Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations.

BACKGROUND: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence. OBJECTIVE: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries. METHODS: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association. RESULTS: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea. CONCLUSIONS: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.

Nordic diet, Mediterranean diet, and the risk of chronic diseases: the EPIC-Potsdam study.

BACKGROUND: The Mediterranean Diet (MedDiet) has been acknowledged as a healthy diet. However, its relation with risk of major chronic diseases in non-Mediterranean countries is inconclusive. The Nordic diet is proposed as an alternative across Northern Europe, although its associations with the risk of chronic diseases remain controversial. We aimed to investigate the association between the Nordic diet and the MedDiet with the risk of chronic disease (type 2 diabetes (T2D), myocardial infarction (MI), stroke, and cancer) in the EPIC-Potsdam cohort. METHODS: The EPIC-Potsdam cohort recruited 27,548 participants between 1994 and 1998. After exclusion of prevalent cases, we evaluated baseline adherence to a score reflecting the Nordic diet and two MedDiet scores (tMDS, reflecting the traditional MedDiet score, and the MedPyr score, reflecting the MedDiet Pyramid). Cox regression models were applied to examine the association between the diet scores and the incidence of major chronic diseases. RESULTS: During a follow-up of 10.6 years, 1376 cases of T2D, 312 of MI, 321 of stroke, and 1618 of cancer were identified. The Nordic diet showed a statistically non-significant inverse association with incidence of MI in the overall population and of stroke in men. Adherence to the MedDiet was associated with lower incidence of T2D (HR per 1 SD 0.93, 95% CI 0.88-0.98 for the tMDS score and 0.92, 0.87-0.97 for the MedPyr score). In women, the MedPyr score was also inversely associated with MI. No association was observed for any of the scores with cancer. CONCLUSIONS: In the EPIC-Potsdam cohort, the Nordic diet showed a possible beneficial effect on MI in the overall population and for stroke in men, while both scores reflecting the MedDiet conferred lower risk of T2D in the overall population and of MI in women.

A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.

BACKGROUND: Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated. METHODS AND FINDINGS: We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding. CONCLUSIONS: A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.

Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study.

BACKGROUND: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. METHODS: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. RESULTS: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. CONCLUSIONS: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.

Dietary Patterns and Type 2 Diabetes: A Systematic Literature Review and Meta-Analysis of Prospective Studies.

Background: Different methodologic approaches for constructing dietary patterns and differences in their composition limit conclusions on healthful patterns for diabetes prevention.Objective: We summarized evidence from prospective studies that examined associations of dietary patterns with type 2 diabetes by considering different methodologic approaches.Methods: The literature search (MEDLINE and Web of Science) identified prospective studies (cohorts or trials) that associated dietary patterns with diabetes incidence in nondiabetic and apparently healthy participants. We summarized evidence by meta-analyses and distinguished different methodologic approaches.Results: The search resulted in 48 articles comprising 16 cohorts. Adherence to the Mediterranean diet (RR for comparing extreme quantiles: 0.87; 95% CI: 0.82, 0.93), Dietary Approaches to Stop Hypertension (DASH) (RR: 0.81; 95% CI: 0.72, 0.92), and Alternative Healthy Eating Index (AHEI) (RR: 0.79; 95% CI: 0.69, 0.90) was associated with significant risk reductions of incident diabetes. Patterns from exploratory factor and principal component analyses characterized by red and processed meat, refined grains, high-fat dairy, eggs, and fried products ("mainly unhealthy") were positively associated with diabetes (RR: 1.44; 95% CI: 1.27, 1.62), whereas patterns characterized by vegetables, legumes, fruits, poultry, and fish ("mainly healthy") were inversely associated with diabetes (RR: 0.84; 95% CI: 0.77, 0.91). Reduced rank regression (RRR) used diabetes-related biomarkers to identify patterns. These patterns were characterized by high intakes of refined grains, sugar-sweetened soft drinks, and processed meat and were all significantly associated with diabetes risk.Conclusions: Our meta-analysis suggests that diets according to the Mediterranean diet, DASH, and AHEI have a strong potential for preventing diabetes, although they differ in some particular components. Exploratory dietary patterns were grouped based on concordant food groups and were significantly associated with diabetes risk despite single-component foods having limited evidence for an association. Still, they remain population-specific observations. Consistent positive associations with diabetes risk were observed for 3 RRR patterns.

Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.

BACKGROUND: Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. METHODS AND FINDINGS: Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. CONCLUSIONS: These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.

Erythrocyte membrane fatty acid fluidity and risk of type 2 diabetes in the EPIC-Potsdam study.

