Person: Mukamal, Kenneth
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Publication Alcohol Consumption, Mediating Biomarkers, and Risk of Type 2 Diabetes Among Middle-Aged Women
(American Diabetes Association, 2008) Beulens, Joline W.J.; Rimm, Eric; Hu, Frank; Hendriks, Henk F.J.; Mukamal, KennethOBJECTIVE—The purpose of this study was to investigate whether adiponectin concentrations and biomarkers of inflammation, endothelial dysfunction, and insulin resistance mediate the association between alcohol consumption and diabetes. RESEARCH DESIGN AND METHODS—In a nested case-control study of 705 women with incident diabetes and 787 matched control subjects, we examined the adjusted relationship between baseline alcohol consumption and risk of diabetes before and after adjustment for markers of inflammation/endothelial dysfunction (C-reactive protein, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, tumor necrosis factor-α receptor 2, and interleukin-6), fasting insulin, and adiponectin concentrations. RESULTS—Alcohol consumption was associated with a decreased risk of diabetes (odds ratio per 12.5 g/day increment in alcohol use 0.58; 95% CI 0.49–0.69; P < 0.001). Adjustment for BMI attenuated the association by 25%. None of the markers of inflammation or fasting insulin appeared to account for >2% of the observed relationship. Without adjustment for BMI, these biomarkers individually explained slightly more of the association, but <10% in all cases. Adiponectin accounted for 25% in a fully adjusted model and for 29% without adjustment for BMI. CONCLUSIONS—In this population of women, alcohol consumption was inversely associated with risk of type 2 diabetes. Adiponectin appeared to be a mediator of this association, but circulating biomarkers of inflammation, endothelial dysfunction, and fasting insulin did not explain this association. These results suggest that further research is needed into the potentially mediating roles of other biomarkers affected by alcohol consumption.
Publication Changes in Alcohol Consumption and Subsequent Risk of Type 2 Diabetes in Men
(American Diabetes Association, 2011) Joosten, Michel M.; Chiuve, Stephanie; Mukamal, Kenneth; Hu, Frank; Hendriks, Henk F. J.; Rimm, EricOBJECTIVE: The objective of this study was to investigate the association of 4-year changes in alcohol consumption with a subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We prospectively examined 38,031 men from the Health Professionals Follow-Up Study who were free of diagnosed diabetes or cancer in 1990. Alcohol consumption was reported on food frequency questionnaires and updated every 4 years. RESULTS: A total of 1,905 cases of type 2 diabetes occurred during 428,497 person-years of follow-up. A 7.5 g/day (approximately half a glass) increase in alcohol consumption over 4 years was associated with lower diabetes risk among initial nondrinkers (multivariable hazard ratio [HR] 0.78; 95% CI: 0.60–1.00) and drinkers initially consuming <15 g/day (HR 0.89; 95% CI: 0.83–0.96), but not among men initially drinking ≥15 g/day (HR 0.99; 95% CI: 0.95–1.02; Pinteraction < 0.01). A similar pattern was observed for levels of total adiponectin and hemoglobin A1c, with a better metabolic profile among abstainers and light drinkers who modestly increased their alcohol intake, compared with men who either drank less or among men who were already moderate drinkers and increased their intake. Likewise, compared with stable light drinkers (0–4.9 g/day), light drinkers who increased their intake to moderate levels (5.0–29.9 g/day) had a significantly lower risk of type 2 diabetes (HR 0.75; 95% CI: 0.62–0.90). CONCLUSIONS: Increases in alcohol consumption over time were associated with lower risk of type 2 diabetes among initially rare and light drinkers. This lower risk was evident within a 4-year period following increased alcohol intake.
