Congenital malformations among offspring of women with type 1 diabetes who use insulin pumps: a prospective cohort study.

AIMS/HYPOTHESIS: Continuous subcutaneous insulin infusion by insulin pump is often superior in improving glycaemic control compared with conventional multiple daily insulin injection (MDI). However, whether pump treatment leads to improved pregnancy outcomes in terms of congenital malformations and perinatal death remains unknown. The present aim was to evaluate the risk of malformations and perinatal and neonatal death in pregnant women with type 1 diabetes treated with pump or MDI. METHODS: We performed a secondary analysis of a prospective multinational cohort of 2088 pregnant women with type 1 diabetes in a real-world setting who were treated by pump (n=750) or MDI (n=1338). ORs for offspring with congenital malformations or perinatal or neonatal death were calculated using crude data and by logistic regression on propensity score-matched data. RESULTS: At enrolment (gestational week 8; 95% CI 4, 14), pump users had a higher educational level (university degree: 37.3% vs 25.1%; p<0.001) and better glycaemic control (mean HbA1c: 51±10 mmol/mol [6.8±0.9%] vs 54±14 mmol/mol [7.1±1.3%], p<0.001) compared with MDI users. Moreover, a greater proportion of pump users had an HbA1c level below 75 mmol/mol (9%) (97.6% vs 91.9%, p<0.001), and more often reported taking folic acid supplementation (86.3% vs 74.8%; p<0.001) compared with MDI users. All clinically important potential confounders were balanced after propensity score matching, and HbA1c remained lower in pump users. The proportion of fetuses with at least one malformation was 13.5% in pump users vs 11.2% in MDI users (crude OR 1.23; 95% CI 0.94, 1.61; p=0.13; propensity score-matched (adjusted) OR 1.11; 95% CI 0.81, 1.52; p=0.52). The proportion of fetuses with at least one major malformation was 2.8% in pump users vs 3.1% in MDI users (crude OR 0.89; 95% CI 0.52, 1.51; p=0.66; adjusted OR 0.78; 95% CI 0.42, 1.45; p=0.43), and the proportions of fetuses carrying one or more minor malformations (but no major malformations) were 10.7% vs 8.1% (crude OR 1.36; 95% CI 1.00, 1.84; p=0.05; adjusted OR 1.23; 95% CI 0.87, 1.75; p=0.25). The proportions of perinatal and neonatal death were 1.6% vs 1.3% (crude OR 1.23; 95% CI 0.57, 2.67; p=0.59; adjusted OR 2.02; 95% CI 0.69, 5.93; p=0.20) and 0.3% vs 0.3% (n=2 vs n=4, p=not applicable), respectively. CONCLUSIONS/INTERPRETATIONS: Insulin pump treatment was not associated with a lower risk of congenital malformations, despite better glycaemic control in early pregnancy compared with MDI. Further studies exploring the efficacy and safety of pump treatment during pregnancy are needed.

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study.

AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Cardiovascular risk factors early in the course of treatment in people with type 2 diabetes without established cardiovascular disease: A population-based observational retrospective cohort study.

AIMS: To characterise the cardiovascular risk of people with type 2 diabetes without established cardiovascular disease but with risk factors, relative to those with established cardiovascular disease, to provide information on which patients could benefit from early use of glucose-lowering therapies that also reduce cardiovascular risk. METHODS: Data from people with type 2 diabetes initiating second-line glucose-lowering medication were retrieved from the UK Clinical Practice Research Datalink GOLD database and linked with Hospital Episode Statistics and Office for National Statistics (2001-2016). Cox proportional hazards models were used to estimate relative risks of major adverse cardiovascular events within groups defined by the presence of selected risk factors in people without versus with established cardiovascular disease. RESULTS: Of 53,182 individuals, 19.4% had established cardiovascular disease (i.e. a prior cardiovascular event). Over 5-7 years' follow-up, the rate of major adverse cardiovascular events was 14.0 and 49.6 events/1000 person-years without and with established cardiovascular disease, respectively (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.26, 0.29). Compared with a reference HR 1.0 for participants with established cardiovascular disease, estimated glomerular filtration rate <60 mL/min was the single factor associated with the highest risk of major adverse cardiovascular events (HR 0.75, 95% CI 0.70, 0.81) and mortality (HR 1.12, 95% CI 1.07, 1.18) in people with type 2 diabetes without established cardiovascular disease. The combination of chronic kidney disease with older age, smoking and/or dyslipidaemia was associated with a similarly high risk of cardiovascular events in people with type 2 diabetes and without cardiovascular disease compared with those having established cardiovascular disease. CONCLUSIONS: These analyses provide important information to identify people who may benefit from primary prevention of cardiovascular disease. Modifiable cardiovascular risk factors should be controlled early in all individuals with type 2 diabetes (as well as in all individuals with cardiovascular disease).

