Adherence to newer second-line oral antidiabetic drugs among people with type 2 diabetes-A systematic review.

The adherence to oral antidiabetic drugs (OADs) among people with type 2 diabetes (T2D) is suboptimal. However, new OADs have been marketed within the last 10 years. As these new drugs differ in mechanism of action, treatment complexity, and side effects, they may influence adherence. Thus, the aim of this study was to assess the adherence to newer second-line OADs, defined as drugs marketed in 2012-2022, among people with T2D. A systematic review was performed in CINAHL, Cochrane Trials, Embase, PubMed, PsycINFO, and Scopus. Articles were included if they were original research of adherence to newer second-line OADs and reported objective adherence quantification. The quality of the articles was assessed using JBI's critical appraisal tools. The overall findings were reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and summarized in a narrative synthesis. All seven included articles were European retrospective cohort studies investigating alogliptin, canagliflozin, dapagliflozin, empagliflozin, and unspecified types of SGLT2i. Treatment discontinuation and medication possession ratio (MPR) were the most frequently reported adherence quantification measures. Within the first 12 months of treatment, 29%-44% of subjects on SGLT2i discontinued the treatment. In terms of MPR, 61.7%-94.9% of subjects on either alogliptin, canagliflozin, dapagliflozin, empagliflozin or an unspecified SGLT2i were adherent. The two investigated adherence quantification measures, treatment discontinuation and MPR, suggest that adherence to the newer second-line OADs may be better than that of older OADs. However, a study directly comparing older and newer OADs should be done to verify this.

Simple Post-Processing of Continuous Glucose Monitoring Measurements Improves Endpoints in Clinical Trials.

BACKGROUND: Continuous glucose monitoring (CGM) is a powerful tool to be considered both in clinical practice and clinical trials. However, CGM has been criticized for being inaccurate for many reasons including a physiological delay. This study sought to investigate the current delay issue and propose a simple post-processing procedure. METHOD: More than a million hours of the Dexcom G4 CGM from 472 subjects investigated in a state-of-the-art clinical trial were analyzed by time shifting the CGM measurements and comparing them to plasma glucose (PG) measurements. The resultant CGM measurements were then assessed in relation to real-world clinical research endpoints. RESULTS: A CGM time shift of -9 minutes was optimal and reduced mean absolute relative difference (MARD) statistically significantly with 1.0% point. The MARD reduction resulted in better clinical research endpoints of hypoglycemia and postprandial glucose increments. CONCLUSIONS: The delay in CGM is still an issue. The delay in this study was identified to be 9 minutes compared to PG. With a simple post-processing approach of time shifting the CGM measurements with -9 minutes, it was possible to obtain a statistically significantly lower MARD and subsequently obtain clinical research endpoints of improved validity.

Prediction of Nocturnal Hypoglycemia From Continuous Glucose Monitoring Data in People With Type 1 Diabetes: A Proof-of-Concept Study.

BACKGROUND: Intensive insulin therapy has documented benefits but may also come at the expense of a higher risk of hypoglycemia. Hypoglycemia is associated with higher all-cause mortality and nocturnal hypoglycemia has been associated with the sudden dead-in-bed syndrome. This proof-of-concept study sought to investigate if nocturnal hypoglycemia can be predicted. METHOD: Continuous glucose monitoring, meal, insulin, and demographics data from 463 people with type 1 diabetes were obtained from a clinical trial. A total of 4721 nights without or with hypoglycemia (429) were available including data from three consecutive days before the night. Thirty-two features were calculated based on these data. Data were split into 20% participants for evaluation and 80% for training. The optimal feature subset was found from forward selection of the 80% participants with linear discriminant analysis as basis for the classifier. RESULTS: The forward selection resulted in a feature subset of four features. The evaluation resulted in an area under the receiver operating characteristics curve (ROC-AUC) of 0.79 leading to a sensitivity and a specificity of, e.g., 75% and 70%. CONCLUSIONS: It was possible to predict nocturnal hypoglycemic episodes with a ROC-AUC of 0.79. A warning at bedtime about nocturnal hypoglycemia could be of great help for people with diabetes to enable preventive actions. Further development of the proposed algorithm is needed for implementation in everyday practice.

