Matthias B Schulze

German Diabetes Center, Düsseldorf, North Rhine-Westphalia, Germany

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Publications (192)1110.04 Total impact

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    ABSTRACT: Objective: Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores in T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigate associations of ferritin, transferrin saturation (TSAT), serum iron, and transferrin with T2D incidence to clarify the role of iron in the pathogenesis of T2D. Research and design methods: The European Prospective Investigation into Cancer and Nutrition-InterAct study includes 12,403 incident T2D cases and a representative subcohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron, and transferrin with incident T2D in 11,052 cases and a random subcohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population. Results: Higher levels of ferritin and transferrin were associated with a higher risk of T2D (hazard ratio [HR] [95% CI] in men and women, respectively: 1.07 [1.01-1.12] and 1.12 [1.05-1.19] per 100 μg/L higher ferritin level; 1.11 [1.00-1.24] and 1.22 [1.12-1.33] per 0.5 g/L higher transferrin level) after adjusting for age, center, BMI, physical activity, smoking status, education, hs-CRP, alanine aminotransferase, and γ-glutamyl transferase. Elevated TSAT (≥45% vs. <45%) was associated with a lower risk of T2D in women (0.68 [0.54-0.86]) but was not statistically significantly associated in men (0.90 [0.75-1.08]). Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (Pinteraction < 0.01). Conclusions: The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D.
    No preview · Article · Feb 2016 · Diabetes Care
  • Norbert Stefan · Hans-Ulrich Häring · Frank B Hu · Matthias B Schulze
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    ABSTRACT: Among chronic non-communicable diseases, cardiometabolic diseases and cancer are the most important causes of morbidity and mortality worldwide. Although high BMI and waist circumference, as estimates of total and abdominal fat mass, are now accepted as predictors of the increasing incidence of these diseases, adult height, which also predicts mortality, has been neglected. Interestingly, increasing evidence suggests that height is associated with lower cardiometabolic risk, but higher cancer risk, associations supported by mendelian randomisation studies. Understanding the complex epidemiology, biology, and pathophysiology related to height, and its association with cardiometabolic diseases and cancer, is becoming even more important because average adult height has increased substantially in many countries during recent generations. Among the mechanisms driving the increase in height and linking height with cardiometabolic diseases and cancer are insulin and insulin-like growth factor signalling pathways. These pathways are thought to be activated by overnutrition, especially increased intake of milk, dairy products, and other animal proteins during different stages of child development. Limiting overnutrition during pregnancy, early childhood, and puberty would avoid not only obesity, but also accelerated growth in children—and thus might reduce risk of cancer in adulthood.
    No preview · Article · Jan 2016 · The Lancet Diabetes & Endocrinology
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    ABSTRACT: Background: Data-reduction methods such as principal component analysis are often used to derive dietary patterns. However, such methods do not assess how foods are consumed in relation to each other. Gaussian graphical models (GGMs) are a set of novel methods that can address this issue. Objective: We sought to apply GGMs to derive sex-specific dietary intake networks representing consumption patterns in a German adult population. Methods: Dietary intake data from 10,780 men and 16,340 women of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort were cross-sectionally analyzed to construct dietary intake networks. Food intake for each participant was estimated using a 148-item food-frequency questionnaire that captured the intake of 49 food groups. GGMs were applied to log-transformed intakes (grams per day) of 49 food groups to construct sex-specific food networks. Semiparametric Gaussian copula graphical models (SGCGMs) were used to confirm GGM results. Results: In men, GGMs identified 1 major dietary network that consisted of intakes of red meat, processed meat, cooked vegetables, sauces, potatoes, cabbage, poultry, legumes, mushrooms, soup, and whole-grain and refined breads. For women, a similar network was identified with the addition of fried potatoes. Other identified networks consisted of dairy products and sweet food groups. SGCGMs yielded results comparable to those of GGMs. Conclusions: GGMs are a powerful exploratory method that can be used to construct dietary networks representing dietary intake patterns that reveal how foods are consumed in relation to each other. GGMs indicated an apparent major role of red meat intake in a consumption pattern in the studied population. In the future, identified networks might be transformed into pattern scores for investigating their associations with health outcomes.
