Adipositas Care and Health Therapy (ACHT) after Bariatric-Metabolic Surgery: A Prospective, Non-Randomized Intervention Study.

INTRODUCTION: Almost 25% of German adults have obesity and numbers are rising, making it an important health issue. Bariatric-metabolic surgery reduces body weight and complications for persons with obesity, but therapeutic success requires long-term postoperative care. Since no German standards for follow-up by family physicians exist, follow-up is provided by surgical obesity centers, but they are reaching their limits. The ACHT study, funded by the German Innovation Fund, is designed to establish and evaluate the follow-up program, with local physicians following patients supported remotely by obesity centers. METHODS: ACHT is a multicenter, prospective, non-randomized control group study. The 18-month ACHT follow-up program is a digitally supported, structured, cross-sectoral, and close-to-home program to improve success after bariatric-metabolic surgery. Four groups are compared: intervention group 1 starts the program immediately (3 weeks) after Roux-en-Y gastric bypass or sleeve gastrectomy (months 1-18 postoperatively), intervention group 2 begins the program 18 months after surgery (months 19-36 postoperatively). Intervention groups are compared to respective control groups that had surgery 18 and 36 months previously. In total, 250 patients, enrolled in the intervention groups, are compared with 360 patients in the control groups, who only receive standard care. RESULTS: The primary endpoint to compare intervention and control groups is the adapted King's score, a composite tool evaluating physical, psychological, socioeconomic, and functional health status. Secondary endpoints include changes in care structures and care processes for the intervention groups. Multivariate regression analyses adjusting for confounders (including the type of surgery) are used to compare intervention and control groups and evaluate determinants in longitudinal analyses. The effect of the intervention on healthcare costs will be evaluated based on health insurance billing data of patients who had bariatric-metabolic surgery in the 3 years prior to the start of the study and of patients who undergo bariatric-metabolic surgery during the study period. CONCLUSIONS: ACHT will be the one of the first evaluated structured, close-to-home follow-up programs for bariatric surgery in Germany. It will evaluate the effectiveness of the implemented program regarding improvements in health status, mental health, quality of life, and the feasibility of such a program outside of specialized obesity centers.

The impact of passive alveolar molding vs. nasoalveolar molding on cleft width and other parameters of maxillary growth in unilateral cleft lip palate.

OBJECTIVE: Passive alveolar molding (PAM) and nasoalveolar molding (NAM) are established presurgical infant orthodontic (PSIO) therapies for cleft lip palate (CLP) patients. PAM guides maxillary growth with a modified Hotz appliance, while NAM also uses extraoral taping and includes nasal stents. The effects of these techniques on alveolar arch growth have rarely been compared. MATERIAL AND METHODS: We retrospectively compared 3D-scanned maxillary models obtained before and after PSIO from infants with unilateral, non-syndromic CLP treated with PAM (n = 16) versus NAM (n = 13). Nine anatomical points were set digitally by four raters and transversal/sagittal distances and rotations of the maxilla were measured. RESULTS: Both appliances reduced the anterior cleft, but NAM percentage wise more. NAM decreased the anterior and medial transversal width compared to PAM, which led to no change. With both appliances, the posterior width increased. The alveolar arch length of the great and small segments and the sagittal length of the maxilla increased with PAM but only partially with NAM. However, NAM induced a significant greater medial rotation of the larger and smaller segment compared to PAM with respect to the lateral angle. CONCLUSIONS: NAM and PAM presented some significant differences regarding maxillary growth. While NAM reduced the anterior cleft and effectively rotated the segments medially, PAM allowed more transversal and sagittal growth. CLINICAL RELEVANCE: The results of this study should be taken into consideration when to decide whether to use PAM or NAM, since they show a different outcome within the first few months. Further studies are necessary regarding long-term differences.

Following Pediatric and Adult IBD Patients through the COVID-19 Pandemic: Changes in Psychosocial Burden and Perception of Infection Risk and Harm over Time.