Publication Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry
(Oxford University Press, 2015) Nettleton, Jennifer A.; Follis, Jack L.; Ngwa, Julius S.; Smith, Caren E.; Ahmad, Shafqat; Tanaka, Toshiko; Wojczynski, Mary K.; Voortman, Trudy; Lemaitre, Rozenn N.; Kristiansson, Kati; Nuotio, Marja-Liisa; Houston, Denise K.; Perälä, Mia-Maria; Qi, Qibin; Sonestedt, Emily; Manichaikul, Ani; Kanoni, Stavroula; Ganna, Andrea; Mikkilä, Vera; North, Kari E.; Siscovick, David S.; Harald, Kennet; Mckeown, Nicola M.; Johansson, Ingegerd; Rissanen, Harri; Liu, Yongmei; Lahti, Jari; Hu, Frank; Bandinelli, Stefania; Rukh, Gull; Rich, Stephen; Booij, Lisanne; Dmitriou, Maria; Ax, Erika; Raitakari, Olli; Mukamal, Kenneth; Männistö, Satu; Hallmans, Göran; Jula, Antti; Ericson, Ulrika; Jacobs,, David R.; Van Rooij, Frank J. A.; Deloukas, Panos; Sjögren, Per; Kähönen, Mika; Djousse, Luc; Perola, Markus; Barroso, Inês; Hofman, Albert; Stirrups, Kathleen; Viikari, Jorma; Uitterlinden, André G.; Kalafati, Ioanna P.; Franco, Oscar H.; Mozaffarian, Dariush; Salomaa, Veikko; Borecki, Ingrid B.; Knekt, Paul; Kritchevsky, Stephen B.; Eriksson, Johan G.; Dedoussis, George V.; Qi, Lu; Ferrucci, Luigi; Orho-Melander, Marju; Zillikens, M. Carola; Ingelsson, Erik; Lehtimäki, Terho; Renström, Frida; Cupples, L. Adrienne; Loos, Ruth J. F.; Franks, PaulObesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist–hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006–0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.
Publication Dietary fiber intake and mortality among survivors of myocardial infarction: prospective cohort study
(BMJ Publishing Group Ltd., 2014) Li, Shanshan; Flint, Alan; Pai, Jennifer K; Forman, John; Hu, Frank; Willett, Walter; Rexrode, Kathryn; Mukamal, Kenneth; Rimm, EricObjective: To evaluate the associations of dietary fiber after myocardial infarction (MI) and changes in dietary fiber intake from before to after MI with all cause and cardiovascular mortality. Design: Prospective cohort study. Setting: Two large prospective cohort studies of US women and men with repeated dietary measurements: the Nurses’ Health Study and the Health Professionals Follow-Up Study. Participants: 2258 women and 1840 men who were free of cardiovascular disease, stroke, or cancer at enrollment, survived a first MI during follow-up, were free of stroke at the time of initial onset of MI, and provided food frequency questionnaires pre-MI and at least one post-MI. Main outcome measures Associations of dietary fiber post-MI and changes from before to after MI with all cause and cardiovascular mortality using Cox proportional hazards models, adjusting for drug use, medical history, and lifestyle factors. Results: Higher post-MI fiber intake was significantly associated with lower all cause mortality (comparing extreme fifths, pooled hazard ratio 0.75, 95% confidence interval 0.58 to 0.97). Greater intake of cereal fiber was more strongly associated with all cause mortality (pooled hazard ratio 0.73, 0.58 to 0.91) than were other sources of dietary fiber. Increased fiber intake from before to after MI was significantly associated with lower all cause mortality (pooled hazard ratio 0.69, 0.55 to 0.87). Conclusions: In this prospective study of patients who survived MI, a greater intake of dietary fiber after MI, especially cereal fiber, was inversely associated with all cause mortality. In addition, increasing consumption of fiber from before to after MI was significantly associated with lower all cause and cardiovascular mortality.
Publication Low Carbohydrate Diet From Plant or Animal Sources and Mortality Among Myocardial Infarction Survivors
(Blackwell Publishing Ltd, 2014) Li, Shanshan; Flint, Alan; Pai, Jennifer K.; Forman, John; Hu, Frank; Willett, Walter; Rexrode, Kathryn; Mukamal, Kenneth; Rimm, EricBackground: The healthiest dietary pattern for myocardial infarction (MI) survivors is not known. Specific long‐term benefits of a low‐carbohydrate diet (LCD) are unknown, whether from animal or vegetable sources. There is a need to examine the associations between post‐MI adherence to an LCD and all‐cause and cardiovascular mortality. Methods and Results: We included 2258 women from the Nurses' Health Study and 1840 men from the Health Professional Follow‐Up Study who had survived a first MI during follow‐up and provided a pre‐MI and at least 1 post‐MI food frequency questionnaire. Adherence to an LCD high in animal sources of protein and fat was associated with higher all‐cause and cardiovascular mortality (hazard ratios of 1.33 [95% CI: 1.06 to 1.65] for all‐cause mortality and 1.51 [95% CI: 1.09 to 2.07] for cardiovascular mortality comparing extreme quintiles). An increase in adherence to an animal‐based LCD prospectively assessed from the pre‐ to post‐MI period was associated with higher all‐cause mortality and cardiovascular mortality (hazard ratios of 1.30 [95% CI: 1.03 to 1.65] for all‐cause mortality and 1.53 [95% CI: 1.10 to 2.13] for cardiovascular mortality comparing extreme quintiles). An increase in adherence to a plant‐based LCD was not associated with lower all‐cause or cardiovascular mortality. Conclusions: Greater adherence to an LCD high in animal sources of fat and protein was associated with higher all‐cause and cardiovascular mortality post‐MI. We did not find a health benefit from greater adherence to an LCD overall after MI.