    No preview · Article · Jan 2016 · Journal of Nutrition
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    ABSTRACT: Aims: Previous studies have provided inconsistent results about the cardiovascular risks for participants with metabolically healthy obesity (MHO). These uncertainties might partly reflect the lack of a uniform definition of MHO. We conducted a systematic review and meta-analysis to examine whether there is a suitable approach that identifies obese participants who are not at an increased risk of cardiovascular events compared with healthy normal-weight participants. Methods and results: Twenty-two prospective studies were eligible for the meta-analysis. Using random-effect models, pooled relative risks (RRs) were calculated for the combined effects of obesity with the presence or absence of metabolic syndrome, insulin resistance, hypertension, diabetes, hyperlipidaemia and any of these metabolic factors. Participants with MHO defined by the absence of metabolic syndrome were at increased risk for cardiovascular events compared with healthy normal-weight participants (pooled RR 1.45, 95% confidence interval (CI) 1.20-1.70), but had lower risks than unhealthy normal-weight (RR 2.07, 95% CI 1.62-2.65) and obese (RR 2.31, 95% CI 1.99-2.69) participants. The risk associated with participants who had MHO was particularly high over the long term. Similar risk estimates were observed when MHO was defined by other approaches. Conclusions: None of the approaches clearly identified an obese subgroup not at increased risk of cardiovascular events compared with normal-weight healthy participants. A benign obese phenotype might be defined by strict definitions, but insufficient studies exist to support this. More research is needed to better define MHO.
    No preview · Article · Dec 2015
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    ABSTRACT: As nutrition-related chronic diseases have become more and more frequent, the importance of dietary prevention has also increased. Dietary fat plays a major role in human nutrition, and modification of fat and/or fatty acid intake could have a preventive potential. The aim of the guideline of the German Nutrition Society (DGE) was to systematically evaluate the evidence for the prevention of the widespread diseases obesity, type 2 diabetes mellitus, dyslipoproteinaemia, hypertension, metabolic syndrome, coronary heart disease (CHD), stroke, and cancer through the intake of fat or fatty acids. The main results can be summarized as follows: it was concluded with convincing evidence that a reduced intake of total and saturated fat as well as a larger intake of polyunsaturated fatty acids (PUFA) at the expense of saturated fatty acids (SFA) reduces the concentration of total and low-density lipoprotein cholesterol in plasma. Furthermore, there is convincing evidence that a high intake of trans fatty acids increases risk of dyslipoproteinaemia and that a high intake of long-chain polyunsaturated n-3 fatty acids reduces the triglyceride concentration in plasma. A high fat intake increases the risk of obesity with probable evidence when total energy intake is not controlled for (ad libitum diet). When energy intake is controlled for, there is probable evidence for no association between fat intake and risk of obesity. A larger intake of PUFA at the expense of SFA reduces risk of CHD with probable evidence. Furthermore, there is probable evidence that a high intake of long-chain polyunsaturated n-3 fatty acids reduces risk of hypertension and CHD. With probable evidence, a high trans fatty acid intake increases risk of CHD. The practical consequences for current dietary recommendations are described at the end of this article.