BACKGROUND: COVID-19-associated restrictions impact societies. We investigated the impact in a large cohort of inflammatory bowel disease (IBD) patients. METHODS: Pediatric (pIBD) and adult patients and pIBD parents completed validated questionnaires for self-perceived stress (Perceived Stress Questionnaire, PSQ) and quality of life from July to October 2020 (1st survey) and March to April 2021 (2nd survey). Analyses were stratified by age groups (6-20, >20-40, >40-60, >60 years). Perceived risk of infection and harm from COVID-19 were rated on a 1-7 scale. An index for severe outcome (SIRSCO) was calculated. Multivariable logistic regression analysis was performed. RESULTS: Of 820 invited patients, 504 (62%, 6-85 years) patients and 86 pIBD parents completed the 1st, thereof 403 (80.4%) the 2nd survey. COVID-19 restrictions resulted in cancelled doctoral appointments (26.7%), decreased physical activity, increased food intake, unintended weight gain and sleep disturbance. PSQ increased with disease activity. Elderly males rated lower compared to females or younger adults. PSQ in pIBD mothers were comparable to moderate/severe IBD adults. Infection risk and harm were perceived high in 36% and 75.4%. Multivariable logistic models revealed associations of higher perceived risk with >3 household members, job conditions and female gender, and of perceived harm with higher SIRSCO, unintended weight change, but not with gender or age. Cancelled clinic-visits were associated with both. SARS-CoV-2 antibodies prior 2nd infection wave were positive in 2/472 (0.4%). CONCLUSIONS: IBD patients report a high degree of stress and self-perceived risk of complications from COVID-19 with major differences related to gender and age. Low seroprevalence may indicate altered immune response.

Impact of interventions to reduce overnutrition on healthcare costs related to obesity and type 2 diabetes: a systematic review.

CONTEXT: In recent decades, obesity and type 2 diabetes mellitus (T2DM) have both become global epidemics associated with substantial healthcare needs and costs. OBJECTIVE: The aim of this review was to critically assess nutritional interventions for their impact on healthcare costs to community-dwelling individuals regarding T2DM or obesity or both, specifically using CHEERS (Consolidated Health Economic Evaluation Reporting Standards) criteria to assess the economic components of the evidence. DATA SOURCES: Searches were executed in Embase, EconLit, AgEcon, PubMed, and Web of Science databases. STUDY SELECTION: Studies were included if they had a nutritional perspective, reported an economic evaluation that included healthcare costs, and focused on obesity or T2DM or both. Studies were excluded if they examined clinical nutritional preparations, dietary supplements, industrially modified dietary components, micronutrient deficiencies, or undernutrition; if they did not report the isolated impact of nutrition in complex or lifestyle interventions; or if they were conducted in animals or attempted to transfer findings from animals to humans. DATA EXTRACTION: A systematic review was performed according to PRISMA guidelines. Using predefined search terms, 21 studies evaluating food habit interventions or taxation of unhealthy foods and beverages were extracted and evaluated using CHEERS criteria. RESULTS: Overall, these studies showed that nutrition interventions and taxation approaches could lead to cost savings and improved health outcomes when compared with current practice. All of the included studies used external sources and economic modeling or risk estimations with population-attributable risks to calculate economic outcomes. CONCLUSIONS: Most evidence supported taxation approaches. The effect of nutritional interventions has not been adequately assessed. Controlled studies to directly measure economic impacts are warranted.

Do adolescents with extreme obesity differ according to previous treatment seeking behavior? The Youth with Extreme obesity Study (YES) cohort.

