Test validation, method comparison and reference range for the measurement of β-hydroxybutyrate in peripheral blood samples

Introduction: The measurement of β-hydroxybutyrate (βOHB) concentrations is a corner stone of the diagnosis of diabetic ketoacidosis and other ketonic states. The aim of this study was to perform a validation of a peripheral blood βOHB assay (Randox) on a Roche cobas c502 analyser and to establish a βOHB reference range for the validated assay. Materials and methods: Precision, linearity and limit of detection and blank (LoD, LoB) were determined according to Clinical and Laboratory Standards Institute (CLSI) EP05-A3, EP 06-A and EP17-A2 guidelines, using commercial control material and residual patient sample pools. As method comparison, for 190 semi-quantitative measurements of urine ketones we determined the corresponding βOHB blood concentration. The reference range was based on the CLSI C28-A3 guideline, using 304 randomly selected serum samples from population based German National Cohort (GNC) study. Results: Coefficients of variation for the validated assay ranged from 1.5% for high concentrations (3.1 mmol/L) to 6.5% for low concentrations (0.1 mmol/L). Detection capacity was LoB = 0.011 mmol/L and LoD = 0.037 mmol/L. Linearity of the assay ranged from 0.10 to 3.95 mmol/L. The agreement between the semi-quantitative urine ketone test and the βOHB blood test was moderate (Kappa = 0.66). The obtained 95% serum reference range was estimated as 0.02 to 0.28 mmol/l βOHB. Conclusions: The Ranbut βOHB assay showed good precision and analytical performance. Our results confirm that βOHB measurement in peripheral blood is indeed a preferable alternative to the semi-quantitative measurement of urine ketones

The effect of home visits as an additional recruitment step on the composition of the final sample: a cross-sectional analysis in two study centers of the German National Cohort (NAKO)

Background: Participation in epidemiologic studies has been declining over the last decades. In addition to postal invitations and phone calls, home visits can be conducted to increase participation. The aim of this study was therefore to evaluate the effects of home visits in terms of response increase and composition of the additionally recruited and final sample. Methods: In the framework of the German National Cohort (NAKO) recruitment process, two of 18 study centers, Halle (Saale) and Berlin-Center, performed home visits as additional recruitment step after postal invitation and reminders. Response increase was calculated and differences between participants recruited via home visits and standard recruitment were examined. Proportions are presented as percentages with 95%-confidence intervals. Results: In the general population in Halle, 21.3-22.8% participated after postal invitation and two reminders in the five assessed recruitment waves. The increase of the overall response was 2.8 percentage points (95%confidence interval: 1.9-4.0) for home visits compared to 2.4 percentage points (95%CI: 1.7-3.3) for alternatively sent third postal reminder. Participants recruited via home visits had similar characteristics to those recruited via standard recruitment. Among persons of Turkish descent in Berlin-Center site of the NAKO, home visits conducted by native speakers increased the participation of women, persons living together with their partner, were born in Turkey, had lower German language skills, lower-income, lower education, were more often smokers and reported more often diabetes and depression to a degree which changed overall estimates for this subsample. Conclusions: As an additional recruitment measure in the general population, home visits increased response only marginally, and the through home visits recruited participants did not differ from those already recruited. Among persons with migration background, home visits by a native speaker increased participation of persons not reached by the standard recruitment, but the effects of using a native speaker approach could not be separated from the effect of home visits

Educational level, prevalence of hysterectomy, and age at amenorrhoea: a cross-sectional analysis of 9536 women from six population-based cohort studies in Germany

BACKGROUND: Hysterectomy prevalence has been shown to vary by education level. Hysterectomy influences age at amenorrhoea. The aim of this study was to examine these associations in Germany within population-based data sets. METHODS: Baseline assessments in six population-based cohorts took place from 1997 through 2006 and included 9,548 women aged 20–84 years. All studies assessed hysterectomy history, school and professional degrees. Degrees were categorized into three levels each. Adjusted prevalence ratios and 95% confidence intervals (95% CI) were estimated. RESULTS: Prevalences were higher in West Germany than East Germany, increased by age, and leveled off starting at 55–64 years. The age- and study-adjusted prevalence ratio (lowest versus highest school level) was 2.61 (95% CI: 1.28-5.30), 1.48 (95% CI: 1.21-1.81), and 1.01 (95% CI: 0.80-1.28) for women aged 20–45, 45–64, and 65 and more years respectively. The estimated adjusted prevalence ratios per one unit decrement of the educational qualification score (range 1 = lowest, 8 = highest) were 1.29 (95% CI: 1.02-1.64), 1.08 (95% CI: 1.04-1.12), and 0.98 (95% CI: 0.93-1.03) for women aged 20–44, 45–64, and 65–84 years respectively. Age at amenorrhoea was on average 6.2 years lower (43.5 years versus 49.7 years) among women with a history of hysterectomy than those without. CONCLUSIONS: Lower educational level was associated with a higher hysterectomy prevalence among women aged 20–64 years. Several mediators associated with educational level and hysterectomy including women’s disease risk, women’s treatment preference, and women’s access to uterus-preserving treatment may explain this association. At population level, hysterectomy decreases the age of amenorrhoea on average by 6.2 years

