Methyl Donor Nutrient Intake and Incidence of Type 2 Diabetes: Results From Three Large U.S. Cohorts.

OBJECTIVE: We examined whether intake of methyl donor nutrients, including vitamins B2, B6, and B12 and folate, from foods and/or supplements is associated with type 2 diabetes risk. RESEARCH DESIGN AND METHODS: We included 203,644 women and men from the Nurses' Health Study (1984-2016), Nurses' Health Study 2 (1991-2017), and Health Professionals Follow-Up Study (1986-2016). Dietary data were collected every 2-4 years with use of semiquantitative food-frequency questionnaires. Cox proportional hazards models with time-varying covariates were used to evaluate associations between each nutrient and type 2 diabetes risk. We combined cohort-specific hazard ratios (HRs) using inverse variance-weighted fixed-effects meta-analyses. RESULTS: During 4,900,181 person-years of follow-up, we documented 19,475 incident type 2 diabetes cases. In multivariable-adjusted meta-analyses, participants in the highest quintiles of total vitamin B2 and B6 intakes had lower risk of diabetes compared with those in the lowest quintiles (HR 0.93 [95% CI 0.89, 0.98] for B2 and 0.93 [0.89, 0.97] for B6). With stratification by source, significant associations remained for B2 from food but not from supplements. Neither association for B6 from food nor association for B6 from supplements attained significance. No association was observed between total B12 intake and diabetes. However, B12 from food was marginally associated with higher diabetes risk (1.05 [1.00-1.11]) but not after additional adjustment for red meat intake (1.04 [0.99-1.10]). No evidence of association was observed between intakes of folate and diabetes. CONCLUSIONS: The results of our study suggest that higher intake of vitamin B2 and B6, especially B2 from food sources, may be associated with a modestly lower type 2 diabetes risk.

Habitual coffee consumption and subsequent risk of type 2 diabetes in individuals with a history of gestational diabetes - a prospective study.

BACKGROUND: Females with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes mellitus (T2D) later in life. OBJECTIVE: This study prospectively examined whether greater habitual coffee consumption was related to a lower risk of T2D among females with a history of GDM. METHODS: We followed 4522 participants with a history of GDM in the NHS II for incident T2D between 1991 and 2017. Demographic, lifestyle factors including diet, and disease outcomes were updated every 2-4 y. Participants reported consumption of caffeinated and decaffeinated coffee on validated FFQs. Fasting blood samples were collected in 2012-2014 from a subset of participants free of diabetes to measure glucose metabolism biomarkers (HbA1c, insulin, C-peptide; n = 518). We used multivariable Cox regression models to calculate adjusted HRs and 95% CIs for the risk of T2D. We estimated the least squares mean of glucose metabolic biomarkers according to coffee consumption. RESULTS: A total of 979 participants developed T2D. Caffeinated coffee consumption was inversely associated with the risk of T2D. Adjusted HR (95% CI) for ≤1 (nonzero), 2-3, and 4+ cups/d compared with 0 cup/d (reference) was 0.91 (0.78, 1.06), 0.83 (0.69, 1.01), and 0.46 (0.28, 0.76), respectively (P-trend = 0.004). Replacement of 1 serving/d of sugar-sweetened beverage and artificially sweetened beverage with 1 cup/d of caffeinated coffee was associated with a 17% (risk ratio [RR] = 0.83, 95% CI: 0.75, 0.93) and 9% (RR = 0.91, 95% CI: 0.84, 0.99) lower risk of T2D, respectively. Greater caffeinated coffee consumption was associated with lower fasting insulin and C-peptide concentrations (all P-trend <0.05). Decaffeinated coffee intake was not significantly related to T2D but was inversely associated with C-peptide concentrations (P-trend = 0.003). CONCLUSIONS: Among predominantly Caucasian females with a history of GDM, greater consumption of caffeinated coffee was associated with a lower risk of T2D and a more favorable metabolic profile.

Associations between predicted vitamin D status, vitamin D intake, and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity.