OBJECTIVES: Adolescent extreme obesity is associated with somatic and psychiatric comorbidity, low quality of life, and social dysfunction. Nevertheless, few adolescents seek obesity treatment, thus many may elope appropriate care. We examine whether previous treatment seeking relates to disease burden, and whether previously non-treatment seeking adolescents accept diagnostic and therapeutic offers. This information is important to inform intervention strategies. METHODS: The Youth with Extreme obesity Study (YES) is a prospective, multicenter cohort study. We developed a novel recruitment strategy to span medical and vocational ascertainment settings and directly compare previously treatment seeking and non-treatment seeking youth. Participants aged 14-24 years; BMI ≥ 30 kg/m2 were enrolled at four medical- and one job centers. We present comorbidity and psycho-social baseline data by sex, obesity WHO grade I-III, and treatment-seeking status, defined as self-reported previous participation in a weight-loss program. RESULTS: Of 431 participants, 47% were male; mean age 16.6 (standard deviation 2.3) years, BMI 39.2 (7.5) kg/m2. Somatic comorbidity increased with obesity grade, p < 0.05: hypertension (42, 55, 64%), dyslipidemia (28, 24, 37%,), dysglycemia (9, 19, 20%,), elevated transaminases (15, 26, 30%). Quality of life (EQ5 D) decreased (74, 71, 70). Rates of psychiatric disorders were stable: depression 11%, attention deficit disorder 6%, substance use disorder 2%, self-injurious behavior 5%, suicide attempt 3%. Only 63% (56, 64, 69%) reported previous treatment seeking. Acceptance of the diagnostic (89%) or therapeutic (28%) program, medical or psychosocial situation did not differ by treatment seeking status. Acceptance of the therapeutic program was generally low, but high at the job center (92%). CONCLUSION: Irrespective of previous treatment seeking, adolescent extreme obesity was associated with high comorbidity and psychosocial burden. Acceptance of the diagnostic program overall and the therapeutic program at the job center were high. This underscores the need of innovative, accessible programs beyond the currently offered care.

A Walnut-Enriched Diet Affects Gut Microbiome in Healthy Caucasian Subjects: A Randomized, Controlled Trial.

Regular walnut consumption is associated with better health. We have previously shown that eight weeks of walnut consumption (43 g/day) significantly improves lipids in healthy subjects. In the same study, gut microbiome was evaluated. We included 194 healthy subjects (134 females, 63 ± 7 years, BMI 25.1 ± 4.0 kg/m²) in a randomized, controlled, prospective, cross-over study. Following a nut-free run-in period, subjects were randomized to two diet phases (eight weeks each); 96 subjects first followed a walnut-enriched diet (43 g/day) and then switched to a nut-free diet, while 98 subjects followed the diets in reverse order. While consuming the walnut-enriched diet, subjects were advised to either reduce fat or carbohydrates or both to account for the additional calories. Fecal samples were collected from 135 subjects at the end of the walnut-diet and the control-diet period for microbiome analyses. The 16S rRNA gene sequencing data was clustered with a 97% similarity into Operational Taxonomic Units (OTUs). UniFrac distances were used to determine diversity between groups. Differential abundance was evaluated using the Kruskal-Wallis rank sum test. All analyses were performed using Rhea. Generalized UniFrac distance shows that walnut consumption significantly affects microbiome composition and diversity. Multidimensional scaling (metric and non-metric) indicates dissimilarities of approximately 5% between walnut and control (p = 0.02). The abundance of Ruminococcaceae and Bifidobacteria increased significantly (p < 0.02) while Clostridium sp. cluster XIVa species (Blautia; Anaerostipes) decreased significantly (p < 0.05) during walnut consumption. The effect of walnut consumption on the microbiome only marginally depended on whether subjects replaced fat, carbohydrates or both while on walnuts. Daily intake of 43 g walnuts over eight weeks significantly affects the gut microbiome by enhancing probiotic- and butyric acid-producing species in healthy individuals. Further evaluation is required to establish whether these changes are preserved during longer walnut consumption and how these are linked to the observed changes in lipid metabolism.

Cost-effectiveness of increasing the reach of smoking cessation interventions in Germany: results from the EQUIPTMOD.

