Motives of contributing personal data for health research: (non-)participation in a Dutch biobank.

BACKGROUND: Large-scale, centralized data repositories are playing a critical and unprecedented role in fostering innovative health research, leading to new opportunities as well as dilemmas for the medical sciences. Uncovering the reasons as to why citizens do or do not contribute to such repositories, for example, to population-based biobanks, is therefore crucial. We investigated and compared the views of existing participants and non-participants on contributing to large-scale, centralized health research data repositories with those of ex-participants regarding the decision to end their participation. This comparison could yield new insights into motives of participation and non-participation, in particular the behavioural change of withdrawal. METHODS: We conducted 36 in-depth interviews with ex-participants, participants, and non-participants of a three-generation, population-based biobank in the Netherlands. The interviews focused on the respondents' decision-making processes relating to their participation in a large-scale, centralized repository for health research data. RESULTS: The decision of participants and non-participants to contribute to the biobank was motivated by a desire to help others. Whereas participants perceived only benefits relating to their participation and were unconcerned about potential risks, non-participants and ex-participants raised concerns about the threat of large-scale, centralized public data repositories and public institutes, such as social exclusion or commercialization. Our analysis of ex-participants' perceptions suggests that intrapersonal characteristics, such as levels of trust in society, participation conceived as a social norm, and basic societal values account for differences between participants and non-participants. CONCLUSIONS: Our findings indicate the fluidity of motives centring on helping others in decisions to participate in large-scale, centralized health research data repositories. Efforts to improve participation should focus on enhancing the trustworthiness of such data repositories and developing layered strategies for communication with participants and with the public. Accordingly, personalized approaches for recruiting participants and transmitting information along with appropriate regulatory frameworks are required, which have important implications for current data management and informed consent procedures.

Correction to: Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study.

The values given for copeptin levels in men in quartiles 1 and 2 (Table 1) were incorrect, and should have read.

An activity stimulation programme during a child's first year reduces some indicators of adiposity at the age of two-and-a-half.

AIM: Obesity tracks from childhood into adulthood. We evaluated the effect of early stimulation of physical activity on growth, body composition, motor activity and motor development in toddlers. METHODS: We performed a cluster randomised controlled single-blinded trial in Dutch Well Baby Clinics, with seven nurses and 96 children (40% girls) randomised to the intervention group and six nurses and 65 children (57% girls) to the control group. Intervention nurses advised parents on stimulating motor development and physical activity during regular visits at 2 weeks and two, four, eight and 11 months. Baseline characteristics such as birthweight and mode of feeding were comparable. Outcomes at two-and-a-half years included anthropometry, skinfold thicknesses, bioelectrical impedance analyses, motor development and daily physical activity. We used linear mixed models with nurses as cluster. RESULTS: We evaluated 143 children (89 intervention, 54 control) as 18 dropped out. Skinfolds were significantly lower in intervention children (29.6 ± 4.7 mm) than controls (32.4 ± 6.0 mm), without differences in motor development or daily physical activity. Female interventions showed lower weight, skinfolds, waist and hip circumference. CONCLUSION: An activity stimulating programme during the child's first year improved indicators of adiposity when they were toddlers, especially in girls. Further research should determine whether these effects persist.

Skipping breakfast and overweight in 2- and 5-year-old Dutch children-the GECKO Drenthe cohort.

Skipping breakfast is associated with higher BMI in children aged 5 years and older. However, not much is known about this association in younger children. In the Dutch GECKO Drenthe birth cohort we examined the association between breakfast skipping and objectively measured overweight at the age of 2 (n=1488) and 5 (n=1366) years. At 2 years, 124 (8.3%) children were overweight and 44 (3.0%) did not eat breakfast daily. At 5 years, 180 (13.2%) children were overweight and 73 (5.3%) did not eat breakfast daily. Children belonging to families of non-Dutch origin, those with lower educated parents and those with single parents skipped breakfast more often. Breakfast skipping in 2- and 5-year-olds is rare in the Netherlands. We found no association between skipping breakfast and overweight, neither at age 2 (odds ratio (OR): 1.85 (95% confidence interval (CI): 0.61-5.64)) nor at age 5 (OR: 0.46 (95% CI: 0.19-1.11)). Also the type of breakfast was not related to overweight at 5 years. An explanation for this finding might be that skipping breakfast is not (yet) an issue in these children.

