Update to the study protocol: minimisation of dialysis risk in hospital patients with chronic kidney disease (MinDial): a multicentre, stepped-wedge, cluster-randomised controlled trial.

This document reports a brief update to the previously published protocol of the MinDial study.Trial registration German Clinical Trials Register DRKS00029691. Registered on 12 Sept. 2022, https://drks.de/search/en/trial/DRKS00029691 .

Minimisation of dialysis risk in hospital patients with chronic kidney disease (MinDial): study protocol for a multicentre, stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: Early identification of patients with chronic kidney disease (CKD) and advancing kidney insufficiency, followed by specialist care, can decelerate the progression of the disease. However, awareness of the importance and possible consequences of kidney insufficiency is low among doctors and patients. Since kidney insufficiency can be asymptomatic even in higher stages, it is often not even known to those belonging to risk groups. This study aims to clarify whether, for hospitalised patients with advanced chronic kidney disease, a risk-based appointment with a nephrology specialist reduces disease progression. METHODS: The target population of the study is hospitalised CKD patients with an increased risk of end-stage renal disease (ESRD), more specifically with an ESRD risk of at least 9% in the next 5 years. This risk is estimated by the internationally validated Kidney Failure Risk Equation (KFRE). The intervention consists of a specific appointment with a nephrology specialist after the hospital stay, while control patients are discharged from the hospital as usual. Eight medical centres include participants according to a stepped-wedge design, with randomised sequential centre-wise crossover from recruiting patients into the control group to recruitment to the intervention. The estimated glomerular filtration rate (eGFR) is measured for each patient during the hospital stay and after 12 months within the regular care by the general practitioner. The difference in the change of the eGFR over this period is compared between the intervention and control groups and considered the primary endpoint. DISCUSSION: This study is designed to evaluate the effect of risk-based appointments with nephrology specialists for hospitalised CKD patients with an increased risk of end-stage renal disease. If the intervention is proven to be beneficial, it may be implemented in routine care. Limitations will be examined and discussed. The evaluation will include further endpoints such as non-guideline-compliant medication, economic considerations and interviews with contributing physicians to assess the acceptance and feasibility of the intervention. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029691 . Registered on 12 September 2022.

Associations of metabolically healthy obesity with prevalence and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall Cohort Study.

BACKGROUND AND AIMS: There is controversy on the potentially benign nature of metabolically healthy obesity (MHO), i.e., obese persons with few or no metabolic abnormalities. So far, associations between MHO and coronary artery calcification (CAC), a measure of subclinical atherosclerosis, have mainly been studied cross-sectionally in Asian populations. We assessed cross-sectional and longitudinal MHO CAC associations in a Caucasian population. METHODS AND RESULTS: In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. For cross-sectional and longitudinal analyses, we included 1585 participants free of coronary heart disease at baseline, with CAC measurements at baseline and at follow-up, and with either normal weight (BMI 18.5-24.9 kg/m2) or obesity (BMI ≥30.0 kg/m2) at baseline. We used four definitions of MHO. In our main analysis, we defined obese persons as metabolically healthy if they met ≤1 of the NCEP ATP III criteria for the definition of the metabolic syndrome - waist circumference was not taken into account because of collinearity with BMI. Persons with MHO had a higher prevalence of CAC than metabolically healthy normal weight (MHNW) persons (prevalence ratio = 1.59 (95% confidence interval 1.38-1.84) for the main analysis). Persons with MHO had slightly larger odds of CAC progression than persons with MHNW (odds ratios ranged from 1.17 (0.69-1.99) to 1.48 (1.02-2.13) depending on MHO definition and statistical approach). CONCLUSION: Our analyses on MHO CAC associations add to the evidence that MHO is not a purely benign health condition.

Does periodontitis affect diabetes incidence and haemoglobin A1c change? An 11-year follow-up study.