AIMS/HYPOTHESIS: The fluidity of cell membranes has been hypothesised as an important link in the association of fatty acids (FAs) with diabetes risk. The lipophilic index, which can be derived from the FA profile of blood or tissues, has recently been proposed as a novel measure of cell membrane FA fluidity. In this study we aimed to evaluate the lipophilic index in relation to the incidence of type 2 diabetes. METHODS: We applied a nested case-cohort design (n = 1,740, including 362 cases) within the EPIC-Potsdam study, which involves 27,548 middle-aged men and women. Erythrocyte membrane FA proportions were measured at baseline and physician-confirmed incident diabetes was assessed during a mean follow-up of 7.0 years. The lipophilic index was calculated as the sum of the products of the FA proportions with the respective FA melting points. RESULTS: After multivariable adjustments, including body size measures, there was a positive association between the lipophilic index and diabetes risk (HR comparing top with bottom quartile 1.59 (95% CI 1.08, 2.34), p for trend across quartiles = 0.005). Adjustment for FAs, which are considered established diabetes risk markers, did not substantially attenuate this association. CONCLUSIONS/INTERPRETATION: A high lipophilic index, reflecting lower membrane fluidity, may be associated with a higher risk of type 2 diabetes. Our data corroborate the hypothesis that membrane fluidity may be an important mediator that links intake and metabolism of FAs to diabetes risk.

A priori-defined diet quality indexes and risk of type 2 diabetes: the Multiethnic Cohort.

AIMS/HYPOTHESIS: Dietary patterns have been associated with the incidence of type 2 diabetes, but little is known about the impact of ethnicity on this relationship. This study evaluated the association between four a priori dietary quality indexes and risk of type 2 diabetes among white individuals, Japanese-Americans and Native Hawaiians in the Hawaii component of the Multiethnic Cohort. METHODS: After excluding participants with prevalent diabetes and missing values, the analysis included 89,185 participants (11,217 cases of type 2 diabetes). Dietary intake was assessed at baseline with a quantitative food frequency questionnaire designed for use in the relevant ethnic populations. Sex- and ethnicity-specific HRs were calculated for the Healthy Eating Index-2010 (HEI-2010), the Alternative HEI-2010 (AHEI-2010), the Alternate Mediterranean Diet Score (aMED) and the Dietary Approaches to Stop Hypertension (DASH). RESULTS: We observed significant inverse associations between higher DASH index scores and risk of type 2 diabetes in white men and women, as well as in Japanese-American women and Native Hawaiian men, with respective risk reductions of 37%, 31%, 19% and 21% (in the highest compared with the lowest index category). A higher adherence to the AHEI-2010 and aMED diet was related to a 13-28% lower risk of type 2 diabetes in white participants but not in other ethnic groups. No significant associations with risk of type 2 diabetes were observed for the HEI-2010 index. CONCLUSIONS/INTERPRETATION: The small ethnic differences in risk of type 2 diabetes associated with scores of a priori-defined dietary patterns may be due to a different consumption pattern of food components and the fact that the original indexes were not based on diets typical for Asians and Pacific Islanders.

Breast-feeding and maternal risk of type 2 diabetes: a prospective study and meta-analysis.

AIMS/HYPOTHESIS: We aimed to examine the association between breast-feeding and maternal risk of type 2 diabetes and to investigate whether this association is mediated by anthropometric and biochemical factors. METHODS: A case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study between 1994 and 2005 including 1,262 childbearing women (1,059 in a random sub-cohort and 203 incident cases) mainly aged between 35 and 64 years at baseline was applied. Self-reported lifetime duration of breast-feeding was assessed by questionnaire. Blood samples were used for biomarker measurement (HDL-cholesterol, triacylglycerols, C-reactive protein, fetuin-A, γ-glutamyltransferase, adiponectin). A systematic literature search and meta-analysis was conducted of prospective cohort studies investigating breast-feeding and risk of type 2 diabetes. RESULTS: The HR for each additional 6 months of breast-feeding was 0.73 (95% CI 0.56, 0.94) in EPIC-Potsdam. Meta-analysis of three previous prospective studies and the current study revealed an inverse association between breast-feeding duration and risk of diabetes (pooled HR for lifetime breast-feeding duration of 6-11 months compared with no breast-feeding 0.89; 95% CI 0.82, 0.97). Adjustment for BMI and waist circumference attenuated the association (HR per six additional months in EPIC-Potsdam 0.80; 95% CI 0.61, 1.04). Further controlling for potentially mediating biomarkers largely explained this association (HR 0.89; 95% CI 0.68, 1.16). CONCLUSIONS/INTERPRETATION: Longer duration of breast-feeding may be related to a lower risk of diabetes. This potentially protective effect seems to be reflected by a more favourable metabolic profile; however, the role of body weight as a mediator or confounder remains uncertain.

Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.

BACKGROUND: Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. METHODS AND FINDINGS: The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction  = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction  = 1.50×10-3) and waist circumference (p for interaction  = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. CONCLUSIONS: The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

Dietary patterns in urban Ghana and risk of type 2 diabetes.

There is epidemiological evidence for associations between dietary patterns and type 2 diabetes. However, for sub-Saharan Africa, information on dietary patterns and their contribution to diabetes is lacking. The aim of the present study was to identify dietary patterns and their associations with type 2 diabetes in an urban Ghanaian population. In a hospital-based case-control study on risk factors for type 2 diabetes in Kumasi, a FFQ was administered to 675 controls and 542 cases. Dietary patterns were identified by using factor analysis including thirty-three food items. Logistic regression was used to evaluate the associations of dietary patterns with type 2 diabetes. Overall, two dietary patterns were identified: (1) a 'purchase' dietary pattern which positively correlated with the consumption of sweets, rice, meat, fruits and vegetables and (2) a 'traditional' dietary pattern that correlated with the intake of fruits, plantain, green leafy vegetables, fish, fermented maize products and palm oil. In the highest quintile of the 'purchase' dietary pattern, participants were younger, leaner and of higher socio-economic status than those in the lower quintiles. In contrast, participants in the highest quintile of the 'traditional' dietary pattern were older, heavier and more deprived compared with those in the lower quintiles. In the multivariate model, the 'purchase' dietary pattern was inversely associated with type 2 diabetes (OR per 1 sd 0·41, 95% CI 0·33, 0·50); the 'traditional' dietary pattern increased the odds of diabetes per 1 sd by 54% (95% CI 1·35, 1·81). In conclusion, two diverse dietary patterns were identified and associated with type 2 diabetes in urban Ghana. The determinants of pattern adherence require further investigation.

Recent insights into the relation of Δ5 desaturase and Δ6 desaturase activity to the development of type 2 diabetes.

PURPOSE OF REVIEW: The Δ5 desaturase (D5D) and Δ6 desaturase (D6D) are key enzymes in the metabolism of polyunsaturated fatty acids. This review aims to summarize recent advances towards understanding the relation of the activities of D5D and D6D to the development of type 2 diabetes. RECENT FINDINGS: Prospective studies that investigated fatty acid product-to-precursor ratios in blood as estimates of desaturase activity reported a clear inverse relation of D5D activity and a strong direct relation of D6D activity to diabetes incidence. Due to the prospective design and comprehensive confounder adjustment in these studies, confounding and reverse causation are unlikely explanations for these findings. Furthermore, studies on genetic variation in the FADS1 and FADS2 genes, which encode D5D and D6D, also point to an influence of D5D and D6D activity on glucose metabolism. The inverse relation of D5D activity and the direct relation of D6D activity to diabetes risk have been corroborated by a Mendelian randomization approach recently. SUMMARY: These recent studies suggest an important role of D5D and D6D activities for the development of type 2 diabetes. Factors which influence the activities of these desaturases are likely to be of public health relevance.

Plasma Industrial and Ruminant Trans Fatty Acids and Incident Type 2 Diabetes in the EPIC-Potsdam Cohort.

OBJECTIVE: Although dietary intake of trans fatty acid (TFA) is a major public health concern because of the associated increase in the risk of cardiovascular events, it remains unclear whether TFAs also influence risk of type 2 diabetes (T2D) and whether industrial TFAs (iTFAs) and ruminant TFAs (rTFAs) exert the same effect on health. RESEARCH DESIGN AND METHODS: To investigate the relationship of 7 rTFAs and iTFAs, including 2 conjugated linoleic acids (CLAs), plasma phospholipid TFAs were measured in a case-cohort study nested within the European Prospective Investigation Into Cancer and Nutrition-Potsdam cohort. The analytical sample was a random subsample (n = 1,248) and incident cases of T2D (n = 801) over a median follow-up of 6.5 years. Using multivariable Cox regression models, we examined associations of TFAs with incident T2D. RESULTS: The TFA subtypes were intercorrelated with each other, with other fatty acids, and with different food sources. After controlling for other TFAs, the iTFAs (18:1n-6t, 18:1n-9t, 18:2n-6,9t) were not associated with diabetes risk. Some rTFA subtypes were inversely associated with diabetes risk: vaccenic acid (18:1n-7t; hazard ratio [HR] per SD 0.72; 95% CI 0.58-0.89) and t10c12-CLA (HR per SD 0.81; 95% CI 0.70-0.94), whereas c9t11-CLA was positively associated (HR per SD 1.39; 95% CI 1.19-1.62). Trans-palmitoleic acid (16:1n-7t) was not associated with diabetes risk when adjusting for the other TFAs (HR per SD 1.08; 95% CI 0.88-1.31). CONCLUSIONS: The TFAs' conformation plays an essential role in their relationship to diabetes risk. rTFA subtypes may have opposing relationships to diabetes risk. Previous observations for reduced diabetes risk with higher levels of circulating trans-palmitoleic acid are likely due to confounding.