Longitudinal measurement of physical activity following kidney transplantation.

The purpose of this longitudinal observational study was to (i) examine the change of daily physical activity in 28 adult kidney transplant recipients over the first 12 months following transplantation; and (ii) to examine the change in metabolic characteristics and renal function. Accelerometer-based daily physical activity and metabolic- and clinical characteristics were measured at six wk (T1), three months (T2), six months (T3) and 12 months (T4) following transplantation. Linear mixed effect analyses showed an increase in steps/d (T1 = 6326 ± 2906; T4 = 7562 ± 3785; F = 3.52; p = 0.02), but one yr after transplantation only 25% achieved the recommended 10 000 steps/d. There was no significant increase in minutes per day spent on moderate-to-vigorous intensity physical activity (T1 = 80.4 ± 63.6; T4 = 93.2 ± 55.1; F = 1.71; p = 0.17). Body mass index increased over time (T1 = 25.4 ± 3.2; T4 = 27.2 ± 3.8; F = 12.62; p < 0.001), mainly due to an increase in fat percentage (T1 = 30.3 ± 8.0; T4 = 34.0 ± 7.9; F = 14.63; p < 0.001). There was no significant change in renal function (F = 0.17; p = 0.92). Although the recipients increased physical activity, the majority did not meet the recommended levels of physical activity after one yr. In addition to the weight gain, this may result in negative health consequences. Therefore, it is important to develop strategies to support kidney transplant recipients to comply with healthy lifestyle recommendations, including regular physical activity.

Predictors of influenza in the adult population during seasonal and A(H1N1)pdm09 pandemic influenza periods.

We aimed to assess whether the characteristics of influenza-like illness (ILI) cases in the general population were similar during the seasonal and pandemic A(H1N1)pdm09 influenza periods. We conducted a study using a general population database, which included demographic (sex, age) and clinical (underlying medical conditions, influenza vaccination status) information on more than 80 000 subjects. We assessed the most important predictors of ILI during each season by using multiple logistic regression. We descriptively compared whether they were similar during different seasons. The model, including all demographic and clinical characteristics, showed that age ⩾60 years decreased the odds for ILI by 52% and 81% during the seasonal and A(H1N1)pdm09 pandemic periods, respectively. Being vaccinated decreased the odds of ILI for seasonal influenza by 32%, while suffering from the comorbidities other than lung or cardiovascular diseases doubled the odds of ILI during the A(H1N1)pdm09 pandemic.

Predictive accuracy of Edinburgh postnatal depression scale assessment during pregnancy for the risk of developing postpartum depressive symptoms: a prospective cohort study.