Association of severe hypoglycemia with mortality for people with diabetes mellitus during a 20-year follow-up in Denmark: a cohort study.

AIMS: Severe hypoglycemia has a significant deteriorating effect on quality of life of the individual and has been associated with increased mortality. The aim of this study was to investigate the mortality among people with type 1 and type 2 diabetes suffering from severe hypoglycemia in Denmark in the last two decades. METHODS: People diagnosed with type 1 (n = 44,033) and type 2 diabetes (n = 333,581) were extracted from the complete population of Denmark from 1996 to 2017 via ICD-10 diabetes codes and ATC diabetes medication codes. People suffering from severe hypoglycemia (type 1 diabetes n = 8808, type 2 diabetes n = 5605) as identified from ICD-10 codes were then matched 1:1 by year of birth, gender and year of diabetes diagnosis with those without severe hypoglycemia. Cox proportional hazards models were constructed to analyze the effect of severe hypoglycemia on mortality. RESULTS: For both people with type 1 (HR 1.11, CI 95% 1.06 to 1.17) and type 2 diabetes (HR 1.77, CI 95% 1.67 to 1.87) suffering from hypoglycemia, an increased mortality risk was observed, compared to people without severe hypoglycemia. An investigation of the death causes did not indicate an association between the severe hypoglycemic episodes and death. CONCLUSION: In this study, severe hypoglycemic episodes increased the mortality risk for people with type 1 and type 2 diabetes. The risk was higher among people with type 2 diabetes. Whether severe hypoglycemia is a symptom of other underlying illnesses increasing mortality risk or a risk factor itself needs further investigation.

Investigating the Association Between Baseline Characteristics (HbA1c and Body Mass Index) and Clinical Outcomes of Fast-Acting Insulin Aspart in People with Diabetes: A Post Hoc Analysis.

INTRODUCTION: The aim of this study was to investigate the association between baseline characteristics [HbA1c and body mass index (BMI)] and the effect of mealtime fast-acting insulin aspart (faster aspart) relative to insulin aspart (IAsp) or basal-only insulin therapy on several efficacy and safety outcomes in people with diabetes. METHODS: Post hoc analysis of three randomised phase 3a trials in people with type 1 diabetes (T1D; onset 1) and type 2 diabetes (T2D; onset 2 and 3). Participants (N = 1686) were stratified according to baseline BMI (< 25 kg/m2, 25-< 30 kg/m2, ≥ 30 kg/m2) or HbA1c (≤ 58 mmol/mol, > 58-< 64 mmol/mol, ≥ 64 mmol/mol; ≤ 7.5%, > 7.5-< 8.0%, ≥ 8.0%). RESULTS: In participants with T2D, the estimated treatment difference for change in HbA1c was similar for all BMI and HbA1c subgroups. No major differences between treatments were observed in risk of overall hypoglycaemia or insulin dose across subgroups. In participants with T1D, change in HbA1c was similar across BMI and HbA1c subgroups, and no major differences between treatments were observed for severe or blood glucose-confirmed hypoglycaemia across subgroups. Total daily insulin dose (U/kg) was similar across all baseline HbA1c groups and the BMI < 25 kg/m2 and 25-30 kg/m2 groups, but was significantly lower with mealtime faster aspart compared with IAsp in the BMI > 30 kg/m2 subgroup. CONCLUSIONS: In participants with T1D and T2D, treatment differences (for change in HbA1c and overall hypoglycaemia) between mealtime faster aspart and insulin comparators were similar to the corresponding overall analysis across baseline HbA1c and BMI subgroups. The finding of a lower total daily insulin dose in participants with obesity (BMI > 30 kg/m2) and T1D treated with faster aspart, versus those treated with IAsp, may warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01831765 (onset 1); NCT01819129 (onset 2); NCT01850615 (onset 3). FUNDING: Novo Nordisk A/S, Søborg, Denmark.

Dietary n-6 PUFA, carbohydrate:protein ratio and change in body weight and waist circumference: a follow-up study.