Prevalence and Infant Mortality of Major Congenital Malformations Stratified by Birthweight.

BACKGROUND: Low birthweight and major congenital malformations (MCMs) are key causes of infant mortality. OBJECTIVES: The aim of this study was to explore the prevalence of MCMs in infants with low and very low birthweight and analyze the impact of MCMs and birthweight on infant mortality. METHODS: We determined prevalence and infant mortality of 28 life-threatening MCMs in very-low-birthweight (<1,500 g, VLBW), low-birthweight (1,500-2,499 g, LBW), or normal-birthweight (≥2,500 g, NBW) infants in a cohort of 2,727,002 infants born in Germany in 2006-2017, using de-identified administrative data of the largest statutory public health insurance system in Germany. RESULTS: The rates of VLBW, LBW, and NBW infants studied were 1.3% (34,401), 4.0% (109,558), and 94.7% (2,583,043). MCMs affected 0.5% (13,563) infants, of whom >75% (10,316) had severe congenital heart disease. The prevalence (per 10,000) of any/cardiac MCM was increased in VLBW (286/176) and LBW (244/143), as compared to NBW infants (38/32). Infant mortality rates were significantly higher in infants with an MCM, as opposed to infants without an MCM, in each birthweight group (VLBW 28.5% vs. 11.5%, LBW 16.7% vs. 0.9%, and NBW 8.6% vs. 0.1%). For most MCMs, observed survival rates in VLBW and LBW infants were lower than expected, as calculated from survival rates of VLBW or LBW infants without an MCM, and NBW infants with an MCM. CONCLUSIONS: Infants with an MCM are more often born with LBW or VLBW, as opposed to infants without an MCM. Many MCMs carry significant excess mortality when occurring in VLBW or LBW infants.

Risk-related short-term clinical outcomes after transcatheter aortic valve implantation and their impact on early mortality: an analysis of claims-based data from Germany.

OBJECTIVES: We aimed to define and assess risk-specific adverse outcomes after transcatheter aortic valve implantation (TAVI) in an all-comers patient population based on German administrative claims data. METHODS: Administrative claims data of patients undergoing transvascular TAVI between 2017 and 2019 derived from the largest provider of statutory health-care insurance in Germany were used. Patients' risk profile was assessed using the established Hospital Frailty Risk (HFR) score and 30-day adverse events were evaluated. Multivariable logistic regression models were applied to investigate the relation of patients' risk factors to clinical outcomes and, subsequently, of clinical outcomes to mortality. RESULTS: A total of 21,430 patients were included in the analysis. Of those, 51% were categorized as low-, 37% as intermediate-, and 12% as high-risk TAVI patients according to HFR score. Whereas low-risk TAVI patients showed low rates of periprocedural adverse events, TAVI patients at intermediate or high risk suffered from worse outcomes. An increase in HFR score was associated with an increased risk for all adverse outcome measures. The strongest association of patients' risk profile and outcome was present for cerebrovascular events and acute renal failure after TAVI. Independent of patients' risk, the latter showed the strongest relation with early mortality after TAVI. CONCLUSIONS: Differentiated outcomes after TAVI can be assessed using claims-based data and are highly dependent on patients' risk profile. The present study might be of use to define risk-adjusted outcome margins for TAVI patients in Germany on the basis of health-insurance data.

Trans Fatty Acid Biomarkers and Incident Type 2 Diabetes: Pooled Analysis of 12 Prospective Cohort Studies in the Fatty Acids and Outcomes Research Consortium (FORCE).

OBJECTIVE: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics. RESULTS: During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P ≥ 0.1). CONCLUSIONS: Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.

Erythrocyte membrane phospholipid polyunsaturated fatty acids are related to plasma C-reactive protein and adiponectin in middle-aged German women and men.