BACKGROUND: Vitamin D may have a role in immune responses to viral infections. However, data on the association between vitamin D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity have been limited and inconsistent. OBJECTIVE: We examined the associations of predicted vitamin D status and intake with risk of SARS-CoV-2 infection and COVID-19 severity. METHODS: We used data from periodic surveys (May 2020 to March 2021) within the Nurses' Health Study II. Among 39,315 participants, 1768 reported a positive test for SARS-CoV-2 infection. Usual vitamin D intake from foods and supplements were measured using a semiquantitative, pre-pandemic food-frequency questionnaire in 2015. Predicted 25-hydroxyvitamin D [25(OH)D] concentration were calculated based on a previously validated model including dietary and supplementary vitamin D intake, UV-B, and other behavioral predictors of vitamin D status. RESULTS: Higher predicted 25(OH)D concentrations, but not vitamin D intake, were associated with a lower risk of SARS-CoV-2 infection. Comparing participants in the highest quintile of predicted 25(OH)D concentrations with the lowest, the multivariable-adjusted OR was 0.76 (95% CI: 0.58, 0.99; P-trend = 0.04). Participants in the highest quartile of UV-B (OR: 0.76; 95% CI: 0.66, 0.87; P-trend = 0.002) and UV-A (OR: 0.76; 95% CI: 0.66, 0.88; P-trend < 0.001) also had a lower risk of SARS-CoV-2 infection compared with the lowest. High intake of vitamin D from supplements (≥400 IU/d) was associated with a lower risk of hospitalization (OR: 0.51; 95% CI: 0.29, 0.91; P-trend = 0.04). CONCLUSIONS: Our study provides suggestive evidence on the association between higher predicted circulating 25(OH)D concentrations and a lower risk of SARS-CoV-2 infection. Greater intake of vitamin D supplements was associated with a lower risk of hospitalization. Our data also support an association between exposure to UV-B or UV-A, independently of vitamin D and SARS-CoV-2 infection, so results for predicted 25(OH)D need to be interpreted cautiously.

Magnesium Intake, Quality of Carbohydrates, and Risk of Type 2 Diabetes: Results From Three U.S. Cohorts.

OBJECTIVE: Magnesium intake is inversely associated with risk of type 2 diabetes in many observational studies, but few have assessed this association in the context of the carbohydrate quality of the diet. We hypothesized that higher magnesium intake is associated with lower risk of type 2 diabetes, especially in the context of a poor carbohydrate-quality diet characterized by low cereal fiber or high glycemic index (GI) or glycemic load (GL). RESEARCH DESIGN AND METHODS: In the Nurses' Health Study (NHS; 1984-2012, n = 69,176), NHS2 (1991-2013, n = 91,471), and the Health Professionals' Follow-Up Study (1986-2012, n = 42,096), dietary intake was assessed from food frequency questionnaires every 4 years. Type 2 diabetes was ascertained by biennial and supplementary questionnaires. We calculated multivariate hazard ratios (HRs) of magnesium intake and incident diabetes, adjusted for age, BMI, family history of diabetes, physical activity, smoking, hypertension, hypercholesterolemia, GL, energy intake, alcohol, cereal fiber, polyunsaturated fats, trans fatty acids, and processed meat, and we considered the joint associations of magnesium and carbohydrate quality on diabetes risk. RESULTS: We documented 17,130 incident cases of type 2 diabetes over 28 years of follow-up. In pooled analyses across the three cohorts, those with the highest magnesium intake had 15% lower risk of type 2 diabetes compared with those with the lowest intake (pooled multivariate HR in quintile 5 vs. 1: 0.85 [95% CI 0.80-0.91], P < 0.0001). Higher magnesium intake was more strongly associated with lower risk of type 2 diabetes among participants with high GI or low cereal fiber than among those with low GI or high cereal fiber (both P interaction <0.001). CONCLUSIONS: Higher magnesium intake is associated with lower risk of type 2 diabetes, especially in the context of lower carbohydrate-quality diets.

Association of Coffee Consumption With Total and Cause-Specific Mortality in 3 Large Prospective Cohorts.

BACKGROUND: The association between consumption of caffeinated and decaffeinated coffee and risk of mortality remains inconclusive. METHODS AND RESULTS: We examined the associations of consumption of total, caffeinated, and decaffeinated coffee with risk of subsequent total and cause-specific mortality among 74,890 women in the Nurses' Health Study (NHS), 93,054 women in the Nurses' Health Study II, and 40,557 men in the Health Professionals Follow-up Study. Coffee consumption was assessed at baseline using a semiquantitative food frequency questionnaire. During 4,690,072 person-years of follow-up, 19,524 women and 12,432 men died. Consumption of total, caffeinated, and decaffeinated coffee were nonlinearly associated with mortality. Compared with nondrinkers, coffee consumption of 1 to 5 cups per day was associated with lower risk of mortality, whereas coffee consumption of more than 5 cups per day was not associated with risk of mortality. However, when restricting to never smokers compared with nondrinkers, the hazard ratios (and 95% confidence intervals) of mortality were 0.94 (0.89-0.99) for 1.0 or less cup per day, 0.92 (0.87-0.97) for 1.1 to 3.0 cups per day, 0.85 (0.79-0.92) for 3.1 to 5.0 cup per day, and 0.88 (0.78-0.99) for more than 5.0 cup per day (P value for nonlinearity = 0.32; P value for trend < 0.001). Significant inverse associations were observed for caffeinated (P value for trend < 0.001) and decaffeinated coffee (P value for trend = 0.022). Significant inverse associations were observed between coffee consumption and deaths attributed to cardiovascular disease, neurologic diseases, and suicide. No significant association between coffee consumption and total cancer mortality was found. CONCLUSIONS: Higher consumption of total coffee, caffeinated coffee, and decaffeinated coffee was associated with lower risk of total mortality.