OBJECTIVE: To investigate the association between the intake of n-6 PUFA and subsequent change in body weight and waist circumference at different levels of the carbohydrate:protein ratio. DESIGN: Follow-up study with anthropometric measurements at recruitment and on average 5·3 years later. Dietary intake was determined at recruitment by using an FFQ that was designed for the study and validated. We applied linear regression models with 5-year change in weight or waist circumference as outcome and including a two-way interaction term between n-6 PUFA and carbohydrate intakes, lower-order terms, protein intake, long-chain n-3 PUFA intake and other potential confounders. Due to adjustment for intake of protein, levels of carbohydrate indirectly reflect levels of the carbohydrate:protein ratio. SETTING: Diet, Cancer and Health follow-up study, Denmark. SUBJECTS: Women and men (n 29 152) aged 55 years. RESULTS: For a high intake of n-6 PUFA (6·9 % of energy) v. a low intake of n-6 PUFA (3·4 % of energy), the difference in 5-year weight change was -189·7 g (95 % CI -636·8, 257·4 g) at a low carbohydrate:protein ratio and -86·7 g (95 % CI -502·9, 329·6 g) at a high carbohydrate:protein ratio; the differences in 5-year waist circumference change were 0·26 cm (95 % CI -0·47, 0·98 cm) and -0·52 cm (95 % CI -1·19, 0·15 cm), respectively. Inclusion of the dietary glycaemic index did not change the results. CONCLUSIONS: No consistent associations between the intake of n-6 PUFA and change in body weight or waist circumference at different levels of the carbohydrate:protein ratio were observed.

Variation in the sodium-dependent vitamin C transporter 2 gene is associated with risk of acute coronary syndrome among women.

BACKGROUND: Vitamin C is associated with a lower risk of coronary heart disease possibly due to its anti-oxidative effects, beneficial effects on endothelial function and importance in collagen synthesis. The sodium-dependent vitamin C transporter 2 is responsible for the transport of vitamin C into various cells and malfunction of this protein leads to reduced vitamin C in tissue, including the arterial wall. We tested the hypothesis that candidate variations rs6139591 and rs1776964 in the gene coding for sodium-dependent vitamin C transporter 2 are associated with development of acute coronary syndrome. DESIGN: In the Danish Diet, Cancer and Health cohort study, we performed a case-cohort study among 57,053 subjects aged 50-64 years. RESULTS: During a mean follow-up period of 6.4 years, we identified 936 cases and randomly selected a sub-cohort (n = 1,580) with full information on genotypes and covariates. Using Cox proportional hazard models, we found that women with the rs6139591 TT genotype and a lower than median dietary vitamin C intake had a higher risk of acute coronary syndrome compared with those with the CC genotype (adjusted HR 5.39, 95% confidence interval, 2.01-14.50). We also observed a not as strong but positive although inconsistent association for women at a higher than median intake of vitamin C rich food. For the rs1776964 polymorphism, we found a higher risk (adjusted HR 3.45, 95% CI, 1.16-10.28) among TT-homozygous women with higher than median vitamin C intake compared with the CC genotype and low vitamin C intake. Among men, weaker and non-significant associations were observed for both polymorphisms. CONCLUSION: Genetic variation in the sodium-dependent vitamin C transporter 2 is associated with risk of incident acute coronary syndrome in women. The genotype effects may not be fully compensated by a higher intake of vitamin C rich food.

Urinary flavonoid excretion and risk of acute coronary syndrome in a nested case-control study.

BACKGROUND: Epidemiologic studies have suggested that a higher intake of flavonoids may be associated with lower risk of ischemic heart disease. However, the traditional estimation of flavonoid intake by using dietary assessment methods is affected by subjective measures. OBJECTIVE: We examined whether the objective measurement of dietary flavonoids excreted in urine is associated with lower risk of acute coronary syndrome (ACS). DESIGN: A case-control study was nested in the Danish Diet, Cancer and Health cohort study. Cases were identified in participants who had received a first-time ACS diagnosis in the Danish National Patient Registry after the time of enrollment into the Diet, Cancer and Health study. The excretion of 10 flavonoids, which represent 5 subclasses, was measured in spot urine samples by using liquid chromatography-mass spectrometry. RESULTS: A total of 393 eligible cases with ACS were identified and matched to 393 noncases by using incidence density sampling. For kaempferol, most of the individual ORs were statistically significant and from 42% to 61% lower when the higher 4 quintiles were compared with the lowest quintile. The P-trend was not significant. For daidzein, individual ORs were 5-38% lower. None of the individual ORs were significant, but the P-trend was 0.041. For the remaining flavonoids, there were no significant relations between urinary excretion and risk of ACS. CONCLUSIONS: Except for kaempferol and daidzein, there were no significant associations between the urinary excretion of flavonoids and risk of ACS. A lack of relations may be a result of the use of short-term exposure measures.

