Type 2 diabetes (T2D) has become a leading health problem throughout the world. It is caused by both environmental and genetic factors and interactions between them. However, until very recently, the T2D susceptibility genes have been poorly understood. During the past 5 years, with the advent of genome-wide association studies (GWAS), a total of 58 T2D susceptibility loci have been associated with T2D risk at a genome-wide significance level (P <5×10−8) and evidence shows that most of these genetic variants influence pancreatic β-cell function. Most novel T2D susceptibility loci were identified through GWAS in European populations and later confirmed in other ethnic groups. Although the recent discovery of novel T2D susceptibility loci has contributed substantially to our understanding of the pathophysiology of the disease, clinical utility of these loci in disease prediction and prognosis is limited. More studies using multiethnic meta-analysis, gene-environment interaction analysis, sequencing analysis, epigenetic analysis, and functional experiments are needed to identify new susceptibility T2D loci and causal variants and to establish biological mechanisms.
Europeans; Genetics; Genome-wide association studies; Type 2 diabetes
cardiovascular disease risk factors; China; diabetes mellitus type 2; diet; Editorials; nutrition
MicroRNAs (miRNAs), a class of small non-coding RNAs, are thought to serve as crucial regulators of gene expression. Dysregulated expression of miRNAs has been described in various diseases and may contribute to related pathologic processes. Our aim was to examine circulating miRNA-146a levels in newly diagnosed type 2 diabetes mellitus (new-T2DM) patients from a Chinese Han population.
Circulating miRNA-146a was extracted from plasma samples of 90 new-T2DM patients and 90 age- and sex-matched controls. Quantitative PCR assessment revealed that circulating miRNA-146a levels were significantly elevated in new-T2DM patients compared with controls. Participants in the highest tertile of circulating miRNA-146a levels showed a notably higher risk for new-T2DM (crude OR 4.333, 95% CI, 1.935 to 9.705, P = 0.001) than persons in the lowest tertile. Controlling for known risk factors and some biochemical indicators did not attenuate the aforementioned association. In addition, receiver operating characteristic (ROC) curves generated for miRNA-146a revealed an area under the curve (AUC) of 0.725 (95% CI, 0.651 to 0.799, P < 0.001). Moreover, higher circulating miRNA-146a levels were significantly associated with higher plasma heme oxygenase-1 (HO-1) concentrations (β coefficient = 0.131, P < 0.001) and lower HOMA-beta (β coefficient = -0.153, P = 0.015).
We found that circulating miRNA-146a levels were significantly elevated in new-T2DM patients compared with healthy controls. Whether expression of circulating miRNA-146a holds predictive value for T2DM warrants further investigations.
IGF-I shares structural homology and in vitro metabolic activity with insulin. Laboratory models suggest that IGF-I and its binding proteins IGFBP-1 and IGFBP-2 have potentially beneficial effects on diabetes risk, whereas IGFBP-3 may have adverse effects. We therefore conducted a prospective nested case-control investigation of incident diabetes (n = 742 case subjects matched 1:1 to control subjects) and its associations with IGF-axis protein levels in the Nurses’ Health Study, a cohort of middle-aged women. The median time to diabetes was 9 years. Statistical analyses were adjusted for multiple risk factors, including insulin and C-reactive protein. Diabetes risk was fivefold lower among women with baseline IGFBP-2 levels in the top versus bottom quintile (odds ratio [OR]q5–q1 = 0.17 [95% CI 0.08–0.35]; P trend < 0.0001) and was also negatively associated with IGFBP-1 levels (ORq5–q1 = 0.37 [0.18–0.73]; P trend = 0.0009). IGFBP-3 was positively associated with diabetes (ORq5–q1 = 2.05 [1.20–3.51]; P trend = 0.002). Diabetes was not associated with total IGF-I levels, but free IGF-I and diabetes had a significant association that varied (P interaction = 0.003) by insulin levels above the median (ORq5–q1 = 0.48 [0.26–0.90]; P trend = 0.0001) versus below the median (ORq5–q1 = 2.52 [1.05–6.06]; P trend < 0.05). Thus, this prospective study found strong associations of incident diabetes with baseline levels of three IGFBPs and free IGF-I, consistent with hypotheses that the IGF axis might influence diabetes risk.
