Is atherosclerosis in diabetes and impaired fasting glucose driven by elevated ldl cholesterol or by decreased hdl cholesterol?: response to Drexel et al.
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Arteriosclerosis↗
Biomedical subjects
Kurt Hoffmann
Publications and source records attributed to Kurt Hoffmann.
Re: "Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study".
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Age of Onset↗
Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC).
The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort-wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors. During 4.7 years of follow-up, 1,879 incident invasive breast cancers were identified. In postmenopausal women, current HRT modified the body size-breast cancer association. Among nonusers, weight, BMI and hip circumference were positively associated with breast cancer risk (all ptrend < or = 0.002); obese women (BMI > 30) had a 31% excess risk compared to women with BMI < 25. Among HRT users, body measures were inversely but nonsignificantly associated with breast cancer. Excess breast cancer risk with HRT was particularly evident among lean women. Pooled RRs per height increment of 5 cm were 1.05 (95% CI 1.00-1.16) in premenopausal and 1.10 (95% CI 1.05-1.16) in postmenopausal women. Among premenopausal women, hip circumference was the only other measure significantly related to breast cancer (ptrend = 0.03), after accounting for BMI. In postmenopausal women not taking exogenous hormones, general obesity is a significant predictor of breast cancer, while abdominal fat assessed as waist-hip ratio or waist circumference was not related to excess risk when adjusted for BMI. Among premenopausal women, weight and BMI showed nonsignificant inverse associations with breast cancer.
Abdomen↗
Application of a new statistical method to derive dietary patterns in nutritional epidemiology.
Because foods are consumed in combination, it is difficult in observational studies to separate the effects of single foods on the development of diseases. A possible way to examine the combined effect of food intakes is to derive dietary patterns by using appropriate statistical methods. The objective of this study was to apply a new statistical method, reduced rank regression (RRR), that is more flexible and powerful than the classic principal component analysis. RRR can be used efficiently in nutritional epidemiology by choosing disease-specific response variables and determining combinations of food intake that explain as much response variation as possible. The authors applied RRR to extract dietary patterns from 49 food groups, specifying four diabetes-related nutrients and nutrient ratios as responses. Data were derived from a nested German case-control study within the European Prospective Investigation into Cancer and Nutrition-Potsdam study consisting of 193 cases with incident type 2 diabetes identified until 2001 and 385 controls. The four factors extracted by RRR explained 93.1% of response variation, whereas the first four factors obtained by principal component analysis accounted for only 41.9%. In contrast to principal component analysis and other methods, the new RRR method extracted a significant risk factor for diabetes.
Alcohol Drinking↗
Agreement of self-reported medical history: comparison of an in-person interview with a self-administered questionnaire.
PURPOSE: To compare history of 22 different diseases reported during an in-person interview with that reported on a mailed self-administered questionnaire. METHODS: 7841 participants of the European Prospective Investigation into Cancer (EPIC)-Potsdam study. The interview at baseline and the questionnaire at follow-up approximately 2 years later included identical questions about whether the participant had ever had a physician diagnosis of each disease. Incident diagnoses occurring in the interval between the interview and questionnaire were excluded from the analysis. RESULTS: Agreement between self-report from the interview and from the questionnaire was highest (kappa = 0.83-0.88) for myocardial infarction, cancer and diabetes mellitus; it was lower (kappa = 0.68-0.77) for gout, hypertension, hay fever, asthma, osteoporosis, ulcer of the duodenum, thyroid disease, stroke, and kidney stones, and was lowest (kappa = 0.39-0.59) for chronic gastritis, ulcer of the stomach, cerebral ischemia, benign tumor, inflammatory bowel disease, angina pectoris, hyperlipidemia, rheumatism, colon polyps and skin disease. The poor agreement for less severe or more transient diseases was primarily a result of disease frequently being reported at the interview but not on the questionnaire. CONCLUSION: Self-administered questionnaires do not generate same information particularly for less severe or transient diseases as personal interviews. For these diseases, self-administered questionnaires are not recommended. Pilot studies that test validity will be necessary.
Adult↗
A dietary pattern derived to explain biomarker variation is strongly associated with the risk of coronary artery disease.