OBJECTIVE: To investigate whether the 10-item Edinburgh Postnatal Depression Scale (EPDS) administered antenatally is accurate in predicting postpartum depressive symptoms, and whether a two-item EPDS has similar predictive accuracy. DESIGN: Prospective cohort study. SETTING: Obstetric care in the Netherlands. POPULATION: One thousand six hundred and twenty women from the general population. METHODS: Mean values, area under the receiver operating characteristics curve (AUC), sensitivity, specificity and predictive values of antenatal EPDS for the likelihood of developing postpartum depressive symptoms were calculated. Analyses were repeated for each trimester, several cut-off values and a two-item EPDS (low mood and anhedonia). MAIN OUTCOME MEASURES: Postpartum depressive symptoms, defined as EPDS score≥10. RESULTS: Mean EPDS scores were significantly higher during each trimester in women with postpartum depressive symptoms than in those without the symptoms (P<0.001). Using the prevailing cut-off (≥13), the AUC was reasonable (0.74), sensitivity was 16.8% (95% CI 11.0-24.1), positive predictive value was 41.8% (95% CI 28.7-55.9), specificity was 97.8% (95% CI 97.0-98.5) and negative predictive value was 92.7% (95% CI 91.3-94.0). Using a lower cut-off value (≥5), sensitivity was 70.8% (95% CI 62.4-78.3) and specificity was 65.4% 4 (95% CI 62.9-67.8), but positive predictive value was low (15.9%, 95% CI 13.1-19.0). Negative predictive value was exceedingly high at 96.0% (95% CI 94.6-97.2). Results were similar during the second and third trimester. The predictive accuracy of the two-item EPDS appeared inferior. CONCLUSIONS: The EPDS was not sufficiently accurate in predicting risk of postpartum depressive symptoms. Nevertheless, when using the ≥5 cut-off value, it may be adequate for initial screening, followed by further assessments and possibly antenatal intervention when positive. Furthermore, when negative, women may be reassured that postpartum depressive symptoms are unlikely. A two-item version showed poor predictive accuracy.

A multidisciplinary intervention programme has positive effects on quality of life in overweight and obese preschool children.

AIM: Up to 18.1% of Dutch children aged 3-5 are overweight and up to 3.3% are obese, with higher levels in girls. This study assessed the effect of a multidisciplinary intervention programme on health-related quality of life (HRQoL) in this patient group. METHODS: We randomised 75 children to a multidisciplinary intervention, comprising dietary advice, exercise sessions and psychological counselling for parents or the standard care programme, providing healthy lifestyle advice. The parents completed quality of life and child health questionnaires at baseline and after 16 weeks and 12 months. RESULTS: At 16 weeks, children in the intervention group experienced more bodily pain and less mental health than the standard care group, but at 12 months, this difference disappeared and they showed a more positive change in HRQoL than the standard care group, especially for the physical domain. When we combined both groups, a decreased BMIz-score over 12 months was associated with increased global health and reduced visceral fat correlated with increased general health. CONCLUSION: At 12 months, a multidisciplinary intervention programme for overweight and obese children aged 3-5 years had beneficial effects on HRQoL, especially for the physical domain. Reduced obesity parameters correlated with several increased HRQoL parameters.

Determinants of HbA1c in nondiabetic Dutch adults: genetic loci and clinical and lifestyle parameters, and their interactions in the Lifelines Cohort Study.

OBJECTIVES: Glycated haemoglobin (HbA1c) is associated with cardiovascular disease risk in individuals without diabetes, and its use has been recommended for diagnosing diabetes. Therefore, it is important to gain further understanding of the determinants of HbA1c. The aim of this study was to investigate the effects of genetic loci and clinical and lifestyle parameters, and their interactions, on HbA1c in nondiabetic adults. DESIGN: Population-based cohort study. SETTING: Three northern provinces of the Netherlands. SUBJECTS: A total of 2921 nondiabetic adults participating in the population-based LifeLines Cohort Study. MEASUREMENTS: Body mass index (BMI), waist circumference, HbA1c, fasting plasma glucose (FPG) and erythrocyte indices were measured. Data on current smoking and alcohol consumption were collected through questionnaires. Genome-wide genotyping was performed, and 12 previously identified single-nucleotide polymorphisms (SNPs) were selected for replication and categorized as 'glycaemic' and 'nonglycaemic' SNPs according to their presumed mechanism(s) of action on HbA1c. Genetic risk scores (GRSs) were calculated as the sum of the weighted effect of HbA1c-increasing alleles. RESULTS: Age, gender, BMI, FPG, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, current smoking and alcohol consumption were independent predictors of HbA1c, together explaining 26.2% of the variance in HbA1c, with FPG contributing 10.9%. We replicated three of the previously identified SNPs and the GRSs were also found to be independently associated with HbA1c. We found a smaller effect of the 'nonglycaemic GRS' in females compared with males and an attenuation of the effect of the GRS of all 12 SNPs with increasing BMI. CONCLUSIONS: Our results suggest that a substantial portion of HbA1c is determined by nonglycaemic factors. This should be taken into account when considering the use of HbA1c as a diagnostic test for diabetes.

