Baseline Characteristics ^a of 4,516 Individuals with Diabetes Mellitus from the European Prospective Investigation into Cancer and Nutrition by Type of Medication Use.

<p>Abbreviations: BMI, body mass index; OHA, oral hypoglycemic agent.</p>a<p>Means (SE) or percentages are shown;</p>b<p>Mean differences in HbA_1c values are given compared with metformin monotherapy.</p

Hazard Ratios (95% CI) of Associations Between a 1% -Increase in HbA_1c and Total Mortality, Stratified for Several Diabetes-Related Variables, and Cause-Specific Mortality in 4,345 Individuals with Diabetes Mellitus.

<p>Abbreviations: CI, confidence interval; CVD, cardiovascular diseases; OHA, Oral Hypoglycemic Agents; HR, Hazard Ratio.</p>a<p>Age- and center-stratified and adjusted for sex, physical activity, smoking status, educational attainment, body mass index, systolic blood pressure and for diabetes medication use, co-morbidities or disease duration when these were not stratified for.</p>b<p><i>P</i> value 0.04 for difference in risk estimate derived from competing risk model versus cancer mortality.</p

Hazard Ratios (95% CI) of Associations between HbA_1c, Diabetes Medication use, Disease Duration and Total Mortality in Individuals with Diabetes.

<p>Abbreviations: CI, confidence interval; HR, Hazard Ratio; OHA, Oral Hypoglycemic Agents; PY, person-years.</p>a<p>Model 1: Age- and center-stratified and adjusted for sex, co-morbidities, physical activity, smoking status, educational attainment, body mass index, and systolic blood pressure;</p>b<p>Model 2: Model 1 additionally adjusted for disease duration, diabetes medication use, or HbA_1c and storage time when adequate.</p

Adjusted Hazard Ratios of Death according to Glycated Hemoglobin (%) Measured in Stored Erythrocytes among 4,345 Individuals with Diabetes.

<p>Solid lines indicate hazard ratios and dashed lines indicate 95% confidence intervals derived from restricted cubic spline regression, with knots placed at the 5^th, 10^th, 25^th, 75^th, 90^th, and 95^th percentiles of the distribution, using the 50^th percentile as a reference. Age- and study center-stratified models were adjusted for sex, storage time, disease duration, diabetes medication use, co-morbidities, physical activity, smoking status, educational attainment, body mass index, and systolic blood pressure. P value for nonlinearity derived from a Wald Chi-square test was P=0.15.</p

Prevalence of anomalies from 2003 to 2012, the annual proportional change during this period and the adjusted annual proportional change after excluding outliers for the 17 anomaly subgroups with statistically significant trends identified in Fig 1.

<p>Prevalence of anomalies from 2003 to 2012, the annual proportional change during this period and the adjusted annual proportional change after excluding outliers for the 17 anomaly subgroups with statistically significant trends identified in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194986#pone.0194986.g001" target="_blank">Fig 1</a>.</p

Prevalence and annual average change in prevalence for tetralogy of fallot and patent ductus arteriosus.

<p>[A] European Prevalence 1981–2012 (95% CI) with trend for 2003–2012 (black line) and trend excluding outliers (red line) [B] Prevalence for 2003–2012: European (99% CI vertical grey line) and registry (95% CI) [C] Annual change in prevalence for 2003–2012: European (black line and 99% CI funnel) and registry (linear trend black dots, non-linear trend open diamonds). Red line is no trend.</p

Prevalence and annual average change in prevalence for limb reduction defects and club foot–congenital talipes equinovarus.

<p>[A] European Prevalence 1981–2012 (95% CI) with trend for 2003–2012 (black line) and trend excluding outliers (red line) [B] Prevalence for 2003–2012: European (99% CI vertical grey line) and registry (95% CI) [C] Annual change in prevalence for 2003–2012: European (black line and 99% CI funnel) and registry (linear trend black dots, non-linear trend open diamonds). Red line is no trend.</p

Prevalence and annual average change in prevalence for microcephaly and severe congenital heart disease.

<p>[A] European Prevalence 1981–2012 (95% CI) with trend for 2003–2012 (black line) and trend excluding outliers (red line) [B] Prevalence for 2003–2012: European (99% CI vertical grey line) and registry (95% CI) [C] Annual change in prevalence for 2003–2012: European (black line and 99% CI funnel) and registry (linear trend black dots, non-linear trend open diamonds). Red line is no trend. Severe CHD includes single ventricle, hypoplastic left heart, hypoplastic right heart, Ebstein anomaly, tricuspid atresia, pulmonary valve atresia, common arterial truncus, atrioventricular septal defects, aortic valve atresia/stenosis, transposition of great vessels, tetralogy of Fallot, total anomalous pulmonary venous return, and coarctation of aorta.</p

Prevalence and annual average change in prevalence for renal dysplasia and congenital hydronephrosis.

<p>[A] European Prevalence 1981–2012 (95% CI) with trend for 2003–2012 (black line) and trend excluding outliers (red line) [B] Prevalence for 2003–2012: European (99% CI vertical grey line) and registry (95% CI) [C] Annual change in prevalence for 2003–2012: European (black line and 99% CI funnel) and registry (linear trend black dots, non-linear trend open diamonds). Red line is no trend.</p

Prevalence and annual average change in prevalence for congenital cystic adenomatous malformation of lung and oesophageal atresia.

<p>[A] European Prevalence 1981–2012 (95% CI) with trend for 2003–2012 (black line) and trend excluding outliers (red line) [B] Prevalence for 2003–2012: European (99% CI vertical grey line) and registry (95% CI) [C] Annual change in prevalence for 2003–2012: European (black line and 99% CI funnel) and registry (linear trend black dots, non-linear trend open diamonds). Red line is no trend.</p