Carbohydrate quality and quantity and risk of type 2 diabetes in US women.

BACKGROUND: Carbohydrate quality may be an important determinant of type 2 diabetes (T2D); however, relations between various carbohydrate quality metrics and T2D risk have not been systematically investigated. OBJECTIVE: The purpose of this study was to prospectively examine the association between carbohydrates, starch, fibers, and different combinations of these nutrients and risk of T2D in women. DESIGN: We prospectively followed 70,025 women free of cardiovascular disease, cancer, and diabetes at baseline from the Nurses' Health Study (1984-2008). Diet information was collected with the use of a validated questionnaire every 4 y. Cox regression was used to evaluate associations with incident T2D. RESULTS: During 1,484,213 person-years of follow-up, we ascertained 6934 incident T2D cases. In multivariable analyses, when extreme quintiles were compared, higher carbohydrate intake was not associated with T2D (RR = 0.98; 95% CI: 0.89, 1.08; P-trend = 0.84), whereas starch was associated with a higher risk (RR = 1.23; 95% CI: 1.12, 1.35; P-trend <0.0001). Total fiber (RR = 0.80; 95% CI: 0.72, 0.89; P-trend < 0.0001), cereal fiber (RR = 0.71, 95% CI: 0.65, 0.78; P-trend < 0.0001), and fruit fiber (RR = 0.79; 95% CI: 0.72, 0.85; P-trend < 0.0001) were associated with a lower T2D risk. The ratio of carbohydrate to total fiber intake was marginally associated with a higher risk of T2D (RR = 1.09; 95% CI: 1.00, 1.20; P-trend = 0.04). On the other hand, we found positive associations between the ratios of carbohydrate to cereal fiber (RR = 1.28; 95% CI: 1.17, 1.39; P-trend < 0.0001), starch to total fiber (RR = 1.12; 95% CI: 1.02, 1.23; P-trend = 0.03), and starch to cereal fiber (RR = 1.39; 95% CI: 1.27, 1.53; P-trend < 0.0001) and T2D. CONCLUSIONS: Diets with high starch, low fiber, and a high starch-to-cereal fiber ratio were associated with a higher risk of T2D. The starch-to-cereal fiber ratio of the diet may be a novel metric for assessing carbohydrate quality in relation to T2D.

Changes in coffee intake and subsequent risk of type 2 diabetes: three large cohorts of US men and women.

AIMS/HYPOTHESIS: Coffee and tea consumption has been associated with a lower type 2 diabetes risk but little is known about how changes in coffee and tea consumption influence subsequent type 2 diabetes risk. We examined the associations between 4 year changes in coffee and tea consumption and risk of type 2 diabetes in the subsequent 4 years. METHODS: We prospectively followed 48,464 women in the Nurses' Health Study (NHS; 1986-2006), 47,510 women in NHS II (1991-2007) and 27,759 men in the Health Professionals Follow-up Study (HPFS; 1986-2006). Diet was assessed every 4 years using a validated food-frequency questionnaire. Self-reported cases of incident type 2 diabetes were validated by supplementary questionnaires. RESULTS: During 1,663,319 person-years of follow-up, we documented 7,269 cases of incident type 2 diabetes. Participants who increased their coffee consumption by more than 1 cup/day (median change = 1.69 cups/day) over a 4 year period had an 11% (95% CI 3%, 18%) lower risk of type 2 diabetes in the subsequent 4 years compared with those who made no changes in consumption. Participants who decreased their coffee intake by more than 1 cup/day (median change = -2 cups/day) had a 17% (95% CI 8%, 26%) higher risk for type 2 diabetes. Changes in tea consumption were not associated with type 2 diabetes risk. CONCLUSIONS/INTERPRETATION: Our data provide novel evidence that increasing coffee consumption over a 4 year period is associated with a lower risk of type 2 diabetes, while decreasing coffee consumption is associated with a higher risk of type 2 diabetes in subsequent years.

Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis.

OBJECTIVE: Previous meta-analyses identified an inverse association of coffee consumption with the risk of type 2 diabetes. However, an updated meta-analysis is needed because new studies comparing the trends of association for caffeinated and decaffeinated coffee have since been published. RESEARCH DESIGN AND METHODS: PubMed and Embase were searched for cohort or nested case-control studies that assessed the relationship of coffee consumption and risk of type 2 diabetes from 1966 to February 2013. A restricted cubic spline random-effects model was used. RESULTS: Twenty-eight prospective studies were included in the analysis, with 1,109,272 study participants and 45,335 cases of type 2 diabetes. The follow-up duration ranged from 10 months to 20 years. Compared with no or rare coffee consumption, the relative risk (RR; 95% CI) for diabetes was 0.92 (0.90-0.94), 0.85 (0.82-0.88), 0.79 (0.75-0.83), 0.75 (0.71-0.80), 0.71 (0.65-0.76), and 0.67 (0.61-0.74) for 1-6 cups/day, respectively. The RR of diabetes for a 1 cup/day increase was 0.91 (0.89-0.94) for caffeinated coffee consumption and 0.94 (0.91-0.98) for decaffeinated coffee consumption (P for difference = 0.17). CONCLUSIONS: Coffee consumption was inversely associated with the risk of type 2 diabetes in a dose-response manner. Both caffeinated and decaffeinated coffee was associated with reduced diabetes risk.

Long-term coffee consumption and risk of cardiovascular disease: a systematic review and a dose-response meta-analysis of prospective cohort studies.

BACKGROUND: Considerable controversy exists on the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. METHODS AND RESULTS: PubMed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1 279 804 participants and 36 352 CVD cases. A nonlinear relationship of coffee consumption with CVD risk was identified (P for heterogeneity=0.09, P for trend <0.001, P for nonlinearity <0.001). Compared with the lowest category of coffee consumption (median, 0 cups per day), the relative risk of CVD was 0.95 (95% confidence interval, 0.87-1.03) for the highest category (median, 5 cups per day) category, 0.85 (95% confidence interval, 0.80-0.90) for the second highest category (median, 3.5 cups per day), and 0.89 (95% confidence interval, 0.84-0.94) for the third highest category (median, 1.5 cups per day). Looking at separate outcomes, coffee consumption was nonlinearly associated with both coronary heart disease (P for heterogeneity=0.001, P for trend <0.001, P for nonlinearity <0.001) and stroke (P for heterogeneity=0.07, P for trend <0.001, P for nonlinearity <0.001; P for trend differences >0.05) risks. CONCLUSIONS: A nonlinear association between coffee consumption and CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with elevated CVD risk.

Caffeinated and caffeine-free beverages and risk of type 2 diabetes.

BACKGROUND: Consumption of caffeinated beverages such as coffee and tea has been associated with a lower risk of type 2 diabetes (T2D). Paradoxically, short-term metabolic studies have shown that caffeine impairs postprandial glycemic control. OBJECTIVE: The objective was to prospectively examine the association of caffeinated compared with caffeine-free beverages, including coffee, tea, sugar-sweetened beverages (SSBs), and carbonated artificially sweetened beverages (ASBs), with T2D risk. DESIGN: We prospectively observed 74,749 women from the Nurses' Health Study (NHS, 1984-2008) and 39,059 men from the Health Professionals Follow-Up Study (HPFS, 1986-2008) who were free of diabetes, cardiovascular diseases, and cancer at baseline. RESULTS: We documented 7370 incident cases of T2D during 24 y of follow-up in the NHS and 2865 new cases during 22 y of follow-up in the HPFS. After major lifestyle and dietary risk factors were controlled for, caffeinated and caffeine-free SSB intake was significantly associated with a higher risk of T2D in the NHS (RR per serving: 13% for caffeinated SSBs, 11% for caffeine-free SSBs; P < 0.05) and in the HPFS (RR per serving: 16% for caffeinated SSBs, 23% for caffeine-free SSBs; P < 0.01). Only caffeine-free ASB intake in NHS participants was associated with a higher risk of T2D (RR: 6% per serving; P < 0.001). Conversely, the consumption of caffeinated and decaffeinated coffee was associated with a lower risk of T2D [RR per serving: 8% for both caffeinated and decaffeinated coffee in the NHS (P < 0.0001) and 4% for caffeinated and 7% for decaffeinated coffee in the HPFS (P < 0.01)]. Only caffeinated tea was associated with a lower T2D risk among NHS participants (RR per serving: 5%; P < 0.0001). CONCLUSION: Irrespective of the caffeine content, SSB intake was associated with a higher risk of T2D, and coffee intake was associated with a lower risk of T2D.

