Differential association of dietary scores with the risk of type 2 diabetes by metabotype.

PURPOSE: We aimed to examine the association between dietary patterns and type 2 diabetes mellitus (T2DM) while considering the potential effect modification by metabolic phenotypes (metabotypes). Additionally, we aimed to explore the association between dietary scores and prediabetes. METHODS: A total of 1460 participants (11.8% with T2DM) from the cross-sectional population-based KORA FF4 study were included. Participants, classified into three metabotype subgroups, had both their FSAm-NPS dietary index (underpinning the Nutri-Score) and ultra-processed foods (UPF) intake (using NOVA classification) calculated. Glucose tolerance status was assessed via oral glucose tolerance tests (OGTT) in non-diabetic participants and was classified according to the American Diabetes Association criteria. Logistic regression models were used for both the overall and metabotype-stratified analyses of dietary scores' association with T2DM, and multinomial probit models for their association with prediabetes. RESULTS: Participants who had a diet with a higher FSAm-NPS dietary index (i.e., a lower diet quality) or a greater percentage of UPF consumption showed a positive association with T2DM. Stratified analyses demonstrated a strengthened association between UPF consumption and T2DM specifically in the metabolically most unfavorable metabotype (Odds Ratio, OR 1.92; 95% Confidence Interval, CI 1.35, 2.73). A diet with a higher FSAm-NPS dietary index was also positively associated with prediabetes (OR 1.19; 95% CI 1.04, 1.35). CONCLUSION: Our study suggests different associations between poorer diet quality and T2DM across individuals exhibiting diverse metabotypes, pointing to the option for stratified dietary interventions in diabetes prevention.

Projected health and economic impacts of sugar-sweetened beverage taxation in Germany: A cross-validation modelling study.

BACKGROUND: Taxes on sugar-sweetened beverages (SSBs) have been implemented globally to reduce the burden of cardiometabolic diseases by disincentivizing consumption through increased prices (e.g., 1 peso/litre tax in Mexico) or incentivizing industry reformulation to reduce SSB sugar content (e.g., tiered structure of the United Kingdom [UK] Soft Drinks Industry Levy [SDIL]). In Germany, where no tax on SSBs is enacted, the health and economic impact of SSB taxation using the experience from internationally implemented tax designs has not been evaluated. The objective of this study was to estimate the health and economic impact of national SSBs taxation scenarios in Germany. METHODS AND FINDINGS: In this modelling study, we evaluated a 20% ad valorem SSB tax with/without taxation of fruit juice (based on implemented SSB taxes and recommendations) and a tiered tax (based on the UK SDIL) in the German adult population aged 30 to 90 years from 2023 to 2043. We developed a microsimulation model (IMPACTNCD Germany) that captures the demographics, risk factor profile and epidemiology of type 2 diabetes, coronary heart disease (CHD) and stroke in the German population using the best available evidence and national data. For each scenario, we estimated changes in sugar consumption and associated weight change. Resulting cases of cardiometabolic disease prevented/postponed and related quality-adjusted life years (QALYs) and economic impacts from healthcare (medical costs) and societal (medical, patient time, and productivity costs) perspectives were estimated using national cost and health utility data. Additionally, we assessed structural uncertainty regarding direct, body mass index (BMI)-independent cardiometabolic effects of SSBs and cross-validated results with an independently developed cohort model (PRIMEtime). We found that SSB taxation could reduce sugar intake in the German adult population by 1 g/day (95%-uncertainty interval [0.05, 1.65]) for a 20% ad valorem tax on SSBs leading to reduced consumption through increased prices (pass-through of 82%) and 2.34 g/day (95%-UI [2.32, 2.36]) for a tiered tax on SSBs leading to 30% reduction in SSB sugar content via reformulation. Through reductions in obesity, type 2 diabetes, and cardiovascular disease (CVD), 106,000 (95%-UI [57,200, 153,200]) QALYs could be gained with a 20% ad valorem tax and 192,300 (95%-UI [130,100, 254,200]) QALYs with a tiered tax. Respectively, €9.6 billion (95%-UI [4.7, 15.3]) and €16.0 billion (95%-UI [8.1, 25.5]) costs could be saved from a societal perspective over 20 years. Impacts of the 20% ad valorem tax were larger when additionally taxing fruit juice (252,400 QALYs gained, 95%-UI [176,700, 325,800]; €11.8 billion costs saved, 95%-UI [€6.7, €17.9]), but impacts of all scenarios were reduced when excluding direct health effects of SSBs. Cross-validation with PRIMEtime showed similar results. Limitations include remaining uncertainties in the economic and epidemiological evidence and a lack of product-level data. CONCLUSIONS: In this study, we found that SSB taxation in Germany could help to reduce the national burden of noncommunicable diseases and save a substantial amount of societal costs. A tiered tax designed to incentivize reformulation of SSBs towards less sugar might have a larger population-level health and economic impact than an ad valorem tax that incentivizes consumer behaviour change only through increased prices.

