Publications by authors named "Geng Zong"

57 Publications

Plasma glycerophospholipid profile, erythrocyte n-3 PUFAs, and metabolic syndrome incidence: a prospective study in Chinese men and women.

Am J Clin Nutr 2021 Apr 7. Epub 2021 Apr 7.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Background: Animal studies have highlighted critical roles of glycerophospholipid (GP) metabolism in various metabolic syndrome (MetS)-related features such as dyslipidemia, obesity, and insulin resistance. However, human prospective studies of associations between circulating GPs and risks of MetS are scarce.

Objectives: We aimed to investigate whether GPs are associated with incidence of MetS in a well-established cohort.

Methods: A total of 1243 community-dwelling Chinese aged 50-70 y without MetS at baseline and followed up for 6 y were included in current analyses. A total of 145 plasma GPs were quantified by high-throughput targeted lipidomics. MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans.

Results: After 6 y, 429 participants developed MetS. Eleven GPs, especially those with long-chain polyunsaturated fatty acids (LCPUFAs) or very-long-chain polyunsaturated fatty acids (VLCPUFAs) at the sn-2 position, including 1 phosphatidylcholine (PC) [PC(18:0/22:6)], 9 phosphatidylethanolamines (PEs) [PE(16:0/22:6), PE(18:0/14:0), PE(18:0/18:1), PE(18:0/18:2), PE(18:0/20:3), PE(18:0/22:5), PE(18:0/22:6), PE(18:1/22:6), and PE(18:2/22:6)], and 1 phosphatidylserine (PS) [PS(18:0/18:0)], were positively associated with incident MetS (RRs: 1.16-1.30 per SD change; Bonferroni-corrected P < 0.05). In network analysis, the strongest positive association for MetS incidence was evidenced in a module mainly composed of PEs containing C22:6 and PSs [RR: 1.21; 95% CI: 1.12, 1.31 per SD change; Bonferroni-corrected P < 0.05]. This association was more pronounced in participants with lower erythrocyte total n-3 PUFA concentrations [Bonferroni-corrected Pinter(P value for the interaction)< 0.05].

Conclusions: Elevated plasma concentrations of GPs, especially PEs with LCPUFAs or VLCPUFAs at the sn-2 position, are associated with higher risk of incident MetS. Future studies are merited to confirm our findings.
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http://dx.doi.org/10.1093/ajcn/nqab050DOI Listing
April 2021

Circulating Glycerolipids, Fatty Liver Index and Incidence of Type 2 Diabetes: A Prospective Study among Chinese.

J Clin Endocrinol Metab 2021 Mar 12. Epub 2021 Mar 12.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Context: Few lipidomic studies have specifically investigated the association of circulating glycerolipids and type 2 diabetes (T2D) risk, especially among Asian populations. It remains unknown whether or to what degree fatty liver could explain the glycerolipids-T2D associations.

Objective: We aimed to assess associations between plasma glycerolipids and incident T2D, and explore a potential role of liver fat accumulation in the associations.

Design: A prospective cohort study with 6-year of follow-up.

Participants: This work included 1,781 Chinese aged 50-70 years.

Main Outcome Measures: T2D.

Results: At 6-year resurvey, 463 participants developed T2D. At the false-discovery rate (FDR) of 5%, 43 of 104 glycerolipids were significantly associated with incident T2D risk after multivariate adjustment for conventional risk factors. After further controlling for glycated hemoglobin (HbA1c), 9 of the 43 glycerolipids remained significant, including 2 diacylglycerols (DAGs)(16:1/20:4, 18:2/20:5) and 7 triacylglycerols (TAGs)(46:1, 48:0, 48:1, 50:0, 50:1, 50:2, and 52:2), with relative risks (RRs) (95% confidence intervals [CIs]) ranging from 1.16 (1.05 to 1.27) to 1.23 (1.11 to 1.36) per SD increment of glycerolipids. However, additional adjustment for fatty liver index (FLI) largely attenuated these findings (RRs [95% CIs] were 0.88 [0.81 to 0.95] to 1.10 [1.01 to 1.21]). Mediation analyses suggested that the FLI explained 12%-28% glycerolipids-T2D associations (all p < 0.01).

Conclusions: Higher plasma levels of DAGs and TAGs were associated with increased incident T2D risk in this Chinese population, which might be partially explained by liver fat accumulation.
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http://dx.doi.org/10.1210/clinem/dgab165DOI Listing
March 2021

Associations among circulating sphingolipids, β-cell function, and risk of developing type 2 diabetes: A population-based cohort study in China.

PLoS Med 2020 12 9;17(12):e1003451. Epub 2020 Dec 9.

Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China.

Background: Animal studies suggest vital roles of sphingolipids, especially ceramides, in the pathogenesis of type 2 diabetes (T2D) via pathways involved in insulin resistance, β-cell dysfunction, and inflammation, but human studies are limited. We aimed to evaluate the associations of circulating sphingolipids with incident T2D and to explore underlying mechanisms.

