Publications

Abstract To examine the association between urinary excretion of isoflavonoids and risk of type 2 diabetes (T2D), we conducted a nested case–control study among 1111 T2D pairs identified during 1995–2008 in the Nurses’ Health Study (NHS) and NHSII, who were free of diabetes, CVD and cancer at urine sample collection. Urinary excretion of daidzein and genistein, as well as their metabolites O -desmethylangolensin ( O -DMA), dihydrogenistein (DHGE) and dihydrodaidzein (DHDE) was assayed using liquid chromatography MS. Self-reported T2D incident cases were confirmed using a validated questionnaire. Higher urinary excretion of daidzein and genistein was associated with a lower risk of T2D in the combined cohorts. Comparing extreme tertiles of the urinary markers, the OR of T2D were 0·71 (95 % CI 0·55, 0·93) for daidzein and 0·74 (95 % CI 0·56, 0·97) for genistein, although the test for linear trend was not significant for genistein ( P trend =0·03 and 0·15, respectively). DMA, DHDE and DHGE were non-significantly associated with a lower T2D risk. The inverse association of daidzein with T2D risk was stronger among post-menopausal women who did not use hormone replacement therapy ( P interaction =0·001): the OR was 0·58 (95 % CI 0·34, 0·97) comparing extreme tertiles among these women. In conclusion, urinary excretion of isoflavones was associated with a lower T2D risk in US women, especially among post-menopausal women who did not use hormone. Further research is warranted to replicate these observations among western populations with similarly low overall isoflavone intake.

In this study, we prospectively assessed the association between adherence to the Mediterranean diet and risk of incident coronary heart disease (CHD) and stroke. 74,886 women aged 38‐63 in the Nurses' Health Study, without a history of cardiovascular disease (CVD) and diabetes were followed from 1984 to 2004. We computed an alternate Mediterranean diet score from dietary data collected through validated food frequency questionnaires administered 6 times during follow‐up. Relative risks for incident CHD, stroke, and combined fatal CVD were estimated using Cox proportional hazards models adjusted for CVD risk factors. During 20 years of follow‐up, 2391 incident cases of CHD, 1763 incident cases of stroke, and 1077 CVD deaths (fatal CHD and strokes combined) were ascertained. Women in the top aMed quintile were at lower risk for both CHD and stroke compared with the bottom quintile (RR=0.71 (95%CI=0.62‐0.82; p trend< 0.0001) for CHD; RR=0.87 (95% CI=0.73‐1.02; p trend=0.03) for stroke). CVD mortality was significantly lower among women in the top quintile of the aMed (RR=0.61, 95g% CI=0.49‐0.76, p trend<0.0001). Conclusion Greater adherence to the Mediterranean diet was associated with a lower risk of incident CHD and stroke in women. Funded by NIH grants CA87969, HL60712, HL34594, HL88521.

OBJECTIVE—The purpose of this study was to determine whether women with type 1 and type 2 diabetes are at higher risk of hip fractures. RESEARCH DESIGN AND METHODS—A total of 109,983 women aged 34–59 years in 1980 were followed through 2002 for the occurrence of hip fracture. At baseline and through biennial follow-up, women were asked about their history and treatment of diabetes and other potential risk factors for hip fracture. RESULTS—During 2.22 million person-years of follow-up, 1,398 women had a hip fracture. Compared with women without diabetes, the age-adjusted relative risk (RRs) of hip fracture was 7.1 (95% CI 4.4–11.4) for women with type 1 diabetes and 1.7 (1.4–2.0) for those with type 2 diabetes. After further adjustment for BMI, smoking, physical activity, menopausal status, daily intake of calcium, vitamin D, protein, and postmenopausal hormone use, the multivariate RR of incident hip fracture in individuals with type 1 diabetes compared with individuals without diabetes was 6.4 (3.9–10.3) and with type 2 diabetes was 2.2 (1.8–2.7). The RRs increased with longer duration of type 2 diabetes (3.1 [2.3–4.0] for ≥12 years compared with no diabetes, P for trend < 0.001) and ever use of insulin. CONCLUSIONS—These data indicate that both type 1 and type 2 diabetes are associated with an increased risk of hip fracture. The results of this study highlight the need for fracture-prevention strategies in women with diabetes.

BACKGROUND Quantitative molecular data from urine are rare in epidemiology and genetics. NMR spectroscopy could provide these data in high throughput, and it has already been applied in epidemiological settings to analyse urine samples. However, quantitative protocols for large-scale applications are not available. METHODS We describe in detail how to prepare urine samples and perform NMR experiments to obtain quantitative metabolic information. Semi-automated quantitative line shape fitting analyses were set up for 43 metabolites and applied to data from various analytical test samples and from 1004 individuals from a population-based epidemiological cohort. Novel analyses on how urine metabolites associate with quantitative serum NMR metabolomics data (61 metabolic measures; n = 995) were performed. In addition, confirmatory genome-wide analyses of urine metabolites were conducted (n = 578). The fully automated quantitative regression-based spectral analysis is demonstrated for creatinine and glucose (n = 4548). RESULTS Intra-assay metabolite variations were mostly <5%, indicating high robustness and accuracy of urine NMR spectroscopy methodology per se. Intra-individual metabolite variations were large, ranging from 6% to 194%. However, population-based inter-individual metabolite variations were even larger (from 14% to 1655%), providing a sound base for epidemiological applications. Metabolic associations between urine and serum were found to be clearly weaker than those within serum and within urine, indicating that urinary metabolomics data provide independent metabolic information. Two previous genome-wide hits for formate and 2-hydroxyisobutyrate were replicated at genome-wide significance. CONCLUSION Quantitative urine metabolomics data suggest broad novelty for systems epidemiology. A roadmap for an open access methodology is provided.