Epidemiologic data regarding the association between ABO blood groups and risk of coronary heart disease (CHD) have been inconsistent. We sought to investigate the associations between ABO blood group and CHD risk in prospective cohort studies.
Methods and Results
Two large, prospective cohort studies (the Nurses’ Health Study [NHS] including 62,073 women and the Health Professionals Follow-up Study [HPFS] including 27, 428 men) were conducted with more than 20 years of follow-up (26 years in NHS and 24 years in HPFS). A meta-analysis was performed to summarize the associations from the present study and previous studies. In NHS, during 1,567,144 person-years of follow-up, 2,055 participants developed CHD; in HPFS, 2,015 participants developed CHD during 517,312 person-years of follow-up. ABO blood group was significantly associated with the risk of developing CHD in both women and men (log-rank test; P = 0.0048 and 0.0002 respectively). In the combined analysis adjusted for cardiovascular risk factors, compared with participants with blood group O, those with blood groups A, B or AB, were more likely to develop CHD (adjusted hazard ratios [95% CI] for incident CHD were 1.06 [ 0.99-1.15], 1.15 [ 1.04-1.26], and 1.23 [1.11-1.36]; respectively). Overall, 6.27% of the CHD cases were attributable to inheriting a non-O blood group. Meta-analysis indicated that non-O blood group had higher risk of CHD (RR= 1.11; 95% CI, 1.05 – 1.18; P = 0.001) compared with O blood group.
These data suggest that ABO blood group is significantly associated with CHD risk. Compared with other blood groups, those with the blood type O have moderately lower risk of developing CHD.
ABO; coronary heart disease; cohort study; meta-analysis
Large-scale genome-wide association studies (GWAS) have identified over 40 genomic regions significantly associated with type 2 diabetes mellitus. However, GWAS results are not always straightforward to interpret, and linking these loci to meaningful disease etiology is often difficult without extensive follow-up studies. The authors expanded on previously reported type 2 diabetes mellitus GWAS from the nested case-control studies of 2 prospective US cohorts by incorporating expression single nucleotide polymorphism (SNP) information and applying SNP set enrichment analysis to identify sets of SNPs associated with genes that could provide further biologic insight to traditional genome-wide analysis. Using data collected between 1989 and 1994 in these previous studies to form a nested case-control study, the authors found that 3 of the most significantly associated SNPs to type 2 diabetes mellitus in their study are expression SNPs to the lymphocyte antigen 75 gene (LY75), the ubiquitin-specific peptidase 36 gene (USP36), and the phosphatidylinositol transfer protein, cytoplasmic 1 gene (PITPNC1). SNP set enrichment analysis of the GWAS results identified enrichment for expression SNPs to the macrophage-enriched module and the Gene Ontology (GO) biologic process fat cell differentiation human, which includes the transcription factor 7-like 2 gene (TCF7L2), as well as other type 2 diabetes mellitus-associated genes. Integrating genome-wide association, gene expression, and gene set analysis may provide valuable biologic support for potential type 2 diabetes mellitus susceptibility loci and may be useful in identifying new targets or pathways of interest for the treatment and prevention of type 2 diabetes mellitus.
expression single nucleotide polymorphism; gene set enrichment analysis; genome-wide association study; integrative genomic analysis; single nucleotide polymorphism; type 2 diabetes
The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant (alpha-linolenic acid, ALA) sources and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95% CIs. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100g/d=1.12, 95% CI=0.94, 1.34); nor were consumption of EPA+DHA (n=16 cohorts; RR per 250mg/d=1.04, 95% CI=0.97, 1.10) or circulating levels of EPA+DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids=0.94, 95% CI=0.75, 1.17). Both dietary ALA (n=7 studies; RR per 0.5g/d=0.93, 95% CI=0.83, 1.04) and circulating ALA biomarker levels (n=6 studies; RR per 0.1% of total fatty acid=0.90, 95% CI=0.80, 1.00, P=0.06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80%) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (<55%) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-Interaction ≤ 0.02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.