    Full-text · Article · Oct 2015 · Annals of Nutrition and Metabolism
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    ABSTRACT: The reliability of single time point measurements of the novel adipokines retinol-binding protein 4 and omentin-1 in the blood has not been evaluated in large samples yet. The present study aimed to assess the amount of biological variation of these two adipokines within individuals. The study sample comprised 207 participants (124 women and 83 men) from Potsdam (Germany) and surrounding areas, with an average age of 56.5 years (SD 4.2). Blood samples were collected from each participant twice, approximately four months apart. Using enzyme linked immunosorbent assays, the concentrations of retinol-binding protein 4 and omentin-1 were determined in EDTA plasma. As indicators of reliability, intraclass correlation coefficients (ICCs) were calculated from the repeated biomarker measurements. The ICCs for repeated retinol-binding protein 4 and omentin-1 measurements were 0.77 (95% CI 0.71, 0.82) and 0.83 (95% CI 0.78, 0.87), respectively, indicating for both adipokines excellent reliability. ICCs were stable across strata according to sex, age, BMI, and blood pressure. Thus, for epidemiological studies it seems reasonable to rely on concentrations of retinol-binding protein 4 and omentin-1 in samples from a single time point if repeated measurements are not available.
    Full-text · Article · Sep 2015 · PLoS ONE
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    ABSTRACT: Aims/hypothesis: Studies on weight cycling and the risk of type 2 diabetes have revealed inconsistent results, possibly due to differences in the definition of weight fluctuations. Here, we investigated whether weight cycling during adulthood is related to diabetes risk in a large cohort study, using a complementary approach to define patterns of weight development. Methods: Weight cycling, weight loss and weight gain were defined (1) a priori, using distinct categories, and (2) by functional principal component analysis (FPCA) to capture weight patterns in greater detail. Associations of weight cycling, weight loss and weight gain with the risk of type 2 diabetes were evaluated by Cox regression models. Results: A priori defined weight cycling was associated with increased diabetes risk, compared with stable weight (HR 1.36 [95% CI 1.09, 1.68]). No significant association between FPCA-derived weight cycling and risk of diabetes was observed after adjustment for concurrent weight patterns (HR 1.19 [95% CI 0.89, 1.60]). Subgroup analyses showed that FPCA-derived weight cycling during net weight gain was associated with a higher risk of diabetes (HR 1.68 [95% CI 1.14, 2.48]). A priori defined weight gain (HR 2.08 [95% CI 1.60, 2.70]) was more clearly related to the risk of diabetes than FPCA-derived weight gain (HR 1.20 [95% CI 0.95, 1.51]), while no significant associations were observed for weight loss. Conclusions/interpretation: Overall, weight cycling may not be an independent risk factor for type 2 diabetes when accounting for concurrent patterns of weight development. However, weight cycling may pose a stronger risk of diabetes than non-cycling during net weight gain.
    No preview · Article · Sep 2015 · Diabetologia
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    ABSTRACT: Author Summary Complex genetic determinants contribute to an inherent susceptibility of type 2 diabetes, characterized by insulin resistance, a dysfunction and loss of insulin-producing beta-cells. We compared the islet expression profile and the genome of two obese mouse strains that react differently when receiving a caloric enriched diet. One mouse (B6-ob/ob) is able to compensate by increasing the beta-cell mass, whereas the other (NZO) develops hyperglycemia due to beta-cells loss. Focusing on differentially expressed genes that are located in susceptibility locus for diabetes and obesity on chromosome 1 we found 6 genes to be only expressed in islets of the diabetes-resistant mouse and one to be exclusively present in islets of the diabetes-prone mouse. Among these, the overexpression of 3 genes (Lefty1, Apoa2, and Pcp4l1) increased and that of Ifi202b decreased the division of primary islet cells. In summary, our data provide new insights into genes inducing or inhibiting islet size and thereby participate in the pathogenesis of type 2 diabetes.
