multi-Ethnic Population Study of 10-Year-Old Children; the Child Heart and Health Study in England (CHASE)

Objective—To examine the association between cardiovascular risk factors and retinal arteriolar tortuosity in a multi-ethnic child population. Methods and Results—Cross sectional study of 986 UK primary school children of South Asian, black African Caribbean, and white European origin aged 10 to 11 years. Anthropometric measurements and retinal imaging were carried out and a fasting blood sample collected. Digital images of retinal arterioles were analyzed using a validated semiautomated measure of tortuosity. Associations between tortuosity and cardiometabolic risk factors were analyzed using multi-level linear regression, adjusted for gender, age, ethnicity, arteriole branch status, month, and school. Levels of arteriolar tortuosity were similar in boys and girls and in different ethnic groups. Retinal arteriolar tortuosity was positively associated with levels of triglyceride, total and LDL cholesterol, and systolic and diastolic blood pressure. One standard deviation increases in these risk factors were associated with 3.7% (95% CI: 1.2%, 6.4%), 3.3% (0.9%, 5.8%), 3.1% (0.6%, 5.6%), 2.0% (−0.3%, 4.2%), and 2.3% (0.1%, 4.6%) increases in tortuosity, respectively. Adiposity, insulin resistance, and blood glucose showed no associations with tortuosity. Conclusion—Established cardiovascular risk factors, strongly linked to coronary heart disease in adulthood, may influence retinal arteriolar tortuosity at the end of the first decade of life.