BACKGROUND: In previous studies, dietary patterns were derived in different populations without regard to a specific outcome. OBJECTIVE: The objective was to apply a new statistical method to construct a specific dietary pattern that is strongly associated with the risk of coronary artery disease (CAD). DESIGN: We applied reduced rank regression to a sample of 200 cases and 255 controls from the Coronary Risk Factors for Atherosclerosis in Women (CORA) Study. The CAD-specific dietary pattern was constructed by choosing intake data for 49 food groups as predictors and 5 established biomarkers for CAD as responses. RESULTS: A high score for the constructed dietary pattern was characterized by high intakes of meat, margarine, poultry, and sauce and low intakes of vegetarian dishes, wine, vegetables, and whole-grain cereals. After adjustment for known CAD risk factors, the relative risks from the lowest to the highest quintiles of the pattern score were 1.0, 1.1, 3.6, 6.2, and 12.3 (95% CI: 4.9, 30.9; P for trend < 0.0001). There was an approximate 4.5-fold difference in C-reactive protein and a 2-fold difference in C-peptide between the highest and lowest score quintiles of the study population. HDL-cholesterol concentrations ranged from 70 mg/dL in the lowest quintile to 49 mg/dL in the highest quintile of dietary pattern score. CONCLUSION: The new statistical method, reduced rank regression, may be a useful tool for identifying dietary patterns that simultaneously affect the concentrations of known CAD biomarkers and the risk of developing CAD.
Adult↗
A modified regression model to adjust for intraindividual variation in serum biomarker concentrations.
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Humans↗
Body mass index and C-174G interleukin-6 promoter polymorphism interact in predicting type 2 diabetes.
Increased levels of IL-6 add further risk to the impact of obesity in respect to the development of type 2 diabetes mellitus (T2DM). A C-174G polymorphism within the IL-6 promoter region was shown to influence transcription rate of IL-6. We made use of a nested case-control study within the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort of 27,548 individuals, selecting 188 T2DM cases and 376 controls to investigate this polymorphism in respect to development of T2DM. This polymorphism was found to modify the correlation between body mass index (BMI) and IL-6 by showing a much stronger increase of IL-6 at increased BMI for CC genotypes compared with GG genotypes. Interestingly, C-174G polymorphism was found to be an effect modifier for the impact of BMI regarding T2DM. Whereas BMI greater than or equal to 28 kg/m(2) increased the risk of T2DM 3.44-fold [95% confidence interval (CI), 1.34- to 8.24-fold] for GG genotypes and 2.94-fold (95% CI, 1.56- to 5.56-fold) for GC genotypes, we found a 17.68-fold (95% CI, 3.57- to 87.66-fold) increase in risk for CC genotypes. In conclusion, obese individuals with BMI greater than or equal to 28 kg/m(2) carrying the CC genotype showed a more than 5-fold increased risk of developing T2DM compared with the remaining genotypes and, hence, might profit most from weight reduction.
Body Mass Index↗
Risk of hypertension among women in the EPIC-Potsdam Study: comparison of relative risk estimates for exploratory and hypothesis-oriented dietary patterns.
Analysis of dietary patterns is considered a useful approach to the examination of diet-disease associations. This study examined the risk of incident hypertension associated with dietary patterns in 8,552 women in the EPIC (European Prospective Investigation into Cancer and Nutrition)-Potsdam Study. The baseline examination was carried out between 1994 and 1998. During 2-4 years of follow-up (through May 15, 2002), 123 incident hypertension cases were verified by medical records. Two exploratory dietary patterns, a "traditional cooking" pattern (meat, cooked vegetables, sauce, potatoes, and poultry) and a "fruits and vegetables" pattern (fruits, raw vegetables, and vegetable oil), were identified by exploratory factor analysis and confirmed by confirmatory factor analysis. Additionally, a hypothesis-oriented pattern based on the Dietary Approaches to Stop Hypertension (DASH) Study was defined (fruits, vegetables, and milk products). Patterns' associations with disease risk were estimated by Cox regression. While no significant associations were observed for the traditional cooking pattern or the fruits and vegetables pattern after adjustment for potential confounders, women in the third quartile of the DASH pattern were at lower risk than women in the lowest quartile (hazard rate ratio = 0.51, 95% confidence interval: 0.29, 0.89). These results suggest that this hypothesis-oriented pattern might play an important role in the risk of hypertension.
Adult↗
Re: "Modeling smoking history: a comparison of different approaches".
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Humans↗
The glutathione synthetase of Schizosaccharomyces pombe is synthesized as a homodimer but retains full activity when present as a heterotetramer.