A Fecal Metabolite Signature of Impaired Fasting Glucose: Results From Two Independent Population-Based Cohorts.

Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings. We linearly combined eight IFG-positively associated metabolites (1-methylxantine, nicotinate, glucuronate, uridine, cholesterol, serine, caffeine, and protoporphyrin IX) into an IFG-metabolite score, which was significantly associated with higher odds ratios (ORs) for IFG (TwinsUK: OR 3.9 [95% CI 3.02-5.02], P < 0.0001, KORA: OR 1.3 [95% CI 1.16-1.52], P < 0.0001) and incident type 2 diabetes (T2D; TwinsUK: hazard ratio 4 [95% CI 1.97-8], P = 0.0002). Although these are host-produced metabolites, we found that the gut microbiome is strongly associated with their fecal levels (area under the curve >70%). Abundances of Faecalibacillus intestinalis, Dorea formicigenerans, Ruminococcus torques, and Dorea sp. AF24-7LB were positively associated with IFG, and such associations were partially mediated by 1-methylxanthine and nicotinate (variance accounted for mean 14.4% [SD 5.1], P < 0.05). Our results suggest that the gut microbiome is linked to prediabetes not only via the production of microbial metabolites but also by affecting intestinal absorption/excretion of host-produced metabolites and xenobiotics, which are correlated with the risk of IFG. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes and T2D onset. ARTICLE HIGHLIGHTS: Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We investigated whether there is a fecal metabolite signature of impaired fasting glucose (IFG) and the possible underlying mechanisms of action. We identified a fecal metabolite signature of IFG associated with prevalent IFG in two independent cohorts and incident type 2 diabetes in a subanalysis. Although the signature consists of metabolites of nonmicrobial origin, it is strongly correlated with gut microbiome composition. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes by affecting intestinal absorption or excretion of host compounds and xenobiotics.

Time-Varying Use of Proton Pump Inhibitors and Cognitive Impairment and Dementia: A Real-World Analysis from Germany.

BACKGROUND: Cumulative evidence of dementia risk in patients taking proton pump inhibitors (PPIs) is still inconclusive, probably due to a variety of study designs. OBJECTIVE: This study aimed to compare how the association between dementia risk and use of PPIs differs by different outcome and exposure definitions. METHODS: We conceptualized a target trial using claims data with 7,696,127 individuals aged 40 years or older without previous dementia or mild cognitive impairment (MCI) from the Association of Statutory Health Insurance Physicians in Bavaria. Dementia was defined as either including or excluding MCI to compare how the results alter by different outcome definitions. We used weighted Cox models to estimate the PPI initiation effect on dementia risk and weighted pooled logistic regression to assess the effect of time-varying use versus non-use during 9 years of study period, including 1 year of wash-out period (2009-2018). The median follow-up time of PPI initiators and non-initiators was 5.4 and 5.8 years, respectively. We also evaluated the association between each PPI agent (omeprazole, pantoprazole, lansoprazole, esomeprazole, and combined use) and dementia risk. RESULTS: A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk. A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk.A total of 105,220 (3.6%) PPI initiators and 74,697 (2.6%) non-initiators were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio (HR) for dementia was 1.04 [95% confidence interval (CI) 1.03-1.05]. The HR for time-varying PPI use versus non-use was 1.85 (1.80-1.90). When MCI was included in the outcome, the number of outcomes increased to 121,922 in PPI initiators and 86,954 in non-initiators, but HRs remained similar, showing 1.04 (1.03-1.05) and 1.82 (1.77-1.86), respectively. Pantoprazole was the most frequently used PPI agent. Although the estimated HRs for the time-varying use effect of each PPI showed different ranges, all agents were associated with an increased dementia risk. CONCLUSION: Our large study supports existing evidence that PPI use is related to an increased risk of dementia.

Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS.

PURPOSE: Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. METHODS: Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. RESULTS: We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. CONCLUSION: This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.

Optimized Metabotype Definition Based on a Limited Number of Standard Clinical Parameters in the Population-Based KORA Study.

The aim of metabotyping is to categorize individuals into metabolically similar groups. Earlier studies that explored metabotyping used numerous parameters, which made it less transferable to apply. Therefore, this study aimed to identify metabotypes based on a set of standard laboratory parameters that are regularly determined in clinical practice. K-means cluster analysis was used to group 3001 adults from the KORA F4 cohort into three clusters. We identified the clustering parameters through variable importance methods, without including any specific disease endpoint. Several unique combinations of selected parameters were used to create different metabotype models. Metabotype models were then described and evaluated, based on various metabolic parameters and on the incidence of cardiometabolic diseases. As a result, two optimal models were identified: a model composed of five parameters, which were fasting glucose, HDLc, non-HDLc, uric acid, and BMI (the metabolic disease model) for clustering; and a model that included four parameters, which were fasting glucose, HDLc, non-HDLc, and triglycerides (the cardiovascular disease model). These identified metabotypes are based on a few common parameters that are measured in everyday clinical practice. These metabotypes are cost-effective, and can be easily applied on a large scale in order to identify specific risk groups that can benefit most from measures to prevent cardiometabolic diseases, such as dietary recommendations and lifestyle interventions.

Fecal Bile Acids and Neutral Sterols Are Associated with Latent Microbial Subgroups in the Human Gut.

Bile acids, neutral sterols, and the gut microbiome are intricately intertwined and each affects human health and metabolism. However, much is still unknown about this relationship. This analysis included 1280 participants of the KORA FF4 study. Fecal metabolites (primary and secondary bile acids, plant and animal sterols) were analyzed using a metabolomics approach. Dirichlet regression models were used to evaluate associations between the metabolites and twenty microbial subgroups that were previously identified using latent Dirichlet allocation. Significant associations were identified between 12 of 17 primary and secondary bile acids and several of the microbial subgroups. Three subgroups showed largely positive significant associations with bile acids, and six subgroups showed mostly inverse associations with fecal bile acids. We identified a trend where microbial subgroups that were previously associated with "healthy" factors were here inversely associated with fecal bile acid levels. Conversely, subgroups that were previously associated with "unhealthy" factors were positively associated with fecal bile acid levels. These results indicate that further research is necessary regarding bile acids and microbiota composition, particularly in relation to metabolic health.

Association between Usual Dietary Intake of Food Groups and DNA Methylation and Effect Modification by Metabotype in the KORA FF4 Cohort.