Routine screening for Coxiella burnetii infection during pregnancy: a clustered randomised controlled trial during an outbreak, the Netherlands, 2010.

Between 2007 and 2010, the Netherlands experienced one of the largest outbreaks of Q fever. Since asymptomatic Coxiella burnetii infection has been associated with maternal and obstetric complications, evidence about the effectiveness of routine screening during pregnancy in outbreak areas is needed. We performed a clustered randomised controlled trial during the Dutch outbreak, in which 55 midwife centres were randomised to recruit pregnant women for an intervention or control strategy. In both groups a serum sample was taken between 20 and 32 weeks of gestation. In the intervention group (n=536), the samples were analysed immediately by indirect immunofluorescence assay for the presence of IgM and IgG (phase I/II) and treatment was given during pregnancy in case of an acute or chronic infection. In the control group (n=693), sera were frozen for analysis after delivery. In both groups 15% were seropositive. In the intervention group 2.2% of the women were seropositive and had an obstetric complication, compared with 1.4% in the control group (Odds ratio: 1.54 (95% confidence interval 0.60-3.96)). During a large Q fever outbreak, routine C. burnetii screening starting at 20 weeks of gestation was not associated with a relevant reduction in obstetric complications and should therefore not be recommended.

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study.

AIMS/HYPOTHESIS: Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately. METHODS: From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7 years. RESULTS: In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p (interaction) < 0.01). The addition of copeptin to the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) clinical model improved the discriminative value (C-statistic,+0.007, p = 0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p < 0.01) in women. However, we observed no improvement in men. The additive value of copeptin in women was maintained when other independent predictors, such as glucose, high sensitivity C-reactive protein (hs-CRP) and 24 h urinary albumin excretion (UAE), were included in the model. CONCLUSIONS/INTERPRETATION: The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women.

The influence of maternal and paternal factors on time to pregnancy--a Dutch population-based birth-cohort study: the GECKO Drenthe study.

BACKGROUND: Both maternal and paternal factors have been suggested to influence a couple's fecundity. To investigate this, we examined the role of several maternal and paternal lifestyle and socio-demographic factors as determinants of time to pregnancy (TTP) in a Dutch birth-cohort. METHODS: Groningen Expert Center for Kids with Obesity (GECKO) Drenthe is a population-based birth-cohort study of children born between April 2006 and April 2007 in Drenthe, a province of The Netherlands. Both partners received extensive questionnaires during pregnancy. Univariable and multivariable Cox regression analyses were used to determine the impact of the investigated factors on TTP. RESULTS: A total of 4778 children were born, and the parents of 2997 children (63%) gave their consent to participate. After excluding unintended pregnancies and pregnancies as a result of fertility treatment, the data of 1924 couples were available for analysis. Hazards ratios and 95% confidence intervals of factors influencing TTP in multivariable Cox regression analysis were: maternal age 1.23 (0.98-1.54) for age <25 years, 1.17 (1.03-1.32) for age 25-30 years and 0.72 (0.61-0.85) for age >35 years (reference category: 30-35 years); paternal age: 1.31 (0.94-1.82) for age <25 years, 1.11 (0.97-1.28) for age 25-30 years and 0.91 (0.80-1.04 for age >35 years (reference category: 30-35 years); nulliparity: 0.76 (0.68-0.85) versus multiparity; menstrual cycle length: 1.12 (0.95-1.30) for 3 weeks, 0.72 (0.62-0.83) for 4-6 weeks, 0.68 (0.40-1.16) for >6 weeks and 0.66 (0.54-0.81) for irregular cycle (reference category: 4 weeks); prior contraceptive use: 0.78 (0.67-0.91) for no contraception, 1.68 (1.45-1.95) for condom use, 1.08 (0.89-1.33) for condom use combined with oral contraception, 1.40 (1.16-1.70) for intrauterine device and 0.50 (0.25-1.01) for contraceptive injection (reference category: oral contraception); and maternal educational level 0.75 (0.62-0.92) for low education level and 0.81 (0.73-0.90) for medium educational level (reference category: high educational level). CONCLUSIONS: This population-based birth-cohort study performed in fertile couples who had conceived revealed neither maternal nor paternal modifiable lifestyle factors were significantly associated with TTP after adjustment for confounding by socio-demographic factors. In contrast, several non-modifiable maternal socio-demographic factors are significant predictors of a couple's fecundity.