AIMS: To evaluate costs, effects and cost-effectiveness of increased reach of specific smoking cessation interventions in Germany. DESIGN: A Markov-based state transition return on investment model (EQUIPTMOD) was used to evaluate current smoking cessation interventions as well as two prospective investment scenarios. A health-care perspective (extended to include out-of-pocket payments) with life-time horizon was considered. A probabilistic analysis was used to assess uncertainty concerning predicted estimates. SETTING: Germany. PARTICIPANTS: Cohort of current smoking population (18+ years) in Germany. INTERVENTIONS: Interventions included group-based behavioural support, financial incentive programmes and varenicline. For prospective scenario 1 the reach of group-based behavioral support, financial incentive programme and varenicline was increased by 1% of yearly quit attempts (= 57 915 quit attempts), while prospective scenario 2 represented a higher reach, mirroring the levels observed in England. MEASUREMENTS: EQUIPTMOD considered reach, intervention cost, number of quitters, quality-of-life years (QALYs) gained, cost-effectiveness and return on investment. FINDINGS: The highest returns through reduction in smoking-related health-care costs were seen for the financial incentive programme (€2.71 per €1 invested), followed by that of group-based behavioural support (€1.63 per €1 invested), compared with no interventions. Varenicline had lower returns (€1.02 per €1 invested) than the other two interventions. At the population level, prospective scenario 1 led to 15 034 QALYs gained and €27 million cost-savings, compared with current investment. Intervention effects and reach contributed most to the uncertainty around the return-on-investment estimates. At a hypothetical willingness-to-pay threshold of only €5000, the probability of being cost-effective is approximately 75% for prospective scenario 1. CONCLUSIONS: Increasing the reach of group-based behavioural support, financial incentives and varenicline for smoking cessation by just 1% of current annual quit attempts provides a strategy to German policymakers that improves the population's health outcomes and that may be considered cost-effective.

A Walnut-Enriched Diet Reduces Lipids in Healthy Caucasian Subjects, Independent of Recommended Macronutrient Replacement and Time Point of Consumption: a Prospective, Randomized, Controlled Trial.

Studies indicate a positive association between walnut intake and improvements in plasma lipids. We evaluated the effect of an isocaloric replacement of macronutrients with walnuts and the time point of consumption on plasma lipids. We included 194 healthy subjects (134 females, age 63 ± 7 years, BMI 25.1 ± 4.0 kg/m²) in a randomized, controlled, prospective, cross-over study. Following a nut-free run-in period, subjects were randomized to two diet phases (8 weeks each). Ninety-six subjects first followed a walnut-enriched diet (43 g walnuts/day) and then switched to a nut-free diet. Ninety-eight subjects followed the diets in reverse order. Subjects were also randomized to either reduce carbohydrates (n = 62), fat (n = 65), or both (n = 67) during the walnut diet, and instructed to consume walnuts either as a meal or as a snack. The walnut diet resulted in a significant reduction in fasting cholesterol (walnut vs. CONTROL: -8.5 ± 37.2 vs. -1.1 ± 35.4 mg/dL; p = 0.002), non-HDL cholesterol (-10.3 ± 35.5 vs. -1.4 ± 33.1 mg/dL; p ≤ 0.001), LDL-cholesterol (-7.4 ± 32.4 vs. -1.7 ± 29.7 mg/dL; p = 0.029), triglycerides (-5.0 ± 47.5 vs. 3.7 ± 48.5 mg/dL; p = 0.015) and apoB (-6.7 ± 22.4 vs. -0.5 ± 37.7; p ≤ 0.001), while HDL-cholesterol and lipoprotein (a) did not change significantly. Neither macronutrient replacement nor time point of consumption significantly affected the effect of walnuts on lipids. Thus, 43 g walnuts/d improved the lipid profile independent of the recommended macronutrient replacement and the time point of consumption.

The Non-Linear Relationship between BMI and Health Care Costs and the Resulting Cost Fraction Attributable to Obesity.