[Possible decrease in the prevalence of nosocomial infections after the accreditation process in the region of Northern Jutland, Denmark]. / Muligt fald i prævalensen af nosokomielle infektioner efter akkrediteringsprocessen i Region Nordjylland.

All hospitals in the region of Northern Jutland, Denmark, were accredited in 2011 according to standards defined by the Danish Healthcare Quality Programme. A retrospective review was performed analysing the prevalence of nosocomial infections before and during the accreditation process. The accreditation process was associated with a decreased prevalence of selected nosocomial infections compared with results from a period immediate prior to the process. However, the findings were not statistically significant when the results were adjusted for patient-time in the hospitals.

Fish consumption and subsequent change in body weight in European women and men.

Fish consumption is the major dietary source of EPA and DHA, which according to rodent experiments may reduce body fat mass and prevent obesity. Only a few human studies have investigated the association between fish consumption and body-weight gain. We investigated the association between fish consumption and subsequent change in body weight. Women and men (n 344,757) participating in the European Prospective Investigation into Cancer and Nutrition were followed for a median of 5.0 years. Linear and logistic regression were used to investigate the associations between fish consumption and subsequent change in body weight. Among women, the annual weight change was 5.70 (95 % CI 4.35, 7.06), 2.23 (95 % CI 0.16, 4.31) and 11.12 (95 % CI 8.17, 14.08) g/10 g higher total, lean and fatty fish consumption per d, respectively. The OR of becoming overweight in 5 years among women who were normal weight at enrolment was 1.02 (95 % CI 1.01, 1.02), 1.01 (95 % CI 1.00, 1.02) and 1.02 (95 % CI 1.01, 1.04) g/10 g higher total, lean and fatty consumption per d, respectively. Among men, fish consumption was not statistically significantly associated with weight change. Adjustment for potential over- or underestimation of fish consumption did not systematically change the observed associations, but the 95 % CI became wider. The results in subgroups from analyses stratified by age or BMI at enrolment were not systematically different. In conclusion, the present study suggests that fish consumption has no appreciable association with body-weight gain.

Modeling gradually changing seasonal variation in count data using state space models: a cohort study of hospitalization rates of stroke in atrial fibrillation patients in Denmark from 1977 to 2011.

BACKGROUND: Seasonal variation in the occurrence of cardiovascular diseases has been recognized for decades. In particular, incidence rates of hospitalization with atrial fibrillation (AF) and stroke have shown to exhibit a seasonal variation. Stroke in AF patients is common and often severe. Obtaining a description of a possible seasonal variation in the occurrence of stroke in AF patients is crucial in clarifying risk factors for developing stroke and initiating prophylaxis treatment. METHODS: Using a dynamic generalized linear model we were able to model gradually changing seasonal variation in hospitalization rates of stroke in AF patients from 1977 to 2011. The study population consisted of all Danes registered with a diagnosis of AF comprising 270,017 subjects. During follow-up, 39,632 subjects were hospitalized with stroke. Incidence rates of stroke in AF patients were analyzed assuming the seasonal variation being a sum of two sinusoids and a local linear trend. RESULTS: The results showed that the peak-to-trough ratio decreased from 1.25 to 1.16 during the study period, and that the times of year for peak and trough changed slightly. CONCLUSION: The present study indicates that using dynamic generalized linear models provides a flexible modeling approach for studying changes in seasonal variation of stroke in AF patients and yields plausible results.

Seasonality, incidence and prognosis in atrial fibrillation and stroke in Denmark and New Zealand.