AIM: As periodontitis may contribute to the pathogenesis of diabetes, the effects of periodontitis on diabetes incidence and HbA1c change was quantified in a prospective cohort. METHODS: Data from an 11-year follow-up of the Study of Health in Pomerania were analyzed to evaluate the effects of periodontitis on incident diabetes and long-term HbA1c changes in 2047 subjects aged 20-81years. Diabetes was based on self-reported physician diagnoses, antidiabetic medication use, or HbA1c≥6.5% or non-fasting blood glucose levels ≥11.1mmol/L. To assess periodontal status, periodontal pockets were probed, and their depth and clinical attachment levels measured. For both measures, means and percentages of sites≥3mm were calculated. In addition, all probing depths≥4mm were summed (cumulative probing depth). Modified Poisson and multivariable linear models were applied, adjusted for age, gender, highest level of general education, marital status, waist circumference, physical activity, smoking status and follow-up time. RESULTS: Over a mean follow-up period of 11.1years, 207 subjects developed diabetes. Baseline mean clinical attachment levels (CAL) and probing depths (PPD) were not significantly associated with either diabetes incidence [mean CALs, fourth quartile, incidence rate ratio=0.819, 95% confidence interval (CI): 0.489-1.370; P=0.446] or long-term changes in HbA1c (mean CAL, fourth quartile, ß=-0.086, 95% CI: -0.187, -0.016; P=0.098). Sensitivity analyses using alternative exposure definitions confirmed these results. CONCLUSION: Contrary to the currently available literature, no convincing evidence was found of any potential association between periodontitis and diabetes incidence or HbA1c change.

[Some Caveats in the Interpretation of Population Attributable Risks]. / Stolpersteine bei der Interpretation des populationsattributablen Risikos.

Population attributable risks (PARs) are often used in health sciences because they offer an apparently easy answer to the question as to the proportion of disease cases that could be prevented in a population if one or more risk factors were eliminated. We discuss some problems in the interpretation of PARs that result from the fact that diseases have more than one cause. Moreover, requirements are discussed which have to be met before PARs can give a realistic idea of the proportion of cases of illness that can be avoided.

Associations between sleep characteristics and weight gain in an older population: results of the Heinz Nixdorf Recall Study.

BACKGROUND/OBJECTIVES: Sleep duration influences weight change in children and young adults, but there is less evidence in middle-aged, and, in particular, older adults. We assessed associations between sleep duration, daytime napping and sleep disturbances, respectively, with change of weight and waist circumference in older subjects. Contrary to previous studies, we also used two points in time to assess sleep characteristics. METHODS: We used data from the population-based Heinz Nixdorf Recall study, a cohort study in Germany with a baseline and two follow-up visits (age 45-74 years, median follow-up 5.1 years for first, 5.2 years for second follow-up visit). In adjusted linear regression models (N=3751), we estimated weight change between baseline and first follow-up visit in relation to various self-reported sleep characteristics measured at baseline. Furthermore, we estimated change of weight and waist circumference, respectively, between first and second follow-up visit in relation to patterns of sleep characteristics measured at baseline and at the first follow-up visit (N=2837). RESULTS: In all analyses, short and long sleep duration, sleep disturbances, and regular daytime napping were associated with <1 kg of weight gain and <1 cm of gain in waist circumference over 5 years compared with the respective reference categories. For example, compared with 7-<8 h night sleep, short night sleep (⩽5 h at baseline) was associated with 0.5 kg of weight gain (95% confidence interval: -0.1; 1.1 kg). CONCLUSIONS: Our study gave no evidence that sleep characteristics were associated with clinically relevant weight gain in the older population.

A clinical screening score for diabetic polyneuropathy: KORA F4 and AusDiab studies.