    Full-text · Article · Sep 2015 · PLoS Genetics
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    ABSTRACT: Early life, adiposity rebound, and puberty represent critical growth periods when food choices could have long-term relevance for cancer risk. We aimed to relate dietary patterns during these periods to the growth hormone-insulin-like-growth-factor (GH-IGF) axis, insulin resistance, and body fatness in adulthood. Data from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study participants with outcome data at 18-37 years, and ≥2 dietary records during early life (1-2 yr; n = 128), adiposity rebound (4-6 years, n = 179), or puberty (girls 9-14, boys 10-15 yr; n = 213) were used. Dietary patterns at these ages were derived by 1) reduced rank regression (RRR) to explain variation in adult IGF-I, IGF-binding protein-3 (IGFBP-3), homoeostasis model assessment for insulin resistance (HOMA-IR) and fat-mass index; 2) principal component analysis (PCA). Regarding RRR, the patterns "cake/canned fruit/cheese & eggs" (early life), "sweets & dairy" (adiposity rebound) and "high-fat foods" (pubertal boys) were independently associated with higher adult HOMA-IR. Furthermore, the patterns "favorable carbohydrate sources" (early life), "snack & convenience foods" (adiposity rebound), and "traditional & convenience carbohydrates" (pubertal boys) were related to adult IGFBP-3 (P trend < 0.01). PCA identified "healthy" patterns for all periods, but none was associated with the outcomes (P trend > 0.1). In conclusion, dietary patterns during sensitive growth periods may be of long-term relevance for adult insulin resistance and IGFBP-3.
    Full-text · Article · Jul 2015 · Nutrition and Cancer
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    ABSTRACT: Reduced rank regression (RRR) is an innovative technique to establish dietary patterns related to biochemical risk factors for type 2 diabetes, but has not been applied in sub-Saharan Africa. In a hospital-based case-control study for type 2 diabetes in Kumasi (diabetes cases, 538; controls, 668) dietary intake was assessed by a specific food frequency questionnaire. After random split of our study population, we derived a dietary pattern in the training set using RRR with adiponectin, HDL-cholesterol and triglycerides as responses and 35 food items as predictors. This pattern score was applied to the validation set, and its association with type 2 diabetes was examined by logistic regression. The dietary pattern was characterized by a high consumption of plantain, cassava, and garden egg, and a low intake of rice, juice, vegetable oil, eggs, chocolate drink, sweets, and red meat; the score correlated positively with serum triglycerides and negatively with adiponectin. The multivariate-adjusted odds ratio of type 2 diabetes for the highest quintile compared to the lowest was 4.43 (95% confidence interval: 1.87–10.50, p for trend < 0.001). The identified dietary pattern increases the odds of type 2 diabetes in urban Ghanaians, which is mainly attributed to increased serum triglycerides.
    Preview · Article · Jul 2015 · Nutrients
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    ABSTRACT: Ethnic minority populations in Western societies suffer from a disproportionate burden of type 2 diabetes (T2D). Insight into the role of dietary patterns in T2D may inform public health nutrition efforts addressing these health disparities. We explored the association between dietary patterns and biomarkers of T2D in 5 ethnic groups living in Amsterdam, Netherlands. A total of 3776 men and women aged 18-70 y of Dutch, South Asian Surinamese, African-Surinamese, Turkish, and Moroccan origin from the HELIUS (HEalthy LIfe in an Urban Setting) study were included. Diet was assessed by using a food-frequency questionnaire, and dietary patterns were derived separately per ethnic group. First, food group-based dietary patterns were derived by using principal components analysis and the association with glycated hemoglobin (HbA1c) and plasma fasting glucose was assessed by using multivariable linear regression. Second, biomarker-driven dietary patterns based on HbA1c and fasting glucose concentrations were derived by applying reduced rank regression. Two comparable food group-based dietary patterns were identified in each ethnic group: a "meat and snack" pattern and a "vegetable" pattern. The meat-and-snack pattern derived within the Dutch origin population was significantly associated with HbA1c (β = 0.09; 95% CI: 0.00, 0.19) and fasting glucose (β = 0.18; 95% CI: 0.09, 0.26) concentrations. A biomarker-derived pattern characterized by red and processed meat was observed among Dutch-origin participants; however, among ethnic minority groups, this pattern was characterized by other foods including ethnicity-specific foods (e.g., roti, couscous). Although similar food group dietary patterns were derived within 5 ethnic groups, the association of the meat-and-snack pattern with fasting glucose concentrations differed by ethnicity. Taken together with the finding of ethnic differences in biomarker-driven dietary patterns, our results imply that addressing T2D risk in multiethnic populations requires ethnicity-specific approaches. © 2015 American Society for Nutrition.