Type 2 diabetes (T2D) shares some common risk factors with psoriasis. We evaluated the association between psoriasis and risk of incident T2D among women and men in the United States in a mixed retrospective-prospective cohort study. 184,395 participants were included from an older cohort of women (the Nurses’ Health Study, NHS) (1996–2008), a younger cohort of women (NHS II) (1991–2007) and an older cohort of men (Health Professionals’ Follow-Up Study, HPFS) (1986–2006). During 2,700,958 person-years of follow-up, 9,938 incident T2D cases were confirmed. We found a significantly increased risk of T2D associated with psoriasis only among younger women (NHS II); multivariate-adjusted relative risk (RR) (95% confidence interval (CI)) was 1.25 1.05–1.49). When only including those younger than 60 years during follow-up (NHS and HPFS), we observed a non-significant trend toward increased risk for T2D. In a pooled-analysis of the three cohorts, psoriatics younger than 60 years were at a higher risk of T2D; RR 1.26 (1.08–1.48) for women, and 1.26 (1.08–1.46) for both sexes combined. Further, the risk of T2D was much higher for those developing psoriasis at an early age. In conclusion, we found an association between psoriasis and risk of T2D among individuals younger than 60 years.
Type 2 diabetes; psoriasis; cohort study; incidence
Few epidemiologic studies have examined the association between an overall fatty acid (FA) profile and coronary heart disease (CHD) risk. To examine a novel index that summarizes individual FA levels based on FA affinity and fluidity in relation to CHD risk in men. In a prospective nested case-control study, FAs in plasma and erythrocytes were measured in 459 CHD cases and 879 matched controls. Lipophilic index (LI) was computed by summing the products between FA levels and melting point of each FA to reflect the overall FA lipophilicity. Among controls, higher plasma LI was significantly correlated with adverse profiles of blood lipids, inflammatory markers, and adiponectin. After multivariate adjustment for age, smoking, body mass index, and other CHD risk factors, plasma LI was significantly associated with an increased risk of CHD: the relative risk was 1.61 (95% confidence interval: 1.03, 2.53; P for trend=0.04) comparing extreme quintiles. This association was attenuated to 1.21 (0.48, 3.09; P for trend = 0.77) after adjusting for plasma levels of total trans FAs, long-chain n-3 FAs, and polyunsaturated to saturated fat ratio. Erythrocyte LI was not significantly associated with CHD risk. Our data indicate that a novel lipophilic index is associated with an adverse profile of cardiovascular risk markers and increased risk of CHD in men, its usefulness as a complement of individual fatty acids in assessing disease risk needs to be elucidated in future studies.
Fatty acids; Lipophilic Index; Lipophilicity; Coronary heart disease
Obesity induced inflammation may promote periodontal tissue destruction and bone resorption inducing tooth loss. We examined the association between measures of adiposity and self-reported periodontal disease, using data from 36,910 healthy male participants of the Health Professionals Follow-Up Study (HPFS) who were free of periodontal disease at baseline and followed for ≤ 20 years (1986–2006). Self-reported height, weight, and periodontal disease data were collected at baseline, weight and periodontal disease were additionally collected on biennial follow-up questionnaires and waist and hip circumference were self-reported in 1987. These self-reported measures have been previously validated. The multivariable adjusted associations between BMI (kg/m2), waist circumference (WC), waist-to-hip ratio (WHR), and first report of periodontal disease diagnosis were evaluated using time-varying Cox models. We observed 2,979 new periodontal disease diagnoses during 596,561 person-years of follow-up. Significant associations and trends were observed between all measures of adiposity and periodontal disease after adjusting for age, smoking, race, dental profession, physical activity, fruit and vegetable intake, alcohol consumption, and diabetes status at baseline. BMI ≥ 30 kg/m2 compared to BMI 18.5–24.9 kg/m2 was significantly associated with greater risk of periodontal disease (hazard ratios (HR) = 1.30; 95% confidence interval (CI): 1.17–1.45). Elevated WC and WHR were significantly associated with a greater risk of periodontal disease (HR for extreme quintiles: WC = 1.27, 95% CI: 1.11–1.46; WHR = 1.34, 95% CI: 1.17–1.54). The associations of BMI and WC were significant even among nondiabetics and never smokers. Given the high prevalence of overweight, obesity, and periodontal disease this association may be of substantial public health importance.
Red meat consumption has been associated with an increased risk of chronic diseases. However, its relationship with mortality remains uncertain.
We prospectively followed 37698 men from the Health Professionals Follow-up Study (1986-2008) and 83644 women from the Nurses' Health Study (1980-2008), who were free of cardiovascular disease (CVD) and cancer at baseline. Diet was assessed by validated food-frequency questionnaires and updated every four years.