Associations between diet and DNA methylation may vary among subjects with different metabolic states, which can be captured by clustering populations in metabolically homogenous subgroups, called metabotypes. Our aim was to examine the relationship between habitual consumption of various food groups and DNA methylation as well as to test for effect modification by metabotype. A cross-sectional analysis of participants (median age 58 years) of the population-based prospective KORA FF4 study, habitual dietary intake was modeled based on repeated 24-h diet recalls and a food frequency questionnaire. DNA methylation was measured using the Infinium MethylationEPIC BeadChip providing data on >850,000 sites in this epigenome-wide association study (EWAS). Three metabotype clusters were identified using four standard clinical parameters and BMI. Regression models were used to associate diet and DNA methylation, and to test for effect modification. Few significant signals were identified in the basic analysis while many significant signals were observed in models including food group-metabotype interaction terms. Most findings refer to interactions of food intake with metabotype 3, which is the metabotype with the most unfavorable metabolic profile. This research highlights the importance of the metabolic characteristics of subjects when identifying associations between diet and white blood cell DNA methylation in EWAS.

Evaluation of the metabotype concept after intervention with oral glucose tolerance test and dietary fiber-enriched food: An enable study.

BACKGROUND AND AIMS: Evidence suggests that people react differently to the same diet due to inter-individual differences. However, few studies have investigated variation in response to dietary interventions based on individuals' baseline metabolic characteristics. This study aims to examine the differential reaction of metabotype subgroups to an OGTT and a dietary fiber intervention. METHODS AND RESULTS: We assigned 356 healthy participants of an OGTT sub-study and a 12-week dietary fiber intervention sub-study within the enable cluster to three metabotype subgroups previously identified in the KORA F4 study population. To explore the association between plasma glucose level and metabotype subgroups, we used linear mixed models adjusted for age, sex, and physical activity. Individuals in different metabotype subgroups showed differential responses to OGTT. Compared to the healthy metabotype (metabotype 1), participants in intermediate metabotype (metabotype 2) and unfavorable metabotype (metabotype 3) had significantly higher plasma glucose concentrations at 120 min after glucose bolus (ß = 7.881, p = 0.005; ß = 32.79, p < 0.001, respectively). Additionally, the linear regression model showed that the Area under the curve (AUC) of plasma glucose concentrations was significantly different across the metabotype subgroups. The associations between metabotype subgroups and metabolic parameters among fiber intervention participants remained insignificant in the multivariate-adjusted linear model. However, the metabotype 3 had the highest mean reduction in insulin, cholesterol parameters (TC, LDLc, and non-HDLc), and systolic and diastolic blood pressure at the end of the intervention period. CONCLUSION: This study supports the use of the metabotype concept to identify metabolically similar subgroups and to develop targeted dietary interventions at the metabotype subgroup level for the primary prevention of diet-related diseases.

Association between Habitual Diet and the Postprandial Glucose Response-An Enable Study.

SCOPE: It is inconclusive which factors influence inter-individual variations of postprandial glucose response (PPGR). This study investigates whether the habitual diet is associated with PPGR. METHODS AND RESULTS: Data from healthy adults (young adults with 18-25 years, middle-aged adults with 40-65 years, and older adults with 75-85 years) is collected at baseline and during an oral glucose tolerance test (OGTT) collected. Habitual diet is assessed by a food frequency questionnaire and two 24-h food lists. Associations between habitual diet and glucose incremental area under the curve (iAUCmin ) are examined by regression models. The intake of cereals and cereal products is negatively associated with glucose iAUCmin (p = 0.002) in the total cohort (N = 459, 50% women, 55 ± 21 years, BMI 26 ± 5 kg m- 2 ). Up to 9% of the variance in the glycemic response is explained by the respective dietary parameters identified in the models of the specific age groups. CONCLUSION: There are age-specific diet-related effects on PPGR. The usual intake of cereals and cereal products seems to play a greater role in PPGR in more than one age group. Further research is needed, to establish how diet can be optimized based on age and PPGR.

Association of eating motives with anthropometry, body composition, and dietary intake in healthy German adults.