OBJECTIVES: There are relatively few large studies of seasonal variation in the occurrence of stroke in patients with atrial fibrillation (AF). We investigated the seasonal variation in incidence rates of hospitalisation with stroke in patients from Denmark and New Zealand. DESIGN: Cohort study. SETTING: Nationwide hospital discharge data from Denmark and New Zealand. PARTICIPANTS: 243 381 (median age 75) subjects having a first-time hospitalisation with AF in Denmark and 51 480 (median age 76) subjects in New Zealand constituted the study population. Subjects with previous hospitalisation with stroke were excluded. PRIMARY AND SECONDARY EFFECT MEASURES: Peak-to-trough ratio of the seasonal variation in incidence rates of stroke in AF patients adjusted for an overall trend was primary effect measure and was assessed using a log-linear Poisson regression model. Secondary effect measures were incidence rate ratios of AF and 30-day case fatality for stroke patients. RESULTS: Incidence rates of AF per 1000 person-years in Denmark increased by 5.4% (95% CI 5.3% to 5.7%) for patients aged <65 and 5% (95% CI 4.9% to 5.1%) for patients aged ≥65, whereas the increase was 0.2% (95% CI -0.2% to 0.6%) for patients aged <65 and 2.6% (95% CI 2.4% to 2.8%) for patients aged ≥65 in New Zealand. In Denmark 36 088 subjects were hospitalised with stroke, and 7518 subjects in New Zealand, both showing peaks during winter with peak-to-trough ratios of 1.22 and 1.27, respectively and a decreasing trend. The 30-day case fatality risk for stroke patients having AF is now (2000-2008) about 20% in both countries. CONCLUSIONS: Although incidence rates of hospitalisation with stroke in patients with AF have decreased in recent years, stroke remains a common AF complication with a high case fatality risk. The marked winter peak in incidence rates of hospitalisation with stroke in AF patients suggests that there are opportunities to reduce this complication. Further studies are necessary to identify how to optimise treatment of AF and prevention of stroke.

Dietary fiber, carbohydrate quality and quantity, and mortality risk of individuals with diabetes mellitus.

BACKGROUND: Dietary fiber, carbohydrate quality and quantity are associated with mortality risk in the general population. Whether this is also the case among diabetes patients is unknown. OBJECTIVE: To assess the associations of dietary fiber, glycemic load, glycemic index, carbohydrate, sugar, and starch intake with mortality risk in individuals with diabetes. METHODS: This study was a prospective cohort study among 6,192 individuals with confirmed diabetes mellitus (mean age of 57.4 years, and median diabetes duration of 4.4 years at baseline) from the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at baseline (1992-2000) with validated dietary questionnaires. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality, while adjusting for CVD-related, diabetes-related, and nutritional factors. RESULTS: During a median follow-up of 9.2 y, 791 deaths were recorded, 306 due to CVD. Dietary fiber was inversely associated with all-cause mortality risk (adjusted HR per SD increase, 0.83 [95% CI, 0.75-0.91]) and CVD mortality risk (0.76[0.64-0.89]). No significant associations were observed for glycemic load, glycemic index, carbohydrate, sugar, or starch. Glycemic load (1.42[1.07-1.88]), carbohydrate (1.67[1.18-2.37]) and sugar intake (1.53[1.12-2.09]) were associated with an increased total mortality risk among normal weight individuals (BMI≤25 kg/m(2); 22% of study population) but not among overweight individuals (P interaction≤0.04). These associations became stronger after exclusion of energy misreporters. CONCLUSIONS: High fiber intake was associated with a decreased mortality risk. High glycemic load, carbohydrate and sugar intake were associated with an increased mortality risk in normal weight individuals with diabetes.

Efforts to change transfusion practice and reduce transfusion rates are effective in coronary artery bypass surgery.