We documented 23926 deaths (including 5910 CVD and 9464 cancer deaths) during 2.96 million person-years of follow-up. After multivariate adjustment for major lifestyle and dietary risk factors, the pooled hazard ratio (HR) and 95% confidence interval of total mortality was 1.13 (1.07-1.20) for 1-serving per day increase of unprocessed red meat, 1.20 (1.15-1.24) for processed red meat. The corresponding HRs were 1.18 (1.13-1.23) and 1.21 (1.13-1.31) for CVD mortality, 1.10 (1.06-1.14) and 1.16 (1.09-1.23) for cancer mortality. We estimated that substitutions of 1-serving per day of other foods (including fish, poultry, nuts, legumes, low-fat dairy, and whole grains) for 1-serving per day of red meat were associated with a 7%-19% lower mortality risk. We also estimated that 9.3% of deaths in men and 7.6% in women in our cohorts could be prevented at the end of follow-up if all individuals consumed <0.5 serving/d (≈42 g/d) of red meat.
Red meat consumption is associated with an increased risk of total, CVD and cancer mortality. Substitution of other healthy protein sources for red meat is associated with a lower mortality risk.
Type 2 diabetes is a global public health crisis that threatens the economies of all nations, particularly developing countries. Fueled by rapid urbanization, nutrition transition, and increasingly sedentary lifestyles, the epidemic has grown in parallel with the worldwide rise in obesity. Asia's large population and rapid economic development have made it an epicenter of the epidemic. Asian populations tend to develop diabetes at younger ages and lower BMI levels than Caucasians. Several factors contribute to accelerated diabetes epidemic in Asians, including the “normal-weight metabolically obese” phenotype; high prevalence of smoking and heavy alcohol use; high intake of refined carbohydrates (e.g., white rice); and dramatically decreased physical activity levels. Poor nutrition in utero and in early life combined with overnutrition in later life may also play a role in Asia's diabetes epidemic. Recent advances in genome-wide association studies have contributed substantially to our understanding of diabetes pathophysiology, but currently identified genetic loci are insufficient to explain ethnic differences in diabetes risk. Nonetheless, interactions between Westernized diet and lifestyle and genetic background may accelerate the growth of diabetes in the context of rapid nutrition transition. Epidemiologic studies and randomized clinical trials show that type 2 diabetes is largely preventable through diet and lifestyle modifications. Translating these findings into practice, however, requires fundamental changes in public policies, the food and built environments, and health systems. To curb the escalating diabetes epidemic, primary prevention through promotion of a healthy diet and lifestyle should be a global public policy priority.
Compelling biological pathways suggest that selenium (Se) may lower onset of type 2 diabetes mellitus (T2DM), but very few studies have evaluated this relationship, with mixed results. We examined the association between toenail Se and incidence of T2DM.
RESEARCH DESIGN AND METHODS
We performed prospective analyses in two separate U.S. cohorts, including 3,630 women and 3,535 men, who were free of prevalent T2DM and heart disease at baseline in 1982–1983 and 1986–1987, respectively. Toenail Se concentration was quantified using neutron activation analysis, and diabetes cases were identified by biennial questionnaires and confirmed by a detailed supplementary questionnaire. Hazard ratios of incident T2DM according to Se levels were calculated using Cox proportional hazards.
During 142,550 person-years of follow-up through 2008, 780 cases of incident T2DM occurred. After multivariable adjustment, the risk of T2DM was lower across increasing quintiles of Se, with pooled relative risks across the two cohorts of 1.0 (reference), 0.91 (95% CI 0.73–1.14), 0.78 (0.62–0.99), 0.72 (0.57–0.91), and 0.76 (0.60–0.97), respectively (P for trend = 0.01). Results were similar excluding the few individuals (4%) who used Se supplements. In semiparametric analyses, the inverse relationship between Se levels and T2DM risk appeared to be linear.
At dietary levels of intake, individuals with higher toenail Se levels are at lower risk for T2DM. Further research is required to determine whether varying results in this study versus prior trials relate to differences in dose, source, statistical power, residual confounding factors, or underlying population risk.