Effective policies to address poor food choices and dietary patterns need to consider the complex set of motives affecting eating behavior. This study examined how different eating motives are associated with anthropometry, body composition, and dietary intake. Our analysis is based on a cross-sectional sample with 429 healthy adults in three different age groups collected in Germany from 2016 to 2018. Dietary intake, Body Mass Index (BMI), waist circumference (WC), and fat-free mass (FFM) were measured by standardized methods. Eating motives were measured using The Eating Motivation Scale (TEMS). Regressing dietary intakes and anthropometric indicators on TEMS motives, we identify the main sources of variation in diet and nutritional status separately for men and women. Results indicated the Health motive to be positively associated with FFM (B±SE=1.72±0.44) and negatively with WC (B±SE=-3.23±0.81) for men. For women, the Need & Hunger motive was positively associated with FFM (B±SE=1.63±0.44) and negatively with WC (B±SE=-2.46±0.81). While Liking and Habits were the most frequently stated eating motives, we did not find them to be significantly related to the nutritional status. Other motives were associated with dietary intake but not anthropometry or body composition. The Price motive was positively and the Convenience motive was negatively associated with energy (B±SE=63.77±19.98;B±SE=-46.96±17.12) and carbohydrate intake (B±SE=7.15±2.65;B±SE=-5.98±2.27) for men. The results highlight the need for more differentiated analyses of eating motives, beyond comparing the relative importance of motives based on mean values, towards the association of motives with dietary intake and nutritional status.

Dietary habits and the presence and degree of asymptomatic diverticular disease by magnetic resonance imaging in a Western population: a population-based cohort study.

BACKGROUND: Despite the worldwide burden of diverticular disease, the connections between diverticular disease and dietary habits remain poorly understood, particularly in an asymptomatic representative sample. We investigated the association between asymptomatic diverticular disease as assessed by magnetic resonance imaging (MRI) and dietary habits in a Western study cohort. METHODS: Participants from a cross-sectional sample of a population-based cohort study underwent whole-body 3T-MRI including an isotropic VIBE-Dixon sequence. The presence and extent of diverticular disease was assessed in blinded fashion. Habitual dietary intake was recorded using a blended approach, applying 24-h food lists and a food-frequency questionnaire. Traditional cardiometabolic risk factors were obtained by interviews and medical examination. Univariate and multivariate associations were calculated. RESULTS: A total of 308 subjects were included in this analysis (56% male, 56.4 ± 9.1 years). 39.9% had any form of diverticular disease and 15.3% had advanced asymptomatic diverticular disease. After adjustment for age, sex and total energy intake a higher intake of fiber and vegetables was associated with a lower odds for asymptomatic diverticular disease (fiber: OR 0.68 95% CI [0.48, 0.95]; vegetables: OR 0.72 95% CI [0.53, 0.97]) and an increased intake of meat was associated with an approximately two-fold higher odds for advanced asymptomatic diverticular disease (OR 1.84 95% CI [1.13, 2.99]). However, after additional adjustment for body-mass-index (BMI), alcohol consumption, smoking behavior and physical activity only a high fiber and vegetables intake remained significantly associated with lower odds of asymptomatic diverticular disease. CONCLUSION: Our results indicate that a high-fiber diet and increased intake of vegetables is associated with lower odds of having asymptomatic diverticular disease, independent of age, sex, total energy intake, BMI and other life-style factors.

Associations between habitual diet, metabolic disease, and the gut microbiota using latent Dirichlet allocation.

