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

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 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

Cumulative incidence of type 2 diabetes (percent) by quartiles of the imputed, unweighted genetic risk score and strata of body mass index, waist circumference, physical activity, and Mediterranean diet score: the InterAct study.

<p>(A) BMI (red: <25 kg/m²; blue: 25 to <30 kg/m²; black: ≥30 kg/m²), (B) WC (red: <94 cm in men and <80 cm in women; blue: 94 to <102 cm in men and 80 to <88 cm in women; black: ≥102 cm in men and ≥88 cm in women), (C) physical activity (red: active; blue: moderately active; green: moderately inactive; black: inactive), and (D) Mediterranean diet score (red: 11–18; blue: 7–10; black: 0–6).</p

Hazard ratios for type 2 diabetes per risk allele for each of 49 SNPs and per standard deviation for additive genetic scores, adjusted for sex and centre: the InterAct study.

<p>Analyses are based on 18,890 participants with data available for the genetic score—8,245 incident cases and 11,133 sub-cohort members (includes 488 incident cases). All models are adjusted for sex and centre, and with age as the underlying time scale. For comparability, HRs for the four genetic scores are presented per SD, where the SD is estimated in the sub-cohort.</p

Baseline characteristics of the random sub-cohort participants in the InterAct study.

<p>Family history of diabetes was not ascertained in Italy, Spain, Heidelberg (Germany), and Oxford (UK) (excluded from these summaries): 7,226/5,719. WC and waist–hip ratio were not measured in Umeå (Sweden) (excluded from these summaries): 1,050/1,007. Weight at age 20 y was not ascertained in France, Spain, Florence (Italy), Ragusa (Italy), Turin (Italy), Netherlands, Heidelberg (Germany), and Umeå (Sweden) (excluded from these summaries): 9,462/7,692. Data from Denmark (<i>n = </i>2,164) are excluded from this table.</p

Hazard ratios for type 2 diabetes per standard deviation (4.4 alleles) increase in the imputed, unweighted genetic risk score within strata defined by sex, diabetes family history, body mass index, waist circumference, age, physical activity, and Mediterranean diet score: the InterAct study.

<p>Prentice-weighted Cox regression models are adjusted for age, sex, and centre. F, female; M, male; Med., Mediterranean.</p

Seven identified SNPs compared to previously published loci.

a<p>The Effect allele refers to a positive effect direction in the discovery stage for the trait and gender, the SNP was selected for;</p>b<p>Gene near this SNP which was published previously from sex-combined analyses.</p><p>The seven SNPs with sex difference are considered to depict a known locus, if the index SNP is close to a published top SNP (<1 cM). These include four of the previously reported sexually dimorphic WHR loci (Heid et al., Nat Genet 2010).</p

Overview of design and findings.

<p>Among the 7 identified loci, we defined those close to (<1 cM) published hits <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003500#pgen.1003500-LangoAllen1" target="_blank">[25]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003500#pgen.1003500-Speliotes1" target="_blank">[29]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003500#pgen.1003500-Heid1" target="_blank">[31]</a> as <i>near published hit</i>s and <i>novel</i> otherwise. Novel loci with sex-combined discovery P-value<5.8×10⁻⁵, which is the P-value cut-off corresponding to 5% FDR, were declared as loci that <i>could have been discovered also with sex-combined analysis</i>, and otherwise that these <i>would have been missed without the sex-stratified analyses</i>. FDR = false discovery rate.</p