Methods And Findings: The current study included 826 men and 1,148 women who were aged 50-70 years, from Beijing and Shanghai, and without T2D in 2005 and who were resurveyed in 2011. Cardiometabolic traits were measured at baseline and follow-up surveys. A total of 76 sphingolipids were quantified using high-coverage targeted lipidomics. Summary data for 2-sample Mendelian randomization were obtained from genome-wide association studies of circulating sphingolipids and the China Health and Nutrition Survey (n = 5,731). During the 6-year period, 529 participants developed T2D. Eleven novel and 3 reported sphingolipids, namely ceramides (d18:1/18:1, d18:1/20:0, d18:1/20:1, d18:1/22:1), saturated sphingomyelins (C34:0, C36:0, C38:0, C40:0), unsaturated sphingomyelins (C34:1, C36:1, C42:3), hydroxyl-sphingomyelins (C34:1, C38:3), and a hexosylceramide (d18:1/20:1), were positively associated with incident T2D (relative risks [RRs]: 1.14-1.21; all P < 0.001), after multivariate adjustment including lifestyle characteristics and BMI. Network analysis further identified 5 modules, and 2 modules containing saturated sphingomyelins showed the strongest associations with increased T2D risk (RRQ4 versus Q1 = 1.59 and 1.43; both Ptrend < 0.001). Mediation analysis suggested that the detrimental associations of 13 sphingolipids with T2D were largely mediated through β-cell dysfunction, as indicated by HOMA-B (mediation proportion: 11.19%-42.42%; all P < 0.001). Moreover, Mendelian randomization evidenced a positive association between a genetically instrumented ceramide (d18:1/20:1) and T2D (odds ratio: 1.15 [95% CI 1.05-1.26]; P = 0.002). Main limitations in the current study included potential undiagnosed cases and lack of an independent population for replication.

Conclusions: In this study, we observed that a panel of novel sphingolipids with unique structures were positively associated with incident T2D, largely mediated through β-cell dysfunction, in Chinese individuals.
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http://dx.doi.org/10.1371/journal.pmed.1003451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725305PMC
December 2020

Genetic susceptibility, dietary cholesterol intake, and plasma cholesterol levels in a Chinese population.

J Lipid Res 2020 11 12;61(11):1504-1511. Epub 2020 Aug 12.

Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China

Accompanied with nutrition transition, non-HDL-C levels of individuals in Asian countries has increased rapidly, which has caused the global epicenter of nonoptimal cholesterol to shift from Western countries to Asian countries. Thus, it is critical to underline major genetic and dietary determinants. In the current study of 2,330 Chinese individuals, genetic risk scores (GRSs) were calculated for total cholesterol (TC; GRS, 57 SNPs), LDL-C (GRS, 45 SNPs), and HDL-C (GRS, 65 SNPs) based on SNPs from the Global Lipid Genetics Consortium study. Cholesterol intake was estimated by a 74-item food-frequency questionnaire. Associations of dietary cholesterol intake with plasma TC and LDL-C strengthened across quartiles of the GRS (effect sizes: -0.29, 0.34, 2.45, and 6.47; = 0.002) and GRS (effect sizes: -1.35, 0.17, 5.45, and 6.07; = 0.001), respectively. Similar interactions with non-HDL-C were observed between dietary cholesterol and GRS ( = 0.001) and GRS ( = 0.004). The adverse effects of GRS on TC (effect sizes across dietary cholesterol quartiles: 0.51, 0.82, 1.21, and 1.31; = 0.023) and GRS on LDL-C (effect sizes across dietary cholesterol quartiles: 0.66, 0.52, 1.12, and 1.56; = 0.020) were more profound in those having higher cholesterol intake compared with those with lower intake. Our findings suggest significant interactions between genetic susceptibility and dietary cholesterol intake on plasma cholesterol profiles in a Chinese population.
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http://dx.doi.org/10.1194/jlr.RA120001009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604728PMC
November 2020

Fatty acids and cardiometabolic health: a review of studies in Chinese populations.

Eur J Clin Nutr 2021 Feb 14;75(2):253-266. Epub 2020 Aug 14.

Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, 310024, China.

Rapid nutrition transition from plant-based traditional diet to westernized diet has led to dramatically heightening burdens of cardiometabolic diseases in China in past decades. Recently, national surveys reported that poor dietary quality including low marine n-3 fatty acids and high intakes of red meat and processed meat was associated with considerably elevated cardiometabolic deaths. Previous studies mainly from Western population-based cohorts have indicated that not only fat quantity but also quality linked with different cardiometabolic outcomes. Compared with Western peoples, Asian peoples, including Chinese, are known to have different dietary patterns and lifestyle, as well as genetic heterogeneities, which may modify fatty acid metabolism and disease susceptibility in certain degree. To date, there were limited prospective studies investigating the relationships between fatty acids and cardiometabolic disease outcomes in Chinese, and most existing studies were cross-sectional nature and within one or two region(s). Notably, shifting dietary patterns could change not only amount, types, and ratio of fatty acids accounting for overall energy intake, but also their food sources and ratio to other macronutrients. Moreover, large geographic and urban-rural variations in prevalence of cardiometabolic diseases among Chinese may also reflect the effects of socioeconomic development and local diets on health status. Therefore, current review will summarize available literatures with more focus on the Chinese-based studies which may extend current knowledge about the roles of fatty acids in pathogenesis of cardiometabolic diseases for Asian populations and also provide useful information for trans-ethnic comparisons with other populations.
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http://dx.doi.org/10.1038/s41430-020-00709-0DOI Listing
February 2021

Fasting Serum Fructose Levels Are Associated With Risk of Incident Type 2 Diabetes in Middle-Aged and Older Chinese Population.

Diabetes Care 2020 09 1;43(9):2217-2225. Epub 2020 Jul 1.

Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China

Objective: We investigated the relationship between fasting serum fructose levels and the risk of incident type 2 diabetes in a prospective Chinese cohort.

Research Design And Methods: Among 949 community-based participants aged ≥40 years without diabetes at baseline, fasting serum fructose levels were measured using liquid chromatography-tandem mass spectrometry. The participants were followed up for the occurrence of diabetes. Cox regression models were performed to analyze the effect of fasting serum fructose levels on risk of incident diabetes.

Results: During a median of 3.5 years' follow-up, 179 of 949 (18.9%) participants developed type 2 diabetes. Elevated fasting serum fructose levels were associated with an increased risk of incident diabetes in a dose-response manner. After adjustment for age, sex, BMI, lipid profiles, blood pressure, liver function, smoking and drinking status, baseline glucose level, and sugar-sweetened beverage consumption, a 1-SD increased fasting fructose level was associated with a 35% (95% CI 1.08-1.67) increased risk of developing diabetes. After further adjustment for serum uric acid and estimated glomerular filtration rate, the association was partially attenuated (hazard ratio 1.33 [95% CI 1.07-1.65]). The association was similar by age, prediabetes status, BMI, and family history of diabetes but attenuated in women ( for heterogeneity = 0.037).

Conclusions: Elevated fasting serum fructose levels were independently associated with increased risk of incident type 2 diabetes in a middle-aged and older Chinese population. Our data suggest that higher fasting serum fructose levels might serve as a biomarker and/or a contributor to incident diabetes.
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http://dx.doi.org/10.2337/dc19-2494DOI Listing
September 2020

Isoflavone Intake and the Risk of Coronary Heart Disease in US Men and Women: Results From 3 Prospective Cohort Studies.

Circulation 2020 04 23;141(14):1127-1137. Epub 2020 Mar 23.

Department of Nutrition (L.M., M.D., G.Z., F.B.H., W.C.W., E.B.R., Q.S.), Harvard T.H. Chan School of Public Health, Boston, MA.

Background: Whether soy products confer health benefits related to coronary heart disease (CHD) remains controversial because of inconsistent evidence.

Methods: A total of 74 241 women from the NHS (Nurses' Health Study; 1984-2012), 94 233 women from the NHSII (Nurses' Health Study II; 1991-2013), and 42 226 men from the Health Professionals Follow-Up Study (1986-2012), who were free of cardiovascular disease and cancer at baseline, were included in the present analysis. Dietary data were updated every 2 to 4 years using a validated food frequency questionnaire. Nonfatal myocardial infarction and CHD deaths were adjudicated through reviewing medical records, death certificates, and other medical documents.

Results: In these cohorts, 8359 incident CHD cases were documented during 4 826 122 person-years of follow-up. In multivariable-adjusted analyses, isoflavone intake was inversely associated with CHD (pooled hazard ratio [HR] comparing the extreme quintiles: 0.87 [95% CI, 0.81-0.94]; =0.008). Consumption of tofu, but not soy milk, was inversely associated with the risk of CHD, with pooled HRs (95% CIs) of 0.82 (0.70-0.95; =0.005) and 0.87 (0.69-1.10; =0.41), respectively, comparing ≥1 serving/week with <1 serving/month. Further analyses showed that, in women, the favorable association of tofu was primarily driven by stronger inverse association of tofu intake observed in younger women before menopause and postmenopausal women without hormone use (=0.002).

Conclusions: Higher intake of isoflavones and tofu was associated with a moderately lower risk of developing CHD, and in women the favorable association of tofu were more pronounced in young women or postmenopausal women without hormone use.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.041306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138725PMC
April 2020

Smoking cessation and weight change in relation to cardiovascular disease incidence and mortality in people with type 2 diabetes: a population-based cohort study.

Lancet Diabetes Endocrinol 2020 02 7;8(2):125-133. Epub 2020 Jan 7.

Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

Background: To reduce their overall substantially increased risk of cardiovascular disease and premature mortality, smoking cessation is especially important for people with diabetes. However, the effect of weight change after quitting smoking on the long-term health consequences of smoking cessation is unclear. We aimed to examine smoking cessation and subsequent weight change in relation to incident cardiovascular disease events and mortality among adults with type 2 diabetes.

Methods: In this population-based cohort study, we analysed data from people with type 2 diabetes from two prospective cohorts in the USA: the Nurses' Health Study (1976-2014) and the Health Professionals Follow-Up Study (1986-2014). We included participants from both cohorts who either had prevalent type 2 diabetes or were diagnosed during the study, and who were either current smokers or never smokers without cardiovascular disease or cancer at diagnosis of diabetes. Information on demographics, newly diagnosed diseases, medical history, and lifestyle factors, including smoking status and weight change, was updated every 2 years through validated questionnaires. We assessed the incidence of cardiovascular disease and all-cause and cause-specific mortality among recent quitters (within 6 years of stopping) and long-term quitters (>6 years) associated with weight change within 6 years of smoking cessation among people with type 2 diabetes. We did a multivariable-adjusted Cox proportional hazard models to estimate hazard ratios (HRs) for the associations of smoking cessation and weight change on the outcomes.