BACKGROUND: The gut microbiome impacts human health through various mechanisms and is involved in the development of a range of non-communicable diseases. Diet is a well-known factor influencing microbe-host interaction in health and disease. However, very few findings are based on large-scale analysis using population-based studies. Our aim was to investigate the cross-sectional relationship between habitual dietary intake and gut microbiota structure in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 study. RESULTS: Fecal microbiota was analyzed using 16S rRNA gene amplicon sequencing. Latent Dirichlet allocation (LDA) was applied to samples from 1992 participants to identify 20 microbial subgroups within the study population. Each participant's gut microbiota was subsequently described by a unique composition of these 20 subgroups. Associations between habitual dietary intake, assessed via repeated 24-h food lists and a Food Frequency Questionnaire, and the 20 subgroups, as well as between prevalence of metabolic diseases/risk factors and the subgroups, were assessed with multivariate-adjusted Dirichlet regression models. After adjustment for multiple testing, eight of 20 microbial subgroups were significantly associated with habitual diet, while nine of 20 microbial subgroups were associated with the prevalence of one or more metabolic diseases/risk factors. Subgroups 5 (Faecalibacterium, Lachnospiracea incertae sedis, Gemmiger, Roseburia) and 14 (Coprococcus, Bacteroides, Faecalibacterium, Ruminococcus) were particularly strongly associated with diet. For example, participants with a high probability for subgroup 5 were characterized by a higher Alternate Healthy Eating Index and Mediterranean Diet Score and a higher intake of food items such as fruits, vegetables, legumes, and whole grains, while participants with prevalent type 2 diabetes mellitus were characterized by a lower probability for subgroup 5. CONCLUSIONS: The associations between habitual diet, metabolic diseases, and microbial subgroups identified in this analysis not only expand upon current knowledge of diet-microbiota-disease relationships, but also indicate the possibility of certain microbial groups to be modulated by dietary intervention, with the potential of impacting human health. Additionally, LDA appears to be a powerful tool for interpreting latent structures of the human gut microbiota. However, the subgroups and associations observed in this analysis need to be replicated in further studies. Video abstract.

Association of Habitual Dietary Intake with Liver Iron-A Population-Based Imaging Study.

Iron-related disorders of the liver can result in serious health conditions, such as liver cirrhosis. Evidence on the role of modifiable lifestyle factors like nutrition in liver iron storage is lacking. Thus, we aimed to assess the association of habitual diet with liver iron content (LIC). We investigated 303 participants from the population-based KORA-MRI study who underwent whole-body magnetic resonance imaging (MRI). Dietary habits were evaluated using repeated 24 h food lists and a food frequency questionnaire. Sex-stratified multiple linear regression models were applied to quantify the association between nutrition variables of interest and LIC, adjusting for liver fat content (LFC), energy intake, and age. Mean age of participants was 56.4 ± 9.0 years and 44.2% were female. Mean LIC was 1.23 ± 0.12 mg/g dry weight, with higher values in men than in women (1.26 ± 0.13 and 1.20 ± 0.10 mg/g, p < 0.001). Alcohol intake was positively associated with LIC (men: ß = 1.94; women: ß = 4.98, p-values < 0.03). Significant negative associations with LIC were found for fiber (ß = -5.61, p < 0.001) and potassium (ß = -0.058, p = 0.034) for female participants only. Furthermore, LIC was highly correlated with liver fat content in both sexes. Our findings suggests that there are sex-specific associations of habitual dietary intake and LIC. Alcohol, fiber, and potassium may play a considerable role in liver iron metabolism.

Association between dietary patterns and prediabetes, undetected diabetes or clinically diagnosed diabetes: results from the KORA FF4 study.

PURPOSE: Diet is one of the most important modifiable risk factors for the development of type 2 diabetes. Here, we aim to identify dietary patterns and to investigate their association with prediabetes, undetected diabetes and prevalent diabetes. METHODS: The present study included 1305 participants of the cross-sectional population-based KORA FF4 study. Oral glucose tolerance test (OGTT) measurements together with a physician-confirmed diagnosis allowed for an accurate categorization of the participants according to their glucose tolerance status into normal glucose tolerance (n = 698), prediabetes (n = 459), undetected diabetes (n = 49), and prevalent diabetes (n = 99). Dietary patterns were identified through principal component analysis followed by hierarchical clustering. The association between dietary patterns and glucose tolerance status was investigated using multinomial logistic regression models. RESULTS: A Prudent pattern, characterized by high consumption of vegetables, fruits, wholegrains and dairy products, and a Western pattern, characterized by high consumption of red and processed meat, alcoholic beverages, refined grains and sugar-sweetened beverages, were identified. Participants following the Western pattern had significantly higher chances of having prediabetes (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.35, 2.73), undetected diabetes (OR 10.12; 95% CI 4.19, 24.43) or prevalent diabetes (OR 3.51; 95% CI 1.85, 6.67), compared to participants following the Prudent pattern. CONCLUSION: To our knowledge, the present study is one of the few investigating the association between dietary patterns and prediabetes or undetected diabetes. The use of a reference group exclusively including participants with normal glucose tolerance might explain the strong associations observed in our study. These results suggest a very important role of dietary habits in the prevention of prediabetes and type 2 diabetes.