Road Traffic and Railway Noise Exposures and Adiposity in Adults: A Cross-Sectional Analysis of the Danish Diet, Cancer, and Health Cohort.

BACKGROUND: Traffic noise has been associated with cardiovascular and metabolic disorders. Potential modes of action are through stress and sleep disturbance, which may lead to endocrine dysregulation and overweight. OBJECTIVES: We aimed to investigate the relationship between residential traffic and railway noise and adiposity. METHODS: In this cross-sectional study of 57,053 middle-aged people, height, weight, waist circumference, and bioelectrical impedance were measured at enrollment (1993-1997). Body mass index (BMI), body fat mass index (BFMI), and lean body mass index (LBMI) were calculated. Residential exposure to road and railway traffic noise exposure was calculated using the Nordic prediction method. Associations between traffic noise and anthropometric measures at enrollment were analyzed using general linear models and logistic regression adjusted for demographic and lifestyle factors. RESULTS: Linear regression models adjusted for age, sex, and socioeconomic factors showed that 5-year mean road traffic noise exposure preceding enrollment was associated with a 0.35-cm wider waist circumference (95% CI: 0.21, 0.50) and a 0.18-point higher BMI (95% CI: 0.12, 0.23) per 10 dB. Small, significant increases were also found for BFMI and LBMI. All associations followed linear exposure-response relationships. Exposure to railway noise was not linearly associated with adiposity measures. However, exposure > 60 dB was associated with a 0.71-cm wider waist circumference (95% CI: 0.23, 1.19) and a 0.19-point higher BMI (95% CI: 0.0072, 0.37) compared with unexposed participants (0-20 dB). CONCLUSIONS: The present study finds positive associations between residential exposure to road traffic and railway noise and adiposity.

Long-term exposure to residential traffic noise and changes in body weight and waist circumference: A cohort study.

BACKGROUND: Traffic noise can act as a stressor and disturb sleep, and has been associated with cardiovascular disease. Recent studies suggest a possible association to metabolic outcomes and adiposity through biological mechanisms related to physiological stress and sleep disturbance. OBJECTIVES: We aimed to investigate the association between long-term residential traffic noise and changes in adiposity. MATERIALS AND METHODS: The study was based on 39,720 middle-aged Danish men and women from a cohort, with information on weight and waist circumference at two points in time. Residential exposure to traffic noise was calculated for all participants' present and historical addresses using the Nordic prediction method. The associations between traffic noise and changes in adiposity measures after a mean follow-up of 5.3 years were analyzed by linear and logistic regression with adjustments for age, sex, socioeconomic position and lifestyle factors in three models with increasing adjustment. RESULTS: In linear models adjusted for sex, age, socioeconomic position and competing noise sources we found road traffic noise to be significantly associated with small gains in both weight and waist circumference. For example, time-weighted mean exposure 5-years preceding follow-up was associated with a yearly weight gain of 15.4 g (95% confidence interval (CI): 2.14; 28.7) and a yearly increase in waist circumference of 0.22 mm (95% CI: 0.018; 0.43) per 10dB. Similarly, in Poisson regression models we found an 10% increased risk for gaining more than 5 kg body weight during follow-up (95% CI: 1.04; 1.15) per 10 dB higher 5 years exposure preceding follow-up. Exposure to railway noise above 55 dB was associated with weight gain (39.9 g/year (95% CI: 10.2; 69.6)), but not with a significant change in waist circumference. We found baseline BMI (p<0.001) and waist circumference (p=0.001) to be significant effect modifiers for the association between road traffic noise and waist circumference, with gain in waist circumference only among the obese (BMI≥30) participants (1.20 mm/year (95% CI: 0.68; 1.72)) and participants with a large waist circumference (0.83 mm/year (95% CI: 0.42; 1.23)). CONCLUSION: The findings supports previous studies suggesting that traffic noise may be associated with development of adiposity. However, the potential effects are small and suggest an effect mainly among obese participants.