Coronary heart disease prevention: nutrients, foods, and dietary patterns.

Diet is a key modifiable risk factor in the prevention and risk reduction of coronary heart disease (CHD). Results from the Seven Countries Study in the early 1970s spurred an interest in the role of single nutrients such as total fat in CHD risk. With accumulating evidence, we have moved away from a focus on total fat to the importance of considering the quality of fat. Recent meta-analyses of intervention studies confirm the beneficial effects of replacing saturated fat with polyunsaturated fatty acids on CHD risk. Scientific evidence for a detrimental role of trans fat intake from industrial sources on CHD risk has led to important policy changes including listing trans fatty acid content on the "Nutrition Facts" panel and banning the use of trans fatty acids in food service establishments in some cities. The effects of such policy changes on changes in CHD incidence are yet to be evaluated. There has been a surging interest in the protective effects of vitamin D in primary prevention. Yet, its associations with secondary events have been mixed and intervention studies are needed to clarify its role in CHD prevention. Epidemiological and clinical trial evidence surrounding the benefit of B vitamins and antioxidants such as carotenoids, vitamin E, and vitamin C, have been contradictory. While pharmacological supplementation of these vitamins in populations with existing CHD has been ineffective and, in some cases, even detrimental, data repeatedly show that consumption of a healthy dietary pattern has considerable cardioprotective effects for primary prevention. Results from these studies and the general ineffectiveness of nutrient-based interventions have shifted interest to the role of foods in CHD risk reduction. The strongest and most consistent protective associations are seen with fruit and vegetables, fish, and whole grains. Epidemiological and clinical trial data also show risk reduction with moderate alcohol consumption. In the past decade, there has been a paradigm shift in nutritional epidemiology to examine associations between dietary patterns and health. Several epidemiological studies show that people following the Mediterranean style diet or the Dietary Approaches to Stop Hypertension (DASH) diet have lower risk of CHD and lower likelihood of developing hypertension. Studies using empirical or data driven dietary patterns have frequently identified two patterns - "Healthy or Prudent" and "Western". In general, the "Healthy", compared to the "Western" pattern has been associated with more favorable biological profiles, slower progression of atherosclerosis, and reduced incidence. Evidence on changes in dietary patterns and changes in CHD risk is still emerging. With the emergence of the concept of personalized nutrition, studies are increasingly considering the role of genetic factors in the modulation of the association between nutrients and CHD. More studies of genetic variation and dietary patterns in relation to CHD are needed.

Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults.

BACKGROUND: Puerto Rican adults have prevalent metabolic abnormalities, but few studies have explored fruit and vegetable (FV) intake and coronary heart disease (CHD) risk in this population. OBJECTIVE: We tested the hypothesis that greater FV intake and variety are associated with a lower 10-y risk of CHD and C-reactive protein (CRP) concentrations. DESIGN: In a cross-sectional study of ≈1200 Puerto Rican adults aged 45-75 y, we assessed FV intake with a food-frequency questionnaire. The 10-y risk of CHD was assessed with the Framingham risk score (FRS) in participants free of cardiovascular disease. CRP was measured in fasting serum. RESULTS: Variety, but not quantity, of FV intake was inversely associated with FRS after adjustment for the following: sex; waist circumference; perceived stress; alcohol use; intakes of energy, trans fatty acids, and saturated fatty acids; and use of supplements, cardiovascular medications, and diabetes medications (P = 0.02). However, the association was attenuated after adjustment for income (P = 0.11). Variety, but not quantity, was associated with a lower serum CRP concentration after adjustment for age, sex, smoking status, alcohol use, servings of FV, white blood cell count, diastolic blood pressure, diabetes, nonsteroidal antiinflammatory medication use, intakes of energy and vitamin B-6, waist circumference, perceived stress, and income. The adjusted odds of a high CRP concentration for those in the highest compared with the lowest tertile of FV variety was 0.68 (95% CI: 0.49, 0.94). CONCLUSIONS: FV variety, but not quantity, appears to be important in reducing inflammation. Although the results are suggestive, larger studies are needed to confirm a possible association with CHD risk score.