Association of Dietary Patterns and Type-2 Diabetes Mellitus in Metabolically Homogeneous Subgroups in the KORA FF4 Study.

There is evidence that a change in lifestyle, especially physical activity and diet, can reduce the risk of developing type-2 diabetes mellitus (T2DM). However, the response to dietary changes varies among individuals due to differences in metabolic characteristics. Therefore, we investigated the association between dietary patterns and T2DM while taking into account these differences. For 1287 participants of the population-based KORA FF4 study (Cooperative Health Research in the Region of Augsburg), we identified three metabolically-homogenous subgroups (metabotypes) using 16 clinical markers. Based on usual dietary intake data, two diet quality scores, the Mediterranean Diet Score (MDS) and the Alternate Healthy Eating Index (AHEI), were calculated. We explored the associations between T2DM and diet quality scores. Multi-variable adjusted models, including metabotype subgroup, were fitted. In addition, analyses stratified by metabotype were carried out. We found significant interaction effects between metabotype and both diet quality scores (p < 0.05). In the analysis stratified by metabotype, significant negative associations between T2DM and both diet quality scores were detected only in the metabolically-unfavorable homogenous subgroup (Odds Ratio (OR) = 0.62, 95% confidence interval (CI) = 0.39-0.90 for AHEI and OR = 0.60, 95% CI = 0.40-0.96 for MDS). Prospective studies taking metabotype into account are needed to confirm our results, which allow for the tailoring of dietary recommendations in the prevention of T2DM.

Seropositivity of selected chronic infections and different measures of obesity.

The impact of sex-specific body fat distribution on the susceptibility to five chronic infections, helicobacter pylori and human herpesviruses 3 to 6 (i.e. varicella-zoster, Epstein-Barr, cytomegalo- and human herpesvirus 6), has not previously been examined. In the present study, seropositivity was determined via multiplex serology in serum samples of study participants collected in 2006/08 and 2013/14 during the follow-up examinations F4 (n = 3080) and FF4 (n = 2279) of the German population-based baseline KORA S4 survey. We quantified the severity of overall and abdominal obesity by body mass index, body adiposity index, waist circumference, waist-to-hip ratio, and waist-to-height ratio. Using sex-specific logistic spline-models, cross-sectional and longitudinal associations between obesity measures and seropositivity of the previously mentioned infections were investigated. Overall and abdominal fat content were significantly associated with seropositivity of varicella-zoster virus in both cross-sectional and longitudinal analyses among women. In addition, a non-significant inverse relationship with Epstein-Barr virus seroprevalence in both sexes and a trend towards a positive association with human herpesvirus 6 seropositivity in women were observed. Therefore, in women total body fat may be associated with VZV-seropositivity and may influence the reactivation of the varicella-zoster virus, independent of adipose tissue distribution.

Evaluation of the Metabotype Concept Identified in an Irish Population in the German KORA Cohort Study.

SCOPE: Previous work identified three metabolically homogeneous subgroups of individuals ("metabotypes") using k-means cluster analysis based on fasting serum levels of triacylglycerol, total cholesterol, HDL cholesterol, and glucose. The aim is to reproduce these findings and describe metabotype groups by dietary habits and by incident disease occurrence. METHODS AND RESULTS: 1744 participants from the KORA F4 study and 2221 participants from the KORA FF4 study are assigned to the three metabotype clusters previously identified by minimizing the Euclidean distances. In both KORA studies, the assignment of participants results in three metabolically distinct clusters, with cluster 3 representing the group of participants with the most unfavorable metabolic characteristics. Individuals of cluster 3 are further characterized by the highest incident disease occurrence during follow-up; they also reveal the most unfavorable diet with significantly lowest intakes of vegetables, dairy products, and fibers, and highest intakes of total, red, and processed meat. CONCLUSION: The three metabotypes originally identified in an Irish population are successfully reproduced. In addition to this validation approach, the observed differences in disease incidence across metabotypes represent an important new finding that strongly supports the metabotyping approach as a tool for risk stratification.