Glutathione synthetase was overexpressed as a histidine-tagged protein in Schizosaccharomyces pombe and purified by two-step affinity chromatography. The recovered enzyme occurred in two different forms: a homodimeric protein consisting of two identical 56-kDa subunits and a heterotetrameric protein composed of two 32-kDa and two 24-kDa subfragments. Both forms are encoded by the GSH2 gene. The 56-Da protein corresponds to the complete GSH2 open reading frame, while the subfragments are produced following the cleavage of this larger protein by a metalloprotease. A stable homodimer was obtained by site-directed mutagenesis to remove the protease cleavage site, and this showed normal activity. A structural model of the fission yeast glutathione synthetase was produced, based on the x-ray coordinates of the human enzyme. According to this model the interacting domains of the proteolytic subfragments are strongly entangled. The subfragments were therefore coexpressed as independent proteins. These subfragments assembled correctly to yield functional heterotetramers with equivalent activity to the wild type enzyme. Furthermore, a permuted version of the protein was created. This also showed normal levels of glutathione synthetase activity. These data provide novel insight into the mechanisms of protein folding and the structure and evolution of the glutathione synthetase family.
Amino Acid Sequence↗
An approach to construct simplified measures of dietary patterns from exploratory factor analysis.
Exploratory factor analysis might work well in elucidating the major dietary patterns prevailing in specific study populations. However, patterns extracted in one study population and their associations with disease risk cannot be reproduced with this data-specific method in other study populations. To construct less population-dependent pattern variables of similar content as original exploratory patterns, we proposed to derive so-called simplified pattern variables. They represent the sum of the unweighted standardised food variables which loaded high at the pattern of interest. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study suggest that these simplified pattern variables might adequately approximate factor analysis-based dietary patterns. A simplified pattern variable based on the six highest loading food variables showed a correlation >0.95 with the originally derived factor score, which consisted of forty-seven food variables. Moreover, simplified pattern variables might adequately approximate patterns across different study populations. A simplified pattern variable showed similar factor loadings, ranging from 0.34 to 0.52, as well as similar associations with nutrient intake as a 'western' pattern originally reported from an US study population. These simplified pattern variables can subsequently be used to study pattern associations with disease risk, especially in multi-centre studies. It is therefore an approach that might overcome one of the most frequently claimed limitations of factor analyses applied in epidemiology: their non-comparable risk estimates.
Diet↗
Evaluating the potential health gain of the World Health Organization's recommendation concerning vegetable and fruit consumption.
OBJECTIVE: The World Health Organization (WHO) recommends a daily intake of at least 400 g of vegetables and fruit. The aim of this paper was to evaluate the public health benefit of meeting this WHO recommendation by applying a statistical method that combines estimated intake distributions and simulated intake changes. DESIGN AND SETTING: The benefit of an increased consumption of vegetables and fruit was quantified by the preventable proportion of diseases. This proportion was estimated by a general formula derived in the paper that incorporates individual relative risks. Three different strategies of increasing usual intake were simulated and compared. The first strategy assumes that all individuals increase their intake by the same amount, the second assumes a constant increase among low consumers, and the third simulates individual increments necessary to meet the WHO recommendation. Calculations were made for three different scenarios with varying relative risks. RESULTS: The third simulation strategy turned out to be the most appropriate one to quantify the potential health gain of the current dietary recommendation. Applying this strategy to prevent cancer, the proportion of preventable cases was country-specific. Estimates for France and Sweden were 21.9% and 19.3%, respectively, which are somewhat lower than the non-specific figure published by the World Cancer Research Fund. CONCLUSIONS: To improve estimates of the preventable proportion of diseases, the estimation formula presented here can be applied. Its application requires intake data to estimate the initial intake distribution in the population and to simulate adequate dietary changes.
Diet Surveys↗
Portion size adds limited information on variance in food intake of participants in the EPIC-Potsdam study.
Food-frequency questionnaire (FFQ) data should reflect interindividual variation and therefore measure variance in intake among populations. We conducted this analysis to evaluate the relevance of separate portion size questions to the interindividual variation in food intake. The contribution of portion size questions to the variance in food intake was quantified and compared with the variance when group-specific portion sizes would be assigned, using 26,764 FFQ of the European Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Groups were defined according to gender, age (<50 y, >/=50 y) or body mass index (BMI) (<26 kg/m(2), >/=26 kg/m(2)). The FFQ inquired about both consumption frequency and portion size. Linear regression models for each food item were fit with intake (g/d) as dependent variables and frequency of intake as independent variables. The mean coefficient of determination (R(2)) for the different food items explained by frequency only was 84.0% (71.2-95.7%). The R(2) for gender-, age- and BMI-specific frequencies of intake did not markedly alter the overall results. We conclude that the omission of individual portion size information would probably result in a notable reduction of interindividual variance. However, to reduce the respondents' burden and to increase data completeness in self-administration in large epidemiologic studies, the assignment of a constant portion size seems to be adequate. The variance was not increased markedly when constant gender-, age- and BMI-specific portion sizes were applied, thus supporting the assignment of an overall portion size.
Age Distribution↗
Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.