Maternal and paternal transmission of type 2 diabetes: influence of diet, lifestyle and adiposity.

OBJECTIVE: Transmission of family history of type 2 diabetes to the next generation is stronger for maternal than paternal diabetes in some populations. The aim of the present study was to investigate whether this difference is explained by diet, lifestyle factors and/or adiposity. METHODS: We analysed 35174 participants from the Dutch contribution to the European Prospective Investigation into Cancer and Nutrition, a prospective population-based cohort (aged 20-70 years) with a median follow-up of 10.2 years. Parental history of diabetes was self-reported. Occurrence of diabetes was mainly identified by self-report and verified by medical records. RESULTS: Amongst 35174 participants, 799 incident cases of diabetes were observed. In age- and sex-adjusted analyses, hazard ratio (HR) and 95% confidence intervals (CIs) for diabetes by maternal and paternal diabetes were 2.66 (2.26-3.14) and 2.40 (1.91-3.02), respectively. Maternal transmission of risk of diabetes was explained by diet (9.4%), lifestyle factors including smoking, alcohol consumption, physical activity and educational level (7.8%) and by adiposity, i.e. body mass index and waist and hip circumference (23.5%). For paternal transmission, the corresponding values were 2.9%, 0.0% and 9.6%. After adjustment for diet, lifestyle factors and adiposity, the HRs for maternal (2.20; 95% CI, 1.87-2.60) and paternal (2.23; 95% CI, 1.77-2.80) transmission of diabetes were comparable. CONCLUSIONS: Both maternal and paternal diabetes are associated with increased risk of type 2 diabetes, independently of diet, lifestyle and adiposity. The slightly higher risk conferred by maternal compared to paternal diabetes was explained by a larger contribution of diet, lifestyle factors and adiposity.

Markers of the hepatic component of the metabolic syndrome as predictors of mortality in renal transplant recipients.

Cardiovascular disease (CVD) is a leading cause of mortality in renal transplant recipients (RTRs). Metabolic syndrome (MS) is highly prevalent in RTRs. Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic component of MS. We investigated associations of NAFLD markers with MS and mortality. RTRs were investigated between 2001 and 2003. NAFLD markers, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) were measured. Bone and nonbone fractions of AP were also determined. Death was recorded until August 2007. Six hundred and two RTRs were studied (age 52+/-12 years, 55% men). At baseline 388 RTRs had MS. Prevalence of MS was positively associated with liver enzymes. During follow-up for 5.3[4.5-5.7] years, 95 recipients died (49 cardiovascular). In univariate Cox regression analyses, GGT (HR=1.43[1.21-1.69], p<0.001) and AP (HR=1.34[1.11-1.63], p=0.003) were associated with mortality, whereas ALT was not. Similar associations were found for cardiovascular mortality. Adjustment for potential confounders, including MS, diabetes and traditional risk factors did not materially change these associations. Results for nonbone AP mirrored that for total AP. ALT, GGT and AP are associated with MS. Of these three enzymes, GGT and AP are associated with mortality, independent of MS. These findings suggest that GGT and AP are independently related to mortality in RTRs.