Our results suggest that levels of toenail selenium are lower among diabetic men with or without CVD than among healthy controls. However, this study could not distinguish between the effects of selenium on diabetes and those on CVD. Randomized clinical trials are needed to study potential benefits of selenium supplementation in the prevention and treatment of diabetes and CVD.

Abstract Background The pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identification of new predictor biomarkers. Biomarkers potentially modifiable with lifestyle changes deserve a special interest. Our aims were to analyze: (a) The associations of lysine, 2-aminoadipic acid (2-AAA) or pipecolic acid with the risk of T2D or CVD in the PREDIMED trial; (b) the effect of the dietary intervention on 1-year changes in these metabolites, and (c) whether the Mediterranean diet (MedDiet) interventions can modify the effects of these metabolites on CVD or T2D risk. Methods Two unstratified case-cohort studies nested within the PREDIMED trial were used. For CVD analyses, we selected 696 non-cases and 221 incident CVD cases; for T2D, we included 610 non-cases and 243 type 2 diabetes incident cases. Metabolites were quantified using liquid chromatography–tandem mass spectrometry, at baseline and after 1-year of intervention. Results In weighted Cox regression models, we found that baseline lysine (HR +1 SD increase = 1.26; 95% CI 1.06–1.51) and 2-AAA (HR +1 SD increase = 1.28; 95% CI 1.05–1.55) were both associated with a higher risk of T2D, but not with CVD. A significant interaction (p = 0.032) between baseline lysine and T2D on the risk of CVD was observed: subjects with prevalent T2D and high levels of lysine exhibited the highest risk of CVD. The intervention with MedDiet did not have a significant effect on 1-year changes of the metabolites. Conclusions Our results provide an independent prospective replication of the association of 2-AAA with future risk of T2D. We show an association of lysine with subsequent CVD risk, which is apparently diabetes-dependent. No evidence of effects of MedDiet intervention on lysine, 2-AAA or pipecolic acid changes was found. Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated age ...

Introduction: The effectiveness of low-fat diets for weight loss has been debated for decades. Dozens of randomized control trials (RCTs) have assessed whether decreasing the intake of total fat leads to weight loss, giving mixed results. Hypothesis: We hypothesized that low-fat dietary interventions do not lead to greater weight loss when comparator diet intervention intensity is considered. Methods: We conducted a systematic review and meta-analysis. RCTs were included if they compared a low-fat dietary intervention to any control diet with at least 1 year of follow-up. We estimated the combined fixed effect inverse variance weighted mean difference of low-fat vs. comparison diets. Several a priori stratified analyses were considered to explore heterogeneity. Results: Fifty studies met inclusion criteria, reporting 1-10 years of follow-up on 70,054 participants. Overall, low-fat dietary interventions resulted in 0.51kg greater weight loss compared to other diets (95% CI = -0.62, -0.40, p&lt;0.001; I2 = 83%). However, when trials where greater attention was given to the low-fat group were excluded, comparator diets led to greater weight loss than low-fat diets (n=30; WMD=0.87, 95% CI=0.56, 1.17, p&lt;0.001). Similarly, when the type of comparator diet was considered, low-fat diets were only beneficial compared to control groups who were simply asked to maintain their usual diet (n=18; WMD = -1.03, 95% CI = -1.18, -0.88, p&lt;0.001). When equal attention was given to intervention groups, low-carbohydrate diets (n=15; WMD = 1.13kg, 95% CI = 0.53, 1.73, p&lt;0.001) and other “healthy” diets without a low-fat component (n=20; WMD = 0.77kg, 95% CI = 0.42, 1.13, p&lt;0.001) led to greater weight loss than low-fat diets. Comparison diets, irrespective of type, were associated with 1.30kg greater weight loss than low-fat diets when the interventions were intended to be isocaloric (n=19; 95% CI = 0.92, 1.69, p&lt;0.001). Conclusions: Low-fat dietary interventions are not more effective than other diets for weight loss when differences in intervention intensity between treatment groups are considered. Rather, evidence from long-term (&gt;=1 year) randomized trials indicates low-carbohydrate or other healthful dietary pattern interventions without a low-fat focus may be more effective for weight loss than low-fat dietary interventions. Further evidence is needed to establish the role of these interventions in longer-term weight loss and weight maintenance.