Background and Purpose
Despite evidence suggesting that vitamin D deficiency may lead to elevated cardiovascular disease risk, results regarding the association of 25(OH)D levels with stroke risk are inconclusive. We aimed to examine this association in a prospective study in women and to summarize all existing data in a meta-analysis.
We measured 25(OH)D levels among 464 women who developed ischemic stroke and an equal number of controls who were free of stroke through 2006 in the Nurses’ Health Study (NHS). We searched MEDLINE and EMBASE for articles published through March 2011 that prospectively evaluated 25(OH)D levels in relation to stroke.
After multivariable adjustment for lifestyle and dietary covariates, lower 25(OH)D levels were associated with an elevated risk of ischemic stroke in the NHS: the odds ratio (95% CI) comparing women in the lowest vs. highest tertiles was 1.49 (1.01, 2.18; Ptrend=0.04). We found 6 other prospective studies that examined 25(OH)D in relation to stroke outcomes. After pooling our results with these prospective studies that included 1,214 stroke cases in total, low 25(OH)D levels were associated with increased risk of developing stroke outcomes in comparison to high levels: the pooled relative risk (95% CI) was 1.52 (1.20, 1.85; I2 = 0.0%, Pheterogeneity=0.63). In two studies that explicitly examined ischemic stroke, this association was 1.59 (1.07, 2.12; I2 = 0.0%, Pheterogeneity=0.80).
These data provide evidence that low vitamin D levels are modestly associated with risk of stroke. Maintaining adequate vitamin D status may lower risk of stroke in women.
vitamin D; stroke; meta-analysis
Higher serum C-peptide concentrations have shown to be associated with an increased risk of colorectal cancer (CRC). Therefore, we used diet information to identify food groups that correlated with fasting serum concentrations of C-peptide and assess the association of this dietary pattern and CRC risk.
Major food contributors to fasting C peptide concentrations was identified with stepwise linear regression in a subsample (n=833) of women from a large cohort. We then summed the consumption frequency of the major food contributors to form a C-peptide dietary pattern for the entire cohort (n=66,714). Risk for CRC was computed using Cox proportional hazard model with the C-peptide dietary pattern score as the predictor.
In up to 20 years of follow-up, we ascertained 985 cases of CRC and 758 colon cancer. After adjusting for confounders, the C-peptide dietary pattern, characterized by higher meat, fish, and sweetened beverage intake, but lower coffee, high fat dairy, and whole grains intake, showed direct association with CRC risk (RR comparing extreme quintiles=1.29, 95% CI=1.05-1.58, p trend=0.048). The same comparison was slightly stronger for colon cancer (RR=1.35, 95% CI=1.07-1.70, p trend=0.009). In stratified analysis, there was no association between the C-peptide dietary pattern and colon cancer among lean and active women. However, for overweight or sedentary women, RR for the same comparison was 1.58 (95% CI=1.20-2.07, p trend=0.002) (p for interaction=0.007).
We derived a dietary pattern that correlated with C peptide concentrations. This pattern was associated with an increase of colon cancer, especially among women who were overweight or sedentary.
colorectal cancer; diet; C-peptide
Examine the association of prepregnancy habitual consumption of fruits and fruit juices and gestational diabetes mellitus (GDM) risk.
RESEARCH DESIGN AND METHODS
A prospective study among women with at least one singleton pregnancy in the Nurses’ Health Study II from 1991 to 2001.
Among 13,475 women, 860 reported a first diagnosis of GDM. The adjusted relative risks (RRs) for GDM from the lowest to highest quintile of whole fruit consumption were 1.00 (referent), 0.80 (95% CI 0.65–0.98), 0.90 (0.73–1.10), 0.80 (0.64–1.00), and 0.93 (0.76–1.16), respectively. The corresponding RRs for fruit juice were 1.00, 0.82 (0.66–1.01), 0.78 (0.63–0.96), 0.84 (0.68–1.04), and 1.00 (0.81–1.23).
These data suggest that prepregnancy higher consumption of whole fruits is not associated with an increased GDM risk. The association between fruit juices and GDM risk appears to be nonlinear.
Epidemiological studies have repeatedly investigated the association between depression and metabolic syndrome (MetS). However, the results have been inconsistent. This meta-analysis aimed to summarize the current evidence from cross-sectional and prospective cohort studies that evaluated this association.