PURPOSE: Modulation of circulating inflammatory markers and adiponectin may link PUFA to risk of diabetes and cardiovascular diseases. We investigated erythrocyte n-6 and n-3 PUFA in relation to plasma C-reactive protein (CRP) and adiponectin, and whether the Pro12Ala polymorphism in the PPARγ2 gene (PPARG2) modified these associations. METHODS: We conducted a cross-sectional analysis among 1,222 women and 758 men participating in the EPIC-Potsdam study. RESULTS: Most notably, in both sexes, higher linoleic acid (LA) was related to lower CRP (geometric mean outcome [mg/L], quintile 1, quintile 5, p for trend ≤ 0.01 unless otherwise stated: 0.95, 0.61 [women], 0.67, 0.51 [men]) and higher adiponectin (7.9, 9.1 [women], 5.3, 6.1 [men]), whereas higher γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA) were related to higher CRP (GLA: 0.63, 0.92 [women], 0.55, 0.70, p = 0.08 [men], DGLA: 0.55, 1.07 [women], 0.52, 0.76 [men]) and lower adiponectin (GLA: 8.6, 8.0 [women], 5.8, 5.4, p = 0.08 [men], DGLA: 9.2, 7.9 [women], 5.9, 5.4, p = 0.08 [men]) adjusting for age and lifestyle. The associations mostly did neither strongly nor significantly vary by PPARG2 genotype. In women, Pro12Ala appeared to interact with arachidonic acid on CRP (p = 0.04), as well as with docosatetraenoic acid on CRP (p = 0.08) and adiponectin (p = 0.02). CONCLUSIONS: Our findings suggest that erythrocyte PUFA, particularly LA and n-6 higher unsaturated fatty acids, are related to circulating CRP and adiponectin. They do not indicate that PUFA strongly interact with the PPARG2 Pro12Ala variant on these risk markers.

A cross-sectional analysis of the associations between adult height, BMI and serum concentrations of IGF-I and IGFBP-1 -2 and -3 in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Height and BMI are risk factors for several types of cancer and may be related to circulating concentrations of insulin-like growth factor-I (IGF-I), a peptide associated with increased cancer risk. AIM: To assess the associations between height, BMI and serum concentrations of IGF-I and IGF binding protein (IGFBP)-1, -2 and -3. SUBJECTS AND METHODS: This cross-sectional analysis included 1142 men and 3589 women aged 32-77 years from the multi-centre study, the European Prospective Investigation of Cancer and Nutrition (EPIC). RESULTS: In men, there was a positive association between height and IGF-I; each 10 cm increment in height was associated with an increase in IGF-I concentrations of 4.3% (95% confidence interval (CI): 1.3-7.5%, p for trend = 0.005), but this association was not statistically significant for women (0.9%, 95% CI: - 0.7 to 2.6%, p for trend = 0.264). In both men and women, the association between IGF-I and BMI was non-linear and those with a BMI of 26-27 kg/m² had the highest IGF-I concentration. BMI was strongly inversely related to concentrations of IGFBP-1 and IGFBP-2 in men and in women (p for trend for all < 0.001). CONCLUSION: Height and BMI are associated with IGF-I and its binding proteins, which may be mechanisms through which body size contributes to increased risk of several cancers.

Region-specific nutrient intake patterns exhibit a geographical gradient within and between European countries.

Until recently, the study of nutrient patterns was hampered at an international level by a lack of standardization of both dietary methods and nutrient databases. We aimed to describe the diversity of nutrient patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) study at population level as a starting point for future nutrient pattern analyses and their associations with chronic diseases in multi-center studies. In this cross-sectional study, 36,034 persons aged 35-74 y were administered a single, standardized 24-h dietary recall. Intake of 25 nutrients (excluding intake from dietary supplements) was estimated using a standardized nutrient database. We used a graphic presentation of mean nutrient intakes by region and sex relative to the overall EPIC means to contrast patterns within and between 10 European countries. In Mediterranean regions, including Greece, Italy, and the southern centers of Spain, the nutrient pattern was dominated by relatively high intakes of vitamin E and monounsaturated fatty acids (MUFA), whereas intakes of retinol and vitamin D were relatively low. In contrast, in Nordic countries, including Norway, Sweden, and Denmark, reported intake of these same nutrients resulted in almost the opposite pattern. Population groups in Germany, The Netherlands, and the UK shared a fatty acid pattern of relatively high intakes of PUFA and SFA and relatively low intakes of MUFA, in combination with a relatively high intake of sugar. We confirmed large variability in nutrient intakes across the EPIC study populations and identified 3 main region-specific patterns with a geographical gradient within and between European countries.