    No preview · Article · Jul 2015 · Journal of Nutrition
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    ABSTRACT: Aims/hypothesis: Intake of dietary fibre has been associated with a reduced risk of type 2 diabetes, but few European studies have been published on this. We evaluated the association between intake of dietary fibre and type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study and in a meta-analysis of prospective studies. Methods: During 10.8 years of follow-up, 11,559 participants with type 2 diabetes were identified and a subcohort of 15,258 participants was selected for the case-cohort study. Country-specific HRs were estimated using Prentice-weighted Cox proportional hazards models and were pooled using a random effects meta-analysis. Eighteen other cohort studies were identified for the meta-analysis. Results: In the EPIC-InterAct Study, dietary fibre intake was associated with a lower risk of diabetes (HRQ4 vs Q1 0.82; 95% CI 0.69, 0.97) after adjustment for lifestyle and dietary factors. Similar inverse associations were observed for the intake of cereal fibre and vegetable fibre, but not fruit fibre. The associations were attenuated and no longer statistically significant after adjustment for BMI. In the meta-analysis (19 cohorts), the summary RRs per 10 g/day increase in intake were 0.91 (95% CI 0.87, 0.96) for total fibre, 0.75 (95% CI 0.65, 0.86) for cereal fibre, 0.95 (95% CI 0.87, 1.03) for fruit fibre and 0.93 (95% CI 0.82, 1.05) for vegetable fibre. Conclusions/interpretation: The overall evidence indicates that the intake of total and cereal fibre is inversely related to the risk of type 2 diabetes. The results of the EPIC-InterAct Study suggest that the association may be partially explained by body weight.
    Full-text · Article · May 2015 · Diabetologia
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    ABSTRACT: Sub-Saharan Africa is facing a double burden of malnutrition: vitamin A deficiency (VAD) prevails, whereas the nutrition-related chronic conditions type 2 diabetes (T2D) and hypertension are emerging. Serum retinol-a VAD marker-increases in kidney disease and decreases in inflammation, which can partly be attributed to alterations in the vitamin A-transport proteins retinol-binding protein 4 (RBP4) and prealbumin. Kidney dysfunction and inflammation commonly accompany T2D and hypertension. Among urban Ghanaians, we investigated the associations of T2D and hypertension with serum retinol as well as the importance of kidney function and inflammation in this regard. A hospital-based, case-control study in individuals for risk factors of T2D, hypertension, or both was conducted in Kumasi, Ghana (328 controls, 197 with T2D, 354 with hypertension, and 340 with T2D plus hypertension). In 1219 blood samples, serum retinol, RBP4, and prealbumin were measured. Urinary albumin and estimated glomerular filtration rate (eGFR) defined kidney function. C-reactive protein (CRP) >5 mg/L indicated inflammation. We identified associations of T2D and hypertension with retinol by linear regression and calculated the contribution of RBP4, prealbumin, urinary albumin, eGFR, and CRP to these associations as the percentages of the explained variance of retinol. VAD (retinol <1.05 μmol/L) was present in 10% of this predominantly female, middle-aged, overweight, and deprived population. Hypertension, but not T2D, was positively associated with retinol (β: 0.12; 95% CI: 0.08, 0.17), adjusted for age, sex, socioeconomic factors, anthropometric measurements, and lifestyle. In addition to RBP4 (72%) and prealbumin (22%), the effect of increased retinol on individuals with hypertension was mainly attributed to impaired kidney function (eGFR: 30%; urinary albumin: 5%) but not to inflammation. In patients with hypertension, VAD might be underestimated because of increased serum retinol in the context of kidney dysfunction. Thus, the interpretation of serum retinol in sub-Saharan Africa should account for hypertension status. © 2015 American Society for Nutrition.