Serum Thyrotropin Concentrations Are Not Associated with the Ankle-Brachial Index: Results from Three Population-Based Studies

Background: There is only limited data on the potential association between thyroid dysfunction and peripheral arterial disease (PAD). Objective: The aim of our study was to investigate the potential association of thyroid function, as defined by serum concentrations of the clinically used primary thyroid function marker thyrotropin [i.e. thyroid-stimulating hormone (TSH)] and 3,5-diiodothyronine (3,5-T2), with the ankle-brachial index (ABI) as a marker of PAD. Methods: We used data from 5,818 individuals from three cross-sectional population-based studies conducted in Northeast (SHIP-2 and SHIP-TREND) and Central Germany (CARLA). Measurement of serum TSH concentrations was conducted in one central laboratory for all three studies. In a randomly selected subpopulation of 750 individuals of SHIP-TREND, serum 3,5-T2 concentrations were measured with a recently developed immunoassay. ABI was measured either by a hand-held Doppler ultrasound using the Huntleigh Dopplex D900 or palpatorily by the OMRON HEM-705CP device. Results: Serum TSH concentrations were not significantly associated with ABI values in any of the three studies. Likewise, groups of individuals with a TSH 2 concentrations did not reveal consistent significant associations with the ABI. No sex-specific associations were detected. Conclusions: The results of our study do not substantiate evidence for an association between thyroid function and PAD, but further studies are needed to investigate the associations of overt forms of thyroid dysfunction with PAD

Inflammation and prolonged QT time: Results from the Cardiovascular Disease, Living and Ageing in Halle (CARLA) study

Background: Previous research found an association of CRP with QT time in population based samples. Even more, there is evidence of a substantial involvement of the tumor necrosis factor-alpha system in the pathophysiology of cardiac arrhythmia, while the role of Interleukin 6 remains inconclusive. Objective: To determine the association between inflammation with an abnormally prolonged QT-time (APQT) in men and women of the elderly general population. Methods: Data descend from the baseline examination of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study. After exclusion of subjects with atrial fibrillation and missing ECG recording the final study cohort consisted of 919 men and 797 women. Blood parameters of inflammation were the soluble TNF-Receptor 1 (sTNF-R1), the high-sensitive C-reactive protein (hsCRP), and Interleukin 6 (IL-6). In accordance with major cardiologic societies we defined an APQT above a QT time of 460 ms in women and 450 ms in men. Effect sizes and the corresponding 95% confidence intervals (CI) were estimated by performing multiple linear and logistic regression analyses including the analysis of sex differences by interaction terms. Results: After covariate adjustment we found an odds ratio (OR) of 1.89 (95% CI: 1.13, 3.17) per 1000 pg/mL increase of sTNF-R1 in women, and 0.74 (95% CI: 0.48, 1.15) in men. In the covariate adjusted linear regression sTNF-R1 was again positively associated with QT time in women (5.75 ms per 1000 pg/mL, 95% CI: 1.32, 10.18), but not in men. Taking possible confounders into account IL-6 and hsCRP were not significantly related to APQT in both sexes. Conclusion: Our findings from cross-sectional analyses give evidence for an involvement of TNF-alpha in the pathology of APQT in women

Blood pressure and lipid management fall far short in persons with type 2 diabetes: results from the DIAB-CORE Consortium including six German population-based studies