Publication Dietary flavonoid intake and weight maintenance: three prospective cohorts of 124 086 US men and women followed for up to 24 years
(BMJ Publishing Group Ltd., 2016) Bertoia, Monica; Rimm, Eric; Mukamal, Kenneth; Hu, Frank; Willett, Walter; Cassidy, AedínObjective: To examine whether dietary intake of specific flavonoid subclasses (including flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, and flavonoid polymers) is associated with weight change over time. Design: Three prospective cohort studies. Setting: Health professionals in the United States. Participants: 124 086 men and women participating in the Health Professionals Follow-up Study (HPFS), Nurses’ Health Study (NHS), and Nurses’ Health Study II (NHS II). Main outcome measure Self reported change in weight over multiple four year time intervals between 1986 and 2011. Results: Increased consumption of most flavonoid subclasses, including flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers, was inversely associated with weight change over four year time intervals, after adjustment for simultaneous changes in other lifestyle factors including other aspects of diet, smoking status, and physical activity. In the pooled results, the greatest magnitude of association was observed for anthocyanins (−0.23 (95% confidence interval −0.30 to −0.15) lbs per additional standard deviation/day, 10 mg), flavonoid polymers (−0.18 (−0.28 to −0.08) lbs per additional SD/day, 138 mg), and flavonols (−0.16 (−0.26 to −0.06) lbs per additional SD/day, 7 mg). After additional adjustment for fiber intake, associations remained significant for anthocyanins, proanthocyanidins, and total flavonoid polymers but were attenuated and no longer statistically significant for other subclasses. Conclusions: Higher intake of foods rich in flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers may contribute to weight maintenance in adulthood and may help to refine dietary recommendations for the prevention of obesity and its potential consequences.
Publication Changes in Intake of Fruits and Vegetables and Weight Change in US Men and Women Followed for up to 24 Years: Analysis from Three Prospective Cohort Studies
(Public Library of Science, 2015) Bertoia, Monica; Mukamal, Kenneth; Cahill, Leah; Hou, Tao; Ludwig, David; Mozaffarian, Dariush; Willett, Walter; Hu, Frank; Rimm, EricBackground
Current dietary guidelines recommend eating a variety of fruits and vegetables. However, based on nutrient composition, some particular fruits and vegetables may be more or less beneficial for maintaining or achieving a healthy weight. We hypothesized that greater consumption of fruits and vegetables with a higher fiber content or lower glycemic load would be more strongly associated with a healthy weight.
Methods and Findings
We examined the association between change in intake of specific fruits and vegetables and change in weight in three large, prospective cohorts of 133,468 United States men and women. From 1986 to 2010, these associations were examined within multiple 4-y time intervals, adjusting for simultaneous changes in other lifestyle factors, including other aspects of diet, smoking status, and physical activity. Results were combined using a random effects meta-analysis. Increased intake of fruits was inversely associated with 4-y weight change: total fruits -0.53 lb per daily serving (95% CI -0.61, -0.44), berries -1.11 lb (95% CI -1.45, -0.78), and apples/pears -1.24 lb (95% CI -1.62, -0.86). Increased intake of several vegetables was also inversely associated with weight change: total vegetables -0.25 lb per daily serving (95% CI -0.35, -0.14), tofu/soy -2.47 lb (95% CI, -3.09 to -1.85 lb) and cauliflower -1.37 lb (95% CI -2.27, -0.47). On the other hand, increased intake of starchy vegetables, including corn, peas, and potatoes, was associated with weight gain. Vegetables having both higher fiber and lower glycemic load were more strongly inversely associated with weight change compared with lower-fiber, higher-glycemic-load vegetables (p < 0.0001). Despite the measurement of key confounders in our analyses, the potential for residual confounding cannot be ruled out, and although our food frequency questionnaire specified portion size, the assessment of diet using any method will have measurement error.
Conclusions
Increased consumption of fruits and non-starchy vegetables is inversely associated with weight change, with important differences by type suggesting that other characteristics of these foods influence the magnitude of their association with weight change.