    Full-text · Article · May 2015 · American Journal of Clinical Nutrition
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    ABSTRACT: Background: Biomarker fatty acids (FAs) reflecting de novo lipogenesis (DNL) are strongly linked to the risk of cardiometabolic diseases. Liver fat accumulation could mediate this relation. There is very limited data from human population-based studies that have examined this relation. Objective: The aim of this study was to investigate the relation between specific FAs in the DNL pathway and liver fat accumulation in a large population-based study. Methods: We conducted a cross-sectional analysis of a subsample (n = 1,562) of the EPIC-Potsdam study, which involves 27,548 middle-aged men and women. Baseline blood samples have been analyzed for proportions of 32 FAs in erythrocyte membranes (determined by gas chromatography) and biomarker concentrations in plasma. As indicators for DNL, the DNL-index (16:0/18:2n-6) and proportions of individual blood FAs in the DNL pathway were used. Plasma parameters associated with liver fat content (fetuin-A, ALT, and GGT) and the algorithm-based fatty liver index (FLI) were used to reflect liver fat accumulation. Results: The DNL-index tended to be positively associated with the FLI and was positively associated with GGT activity in men (p for trend: 0.12 and 0.003). Proportions of 14:0 and 16:0 in erythrocytes were positively associated with fetuin-A, whereas 16:1n-7 were positively associated with the FLI and GGT activity (all p for trends in both sexes at least 0.004). Furthermore, the proportion of 16:1n-7 was positively related to fetuin-A in women and ALT activity in men (all p for trend at least 0.03). The proportion of 16:1n-9 showed positive associations with the FLI and GGT activity in men and fetuin-A in both sexes, whereas 18:1n-7 was positively associated with GGT activity in men (all p for trend at least 0.048). Conclusion: Findings from this large epidemiological study suggest that liver fat accumulation could link erythrocyte FAs in the DNL pathway to the risk of cardiometabolic diseases.
    Full-text · Article · May 2015 · PLoS ONE
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    ABSTRACT: An association between desaturase activity and risk of type 2 diabetes (T2D) has been found in epidemiologic studies, but little is known about potential mediators of this association. We aimed to investigate the potential role of diabetes-related biomarkers as mediators of the association between estimated Δ5 desaturase (D5D), Δ6 desaturase (D6D), and stearoyl-CoA desaturase (SCD) activity and T2D risk. We analyzed a case-cohort study (subcohort: n = 1533; verified incident T2D cases: n = 400), nested within the European Prospective Investigation into Cancer and Nutrition-Potsdam Study involving 27,548 middle-aged participants. We evaluated the impact of adjustment for several T2D-related biomarkers reflecting liver fat accumulation [reflected by γ-glutamyltransferase (GGT), alanine transaminase (ALT), fetuin-A, and the algorithm-based fatty liver index (FLI)], dyslipidemia (high-density lipoprotein cholesterol, triglycerides), inflammation [C-reactive protein (CRP)], and adiponectin on the association between D5D, D6D, and SCD activity, estimated with fatty acid product-to-precursor ratios derived from erythrocyte membrane proportions, and T2D risk. Estimated D5D activity was inversely associated with T2D risk, whereas D6D and SCD activities were positively associated with risk of T2D [HRs (95% CIs) (highest vs. lowest tertile): 0.51 (0.36, 0.73), 1.68 (1.18, 2.39), and 1.82 (1.29, 2.58), respectively]. The association between estimated D5D, D6D, and SCD activities and risk of T2D was statistically significantly and markedly attenuated after adjustment for the FLI and, to a lesser extent, after adjustment for triglycerides, whereas adjustment for other desaturase-associated biomarkers (CRP, fetuin-A, ALT, and GGT) did not lead to appreciable attenuations. Liver fat accumulation, as reflected by the FLI, and dyslipidemia, as reflected by triglycerides, may partly explain the association between estimated D5D, D6D, and SCD activity and T2D risk. © 2015 American Society for Nutrition.