A subclinical inflammatory reaction has been shown to precede the onset of type 2 (non-insulin-dependent) diabetes. We therefore examined prospectively the effects of the central inflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) on the development of type 2 diabetes. We designed a nested case-control study within the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study including 27,548 individuals. Case subjects were defined to be those who were free of type 2 diabetes at baseline and subsequently developed type 2 diabetes during a 2.3-year follow-up period. A total of 192 cases of incident type 2 diabetes were identified and matched with 384 non-disease-developing control subjects. IL-6 and TNF-alpha levels were found to be elevated in participants with incident type 2 diabetes, whereas IL-1beta plasma levels did not differ between the groups. Analysis of single cytokines revealed IL-6 as an independent predictor of type 2 diabetes after adjustment for age, sex, BMI, waist-to-hip ratio (WHR), sports, smoking status, educational attainment, alcohol consumption, and HbA(1c) (4th vs. the 1st quartile: odds ratio [OR] 2.6, 95% CI 1.2-5.5). The association between TNF-alpha and future type 2 diabetes was no longer significant after adjustment for BMI or WHR. Interestingly, combined analysis of the cytokines revealed a significant interaction between IL-1beta and IL-6. In the fully adjusted model, participants with detectable levels of IL-1beta and elevated levels of IL-6 had an independently increased risk to develop type 2 diabetes (3.3, 1.7-6.8), whereas individuals with increased concentrations of IL-6 but undetectable levels of IL-1beta had no significantly increased risk, both compared with the low-level reference group. These results were confirmed in an analysis including only individuals with HbA(1c) <5.8% at baseline. Our data suggest that the pattern of circulating inflammatory cytokines modifies the risk for type 2 diabetes. In particular, a combined elevation of IL-1beta and IL-6, rather than the isolated elevation of IL-6 alone, independently increases the risk of type 2 diabetes. These data strongly support the hypothesis that a subclinical inflammatory reaction has a role in the pathogenesis of type 2 diabetes.
Adult↗
Standardization of dietary intake measurements by nonlinear calibration using short-term reference data.
Statistical analysis of pooled dietary intake data in multicenter and multiethnic studies is often hampered by lack of comparability due to application of different food frequency questionnaires (FFQs). To remove this deficiency, dietary intake measurements should be standardized. This paper presents a standardization procedure based on nonlinear calibration, which aims to approximate the usual intake distribution estimated by reference measurements. The method can be applied in studies with repeated standardized reference measurements that can refer to time periods different from that of the FFQ. It was developed especially for short-term reference assessment methods, such as 24-hour recalls, diet records, and biomarkers. Similar to linear calibration, the proposed method does not change the rankings of subjects in each center or group; therefore, it maintains the within-center validity of the FFQ data. In contrast to linear calibration, the mixture of nonlinearly calibrated intake measurements from different centers or groups corresponds to the mixture of usual intake expected from the reference measurements. This paper illustrates this property of achieving high between-center validity by using macronutrient intake data from the 1995-1996 European Prospective Investigation into Cancer and Nutrition-Potsdam validation study. Here, the proposed method is compared with three linear calibration methods.
Calibration↗
Food groups as predictors for short-term weight changes in men and women of the EPIC-Potsdam cohort.
This study examined the effect of food group intake on subsequent 2-y weight change. Food-frequency questionnaire-based food intake data of 17,369 nonsmoking subjects of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort were examined in their relation to a subsequent weight change. Dietary data, collected from 1994 to 1998, were grouped into 24 food groups. Weight change per year follow-up was the outcome of interest; large weight gain was defined as > or =2 kg; small weight gain as > or =1 kg to <2 kg; large weight loss as < or = -2 kg; small weight loss as < or = -1 kg to > -2 kg and weight maintenance as +/- 1 kg. For each food group, a separate polytomous logistic regression model with stable weight as the reference group was constructed, controlling for age, body mass index, previous weight change, and behavioral and lifestyle factors. Odds ratios (OR) and 95% confidence intervals (CI) estimated the increase in risk associated with each 100 g/d increment in food group intake. In women, consumption of high energy, high fat food groups significantly predicted large weight gain, e.g., fats (OR = 1.75; 95% CI, 1.01-3.06), sauces (OR = 2.12; 95% CI, 1.17-3.82) and meat (OR = 1.36; 95% CI, 1.04-1.79), and the consumption of cereals predicted large weight loss (OR = 1.43; 95% CI, 1.09-1.88). In men, intake of high energy, high sugar foods, i.e., sweets, was significantly predictive of large weight gain (OR = 1.48; 95% CI, 1.03-2.13). Our data show that a diet rich in high fat and high energy foods predicts short-term weight gain even if controlled for many potential confounding factors.
Adult↗