OBJECTIVES: Efforts to decrease allogeneic blood transfusion and avoid unnecessary transfusions in cardiac surgery are important because transfusions are associated with increased postoperative morbidity and mortality. The purpose of the present study was to evaluate the long-term effects of multidisciplinary efforts to reduce allogeneic blood transfusion rates and avoid unnecessary red blood cell (RBC) transfusions in primary elective coronary artery bypass graft (CABG) surgery. DESIGN: A retrospective observational study. SETTING: A single center study in a university-affiliated hospital. PARTICIPANTS: A total of 450 patients undergoing primary elective CABG surgery during 2004, 2008, or 2010. INTERVENTIONS: The application of systematic multimodal perioperative blood-sparing techniques and interventions directed to change transfusion behaviors. MEASUREMENTS AND MAIN RESULTS: The results from an audit on transfusion practices in 2004 were compared with similar audits performed in 2008 and 2010 using a before-and-after study design. The patient populations were comparable throughout the years. The median postoperative chest tube bleeding was decreased from 950 mL in 2004 to 750 mL in 2010. The proportion of patients transfused with allogeneic blood products was decreased from 64% to 47%. Overtransfusion with allogeneic RBCs defined as the proportion of patients transfused with RBCs discharged with hemoglobin >7 mmol/L (11.3 g/dL) was reduced from 36% to 16%. CONCLUSIONS: Multimodal efforts to change transfusion behaviors and decrease transfusion rates in CABG surgery have persistent effects for several years.

Adiposity in 277 young adult male offspring of women with diabetes compared with controls: a Danish population-based cohort study.

OBJECTIVE: To examine the associations of maternal diabetes, overall and stratified according to treatment of diabetes, with weight-related outcomes at the time of military conscription, at age 18-20 years. DESIGN AND SETTING: Cohort study of 277 Danish male offspring of mothers with recognized pre-gestational or gestational diabetes. As population-based controls we selected 870 men matched from the Civil Registration Office. METHODS: Data on weight-related outcomes were retrieved from the Danish military conscription registry. MAIN OUTCOME MEASURES: Military rejection due to adiposity and body mass index (BMI) at conscription. RESULTS: Army rejection rate due to adiposity was 5.8% (n= 16) among 277 diabetes mellitus-exposed men compared with 3.1% (n= 27) in 870 controls (risk difference 2.7 (95% confidence interval (CI) -0.3-5.7)) and mean BMI at conscription was 1.4 kg/m(2) (95%CI 0.8-2.0) higher among those diabetes mellitus-exposed men. In analyses adjusted for birthweight and gestational age, compared with controls, the BMI was 0.6 kg/m(2) (95%CI -0.3-1.5) higher in sons of mothers with pre-gestational and 2.7 kg/m(2) (95% (CI): 0.9-4.5) higher with gestational diabetes. The greatest BMI difference was in offspring of mothers with gestational diabetes in whom insulin was initiated during pregnancy. We found no difference in conscript height. CONCLUSIONS: Compared with controls, male offspring of women with diabetes had a higher rejection rate due to adiposity and higher adult BMI. Subgroup analyses showed that the association was most pronounced in sons of mothers with gestational diabetes, whereas pre-gestational diabetes was only weakly associated with higher offspring BMI.

Self-rated health and mortality in individuals with diabetes mellitus: prospective cohort study.

OBJECTIVES: To investigate whether low self-rated health (SRH) is associated with increased mortality in individuals with diabetes. DESIGN: Population-based prospective cohort study. SETTING: Enrolment took place between 1992 and 2000 in four centres (Bilthoven, Heidelberg, Potsdam, Umeå) in a subcohort nested in the European Prospective Investigation into Cancer and Nutrition. PARTICIPANTS: 3257 individuals (mean ± SD age was 55.8±7.6 years and 42% women) with confirmed diagnosis of diabetes mellitus. PRIMARY OUTCOME MEASURE: The authors used Cox proportional hazards modelling to estimate HRs for total mortality controlling for age, centre, sex, educational level, body mass index, physical inactivity, smoking, insulin treatment, hypertension, hyperlipidaemia and history of myocardial infarction, stroke or cancer. RESULTS: During follow-up (mean follow-up ± SD was 8.6±2.3 years), 344 deaths (241 men/103 women) occurred. In a multivariate model, individuals with low SRH were at higher risk of mortality (HR 1.38, 95% CI 1.10 to 1.73) than those with high SRH. The association was mainly driven by increased 5-year mortality and was stronger among individuals with body mass index of <25 kg/m(2) than among obese individuals. In sex-specific analyses, the association was statistically significant in men only. There was no indication of heterogeneity across centres. CONCLUSIONS: Low SRH was associated with increased mortality in individuals with diabetes after controlling for established risk factors. In patients with diabetes with low SRH, the physician should consider a more detailed consultation and intensified support.