Findings: Of 173 229 total cohort participants (121 700 from the Nurses' Health Study and 51 529 from the Health Professionals Follow-Up Study), 10 809 people with type 2 diabetes were included in the incident cardiovascular disease analysis and 9688 were included in the mortality analysis. 2580 incident cases of cardiovascular disease occurred during 153 166 person-years of follow-up, and 3827 deaths occurred during 152 811 person-years of follow-up. Recent quitters (2-6 consecutive years since smoking cessation) without weight gain within the first 6 years of quitting had a significantly lower risk of cardiovascular disease than people who continued to smoke (multivariable-adjusted HR 0·83 [95% CI 0·70-0·99] among all recent quitters, 0·77 [0·62-0·95] among recent quitters without weight gain, 0·99 [0·70-1·41] among recent quitters with weight gain of 0·1-5·0 kg, 0·89 [0·65-1·23] among recent quitters with weight gain of >5·0 kg, and 0·72 [0·61-0·84] among longer-term quitters [>6 consecutive years since smoking cessation]). Weight gain within 6 years after smoking cessation did not attenuate the inverse relation between long-term cessation and all-cause mortality (multivariable-adjusted HR 0·69 [95% CI 0·58-0·82] among long-term quitters without weight gain, 0·57 [0·45-0·71] among long-term quitters with weight gain of 0·1-5·0 kg, and 0·51 [0·42-0·62] among long-term quitters with weight gain of >5·0 kg), with similar results observed for cardiovascular disease and cancer mortality.

Interpretation: Smoking cessation without subsequent weight gain is associated with a reduced risk of cardiovascular disease and mortality among smokers with type 2 diabetes. Weight gain after smoking cessation attenuates the reduction in risk of developing cardiovascular disease, but does not attenuate the beneficial effect of smoking cessation with respect to mortality. These findings confirm the overall health benefits of quitting smoking among people with type 2 diabetes, but also emphasise the importance of weight management after smoking cessation to maximise its health benefits.

Funding: US National Institutes of Health.
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http://dx.doi.org/10.1016/S2213-8587(19)30413-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986932PMC
February 2020

Dietary fats and mortality among patients with type 2 diabetes: analysis in two population based cohort studies.

BMJ 2019 07 2;366:l4009. Epub 2019 Jul 2.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

Objective: To assess the association of dietary fatty acids with cardiovascular disease mortality and total mortality among patients with type 2 diabetes.

Design: Prospective, longitudinal cohort study.

Setting: Health professionals in the United States.

Participants: 11 264 participants with type 2 diabetes in the Nurses' Health Study (1980-2014) and Health Professionals Follow-Up Study (1986-2014).

Exposures: Dietary fat intake assessed using validated food frequency questionnaires and updated every two to four years.

Main Outcome Measure: Total and cardiovascular disease mortality during follow-up.

Results: During follow-up, 2502 deaths including 646 deaths due to cardiovascular disease were documented. After multivariate adjustment, intake of polyunsaturated fatty acids (PUFAs) was associated with a lower cardiovascular disease mortality, compared with total carbohydrates: hazard ratios comparing the highest with the lowest quarter were 0.76 (95% confidence interval 0.58 to 0.99; P for trend=0.03) for total PUFAs, 0.69 (0.52 to 0.90; P=0.007) for marine n-3 PUFAs, 1.13 (0.85 to 1.51) for α-linolenic acid, and 0.75 (0.56 to 1.01) for linoleic acid. Inverse associations with total mortality were also observed for intakes of total PUFAs, n-3 PUFAs, and linoleic acid, whereas monounsaturated fatty acids of animal, but not plant, origin were associated with a higher total mortality. In models that examined the theoretical effects of substituting PUFAs for other fats, isocalorically replacing 2% of energy from saturated fatty acids with total PUFAs or linoleic acid was associated with 13% (hazard ratio 0.87, 0.77 to 0.99) or 15% (0.85, 0.73 to 0.99) lower cardiovascular disease mortality, respectively. A 2% replacement of energy from saturated fatty acids with total PUFAs was associated with 12% (hazard ratio 0.88, 0.83 to 0.94) lower total mortality.

Conclusions: In patients with type 2 diabetes, higher intake of PUFAs, in comparison with carbohydrates or saturated fatty acids, is associated with lower total mortality and cardiovascular disease mortality. These findings highlight the important role of quality of dietary fat in the prevention of cardiovascular disease and total mortality among adults with type 2 diabetes.
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http://dx.doi.org/10.1136/bmj.l4009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603712PMC
July 2019

Associations of Amino Acid and Acylcarnitine Profiles With Incident Hyperuricemia in Middle-Aged and Older Chinese Individuals.

Arthritis Care Res (Hoboken) 2020 09;72(9):1305-1314

University of Chinese Academy of Sciences, Shanghai, China.

Objective: Little is known about how metabolic perturbations are linked to hyperuricemia in the general population. Therefore we aimed to examine metabolomics profiles in relation to uric acid change and incident hyperuricemia.

Methods: This study included 1,621 community-dwelling Chinese participants ages 50-70 years without hyperuricemia at baseline, with a mean duration of follow-up of 6 years. A total of 56 metabolites (22 amino acids and 34 acylcarnitines) at baseline were quantified by gas or liquid chromatography coupled to mass spectrometry. Annual change in uric acid was calculated, and incident hyperuricemia was defined as plasma uric acid >420 μmoles/liter in men and >360 μmoles/liter in women.