RESEARCH DESIGN AND METHODS
MEDLINE, EMBASE, and PsycINFO databases were searched for articles published up to January 2012. Cross-sectional and cohort studies that reported an association between the two conditions in adults were included. Data on prevalence, incidence, unadjusted or adjusted odds ratio (OR), and 95% CI were extracted or provided by the authors. The pooled OR was calculated separately for cross-sectional and cohort studies using random-effects models. The I2 statistic was used to assess heterogeneity.
The search yielded 29 cross-sectional studies (n = 155,333): 27 studies reported unadjusted OR with a pooled estimate of 1.42 (95% CI 1.28–1.57; I2 = 55.1%); 11 studies reported adjusted OR with depression as the outcome (1.27 [1.07–1.57]; I2 = 60.9%), and 12 studies reported adjusted OR with MetS as the outcome (1.34 [1.18–1.51]; I2 = 0%). Eleven cohort studies were found (2 studies reported both directions): 9 studies (n = 26,936 with 2,316 new-onset depression case subjects) reported adjusted OR with depression as the outcome (1.49 [1.19–1.87]; I2 = 56.8%), 4 studies (n = 3,834 with 350 MetS case subjects) reported adjusted OR with MetS as the outcome (1.52 [1.20–1.91]; I2 = 0%).
Our results indicate a bidirectional association between depression and MetS. These results support early detection and management of depression among patients with MetS and vice versa.
Sugar-sweetened beverage consumption is associated with weight gain and risk of type 2 diabetes. Few studies have tested for a relationship with coronary heart disease (CHD), or intermediate biomarkers. The role of artificially sweetened beverages is also unclear.
Methods and Results
We performed an analysis of the Health Professionals Follow-up study, a prospective cohort study including 42 883 men. Associations of cumulatively averaged sugar-sweetened (e.g. sodas) and artificially sweetened (e.g. diet sodas) beverage intake with incident fatal and non-fatal CHD (myocardial infarction) were examined using proportional hazard models. There were 3683 CHD cases over 22 years of follow-up. Participants in the top quartile of sugar-sweetened beverage intake had a 20% higher relative risk of CHD than those in the bottom quartile (RR=1.20, 95% CI: 1.09, 1.33, p for trend < 0.01) after adjusting for age, smoking, physical activity, alcohol, multivitamins, family history, diet quality, energy intake, BMI, pre-enrollment weight change and dieting. Artificially sweetened beverage consumption was not significantly associated with CHD (multivariate RR=1.02, 95% CI: 0.93, 1.12, p for trend = 0.28). Adjustment for self-reported high cholesterol, high triglycerides, high blood pressure and diagnosed type 2 diabetes slightly attenuated these associations. Intake of sugar-sweetened but not artificially sweetened beverages was significantly associated with increased triglycerides, CRP, IL6, TNFr1, TNFr2, decreased HDL, Lp(a), and leptin (p values < 0.02).
Consumption of sugar-sweetened beverages was associated with increased risk of CHD and some adverse changes in lipids, inflammatory factors, and leptin. Artificially sweetened beverage intake was not associated with CHD risk or biomarkers.
nutrition; myocardial infarction; inflammation; lipids; epidemiology
Although it has been hypothesized that the depression-obesity relation is bidirectional, few studies have addressed this hypothesis in a prospective setting. We aimed to examine the bidirectional relationship in middle-aged and elderly women.
A total of 65,955 women aged 54–79 years in the Nurses’ Health Study were prospective followed from 1996 to 2006 with updated information on body weight, depression status and various covariates every two years. Depression was defined as self-report of physician-diagnosed depression and/or antidepressant use. Obesity was defined as a body mass index ≥30.0 kg/m2. The first three waves (1996–2000) were used as the baseline period, and the last three waves (2002–2006) were used as the follow-up period.
After adjusting for baseline age, physical activity, comorbidities, body mass index (BMI) and other covariates, depression at the baseline period was associated with an increased risk of obesity at the follow-up period in all women (multivariate-adjusted odds ratio [OR], 1.38; 95% CI, 1.24–1.53) and baseline non-obese women (OR, 1.51; 95% CI, 1.36–1.67). In the opposite direction, after adjusting for baseline age, physical activity, comorbidities, depression status and other covariates, obese women at baseline had a moderately increased risk of depression at the follow-up period compared with normal weight women (OR, 1.11; 95% CI, 1.03–1.18); and this association was similar for new onset of depression (OR for obese vs. normal weight women, 1.10; 95% CI, 1.02–1.20).