AIMS: Since screening for distal sensorimotor polyneuropathy (DSPN) in individuals with diabetes is being underused, our aim was to develop a clinical screening score for identifying individuals with DSPN. METHODS: All participants with type 2 diabetes and aged 61-82 years from the German population-based KORA F4 Study (n=177) and the Australian population-based AusDiab Study (n=244) were combined into one study sample. Risk indicators of DSPN were identified and entered into a stepwise model-selection procedure, constructing two consecutive scores with increasing complexity (a base and clinical model). RESULTS: The prevalence of DSPN was 18.2% (95% confidence interval (CI): 14.7-22.3). The base model comprised age (years), height (cm), weight (kg), pain or discomfort in the feet and/or legs (yes/no), and duration of diabetes (years), yielding an area under the receiver operating characteristics curve (AUC) of 0.80 (95% CI: 0.76-0.85). The clinical model additionally included diastolic blood pressure (mmHg) and serum creatinine levels (mmol/l). The AUC increased only marginally to 0.82 (0.77-0.87) (p for AUC comparison=0.188). The internal validation of the scores produced similar AUCs. CONCLUSIONS: The screening scores developed in this study are a simple tool to differentiate between a high and low likelihood of having DSPN among individuals with type 2 diabetes.

Plasma MR-proANP levels are associated with carotid intima-media thickness in the general community: the KORA F4 study.

OBJECTIVE: Subjects with metabolic syndrome (MetS) and individuals with type 2 diabetes are at high risk for vascular complications. Hormones acting on vascular endothelium may be involved in the atherogenic process associated with metabolic disorders. The objective of this study was to determine the correlation of pro-atrial natriuretic hormone (proANP) with the presence of subclinical atherosclerosis. METHODS: In 1272 subjects participating in the KORA F4 study, we determined plasma levels of mid-regional proANP (MR-proANP) and the intima-media thickness (IMT) of the carotid artery. We used logistic regression models to investigate the relation of MR-proANP with components of MetS and IMT. RESULTS: In multiple adjusted regression models, MR-proANP levels were inversely associated with MetS (OR = 0.66, 95% CI 0.47-0.93), central obesity (OR = 0.67, 95% CI 0.46-0.96), raised triglyceride levels (OR = 0.53, 95% CI 0.37-0.77), prediabetes (OR = 0.62, 95%, CI 0.44-0.87) and type 2 diabetes (OR = 0.55, 95% CI 0.35-0.88) when comparing the top quartile vs. the lower three quartiles. Furthermore, there was an inverse relationship between MR-proANP and IMT. After adjustment for traditional cardiovascular risk markers, individuals with high MR-proANP plasma levels in the top quartile (Q4) had significantly lower IMT values (Q4 vs. Q1-Q3: ß -0.0178, 95% CI -0.0344; -0.0013). CONCLUSIONS: In this population-based study, high plasma concentrations of MR-proANP were significantly associated with a lower incidence of MetS components and lower measures of early atherosclerosis. The data suggest a link between MR-proANP levels and the development of vascular complications.

Serum potassium is associated with prediabetes and newly diagnosed diabetes in hypertensive adults from the general population: the KORA F4-study.

AIMS/HYPOTHESIS: Evidence suggests that low serum potassium concentrations or hypokalaemia induced by the intake of diuretics are associated with incident diabetes and increased risk for diabetes in persons with hypertension. We examined a possible association between serum potassium and prediabetes (defined as isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT] or combined IFG/IGT), as well as known and newly diagnosed diabetes (NDD), in 32- to 81-year-old men and women with and without hypertension. METHODS: This cross-sectional analysis was based on 2,948 participants in the Cooperative Health Research in the Region of Augsburg (KORA) F4 study conducted in 2006-2008 in southern Germany. Serum concentrations of potassium were measured by indirect potentiometry. RESULTS: In the total sample there was no association between serum potassium concentrations and prediabetes. In hypertensive persons however serum potassium levels in the first and second quartile compared with the highest quartile were independently significantly associated with prediabetes after multivariable adjustment (OR for prediabetes, 2.02 [95% CI 1.27, 3.21] for quartile 2 and 2.00 [95% CI 1.27, 3.15] for quartile 1), while in persons without hypertension no association was found. In multinomial logistic regression analysis these findings could be confirmed. In hypertensive participants after multivariable adjustment the associations were statistically significant for i-IGT and NDD (i-IGT OR 1.23; NDD OR 1.41). However, in non-hypertensive persons, all associations between serum potassium levels and each of the categories of impaired glucose regulation were non-significant. CONCLUSIONS/INTERPRETATION: Serum potassium levels were independently associated with prediabetes and NDD in hypertensive adults from the general population.