Results: The mean ± SD annual change in uric acid was 9.6 ± 12.1 μmoles/liter and the incidence of hyperuricemia was 23.1% (375 of 1,621). After adjustment for conventional risk factors, 9 metabolites (cysteine, glutamine, phenylalanine, threonine, and long-chain acylcarnitines C14:1OH, C18, C18:2, C20, and C20:4) were significantly associated with uric acid change (Bonferroni corrected P < 0.05) and with incident hyperuricemia (relative risks ranged from 1.14 to 1.21 per SD increment of metabolites; P < 0.05). A network analysis showed significant associations between the module containing long-chain acylcarnitines and incident hyperuricemia. Moreover, levels of these 9 metabolites were specifically correlated with intake of foods, including red and processed meat or soy products.

Conclusion: Plasma cysteine, glutamine, phenylalanine, threonine, and long-chain acylcarnitines are positively associated with incident hyperuricemia. The levels of these metabolites may be partially driven by intakes of meat and soy products that are associated with hyperuricemia.
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http://dx.doi.org/10.1002/acr.24013DOI Listing
September 2020

Associations Between Linoleic Acid Intake and Incident Type 2 Diabetes Among U.S. Men and Women.

Diabetes Care 2019 08 10;42(8):1406-1413. Epub 2019 Jun 10.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA

Objective: To investigate the association between intakes of n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk in three prospective cohort studies of U.S. men and women.

Research Design And Methods: We followed 83,648 women from the Nurses' Health Study (NHS) (1980-2012), 88,610 women from NHSII (1991-2013), and 41,771 men from the Health Professionals Follow-Up Study (HPFS) (1986-2012). Dietary data were collected every 2-4 years by using validated food-frequency questionnaires. Self-reported incident diabetes, identified biennially, was confirmed by using a validated supplementary questionnaire.

Results: During 4.93 million person-years of follow-up, 18,442 type 2 diabetes cases were documented. Dietary n-6 PUFAs accounted for 4.4-6.8% of total energy, on average, and consisted primarily of linoleic acid (LA) (≥98%). In multivariate-adjusted models, hazard ratios (95% CIs) of type 2 diabetes risk comparing extreme n-6 PUFA quintiles (highest vs. lowest) were 0.91 (0.85, 0.96) ( = 0.002) for total n-6 PUFAs and 0.92 (0.87, 0.98) ( = 0.01) for LA. In an isocaloric substitution model, diabetes risk was 14% (95% CI 5%, 21%) ( = 0.002) lower when LA isocalorically replaced saturated fats (5% of energy), 17% (95% CI 9%, 24%) ( < 0.001) lower for fats (2% of energy), or 9% (95% CI 17%, 0.1%) ( = 0.047) lower for carbohydrates (5% of energy). Replacing n-3 PUFAs or monounsaturated fats with LA was not significantly associated with type 2 diabetes risk.

Conclusions: Our study provides additional evidence that LA intake is inversely associated with risk of type 2 diabetes, especially when replacing saturated fatty acids, fats, or carbohydrates.
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http://dx.doi.org/10.2337/dc19-0412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647042PMC
August 2019

Associations of Monounsaturated Fatty Acids From Plant and Animal Sources With Total and Cause-Specific Mortality in Two US Prospective Cohort Studies.

Circ Res 2019 04;124(8):1266-1275

From the Department of Nutrition (M.G.-F., G.Z., W.C.W., F.B.H., Q.S.), Harvard T.H. Chan School of Public Health, Boston, MA.

Rationale: Dietary monounsaturated fatty acids (MUFAs) can come from both plant and animal sources with divergent nutrient profiles that may potentially obscure the associations of total MUFAs with chronic diseases.

Objective: To investigate the associations of cis-MUFA intake from plant (MUFA-P) and animal (MUFA-A) sources with total and cause-specific mortality.

Methods And Results: We followed 63 412 women from the NHS (Nurses' Health Study; 1990-2012) and 29 966 men from the HPFS (Health Professionals Follow-Up Study; 1990-2012). MUFA-Ps and MUFA-As were calculated based on data collected through validated food frequency questionnaires administered every 4 years and updated food composition databases. During 1 896 864 person-years of follow-up, 20 672 deaths occurred. Total MUFAs and MUFA-Ps were inversely associated with total mortality after adjusting for potential confounders, whereas MUFA-As were associated with higher mortality. When MUFA-Ps were modeled to isocalorically replace other macronutrients, hazard ratios (HRs, 95% CIs) of total mortality were 0.84 (0.77-0.92; P<0.001) for replacing saturated fatty acids, 5% of energy); 0.86 (0.82-0.91; P<0.001) for replacing refined carbohydrates (5% energy); 0.91 (0.85-0.97; P<0.001) for replacing trans fats (2% energy), and 0.77 (0.71-0.82; P<0.001) for replacing MUFA-As (5% energy). For isocalorically replacing MUFA-As with MUFA-Ps, HRs (95% CIs) were 0.74 (0.64-0.86; P<0.001) for cardiovascular mortality; 0.73 (0.65-0.82; P<0.001) for cancer mortality, and 0.82 (0.73-0.91; P<0.001) for mortality because of other causes.

Conclusions: Higher intake of MUFA-Ps was associated with lower total mortality, and MUFA-As intake was associated with higher mortality. Significantly lower mortality risk was observed when saturated fatty acids, refined carbohydrates, or trans fats were replaced by MUFA-Ps, but not MUFA-As. These data suggest that other constituents in animal foods, such as saturated fatty acids, may confound the associations for MUFAs when they are primarily derived from animal products. More evidence is needed to elucidate the differential associations of MUFA-Ps and MUFA-As with mortality.
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http://dx.doi.org/10.1161/CIRCRESAHA.118.313996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459723PMC
April 2019

Dietary nitrate consumption and risk of CHD in women from the Nurses' Health Study.