Our results suggest a bidirectional association between depression and obesity in middle-aged and elderly women. Future studies are needed to confirm our findings in different populations, and investigate the potential mechanisms underlying this association. Our results underscore the importance of early detection and proper behavioral modifications to lower the burden of both conditions.
obesity; depression; prospective cohort study
The results of most case-control studies have suggested a positive association between eating frequency and colorectal cancer risk. Because no prospective cohort studies have done so to date, the authors prospectively examined this association. In 1992, eating frequency was assessed in a cohort of 34,968 US men in the Health Professionals Follow-up Study. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals for various levels of eating frequency. Effect modifications by overall dietary quality (assessed using the Diet Approaches to Stop Hypertension score) and by factors that influence insulin resistance were further assessed. Between 1992 and 2006, a total of 583 cases of colorectal cancer were diagnosed. When comparing the highest eating frequency category (5–8 times/day) with the reference category (3 times/day), the authors found no evidence of an increased risk of colorectal cancer (multivariate relative risk = 0.88, 95% confidence interval: 0.62, 1.26) or colon cancer (multivariate relative risk = 0.78, 95% confidence interval: 0.49, 1.25). There was an implied inverse association with eating frequency among participants who had healthier diets (high Diet Approaches to Stop Hypertension score; P for interaction = 0.01), especially among men in the high-insulin-sensitivity group (body mass index (weight (kg)/height (m)2) <25, ≥2 cups of coffee/day, and more physical activity; P for interaction < 0.01, P for trend = 0.01). There was an implied protective association between increased eating frequency of healthy meals and colorectal cancer risk and in men with factors associated with higher insulin sensitivity.
colorectal neoplasms; diet; food; nutritional status
Circulating estrogens are an established risk factor for breast cancer and some data suggested that diet may influence estrogen levels. Therefore, using a subsample (n=550) of women from a large cohort, we applied reduced rank regression to identify a dietary pattern that is correlated with estradiol and estrone sulfate. We then adapted the pattern to be used with the full cohort (n=67,802) and prospectively assessed its association with postmenopausal breast cancer. The estrogen food pattern, characterized by higher intakes of red meat, legumes, and pizza, but lower intakes of coffee and whole grains, was modestly but significantly correlated with estradiol (r=0.14) and estrone sulfate (r=0.20). During 22 years of follow-up, we ascertained 4,596 incident breast cancer, with 2,938 estrogen receptor positive tumors and 689 estrogen receptor negative tumors. However, after adjusting for potential confounders, we did not observe any association with overall, estrogen receptor positive, or estrogen receptor negative breast cancer. In conclusion, diet pattern appeared to only have modest association with estrogens, and was not associated to postmenopausal breast cancer risk. Although these results were null, it should be repeated in other populations as differences in food intake may yield a dietary pattern with stronger association with estrogens.
diet; reduced rank regression; estrogen; breast cancer
In recent decades, temporal patterns in SSB intake have shown a close parallel between the upsurge in obesity and rising levels of SSB consumption. SSBs are beverages that contain added caloric sweeteners such as sucrose, high-fructose corn syrup or fruit-juice concentrates, all of which result in similar metabolic effects. They include the full spectrum of soft drinks, carbonated soft drinks, fruitades, fruit drinks, sports drinks, energy and vitamin water drinks, sweetened iced tea, cordial, squashes, and lemonade, which collectively are the largest contributor to added sugar intake in the US. It has long been suspected that SSBs have an etiologic role in the obesity epidemic, however only recently have large epidemiological studies been able to quantify the relationship between SSB consumption and long-term weight-gain, type 2 diabetes (T2DM) and cardiovascular disease (CVD) risk. Experimental studies have provided important insight into potential underlying biological mechanisms. It is thought that SSBs contribute to weight gain in part by incomplete compensation for energy at subsequent meals following intake of liquid calories. They may also increase risk of T2DM and CVD as a contributor to a high dietary glycemic load leading to inflammation, insulin resistance and impaired β-cell function. Additional metabolic effects from the fructose fraction of these beverages may also promote accumulation of visceral adiposity, and increased hepatic de novo lipogenesis, and hypertension due to hyperuricemia. Consumption of SSBs should therefore be replaced by healthy alternatives such as water, to reduce risk of obesity and chronic diseases.