Background: Although most deaths among patients with type 2 diabetes (T2D) are attributable to cardiovascular disease, modifiable cardiovascular risk factors appear to be inadequately treated in medical practice. The aim of this study was to describe hypertension, dyslipidemia and medical treatment of these conditions in a large population-based sample. Methods: The present analysis was based on the DIAB-CORE project, in which data from five regional population-based studies and one nationwide German study were pooled. All studies were conducted between 1997 and 2006. We assessed the frequencies of risk factors and co-morbidities, especially hypertension and dyslipidemia, in participants with and without T2D. The odds of no or insufficient treatment and the odds of pharmacotherapy were computed using multivariable logistic regression models. Types of medication regimens were described. Results: The pooled data set comprised individual data of 15, 071 participants aged 45–74 years, including 1287 (8.5%) participants with T2D. Subjects with T2D were significantly more likely to have untreated or insufficiently treated hypertension, i.e. blood pressure of > = 140/90 mmHg (OR = 1.43, 95% CI 1.26-1.61) and dyslipidemia i.e. a total cholesterol/HDL-cholesterol ratio > = 5 (OR = 1.80, 95% CI 1.59-2.04) than participants without T2D. Untreated or insufficiently treated blood pressure was observed in 48.9% of participants without T2D and in 63.6% of participants with T2D. In this latter group, 28.0% did not receive anti-hypertensive medication and 72.0% were insufficiently treated. In non-T2D participants, 28.8% had untreated or insufficiently treated dyslipidemia. Of all participants with T2D 42.5% had currently elevated lipids, 80.3% of these were untreated and 19.7% were insufficiently treated. Conclusions: Blood pressure and lipid management fall short especially in persons with T2D across Germany. The importance of sufficient risk factor control besides blood glucose monitoring in diabetes care needs to be emphasized in order to prevent cardiovascular sequelae and premature death

which marker is best for prediction? Pooled analysis of four German population-based cohort studies and comparison with a nationwide cohort study

Objective To compare the association between different anthropometric measurements and incident type 2 diabetes mellitus (T2DM) and to assess their predictive ability in different regions of Germany. Methods Data of 10 258 participants from 4 prospective population-based cohorts were pooled to assess the association of body weight, body mass index (BMI), waist circumference (WC), waist-to-hip-ratio (WHR) and waist-to-height-ratio (WHtR) with incident T2DM by calculating HRs of the crude, adjusted and standardised markers, as well as providing receiver operator characteristic (ROC) curves. Differences between HRs and ROCs for the different anthropometric markers were calculated to compare their predictive ability. In addition, data of 3105 participants from the nationwide survey were analysed separately using the same methods to provide a nationally representative comparison. Results Strong associations were found for each anthropometric marker and incidence of T2DM. Among the standardised anthropometric measures, we found the strongest effect on incident T2DM for WC and WHtR in the pooled sample (HR for 1 SD difference in WC 1.97, 95% CI 1.75 to 2.22, HR for WHtR 1.93, 95% CI 1.71 to 2.17 in women) and in female DEGS participants (HR for WC 2.24, 95% CI 1.91 to 2.63, HR for WHtR 2.10, 95% CI 1.81 to 2.44), whereas the strongest association in men was found for WHR among DEGS participants (HR 2.29, 95% CI 1.89 to 2.78). ROC analysis showed WHtR to be the strongest predictor for incident T2DM. Differences in HR and ROCs between the different markers confirmed WC and WHtR to be the best predictors of incident T2DM. Findings were consistent across study regions and age groups (<65 vs ≥65 years). Conclusions We found stronger associations between anthropometric markers that reflect abdominal obesity (ie, WC and WHtR) and incident T2DM than for BMI and weight. The use of these measurements in risk prediction should be encouraged

Anthropometric markers and their association with incident type 2 diabetes mellitus: which marker is best for prediction? Pooled analysis of four German population-based cohort studies and comparison with a nationwide cohort study

Objective: To compare the association between different anthropometric measurements and incident type 2 diabetes mellitus (T2DM) and to assess their predictive ability in different regions of Germany. Methods: Data of 10 258 participants from 4 prospective population-based cohorts were pooled to assess the association of body weight, body mass index (BMI), waist circumference (WC), waist-to-hip-ratio (WHR) and waist-to-height-ratio (WHtR) with incident T2DM by calculating HRs of the crude, adjusted and standardised markers, as well as providing receiver operator characteristic (ROC) curves. Differences between HRs and ROCs for the different anthropometric markers were calculated to compare their predictive ability. In addition, data of 3105 participants from the nationwide survey were analysed separately using the same methods to provide a nationally representative comparison. Results: Strong associations were found for each anthropometric marker and incidence of T2DM. Among the standardised anthropometric measures, we found the strongest effect on incident T2DM for WC and WHtR in the pooled sample (HR for 1 SD difference in WC 1.97, 95% CI 1.75 to 2.22, HR for WHtR 1.93, 95% CI 1.71 to 2.17 in women) and in female DEGS participants (HR for WC 2.24, 95% CI 1.91 to 2.63, HR for WHtR 2.10, 95% CI 1.81 to 2.44), whereas the strongest association in men was found for WHR among DEGS participants (HR 2.29, 95% CI 1.89 to 2.78). ROC analysis showed WHtR to be the strongest predictor for incident T2DM. Differences in HR and ROCs between the different markers confirmed WC and WHtR to be the best predictors of incident T2DM. Findings were consistent across study regions and age groups