Modifying effect of metabotype on diet-diabetes associations.

PURPOSE: Inter-individual metabolic differences may be a reason for previously inconsistent results in diet-diabetes associations. We aimed to investigate associations between dietary intake and diabetes for metabolically homogeneous subgroups ('metabotypes') in a large cross-sectional study. METHODS: We used data of 1517 adults aged 38-87 years from the German population-based KORA FF4 study (2013/2014). Dietary intake was estimated based on the combination of a food frequency questionnaire and multiple 24-h food lists. Glucose tolerance status was classified based on an oral glucose tolerance test in participants without a previous diabetes diagnosis using American Diabetes Association criteria. Logistic regression was applied to examine the associations between dietary intake and diabetes for two distinct metabotypes, which were identified based on 16 biochemical and anthropometric parameters. RESULTS: A low intake of fruits and a high intake of total meat, processed meat and sugar-sweetened beverages (SSB) were significantly associated with diabetes in the total study population. Stratified by metabotype, associations with diabetes remained significant for intake of total meat (OR 1.67, 95% CI 1.04-2.67) and processed meat (OR 2.23, 95% CI 1.24-4.04) in the metabotypes with rather favorable metabolic characteristics, and for intake of fruits (OR 0.83, 95% CI 0.68-0.99) and SSB (OR:1.21, 95% CI 1.09-1.35) in the more unfavorable metabotype. However, only the association between SSB intake and diabetes differed significantly by metabotype (p value for interaction = 0.01). CONCLUSIONS: Our findings suggest an influence of metabolic characteristics on diet-diabetes associations, which may help to explain inconsistent previous results. The causality of the observed associations needs to be confirmed in prospective and intervention studies.

Usual Dietary Intake Estimation Based on a Combination of Repeated 24-H Food Lists and a Food Frequency Questionnaire in the KORA FF4 Cross-Sectional Study.

Background: Estimation of usual dietary intake poses a challenge in epidemiological studies. We applied a blended approach that combines the strengths provided by repeated 24-h food lists (24HFLs) and a food frequency questionnaire (FFQ). Methods: At least two web-based 24HFLs and one FFQ were completed by 821 participants in the KORA FF4 study. Consumption probabilities were estimated using logistic mixed models, adjusting for covariates and the FFQ data on consumption frequency. Intake amount of a consumed food item was predicted for each participant based on the results of the second Bavarian Food Consumption Survey (BVS II). By combining consumption probability and estimated consumption amount, the usual food intake for each participant was estimated. These results were compared to results obtained without considering FFQ information for consumption probability estimation, as well as to conventional FFQ data. Results: The results of the blended approach for food group intake were often higher than the FFQ-based results. Intraclass correlation coefficients between both methods ranged between 0.21 and 0.86. Comparison of both methods resulted in weighted kappa values based on quintiles ranging from fair (0.34) to excellent agreement (0.84). Omission of FFQ information in the consumption probability models distinctly affected the results at the group level, though individual intake data were slightly affected, for the most part. Conclusions: Usual dietary intake data based on the blended approach differs from the FFQ-based results both in absolute terms and in classification according to quintiles. The application of the blended approach has been demonstrated as a possible tool in nutritional epidemiology, as a comparison with published studies showed that the blended approach yields reasonable estimates. The inclusion of the FFQ information is valuable especially with regard to irregularly consumed foods. A validation study including biomarkers of dietary intake is warranted.