    Full-text · Article · May 2015 · American Journal of Clinical Nutrition
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    ABSTRACT: Habitual red meat consumption was consistently related to a higher risk of type 2 diabetes in observational studies. Potentially underlying mechanisms are unclear. This study aimed to identify blood metabolites that possibly relate red meat consumption to the occurrence of type 2 diabetes. Analyses were conducted in the prospective European Prospective Investigation into Cancer and Nutrition-Potsdam cohort (n = 27,548), applying a nested case-cohort design (n = 2681, including 688 incident diabetes cases). Habitual diet was assessed with validated semiquantitative food-frequency questionnaires. Total red meat consumption was defined as energy-standardized summed intake of unprocessed and processed red meats. Concentrations of 14 amino acids, 17 acylcarnitines, 81 glycerophospholipids, 14 sphingomyelins, and ferritin were determined in serum samples from baseline. These biomarkers were considered potential mediators of the relation between total red meat consumption and diabetes risk in Cox models. The proportion of diabetes risk explainable by biomarker adjustment was estimated in a bootstrapping procedure with 1000 replicates. After adjustment for age, sex, lifestyle, diet, and body mass index, total red meat consumption was directly related to diabetes risk [HR for 2 SD (11 g/MJ): 1.26; 95% CI: 1.01, 1.57]. Six biomarkers (ferritin, glycine, diacyl phosphatidylcholines 36:4 and 38:4, lysophosphatidylcholine 17:0, and hydroxy-sphingomyelin 14:1) were associated with red meat consumption and diabetes risk. The red meat-associated diabetes risk was significantly (P < 0.001) attenuated after simultaneous adjustment for these biomarkers [biomarker-adjusted HR for 2 SD (11 g/MJ): 1.09; 95% CI: 0.86, 1.38]. The proportion of diabetes risk explainable by respective biomarkers was 69% (IQR: 49%, 106%). In our study, high ferritin, low glycine, and altered hepatic-derived lipid concentrations in the circulation were associated with total red meat consumption and, independent of red meat, with diabetes risk. The red meat-associated diabetes risk was largely attenuated after adjustment for selected biomarkers, which is consistent with the presumed mediation hypothesis. © 2015 American Society for Nutrition.
    Full-text · Article · May 2015 · American Journal of Clinical Nutrition
  • Kristin Mühlenbruch · Matthias Schulze

    No preview · Article · May 2015 · Diabetes aktuell
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    ABSTRACT: The fatty liver index (FLI) predicts fatty liver by using BMI, waist circumference, γ-glutamyltransferase and triglycerides. We investigated the association between the FLI and the risk of type 2 diabetes and evaluated to what extent single FLI components contribute to the diabetes risk. We analysed a case-cohort study (random sub-cohort: 1922; incident cases: 563) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. The proportion of exposure effect (PEE) explained by single FLI components was evaluated and effect decomposition using inverse probability weighting (IPW) was applied. Women and men with a FLI ≥60 compared to those with a FLI <30 had a multivariable-adjusted Hazard Ratio (HR) of 17.6; 95% confidence interval (CI) 11.1-28.0 and HR: 10.9; 95% CI 6.22-19.2, respectively. Adjustment for BMI or waist circumference attenuated this association in men [PEEBMI (95% CI) = 53.8% (43.9%-65.8%); PEEwaist (95% CI) = 54.8% (44.2%-68.8%)]. In women, adjustment for waist circumference attenuated the association to a lesser degree than in men [PEEwaist (95% CI) = 31.1%; (21.9%-43.1%)] while BMI had no appreciable effect [PEEBMI (95% CI) = 11.0% (2.68%-21.0%)]. γ-glutamyltransferase and triglycerides showed only a small attenuation in women [PEEGGT(95% CI) = 3.11% (-0.72%-4.48%); PEETG (95% CI) = 6.36% (3.81%-9.92%)] and in men [PEEGGT = 0%; PEETG (95% CI) = 6.23% (2.03%-11.8%)]. In women, the total effect was decomposed into a direct effect and 4 indirect effects (HRBMI = 1.10; HRwaist = 1.28; HRGGT = 0.97 and HRTG = 1.03). In men, the 4 indirect effects were HRBMI = 1.25; HRwaist = 1.29; HRGGT = 0.97 and HRTG = 0.99. These data suggest that the FLI, as a proxy for fatty liver, is associated with risk of type 2 diabetes. This association is only partly explained by standard estimates of overall and abdominal body fatness, particularly among women.