Association between alcohol consumption and diabetic retinopathy and visual acuity-the AdRem Study.

AIMS: We investigated the association between alcohol consumption and diabetic retinopathy and deterioration of visual acuity in individuals with Type 2 diabetes. METHODS: We conducted a cohort analysis of 1239 participants with Type 2 diabetes aged 55-81 years enrolled in the AdRem study, a sub-study of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. Current and past consumption of wine, spirits and beer was measured by self-report. Moderate and heavy alcohol consumption was defined as 1-14 and >14 drinks/week, respectively. Diabetic retinopathy, measured by mydriatic stereoscopic seven-field retinal photography, was defined by a 2-step progression in the Early Treatment of Diabetic Retinopathy Study (ETDRS) score or the presence of any retinal vascular lesions. Deterioration of visual acuity was defined by a decrease of two lines in best vision in either eye, measured corrected, or through a pinhole using a Snellen chart. RESULTS: In a mean follow-up of 5.5 years, we identified 182 participants with a 2-step progression in the ETDRS score, 640 participants with the presence of any retinal vascular lesions and 693 participants with a deterioration of visual acuity. Current moderate consumption of alcohol, compared with no current consumption, was not associated with presence or progression of diabetic retinopathy; however, it was associated with higher risk of deterioration of visual acuity (multivariable-adjusted OR 1.83; 95% CI 1.34-2.48; P<0.001). CONCLUSIONS: Alcohol consumption is associated with increased risk of deterioration of visual acuity, but not with retinopathy in individuals with Type 2 diabetes.

How do parents of 4- to 5-year-old children perceive the weight of their children?

INTRODUCTION: A heavier weight in adults is becoming the norm rather than an abnormal weight. Whether the same trend is happening in children is unknown. OBJECTIVE: To assess the perception of the weight of 4- to 5-year-old children and the recognition of overweight by both parents. DESIGN: Population-based survey. PARTICIPANTS: A questionnaire was sent to parents of 1155 4- to 5-year-old children. RESULTS: In total, 439 questionnaires (35%) were returned. Of all, 90% of the children had a normal weight, 9.3% were overweight and 4.1% were obese. For all weight classes, the parents depicted the child as lighter on both the verbal and visual scale. Of all, 75% of mothers of overweight children stated that the child had a normal weight. In obese children, 50% of the mothers believed that the child had a normal weight. CONCLUSION: Children with a weight in the normal range were considered by their parents as a little too light or too light. Overweight was considered as normal weight, and obesity as normal or a little too heavy. The perception of a normal weight in children at 4-5 years is distorted.

Bivariate genetic modelling of the response to an oral glucose tolerance challenge: a gene x environment interaction approach.

AIMS/HYPOTHESIS: Twin and family studies have shown the importance of genetic factors influencing fasting and 2 h glucose and insulin levels. However, the genetics of the physiological response to a glucose load has not been thoroughly investigated. METHODS: We studied 580 monozygotic and 1,937 dizygotic British female twins from the Twins UK Registry. The effects of genetic and environmental factors on fasting and 2 h glucose and insulin levels were estimated using univariate genetic modelling. Bivariate model fitting was used to investigate the glucose and insulin responses to a glucose load, i.e. an OGTT. RESULTS: The genetic effect on fasting and 2 h glucose and insulin levels ranged between 40% and 56% after adjustment for age and BMI. Exposure to a glucose load resulted in the emergence of novel genetic effects on 2 h glucose independent of the fasting level, accounting for about 55% of its heritability. For 2 h insulin, the effect of the same genes that already influenced fasting insulin was amplified by about 30%. CONCLUSIONS/INTERPRETATION: Exposure to a glucose challenge uncovers new genetic variance for glucose and amplifies the effects of genes that already influence the fasting insulin level. Finding the genes acting on 2 h glucose independently of fasting glucose may offer new aetiological insight into the risk of cardiovascular events and death from all causes.

Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of the present study was to investigate the effect of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in type 2 diabetic patients. METHODS: The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) Retinal Measurements study, a substudy of ADVANCE, is a randomised (using a central, computer-based procedure) controlled 2 x 2 factorial trial comprising a double-blind comparison of blood pressure lowering with perindopril-indapamide vs placebo, and an open comparison of standard vs intensive glucose control targeting a HbA(1c) of < or = 6.5% in 1,602 diabetic patients from ADVANCE centres with access to retinal cameras conducted from 2001 to 2008. At baseline and the final visit, seven-field stereoscopic retinal photographs were taken and graded by blinded readers (gradeable baseline and final photographs from 1,241 patients). Progression of > or =2 steps in the Early Treatment of Diabetic Retinopathy Study classification (using the eye with worst grading) was the primary outcome. RESULTS: Retinopathy progressed in 59 (4.8%) patients and developed in 128 (10.3%) patients over 4.1 years. Fewer patients on blood pressure-lowering treatment (n = 623) experienced incidence or progression of retinopathy compared with patients on placebo (n = 618), but the difference was not significant (OR 0.78; 95% CI 0.57-1.06; p = 0.12). Blood pressure-lowering treatment reduced the occurrence of macular oedema (OR 0.50; 95% CI 0.29-0.88; p = 0.016) and arteriovenous nicking compared with placebo (OR 0.60; 95% CI 0.38-0.94; p = 0.025). Compared with standard glucose control (n = 611), intensive glucose control (n = 630) did not reduce (p = 0.27) the incidence and progression of retinopathy (OR 0.84; 95% CI 0.61-1.15). Lower, borderline significant risks of microaneurysms, hard exudates and macular oedema were observed with intensive glucose control, adjusted for baseline retinal haemorrhages. These effects of the two treatments were independent and additive. Adverse events in the ADVANCE study are reported elsewhere. CONCLUSIONS/INTERPRETATION: Blood pressure lowering or intensive glucose control did not significantly reduce the incidence and progression of retinopathy, although consistent trends towards a benefit were observed, with significant reductions in some lesions observed with both interventions. TRIAL REGISTRATION: ClinicalTrials.gov ID no. NCT00145925. FUNDING: Grants from Servier and the National Health and Medical Research Council of Australia.

HbA(1c) levels in non-diabetic Dutch children aged 8-9 years: the PIAMA birth cohort study.

AIM: Glycated haemoglobin (HbA(1c)) is considered the best index of glycaemic control in established diabetes. It may also be useful in the diagnosis of diabetes and as a screening tool. Little is known about the distribution of HbA(1c) in healthy children and its predictors. The aim of this study is to describe the distribution of HbA(1c) in non-diabetic Dutch children aged 8-9 years and to investigate potential associations of HbA(1c) in this group. METHODS: HbA(1c) was measured in 788 non-diabetic children aged 8-9 years participating in the PIAMA birth cohort study. Data on parents and children were collected prospectively by questionnaires. Weight, height and waist and hip circumference of the children were measured when blood samples were taken. RESULTS: Mean (SD) HbA(1c) was 4.9 +/- 0.33%, range 3.5-6.0%. HbA(1c) was significantly higher in boys (4.9 +/- 0.31 vs. 4.9 +/- 0.33%) and in children of mothers with gestational diabetes (5.0 +/- 0.37 vs. 4.9 +/- 0.32%). We found a significant inverse association between HbA(1c) and haemoglobin (regression coefficient: -0.169 (95% CI -0.221 to -0.118), P < 0.001). HbA(1c) was not significantly associated with age, body mass index, waist circumference, parental diabetes or maternal body mass index. CONCLUSIONS: We found no significant relation between known risk factors for Type 2 diabetes and HbA(1c) at age 8-9 years. Moreover, there was a significant inverse association between haemoglobin and HbA(1c). These results suggest that HbA(1c) may not only reflect the preceding blood glucose levels, but seems to be determined by other factors as well.