Associations between longevity of parents and glucose regulation in their offspring: the KORA S4/F4 Study.

AIMS: Type 2 diabetes was less prevalent in studies of the offspring of centenarians and a separate study of nonagenarian siblings. We examined whether this reduction would also be found when less extreme criteria of parental longevity (a lifespan of at least 80 years) were applied. Moreover, we looked for an association between parental longevity and incidence of dysglycaemia, which has not yet been reported for a population-based study group. METHODS: Baseline and 7-year follow-up data on 55-74-year-old participants in the population-based German Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort study were used for the analyses. Participants whose parents had died from traumatic causes were excluded. Diabetes was assessed by validated physician diagnosis or OGTTs. Using logistic regression models, adjusted OR and 95% CIs were calculated for the associations between parental longevity and the prevalence or incidence of dysglycaemia, which was defined as including either type 2 diabetes or prediabetes (defined in this study as comprising impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]). RESULTS: In age- and sex-adjusted models, the prevalence of type 2 diabetes was lower in individuals with one (OR 0.63, 95% CI 0.43, 0.93) or two (OR 0.46, 95% CI 0.25, 0.85) long-lived parents. Among participants with normal glucose tolerance at baseline, the odds of incident dysglycaemia were lower in those with one (OR 0.65, 95% CI 0.40, 1.03) or two long-lived parents (OR 0.46, 95% CI 0.22, 0.96) after adjustment for age and sex. CONCLUSIONS/INTERPRETATION: This study showed that longevity of the parents, defined by a lifespan of at least 80 years, was associated with a lower prevalence and incidence of dysglycaemia in their offspring in an older German population.

Age at menarche is associated with prediabetes and diabetes in women (aged 32-81 years) from the general population: the KORA F4 Study.

AIMS/HYPOTHESIS: The aim of this study was to examine the association between age at menarche and prediabetes as well as diabetes, considering confounding factors and the possible mediating role of adult obesity. METHODS: This cross-sectional study analysed data on 1,503 women aged 32-81 years from the German population-based KORA (Cooperative Health Research in the Region of Augsburg, South Germany) F4 Study (2006-2008). Data were collected by standardised interviews, physical examinations, and whole blood and serum measurements, including administration of an OGTT in non-diabetic participants. RESULTS: Of the 1,503 women, 226 showed a prediabetic state (impaired fasting glucose and/or impaired glucose tolerance) and 140 persons had diabetes (45 participants with previously undiagnosed diabetes and 95 with known diabetes). In Poisson regression analysis, age at menarche was significantly inversely associated with prediabetes or diabetes after adjustment for year of birth (RR 0.88; 95% CI 0.82, 0.94, p < 0.0001 per additional year of menarche) and after additional adjustment for a number of confounding factors (RR 0.88; 95% CI 0.83, 0.94, p = 0.0001). Further adjustment for current BMI slightly attenuated the association with prediabetes or diabetes (RR 0.89; 95% CI 0.83, 0.95, p = 0.0009), but the association remained clearly significant. CONCLUSIONS/INTERPRETATION: Age at menarche seems to be inversely associated with prediabetes and diabetes independent of confounding factors including current BMI. Women at risk for diabetes might be identified by a history of young age at menarche.

Impact of weight and weight change on normalization of prediabetes and on persistence of normal glucose tolerance in an older population: the KORA S4/F4 study.