Space-time analysis of testicular cancer clusters using residential histories: a case-control study in Denmark.

Though the etiology is largely unknown, testicular cancer incidence has seen recent significant increases in northern Europe and throughout many Western regions. The most common cancer in males under age 40, age period cohort models have posited exposures in the in utero environment or in early childhood as possible causes of increased risk of testicular cancer. Some of these factors may be tied to geography through being associated with behavioral, cultural, sociodemographic or built environment characteristics. If so, this could result in detectable geographic clusters of cases that could lead to hypotheses regarding environmental targets for intervention. Given a latency period between exposure to an environmental carcinogen and testicular cancer diagnosis, mobility histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q-statistics allow for the incorporation of changes in residency in spatial disease cluster detection. Using these methods, a space-time cluster analysis was conducted on a population-wide case-control population selected from the Danish Cancer Registry with mobility histories since 1971 extracted from the Danish Civil Registration System. Cases (N=3297) were diagnosed between 1991 and 2003, and two sets of controls (N=3297 for each set) matched on sex and date of birth were included in the study. We also examined spatial patterns in maternal residential history for those cases and controls born in 1971 or later (N= 589 case-control pairs). Several small clusters were detected when aligning individuals by year prior to diagnosis, age at diagnosis and calendar year of diagnosis. However, the largest of these clusters contained only 2 statistically significant individuals at their center, and were not replicated in SaTScan spatial-only analyses which are less susceptible to multiple testing bias. We found little evidence of local clusters in residential histories of testicular cancer cases in this Danish population.

Long-term exposure to road traffic noise and incident diabetes: a cohort study.

BACKGROUND: Road traffic noise at normal urban levels can lead to stress and sleep disturbances. Both excess of stress hormones and reduction in sleep quality and duration may lead to higher risk for type 2 diabetes. OBJECTIVE: We investigated whether long-term exposure to residential road traffic noise is associated with an increased risk of diabetes. METHODS: In the population-based Danish Diet, Cancer and Health cohort of 57,053 people 50-64 years of age at enrollment in 1993-1997, we identified 3,869 cases of incident diabetes in a national diabetes registry between enrollment and 2006. The mean follow-up time was 9.6 years. Present and historical residential addresses from 1988 through 2006 were identified using a national register, and exposure to road traffic noise was estimated for all addresses. Associations between exposure to road traffic noise and incident diabetes were analyzed in a Cox regression model. RESULTS: A 10-dB higher level of average road traffic noise at diagnosis and during the 5 years preceding diagnosis was associated with an increased risk of incident diabetes, with incidence rate ratios (IRR) of 1.08 (95% CI: 1.02, 1.14) and 1.11 (95% CI: 1.05, 1.18), respectively, after adjusting for potential confounders including age, body mass index, waist circumference, education, air pollution (nitrogen oxides), and lifestyle characteristics. After applying a stricter definition of diabetes (2,752 cases), we found IRRs of 1.11 (95% CI: 1.03, 1.19) and 1.14 (95% CI: 1.06, 1.22) per 10-dB increase in road traffic noise at diagnosis and during the 5 years preceding diagnosis, respectively. CONCLUSION: Exposure to residential road traffic noise was associated with a higher risk of diabetes. This study provides further evidence that urban noise may adversely influence population health.

Road traffic noise and incident myocardial infarction: a prospective cohort study.