This study aims to analyse the non-linear relationship between Body Mass Index (BMI) and direct health care costs, and to quantify the resulting cost fraction attributable to obesity in Germany. Five cross-sectional surveys of cohort studies in southern Germany were pooled, resulting in data of 6757 individuals (31-96 years old). Self-reported information on health care utilisation was used to estimate direct health care costs for the year 2011. The relationship between measured BMI and annual costs was analysed using generalised additive models, and the cost fraction attributable to obesity was calculated. We found a non-linear association of BMI and health care costs with a continuously increasing slope for increasing BMI without any clear threshold. Under the consideration of the non-linear BMI-cost relationship, a shift in the BMI distribution so that the BMI of each individual is lowered by one point is associated with a 2.1% reduction of mean direct costs in the population. If obesity was eliminated, and the BMI of all obese individuals were lowered to 29.9 kg/m², this would reduce the mean direct costs by 4.0% in the population. Results show a non-linear relationship between BMI and health care costs, with very high costs for a few individuals with high BMI. This indicates that population-based interventions in combination with selective measures for very obese individuals might be the preferred strategy.

Current health status and medical therapy of patients with pediatric-onset inflammatory bowel disease: a survey-based analysis on 1280 patients aged 10-25 years focusing on differences by age of onset.

OBJECTIVE: There are inconsistent reports on age-related differences in inflammatory bowel disease (IBD). On the basis of patient information, we describe the clinical presentation and therapy in relation to age at diagnosis in longstanding pediatric IBD. PATIENTS AND METHODS: Two surveys were conducted in children and young adults (age: 10-25 years) by pretested postal questionnaires. The main analyses are descriptive, showing proportions and distributions per grouped age of diagnosis. Exploratory logistic regression was used to identify sociodemographic and disease-related factors associated with prognosis. Recent disease course, use of biological therapy, and resecting surgery were chosen as indicators of disease severity. Patients with a diagnosis in infancy (<2 years of age) are presented as a case series. RESULTS: Information of 1280 cases was available [804 Crohn's disease (CD), 382 ulcerative colitis (UC), 94 IBD not specified] (response: 44.6 and 49.6%). Stable remission during the preceding year was reported by 675 (56.7%) patients; 825 (60.9%) patients reported feeling currenty well. Anti-tumor necrosis factor therapy was reported by 33% of CD patients and 9.3% of UC patients, immunomodulation in 82.1 and 63.2%, and corticosteroids by 78.4 and 76.1%, respectively (ever use). Age at diagnosis was not associated with indicators of severe disease. Diagnosis in infancy was reported by 37 patients. CONCLUSION: Our data do not support age at diagnosis-related differences in prognosis in pediatric-onset IBD.

The Economic Burden of Obesity in Germany: Results from the Population-Based KORA Studies.

OBJECTIVE: To estimate the excess costs of obese compared to normal-weight persons in Germany based on self-reported resource utilisation and work absence. METHODS: Five cross sectional surveys of cohort studies in southern Germany were pooled resulting in 9,070 observations for 6,731 individuals (31-96 years). BMI was measured in the study centre. Self-reported health care utilisation and work absence was used to estimate direct and indirect costs for the year 2011 based on unit costs. Using regression analyses, adjusted costs for different BMI groups were calculated. RESULTS: Overweight and obese people showed significantly higher odds of health care utilisation and productivity losses compared with normal-weight people in most categories. Total direct/indirect costs were significantly higher with increasing severity of obesity (pre-obese (1.05 (0.90-1.23) / 1.38 (1.11-1.71)), obesity level I (1.18 (1.00-1.39) / 1.33 (1.02-1.73)), obesity level II (1.46 (1.14-1.87) / 1.77 (1.18-2.65)) or level III (2.04 (1.40-2.97) / 1.99 (1.20-3.30)) compared to normal-weight participants. In particular, higher obesity classes were significantly associated with increased costs for medication, general practitioner utilisation and work absence. CONCLUSION: Our results show that overweight and obesity are associated with enormous societal direct and indirect costs in Germany. This supports the evidence from previous top-down studies, but provides important new information based on a large pooled data set and measured BMI.

Cost burden of type 2 diabetes in Germany: results from the population-based KORA studies.