Dyslipidemia has been associated with type 2 diabetes, but it remains unclear whether dyslipidemia plays a causal role in type 2 diabetes. We aimed to examine the association between the genetic predisposition to dyslipdemia and type 2 diabetes risk. The current study included 2,447 patients with type 2 diabetes and 3,052 control participants of European ancestry from the Nurses’ Health Study and the Health Professionals Follow-up Study. Genetic predisposition to dyslipidemia was estimated by three genotype scores of lipids (LDL cholesterol, HDL cholesterol, and triglycerides) on the basis of the established loci for blood lipids. Linear relation analysis indicated that the HDL cholesterol and triglyceride genotype scores, but not the LDL cholesterol genotype score, were linearly related to elevated type 2 diabetes risk. Each point of the HDL cholesterol and triglyceride genotype scores was associated with a 3% (odds ratio [OR] 1.03 [95% CI 1.01–1.04]) and a 2% (1.02 [1.00–1.04]) increased risk of developing type 2 diabetes, respectively. The ORs were 1.39 (1.17–1.65) and 1.19 (1.01–1.41) for type 2 diabetes by comparing extreme quartiles of the HDL cholesterol genotype score and triglyceride genotype score, respectively. In conclusion, genetic predisposition to low HDL cholesterol or high triglycerides is related to elevated type 2 diabetes risk.
Background and Purpose
Few dietary protein sources have been studied prospectively in relation to stroke. We examined the relation between foods that are major protein sources and risk of stroke.
We prospectively followed 84,010 women aged 30–55 years at baseline and 43,150 men aged 40–75 years at baseline without diagnosed cancer, diabetes, or cardiovascular disease. Diet was assessed repeatedly by a standardized and validated questionnaire. We examined the association between protein sources and incidence of stroke using a proportional hazard model adjusted for stroke risk factors.
During 26 and 22 years of follow-up in women and men, respectively, we documented 2,633 and 1,397 strokes, respectively. In multivariable analyses, higher intake of red meat was associated with an elevated risk of stroke, while a higher intake of poultry was associated with lower risk. In models estimating the effects of exchanging different protein sources, compared to one serving/day of red meat, one serving/day of poultry was associated with a 27% (95% CI: 12% to 39%) lower risk of stroke, nuts with a 17% (95% CI: 4% to 27%) lower risk, fish with a 17% (95% CI: 0% to 30%) lower risk, low-fat dairy with an 11% (95% CI: 5% to 17%) lower risk, and whole-fat dairy with a 10% (95% CI: 4% to 16%) lower risk. We did not see significant associations with exchanging legumes or eggs for red meat.
These data suggest that stroke risk may be reduced by replacing red meat with other dietary sources of protein.
men; women; diet; protein; nutrition; stroke
To investigate the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes.
RESEARCH DESIGN AND METHODS
Prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multicenter trial comparing different strategies for prevention of diabetes in patients with prediabetes. We assessed the association between plasma 25-hydroxyvitamin D, measured repeatedly during follow-up, and incident diabetes in the combined placebo (n = 1,022) and intensive lifestyle (n = 1,017) randomized arms of the DPP. Variables measured at multiple study time points (25-hydroxyvitamin D, BMI, and physical activity) entered the analyses as time-varying “lagged” covariates, as the mean of the previous and current visits at which diabetes status was assessed.
After multivariate adjustment, including for the DPP intervention, participants in the highest tertile of 25-hydroxyvitamin D (median concentration, 30.1 ng/mL) had a hazard ratio of 0.72 (95% CI 0.56–0.90) for developing diabetes compared with participants in the lowest tertile (median concentration, 12.8 ng/mL). The association was in the same direction in placebo (0.70; 0.52–0.94) versus lifestyle arm (0.80; 0.54–1.17).
Higher plasma 25-hydroxyvitamin D, assessed repeatedly, was associated with lower risk of incident diabetes in high-risk patients, after adjusting for lifestyle interventions (dietary changes, increased physical activity, and weight loss) known to decrease diabetes risk. Because of the observational nature of the study, the potential association between vitamin D and diabetes needs to be confirmed in intervention studies.