BACKGROUND: Both road traffic noise and ambient air pollution have been associated with risk for ischemic heart disease, but only few inconsistent studies include both exposures. METHODS: In a population-based cohort of 57 053 people aged 50 to 64 years at enrolment in 1993-1997, we identified 1600 cases of first-ever MI between enrolment and 2006. The mean follow-up time was 9.8 years. Exposure to road traffic noise and air pollution from 1988 to 2006 was estimated for all cohort members from residential address history. Associations between exposure to road traffic noise and incident MI were analysed in a Cox regression model with adjustment for air pollution (NO(x)) and other potential confounders: age, sex, education, lifestyle confounders, railway and airport noise. RESULTS: We found that residential exposure to road traffic noise (L(den)) was significantly associated with MI, with an incidence rate ratio IRR of 1.12 per 10 dB for both of the two exposure windows: yearly exposure at the time of diagnosis (95% confidence interval (CI): 1.02-1.22) and 5-years time-weighted mean (95% CI: 1.02-1.23) preceding the diagnosis. Visualizing of the results using restricted cubic splines showed a linear dose-response relationship. CONCLUSIONS: Exposure to long-term residential road traffic noise was associated with a higher risk for MI, in a dose-dependent manner.

Exposure to road traffic and railway noise and associations with blood pressure and self-reported hypertension: a cohort study.

BACKGROUND: Epidemiological studies suggest that long-term exposure to transport noise increases the risk for cardiovascular disorders. The effect of transport noise on blood pressure and hypertension is uncertain. METHODS: In 1993-1997, 57,053 participants aged 50-64 year were enrolled in a population-based cohort study. At enrollment, systolic and diastolic blood pressure was measured. Incident hypertension during a mean follow-up of 5.3 years was assessed by questionnaire. Residential long-term road traffic noise (Lden) was estimated for 1- and 5-year periods preceding enrollment and preceding diagnosis of hypertension. Residential exposure to railway noise was estimated at enrollment. We conducted a cross-sectional analysis of associations between road traffic and railway noise and blood pressure at enrollment with linear regression, adjusting for long-term air pollution, meteorology and potential lifestyle confounders (N = 44,083). Incident self-reported hypertension was analyzed with Cox regression, adjusting for long-term air pollution and potential lifestyle confounders. RESULTS: We found a 0.26 mm Hg higher systolic blood pressure (95% confidence intervals (CI): -0.11; 0.63) per 10 dB(A) increase in 1-year mean road traffic noise levels, with stronger associations in men (0.59 mm Hg (CI: 0.13; 1.05) per 10 dB(A)) and older participants (0.65 mm Hg (0.08; 1.22) per 10 dB(A)). Road traffic noise was not associated with diastolic blood pressure or hypertension. Exposure to railway noise above 60 dB was associated with 8% higher risk for hypertension (95% CI: -2%; 19%, P = 0.11). CONCLUSIONS: While exposure to road traffic noise was associated with systolic blood pressure in subgroups, we were not able to identify associations with hypertension.

Road traffic noise and stroke: a prospective cohort study.

AIMS: Epidemiological studies suggest that long-term exposure to road traffic noise increases the risk of cardiovascular disorders. The aim of this study was to investigate the relation between exposure to road traffic noise and risk for stroke, which has not been studied before. METHODS AND RESULTS: In a population-based cohort of 57,053 people, we identified 1881 cases of first-ever stroke in a national hospital register between 1993-1997 and 2006. Exposure to road traffic noise and air pollution during the same period was estimated for all cohort members from residential address history. Associations between exposure to road traffic noise and stroke incidence were analysed in a Cox regression model with stratification for gender and calendar-year and adjustment for air pollution and other potential confounders. We found an incidence rate ratio (IRR) of 1.14 for stroke [95% confidence interval (CI): 1.03-1.25] per 10 dB higher level of road traffic noise (L(den)). There was a statistically significant interaction with age (P < 0.001), with a strong association between road traffic noise and stroke among cases over 64.5 years (IRR: 1.27; 95% CI: 1.13-1.43) and no association for those under 64.5 years (IRR: 1.02; 95% CI: 0.91-1.14). CONCLUSION: Exposure to residential road traffic noise was associated with a higher risk for stroke among people older than 64.5 years of age.