Br J Nutr 2019 04 23;121(7):831-838. Epub 2019 Jan 23.

6Centre for Clinical Epidemiology and Biostatistics,Hunter Medical Research Institute,University of Newcastle,Lot 1,Kookaburra Circuit,New Lambton Heights,New South Wales2305,Australia.

The consumption of nitrate-rich vegetables can acutely lower blood pressure and improve mediators shown to optimise vascular health. However, we do not yet understand the impact of long-term habitual dietary nitrate intake and its association with CVD. Therefore, the aim of this investigation was to examine the relationship between habitual dietary nitrate intakes and risk of CHD in women from the Nurses' Health Study. We prospectively followed 62 535 women who were free from diabetes, CVD and cancer at baseline in 1986. Information on diet was updated every 4 years with validated FFQ. The main outcome was CHD defined by the occurrence of non-fatal myocardial infarction or fatal CHD. Cox proportional hazard regression models were used to estimate the relative risks (RR) and 95 % CI. During 26 years of follow-up, 2257 cases of CHD were identified. When comparing the highest quintile of nitrate intake with the lowest quintile, in aged-adjusted analysis there was a protective association for CHD (RR=0·77, 95 % CI 0·68, 0·97; P=0·0002) which dissipated after further adjustment for smoking, physical activity, BMI and race (RR=0·91; 95 % CI 0·80, 1·04; P=0·27). This magnitude of association was further attenuated once we adjusted for the Alternative Healthy Eating Index excluding vegetable and fruit consumption (RR=1·04, 95 % CI 0·91, 1·20; P=0·34). Dietary nitrate intake was not related to the risk of CHD after adjustment for other lifestyle and non-vegetable dietary factors in a large group of US women.
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http://dx.doi.org/10.1017/S0007114519000096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438750PMC
April 2019

Erythrocyte PUFAs, circulating acylcarnitines, and metabolic syndrome risk: a prospective study in Chinese.

J Lipid Res 2019 02 14;60(2):421-429. Epub 2018 Dec 14.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Chinese Academy of Sciences, Shanghai 200031, China

The effects of PUFAs on metabolic syndrome (MetS) remain to be characterized, particularly in Asians. We aimed to investigate the prospective associations of PUFAs with MetS and the role of acylcarnitines in these associations in Chinese individuals. Among 1,245 Chinese men and women aged 50-70 years who completed a 6 year follow-up, baseline erythrocyte FAs and plasma acylcarnitines were profiled using gas chromatography coupled with positive chemical ionization and liquid chromatography-tandem mass spectrometry, respectively. Total n-6 PUFAs and three 22-carbon n-6 PUFAs were significantly associated with lower MetS risk comparing extreme quartiles: relative risks (RRs) (95% CIs) were 0.75 (0.57, 0.97) for total n-6 PUFAs, 0.69 (0.56, 0.85) for 22:2n-6, 0.76 (0.59, 0.99) for 22:4n-6, and 0.74 (0.58, 0.94) for 22:5n-6, while 18:3n-3 and 18:3n-6 were positively associated with MetS risk. In a network analysis, a module mostly consisting of long-chain n-6 PUFAs and very-long-chain saturated FAs was inversely associated with incident MetS (RR per SD: 0.84; 95% CI: 0.76, 0.92), and this module was more strongly associated with lower MetS risk when a short- to medium-chain acylcarnitine (C5-C10) module score was lower ( = 0.03). Our data suggested inverse associations of total n-6 and certain long-chain n-6 PUFAs with cardiometabolic disorders, and this association might be modified by certain acy-l-carnitines.
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http://dx.doi.org/10.1194/jlr.P088005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358288PMC
February 2019

Rotating night shift work and adherence to unhealthy lifestyle in predicting risk of type 2 diabetes: results from two large US cohorts of female nurses.

BMJ 2018 11 21;363:k4641. Epub 2018 Nov 21.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

Objectives: To prospectively evaluate the joint association of duration of rotating night shift work and lifestyle factors with risk of type 2 diabetes risk, and to quantitatively decompose this joint association to rotating night shift work only, to lifestyle only, and to their interaction.

Design: Prospective cohort study.

Setting: Nurses' Health Study (1988-2012) and Nurses' Health Study II (1991-2013).

Participants: 143 410 women without type 2 diabetes, cardiovascular disease, or cancer at baseline.

Exposures: Rotating night shift work was defined as at least three night shifts per month in addition to day and evening shifts in that month. Unhealthy lifestyles included current smoking, physical activity levels below 30 minutes per day at moderate to vigorous intensity, diet in the bottom three fifths of the Alternate Healthy Eating Index score, and body mass index of 25 or above.

Main Outcome Measures: Incident cases of type 2 diabetes were identified through self report and validated by a supplementary questionnaire.

Results: During 22-24 years of follow-up, 10 915 cases of incident type 2 diabetes occurred. The multivariable adjusted hazard ratios for type 2 diabetes were 1.31 (95% confidence interval 1.19 to 1.44) per five year increment of duration of rotating night shift work and 2.30 (1.88 to 2.83) per unhealthy lifestyle factor (ever smoking, low diet quality, low physical activity, and overweight or obesity). For the joint association of per five year increment rotating night shift work and per unhealthy lifestyle factor with type 2 diabetes, the hazard ratio was 2.83 (2.15 to 3.73) with a significant additive interaction (P for interaction <0.001). The proportions of the joint association were 17.1% (14.0% to 20.8%) for rotating night shift work alone, 71.2% (66.9% to 75.8%) for unhealthy lifestyle alone, and 11.3% (7.3% to 17.3%) for their additive interaction.