BACKGROUND AND AIMS: In a population-based cohort study with older subjects and without specific interventions, we investigated the impact of body mass index (BMI) and BMI change (as well as waist circumference and change of waist circumference) on reversion from prediabetes to normal glucose tolerance (NGT) and on long-term persistence of NGT. MATERIALS AND METHODS: Oral glucose tolerance tests were conducted at baseline and at follow-up in a cohort study in Southern Germany (KORA S4/F4; 1223 subjects without diabetes aged 55-74 years at baseline in 1999-2001; 887 subjects (73%), of whom 436 had prediabetes at baseline, participated in the follow-up 7 years later). RESULTS: BMI reduction, but not initial BMI, predicted reversion from prediabetes to NGT. The odds ratio (OR) for returning to NGT was 1.43 (95% CI: 1.18-1.73) for a BMI decrease of 1 kg m(-2), after adjustment for age, sex, baseline glucose values and lifestyle factors. Initial BMI had no effect on reversion to NGT (OR=0.98, 95% CI: 0.91-1.06, per kg m(-2)). Persistence of NGT was associated with baseline BMI (OR=0.94, 95% CI: 0.88-0.998) and BMI reduction (OR=1.16, 95% CI: 1.02-1.33, per decrease by 1 kg m(-2)). For waist circumference and change of waist circumference similar results were obtained. CONCLUSION: In older adults, weight loss strongly increased the chances of returning from prediabetes to NGT irrespective of initial BMI. Long-term persistence of NGT depended both on initial BMI and on BMI change.

Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study.

AIMS/HYPOTHESIS: Lower adiponectin levels are associated with higher risk of incident type 2 diabetes. Most analyses have been adjusted for confounding factors, but few have taken into account insulin resistance per se. We tested the hypothesis that the association of adiponectin levels with incident type 2 diabetes differs between insulin-resistant and insulin-sensitive individuals. METHODS: We studied two prospective cohorts: the Framingham Offspring Study (n = 2,023) and the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study (n = 887) cohorts. Insulin resistance was estimated by HOMA-insulin resistance (HOMA-IR). We used logistic regression analysis to test the association between adiponectin and incident type 2 diabetes overall and in insulin-resistant vs insulin-sensitive individuals (defined by ≥ vs <75th percentile of HOMA-IR). RESULTS: At baseline, Framingham's participants were 60 ± 9 years old and 56% were women; KORA's participants were 63 ± 5 years old and 49% were women. Type 2 diabetes incidence was 5.4% over 6.5 years (n = 109) in Framingham and 10.5% over 8 years (n = 93) in KORA. Lower adiponectin levels were associated with type 2 diabetes incidence in both cohorts. In insulin-resistant individuals, lower adiponectin levels were associated with higher risk of type 2 diabetes incidence (OR 1.60 [95% CI 1.10-2.31] per SD decrease in Framingham, p = 0.01; and OR 2.34 [95% CI 1.16-4.73] in KORA, p = 0.02); while this was not observed in insulin-sensitive individuals (OR 1.10 [95% CI 0.73-1.67] in Framingham, p = 0.64; and OR 1.34 [95%CI: 0.88-2.03] in KORA, p = 0.18). CONCLUSIONS/INTERPRETATION: We conclude that lower adiponectin levels are associated with higher risk of type 2 diabetes in insulin-resistant but not in insulin-sensitive individuals. This suggests that some level of insulin resistance is needed to see deleterious effects of low adiponectin.

Prediction models for incident type 2 diabetes mellitusin the older population: KORA S4/F4 cohort study.