OBJECTIVE: To examine the impact of type 2 diabetes on direct and indirect costs and to describe the effect of relevant diabetes-related factors, such as type of treatment or glycaemic control on direct costs. DESIGN: Bottom-up excess cost analysis from a societal perspective based on population-based survey data. PARTICIPANTS: 9160 observations from 6803 individuals aged 31-96 years (9.6% with type 2 diabetes) from the population-based KORA (Cooperative Health Research in the Region of Augsburg) studies in Southern Germany. OUTCOME MEASURES: Healthcare usage, productivity losses, and resulting direct and indirect costs. METHODS: Information on diabetes status, biomedical/sociodemographic variables, medical history and on healthcare usage and productivity losses was assessed in standardised interviews and examinations. Healthcare usage and productivity losses were costed with reference to unit prices and excess costs of type 2 diabetes were calculated using generalised linear models. RESULTS: Individuals with type 2 diabetes had 1.81 (95% CI 1.56 to 2.11) times higher direct (€3352 vs €1849) and 2.07 (1.51 to 2.84) times higher indirect (€4103 vs €1981) annual costs than those without diabetes. Cardiovascular complications, a long diabetes duration and treatment with insulin were significantly associated with increased direct costs; however, glycaemic control was only weakly insignificantly associated with costs. CONCLUSIONS: This study illustrates the substantial direct and indirect societal cost burden of type 2 diabetes in Germany. Strong effort is needed to optimise care to avoid progression of the disease and costly complications.

The Burden of Diabetes Mellitus in Patients with Coronary Heart Disease: A Methodological Approach to Assess Quality-Adjusted Life-Years Based on Individual-Level Longitudinal Survey Data.

BACKGROUND: Reliable burden of disease (BOD) estimates are needed to support decision making in health care. OBJECTIVES: The objective of this study was to introduce an analysis approach based on individual-level longitudinal survey data that estimates the burden of diabetes in patients with coronary heart disease in terms of quality-adjusted life-years (QALYs) lost. METHODS: Data from two postal surveys (2006, N = 1022; 2010-2011, N = 716) of survivors from the KORA Myocardial Infarction Registry in Southern Germany were analyzed. Accumulated QALYs were calculated for each participant over a mean observation time of 4.1 years, considering the noninformative censoring structure of the follow-up study. Linear regression models were used to estimate the loss in (quality-unadjusted) life-years and QALYs between patients with and without diabetes, and generalized additive models were used to analyze the nonlinear association with age. The cross-sectional and longitudinal association with quality of life (QOL) and QOL change and the impact on mortality were analyzed to enhance the understanding of the observed results. RESULTS: Diabetes was associated with a reduced QOL at baseline (cross-sectional: ß = -0.069; P < 0.001), but not with a significant longitudinal QOL change. Mortality in patients with diabetes was increased (hazard ratio = 1.68; P < 0.005). This resulted in a loss of 0.14 life-years (P = 0.003) and 0.37 QALYs (P < 0.001). Results from generalized additive models indicated that the burden of diabetes is less pronounced in older subjects. CONCLUSIONS: The application of the proposed approach provides confounder-adjusted BOD estimates for the studied time horizon and can be used to compare the BOD across different chronic conditions. Curative efforts are needed to diminish the substantial diabetes-related QALY gap.

The effectiveness of German disease management programs (DMPs) in patients with type 2 diabetes mellitus and coronary heart disease: results from an observational longitudinal study.