Conclusions: Among female nurses, both rotating night shift work and unhealthy lifestyle were associated with a higher risk of type 2 diabetes. The excess risk of rotating night shift work combined with unhealthy lifestyle was higher than the addition of risk associated with each individual factor. These findings suggest that most cases of type 2 diabetes could be prevented by adhering to a healthy lifestyle, and the benefits could be greater in rotating night shift workers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247172PMC
http://dx.doi.org/10.1136/bmj.k4641DOI Listing
November 2018

Urinary cadmium concentrations and metabolic syndrome in U.S. adults: The National Health and Nutrition Examination Survey 2001-2014.

Environ Int 2018 12 20;121(Pt 1):349-356. Epub 2018 Sep 20.

Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, United States of America; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, United States of America; Division of Women's Health, Department of Medicine, Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, United States of America. Electronic address:

Background: Low to moderate acute cadmium exposure has been associated with increased risk of chronic diseases, such as cardiovascular and kidney disease. Little is known about the association between urinary cadmium levels-an indicator of longer-term exposure-and metabolic syndrome (MetS).

Methods: We analysed data from 3982 participants aged 20-<80 years of the National Health and Nutrition Examination Survey 2001-2014. Urinary cadmium levels were measured and adjusted for creatinine using spot urine samples. Cadmium levels were evaluated in quintiles (Q). MetS was defined by National Cholesterol Education Program's Adult Treatment Panel III report criteria. Prevalence odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression accounting for complex survey design, while adjusting for potential confounders and stratifying by sex and smoking status.

Results: In the overall study population, there was a marginal inverse association between urinary cadmium and MetS (adj. OR for Q5 versus Q1: 0.7; 95% CI: 0.5-1.0). Sex stratified models were similar. When examining individual components of MetS, participants with higher levels of urinary cadmium had decreased odds of abdominal obesity (adj. OR for Q5 versus Q1 0.4; 95% CI: 0.3-0.6), but increased odds for low HDL (adj. OR for Q5 versus Q1 2.1; 95% CI: 1.4-3.1). Among current smokers, higher urinary cadmium was associated with increased odds of MetS, hypertension, and low HDL even after accounting for serum cotinine-a marker of smoking intensity.

Conclusions: Higher levels of urinary cadmium, a marker of long term exposure, were not associated with an increased risk of MetS in the overall study population. However, higher urine cadmium was associated with altered MetS components. Current smokers were the most vulnerable group, with higher long-term cadmium exposure being associated with increased risk of MetS, low HDL, and hypertension.
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http://dx.doi.org/10.1016/j.envint.2018.08.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786759PMC
December 2018

Smoking Cessation, Weight Change, Type 2 Diabetes, and Mortality.

N Engl J Med 2018 08;379(7):623-632

From the Departments of Nutrition (Y.H., G.Z., G.L., W.C.W., F.B.H., Q.S.), Epidemiology (Y.H., M.W., W.C.W., J.E.M., F.B.H.), and Biostatistics (M.W., B.R.), Harvard T.H. Chan School of Public Health, and the Channing Division of Network Medicine (M.W., W.C.W., J.E.M., F.B.H., Q.S.) and the Division of Preventive Medicine (J.E.M.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School - all in Boston; and the Key Laboratory of Nutrition, Metabolism, and Food Safety, Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai (G.Z.), and the Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (A.P.) - both in China.

Background: Whether weight gain after smoking cessation attenuates the health benefits of quitting is unclear.

Methods: In three cohort studies involving men and women in the United States, we identified those who had reported quitting smoking and we prospectively assessed changes in smoking status and body weight. We estimated risks of type 2 diabetes, death from cardiovascular disease, and death from any cause among those who had reported quitting smoking, according to weight changes after smoking cessation.

Results: The risk of type 2 diabetes was higher among recent quitters (2 to 6 years since smoking cessation) than among current smokers (hazard ratio, 1.22; 95% confidence interval [CI], 1.12 to 1.32). The risk peaked 5 to 7 years after quitting and then gradually decreased. The temporary increase in the risk of type 2 diabetes was directly proportional to weight gain, and the risk was not increased among quitters without weight gain (P<0.001 for interaction). In contrast, quitters did not have a temporary increase in mortality, regardless of weight change after quitting. As compared with current smokers, the hazard ratios for death from cardiovascular disease were 0.69 (95% CI, 0.54 to 0.88) among recent quitters without weight gain, 0.47 (95% CI, 0.35 to 0.63) among those with weight gain of 0.1 to 5.0 kg, 0.25 (95% CI, 0.15 to 0.42) among those with weight gain of 5.1 to 10.0 kg, 0.33 (95% CI, 0.18 to 0.60) among those with weight gain of more than 10.0 kg, and 0.50 (95% CI, 0.46 to 0.55) among longer-term quitters (>6 years since smoking cessation). Similar associations were observed for death from any cause.

Conclusions: Smoking cessation that was accompanied by substantial weight gain was associated with an increased short-term risk of type 2 diabetes but did not mitigate the benefits of quitting smoking on reducing cardiovascular and all-cause mortality. (Funded by the National Institutes of Health.).
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http://dx.doi.org/10.1056/NEJMoa1803626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165582PMC
August 2018

Gluten intake and risk of type 2 diabetes in three large prospective cohort studies of US men and women.