BACKGROUND: The aim was to derive Type 2 diabetes prediction models for the older population and to check to what degree addition of 2-h glucose measurements (oral glucose tolerance test) and biomarkers improves the predictive power of risk scores which are based on non-biochemical as well as conventional clinical parameters. METHODS: Oral glucose tolerance tests were carried out in a population-based sample of 1353 subjects, aged 55-74 years (62% response) in Augsburg (Southern Germany) from 1999 to 2001. The cohort was reinvestigated in 2006-2008. Of those individuals without diabetes at baseline, 887 (74%) participated in the follow-up. Ninety-three (10.5%) validated diabetes cases occurred during the follow-up. In logistic regression analyses for model 1, variables were selected from personal characteristics and additional variables were selected from routinely measurable blood parameters (model 2) and from 2-h glucose, adiponectin, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (model 3). RESULTS: Age, sex, BMI, parental diabetes, smoking and hypertension were selected for model 1. Model 2 additionally included fasting glucose, HbA(1c) and uric acid. The same variables plus 2-h glucose were selected for model 3. The area under the receiver operating characteristic curve significantly increased from 0.763 (model 1) to 0.844 (model 2) and 0.886 (model 3) (P<0.01). Biomarkers such as adiponectin and insulin did not improve the predictive abilities of models 2 and 3. Cross-validation and bootstrap-corrected model performance indicated high internal validity. CONCLUSIONS: This longitudinal study in an older population provides models to predict the future risk of Type 2 diabetes. The OGTT, but not biomarkers, improved discrimination of incident diabetes.

Mobile phone base stations and adverse health effects: phase 2 of a cross-sectional study with measured radio frequency electromagnetic fields.

OBJECTIVE: The aim of the cross-sectional study was to test the hypothesis that exposure to continuous low-level radio frequency electromagnetic fields (RF-EMFs) emitted from mobile phone base stations was related to various health disturbances. METHODS: For the investigation people living mainly in urban regions were selected from a nationwide study in 2006. In total, 3526 persons responded to a questionnaire (response rate 85%). For the exposure assessment a dosimeter measuring different RF-EMF frequencies was used. Participants answered a postal questionnaire on how mobile phone base stations affected their health and they gave information on sleep disturbances, headaches, health complaints and mental and physical health using standardised health questionnaires. Information on stress was also collected. Multiple linear regression models were used with health outcomes as dependent variables (n = 1326). RESULTS: For the five health scores used, no differences in their medians were observed for exposed versus non-exposed participants. People who attributed adverse health effects to mobile phone base stations reported significantly more sleep disturbances and health complaints, but they did not report more headaches or less mental and physical health. Individuals concerned about mobile phone base stations did not have different well-being scores compared with those who were not concerned. CONCLUSIONS: In this large population-based study, measured RF-EMFs emitted from mobile phone base stations were not associated with adverse health effects.

Mobile phone base stations and adverse health effects: phase 1 of a population-based, cross-sectional study in Germany.

OBJECTIVE: The aim of this first phase of a cross-sectional study from Germany was to investigate whether proximity of residence to mobile phone base stations as well as risk perception is associated with health complaints. METHODS: The researchers conducted a population-based, multi-phase, cross-sectional study within the context of a large panel survey regularly carried out by a private research institute in Germany. In the initial phase, reported on in this paper, 30,047 persons from a total of 51,444 who took part in the nationwide survey also answered questions on how mobile phone base stations affected their health. A list of 38 health complaints was used. A multiple linear regression model was used to identify predictors of health complaints including proximity of residence to mobile phone base stations and risk perception. RESULTS: Of the 30,047 participants (response rate 58.6%), 18.7% of participants were concerned about adverse health effects of mobile phone base stations, while an additional 10.3% attributed their personal adverse health effects to the exposure from them. Participants who were concerned about or attributed adverse health effects to mobile phone base stations and those living in the vicinity of a mobile phone base station (500 m) reported slightly more health complaints than others. CONCLUSIONS: A substantial proportion of the German population is concerned about adverse health effects caused by exposure from mobile phone base stations. The observed slightly higher prevalence of health complaints near base stations can not however be fully explained by attributions or concerns.