BACKGROUND: Although the population-based German disease management programs (DMPs) for diabetes mellitus (DM) and coronary heart disease (CHD) are among the biggest worldwide, evidence on the effectiveness of these programs is still inconclusive or missing, particularly for high risk patients with comorbidities. The objective of this study was therefore to analyze the impact of DMPs on process and outcome parameters in patients with both, type 2 DM and CHD. METHODS: Analyses are based on two postal surveys of patients from the KORA myocardial infarction registry (southern Germany) with type 2 DM and on two postal validation studies with patients' general physicians (2006, n = 312 and 2011, n = 212). The association between DMP enrollment (being enrolled in either DMP-DM or DMP-CHD) and guideline care (defined by several process indicators) at baseline (2006) and its development until follow-up (2011) was analyzed using logistic regression models accounting for the repeated measurements structure. The impact of DMP enrollment/guideline care on cumulated (quality-adjusted) life years ((QA)LYs) over a 4-year time horizon (2006-2010) was assessed using multiple linear regression methods. Logistic regression models were applied to analyze the association between DMP status and patient self-management at follow-up. RESULTS: Being enrolled in a DMP was associated with better guideline care at baseline [OR = 2.3 (95 % CI 1.27-4.03)], but not at follow-up [OR = 0.80 (95 % CI 0.40-1.58); p value for time-interaction <0.01]. DMP enrollment was not significantly [+0.15 LYs (95 % CI -0.07, 0.37); +0.06 QALYs (95 % CI -0.15, 0.26)], but treatment according to guideline care significantly [+0.40 LYs (95 % CI 0.21-0.60); +0.28 QALYs (95 % CI 0.10-0.45)] associated with higher (quality-adjusted) survival over the 4-year follow-up period. DMP enrollees further reported a somewhat better self-management than patients not being enrolled into a DMP. CONCLUSIONS: The results of this study concerning the effectiveness of DMPs in patients with DM and CHD are mixed, but are weakly in favor of DMPs. However, we found a clear positive impact of guideline care on quality adjusted survival in this patient group. The development of the association between DMP enrollment and guideline care over the follow-up time indicates some external effects, which should be the subject of further investigations.

Effects of metformin on metabolite profiles and LDL cholesterol in patients with type 2 diabetes.

OBJECTIVE: Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin. RESEARCH DESIGN AND METHODS: We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metformin-associated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways. RESULTS: We found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years' follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target. CONCLUSIONS: Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease.

Towards patient-oriented diabetes care: results from two KORA surveys in southern Germany.

OBJECTIVE: This study aims to examine the relationship of diabetes care processes and patient outcomes with an expanded set of indicators regarding patient-oriented care delivery, such as treatment satisfaction, the quality of patient-physician relationship, and a wider range of patient outcomes such as self-management, health behaviour, disease-related burden, and health-related quality of life (HRQL). METHODS: The study population consisted of 486 participants with type 2 diabetes in two population-based follow-up surveys, conducted in 2003 to 2005 and 2006 to 2008 in Southern Germany. Data were self-reported and questionnaire-based, including the SF-12 for HRQL. Multiple regression models were used to identify associations between care processes and outcomes with adjustment for confounders. RESULTS: Frequent medical examinations increased the likelihood of self-monitoring activities, such as foot care. A positive patient experienced relationship with their physician is associated with higher adherence to medical recommendations, such as medication intake, and the score of the SF-12 mental component. Participants with diabetes-related complications reported higher levels of medical examinations and multiprofessional care. CONCLUSIONS: Indicators of patient-oriented care should become an indispensable part of diabetes clinical practice guidelines with the aim of striving for more effective support of patients.

Improving care of post-infarct patients: effects of disease management programmes and care according to international guidelines.

BACKGROUND: Cardiac disease management programmes (CHD-DMPs) and secondary cardiovascular prevention guidelines aim to improve complex care of post-myocardial infarction (MI) patients. In Germany, CHD-DMPs, in addition to incorporating medical care according to guidelines (guideline-care), also ensure regular quarterly follow-up. Thus, our aim was to examine whether CHD-DMPs increase the frequency of guideline-care and whether CHD-DMPs and guideline-care improve survival over 4 years. METHODS: The study included 975 post-MI patients, registered by the KORA-MI Registry (Augsburg, Germany), who completed a questionnaire in 2006. CHD-DMP enrolment was reported by physicians. Guideline-care was based on patient reports regarding medical advice (smoking, diet, or exercise) and prescribed medications (statins and platelet aggregation inhibitors plus beta-blockers or renin-angiotensin inhibitors). All-cause mortality until December 31, 2010 was based on municipal registration data. Cox regression analyses were adjusted for age, sex, education, years since last MI, and smoking and diabetes. RESULTS: Physicians reported that 495 patients were CHD-DMP participants. CHD-DMP participation increased the likelihood of receiving guideline-care (odds ratio 1.55, 95% CI 1.20; 2.02) but did not significantly improve survival (hazard rate 0.90, 95% CI 0.64-1.27). Guideline-care significantly improved survival (HR 0.41, 95% CI 0.28; 0.59). Individual guideline-care components, which significantly improved survival, were beta-blockers, statins and platelet aggregation inhibitors. However, these improved survival less than guideline-care. CONCLUSIONS: This study shows that CHD-DMPs increase the likelihood of guideline care and that guideline care is the important component of CHD-DMPs for increasing survival. A relatively high percentage of usual care patients receiving guideline-care indicate high quality of care of post-MI patients. Reasons for not implementing guideline-care should be investigated.

Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: a randomized controlled cross-over clinical trial.

BACKGROUND: Walnut consumption is associated with reduced risk of coronary heart disease (CHD). OBJECTIVE: We assessed the effect of walnuts on lipid and glucose metabolism, adipokines, inflammation and endothelial function in healthy Caucasian men and postmenopausal women ≥50years old. DESIGN: Forty subjects (mean±SEM: age 60±1years, BMI 24.9±0.6kg/m(2); 30 females) were included in a controlled, cross-over study and randomized to receive first a walnut-enriched (43g/d) and then a Western-type (control) diet or vice-versa, with each lasting 8weeks and separated by a 2-week wash-out. At the beginning and end of each diet phase, measurements of fasting values, a mixed meal test and an assessment of postprandial endothelial function (determination of microcirculation by peripheral artery tonometry) were conducted. Area under the curve (AUC), incremental AUC (iAUC) and treatment×time interaction (shape of the curve) were evaluated for postprandial triglycerides, VLDL-triglycerides, chylomicron-triglycerides, glucose and insulin. RESULTS: Compared with the control diet, the walnut diet significantly reduced non-HDL-cholesterol (walnut vs. control: -10±3 vs. -3±2mg/dL; p=0.025) and apolipoprotein-B (-5.0±1.3 vs. -0.2±1.1mg/dL; p=0.009) after adjusting for age, gender, BMI and diet sequence. Total cholesterol showed a trend toward reduction (p=0.073). Fasting VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glucose, insulin, HOMA-IR, and HbA1c did not change significantly. Similarly, fasting adipokines, C-reactive protein, biomarkers of endothelial dysfunction, postprandial lipid and glucose metabolism and endothelial function were unaffected. CONCLUSION: Daily consumption of 43g of walnuts for 8weeks significantly reduced non-HDL-cholesterol and apolipoprotein-B, which may explain in part the epidemiological observation that regular walnut consumption decreases CHD risk.

The performance of a value set for the EQ-5D based on experienced health states in patients with inflammatory bowel disease.

OBJECTIVES: To compare in patients with inflammatory bowel disease the performance of a value set for the EQ-5D based on experienced health states (EHSs) with value sets based on given health states (GHSs). METHODS: A value set based on EHSs and valuation by the visual analogue scale (VAS) in the German general population was compared with a German and a U.K. value set, both based on GHSs and time-trade off valuation. Accuracy in the prediction of actual VAS ratings by patients was assessed using correlation and mean absolute error. Construct validity was tested by correlation with established disease activity indices and test-retest reliability by intraclass correlation between two measurements. Data originated from a survey of 270 patients with Crohn's disease and 232 patients with ulcerative colitis. RESULTS: EHS-VAS correlates best with actual VAS ratings for all patients but not for all subgroups. EHS-VAS has the lowest mean absolute error for almost all analyzed groups except for measured differences between two time points. Regarding test-retest reliability in all patients, EHS-VAS correlations were closest to those of actual VAS ratings. CONCLUSION: EHS-VAS renders experience-based valuations but not decision utilities. GHS-based approaches cover severe health states more extensively, but study patients reported health states similar to those of a general population. Compared to GHS time-trade off value sets, the EHS-VAS value set predicted EQ-5D VAS valuations by patients with inflammatory bowel disease equally well and partly better. It performed partly better with respect to test-retest reliability and the same with respect to construct validity.