    Preview · Article · Apr 2015 · PLoS ONE
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    ABSTRACT: Objective. A proportion of type 2 diabetes cases arise from normal-weight individuals who can therefore be considered to be "metabolically unhealthy normal-weight" (MUH-NW). It remains unclear which factors account for this access risk. Our aims were to identify risk factors for type 2 diabetes in normal-weight individuals and to compare the strengths of their associations with type 2 diabetes to that observed in overweight and obese participants. Methods. A case-cohort, including 2027 sub-cohort participants and 706 incident type 2 cases, was designed within the population-based European Prospective Investigation into Cancer and Nutrition Potsdam study. Adjusted means and relative frequencies of anthropometric, lifestyle and biochemical risk factors were calculated in groups stratified by BMI and incident diabetes status. Cox regressions were applied to evaluate associations between these variables and diabetes risk stratified by BMI category. Results. MUH-NW individuals were characterized by known diabetes risk factors, e.g. They were significantlymore likely to bemale, formersmokers, hypertensive, and less physically active compared to normal-weight individuals without incident diabetes. Higher waist circumference (women: 75.5 vs. 73.1 cm; men: 88.0 vs. 85.1 cm), higher HbA1c (6.1 vs. 5.3%), higher triglycerides (1.47 vs. 1.11 mmol/l), and higher levels of high sensitive C-reactive protein (0.81 vs. 0.51 mg/l) as well as lower levels of HDL-cholesterol (1.28 vs. 1.49 mmol/l) and adiponectin (6.32 vs. 8.25 μg/ml) characterized this phenotype. Stronger associations with diabetes among normal-weight participants compared to overweight and obese (p for interaction < 0.05) were observed for height, waist circumference, former smoking, and hypertension.
    Preview · Article · Mar 2015 · Metabolism: clinical and experimental
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    ABSTRACT: The Net Reclassification Improvement (NRI) has become a popular metric for evaluating improvement in disease prediction models through the past years. The concept is relatively straightforward but usage and interpretation has been different across studies. While no thresholds exist for evaluating the degree of improvement, many studies have relied solely on the significance of the NRI estimate. However, recent studies recommend that statistical testing with the NRI should be avoided. We propose using confidence ellipses around the estimated values of event and non-event NRIs which might provide the best measure of variability around the point estimates. Our developments are illustrated using practical examples from EPIC-Potsdam study.
    Preview · Article · Feb 2015 · European Journal of Epidemiology

Publication Stats

11k Citations
1,110.04 Total Impact Points

Institutions

  • 2012-2015
    • German Diabetes Center
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1999-2015
    • German Institute of Human Nutrition
      • • Department of Molecular Epidemiology
      • • Department of Epidemiology
      Berlín, Berlin, Germany
  • 2014
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
  • 2008-2011
    • University of Technology Munich
      • • Chair of Public Health Nutrition
      • • Department of Nutrition and Food Sciences
      München, Bavaria, Germany
  • 2006
    • Harvard University
      • Department of Nutrition
      Cambridge, Massachusetts, United States
  • 2002-2005
    • Harvard Medical School
      • Division of Nutrition
      Boston, Massachusetts, United States
  • 2003-2004
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States
  • 1999-2001
    • German Cancer Research Center
      • Division of Cancer Epidemiology
      Heidelburg, Baden-Württemberg, Germany