Fish consumption does not prevent increase in waist circumference in European women and men.

Fish consumption is the major dietary source of EPA and DHA, which according to rodent experiments may reduce body fat mass and prevent obesity. However, human studies have suggested that fish consumption has no appreciable association with body-weight gain. We investigated the associations between fish consumption and subsequent change in waist circumference. Sex, age and waist circumference at enrolment were considered as potential effect modifiers. Women and men (n 89 432) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 5·5 years. Mixed-effect linear regression was used to investigate the associations between fish consumption and subsequent change in waist circumference. Among all participants, the average annual change in waist circumference was - 0·01 cm/10 g higher total fish consumption per d (95 % CI - 0·01, 0·00) and - 0·01 cm/10 g higher fatty fish consumption per d (95 % CI - 0·02, - 0·01), after adjustment for potential confounders. Lean fish consumption was not associated with change in waist circumference. Adjustment for potential over- or underestimation of fish consumption measurements did not systematically change the observed associations, but the 95 % CI became slightly wider. The results in subgroups from analyses stratified by sex, age or waist circumference at enrolment were not systematically different. In conclusion, the present study suggests that fish consumption does not prevent increase in waist circumference.

Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change.

OBJECTIVE: We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. METHOD: A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. RESULTS: The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was -0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: -20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. CONCLUSION: The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population.

Marine n-3 polyunsaturated fatty acids in adipose tissue and the risk of acute coronary syndrome.

BACKGROUND: Marine n-3 polyunsaturated fatty acids may reduce coronary mortality. Previous data in relation to nonfatal coronary disease, however, have been inconsistent, which may be explained by the use of heterogeneous methods to assess the intake of marine n-3 polyunsaturated fatty acids. We investigated the hypothesis that the content of total and individual marine n-3 polyunsaturated fatty acids in adipose tissue is negatively associated with the incidence of acute coronary syndrome (ACS), including both fatal and nonfatal coronary disease. METHODS AND RESULTS: In the Diet, Cancer and Health, a Danish cohort study, 57 053 subjects were enrolled and had an adipose tissue biopsy taken at inclusion. During a mean follow-up period of 7.6 years, we identified and verified all cases (n=1012) with an incident acute coronary syndrome diagnosis, and a random sample of the cohort (n=1630) had their fatty acid composition in adipose tissue determined by gas chromatography. We found negative dose-response associations between the content of total marine n-3 polyunsaturated fatty acids and individual n-3 polyunsaturated fatty acids in adipose tissue and the risk of acute coronary syndrome. Comparing men in the highest and lowest quintiles gave a hazard ratio of 0.65 (95% confidence interval, 0.45 to 0.95) for total n-3 polyunsaturated fatty acids and 0.51 (95% confidence interval, 0.36 to 0.73) for docosahexaenoic acid. Nonfatal cases constituted >86% of cases, and the association was driven primarily by a reduction in the risk of nonfatal acute coronary syndrome. No consistent associations were found among women. CONCLUSION: Intake of marine n-3 polyunsaturated fatty acids may protect against acute coronary syndrome in men.

Exploring dietary patterns by using the treelet transform.

Principal component analysis (PCA) has been used extensively in the field of nutritional epidemiology to derive patterns that summarize food and nutrient intake, but interpreting it can be difficult. The authors propose the use of a new statistical technique, the treelet transform (TT), as an alternative to PCA. TT combines the quantitative pattern extraction capabilities of PCA with the interpretational advantages of cluster analysis and produces patterns involving only naturally grouped subsets of the original variables. The authors compared patterns derived using TT with those derived using PCA in a study of dietary patterns and risk of myocardial infarction among 26,155 male participants in a prospective Danish cohort. Over a median of 11.9 years of follow-up, 1,523 incident cases of myocardial infarction were ascertained. The 7 patterns derived with TT described almost as much variation as the first 7 patterns derived with PCA, for which interpretation was less clear. When the authors used multivariate Cox regression models to estimate relative risk of myocardial infarction, the significant risk factors were comparable whether the model was based on PCA or TT factors. The present study shows that TT may be a useful alternative to PCA in epidemiologic studies, leading to patterns that possess comparable explanatory power and are simple to interpret.