Diabetologia 2018 10 3;61(10):2164-2173. Epub 2018 Aug 3.

Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.

Aims/hypothesis: We investigated the association between gluten intake and long-term type 2 diabetes risk among Americans.

Methods: We followed women from the Nurses' Health Study (NHS, n = 71,602, 1984-2012) and NHS II (n = 88,604, 1991-2013) and men from the Health Professionals Follow-Up Study (HPFS, n = 41,908, 1986-2012). Gluten intake was estimated using a validated food frequency questionnaire every 2-4 years. Incident type 2 diabetes was defined as self-reported physician-diagnosed diabetes confirmed using a supplementary questionnaire.

Result: Gluten intake was strongly correlated with intakes of carbohydrate components, especially refined grains, starch and cereal fibre (Spearman correlation coefficients >0.6). During 4.24 million years of follow-up, 15,947 people were confirmed to have type 2 diabetes. After multivariate adjustment, pooled HRs and 95% CIs for type 2 diabetes, from low to high gluten quintiles, were (p < 0.001): 1 (reference); 0.89 (0.85, 0.93); 0.84 (0.80, 0.88); 0.78 (0.74, 0.82) and 0.80 (0.76, 0.84). The association was slightly weakened after further adjusting for cereal fibre, with pooled HRs (95% CIs) of (p < 0.001): 1 (reference); 0.91 (0.87, 0.96); 0.88 (0.83, 0.93); 0.83 (0.78, 0.88) and 0.87 (0.81, 0.93). Dose-response analysis supported a largely linear inverse relationship between gluten intake up to 12 g/day and type 2 diabetes. The association between gluten intake and type 2 diabetes was stronger when intake of added bran was also higher (p = 0.02).

Conclusions/interpretation: Gluten intake is inversely associated with type 2 diabetes risk among largely healthy US men and women. Limiting gluten in the diet is associated with lower intake of cereal fibre and possibly other beneficial nutrients that contribute to good health.
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http://dx.doi.org/10.1007/s00125-018-4697-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182774PMC
October 2018

Intake of glucosinolates and risk of coronary heart disease in three large prospective cohorts of US men and women.

Clin Epidemiol 2018 29;10:749-762. Epub 2018 Jun 29.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA,

Importance: Glucosinolates, a group of phytochemicals abundant in cruciferous vegetables, may have cardioprotective properties. However, no prospective study has evaluated the association of intake of glucosinolates with the risk of coronary heart disease (CHD).

Objective: The objective of the study was to evaluate the association between the intake of glucosinolates and incident CHD in US men and women.

Design: Prospective longitudinal cohort study.

Setting: Health professionals in the USA.

Participants: We followed 74,241 women in the Nurses' Health Study (NHS; 1984-2012), 94,163 women in the NHSII (1991-2013), and 42,170 men in the Health Professionals Follow-Up Study (1986-2012), who were free of cardiovascular disease and cancer at baseline.

Exposure: Glucosinolate intake was assessed using validated semi-quantitative food frequency questionnaires at baseline and updated every 2-4 years during follow-up.

Main Outcome Measures: Incident cases of CHD were confirmed by medical record review.

Results: During 4,824,001 person-years of follow-up, 8,010 cases of CHD were identified in the three cohorts. After adjustment for major lifestyle and dietary risk factors of CHD, weak but significantly positive associations were observed for glucosinolates with CHD risk when comparing the top with bottom quintiles (hazard ratio [HR]:1.09; 95% CI: 1.01, 1.17; <0.001). Higher intakes of three major subtypes of glucosinolates were consistently associated with a higher CHD risk, although the association for indolylglucosinolate did not achieve statistical significance. Regarding cruciferous vegetable intake, participants who consumed one or more servings per week of Brussels sprouts (HR: 1.16; 95% CI: 1.06, 1.26; <0.001) and cabbage (HR: 1.09; 95% CI: 1.02, 1.17; =0.009) had a significantly higher CHD risk than those who consumed these cruciferous vegetables less than once per month.

Conclusion And Relevance: In these three prospective cohort studies, dietary glucosinolate intake was associated with a slightly higher risk of CHD in US adults. These results warrant replications in further studies including biomarker-based studies. Further studies are needed to confirm these findings and elucidate mechanistic pathways that may underlie these associations.
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http://dx.doi.org/10.2147/CLEP.S164497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029595PMC
June 2018

Influence of Lifestyle on Incident Cardiovascular Disease and Mortality in Patients With Diabetes Mellitus.

J Am Coll Cardiol 2018 06;71(25):2867-2876

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Evidence is limited regarding the impact of healthy lifestyle practices on the risk of subsequent cardiovascular events among patients with diabetes.

Objectives: The purpose of this study was to examine the associations of an overall healthy lifestyle, defined by eating a high-quality diet (top two-fifths of Alternative Healthy Eating Index), nonsmoking, engaging in moderate- to vigorous-intensity physical activity (≥150 min/week), and drinking alcohol in moderation (5 to 15 g/day for women and 5 to 30 g/day for men), with the risk of developing cardiovascular disease (CVD) and CVD mortality among adults with type 2 diabetes (T2D).

Methods: This prospective analysis included 11,527 participants with T2D diagnosed during follow-up (8,970 women from the Nurses' Health Study and 2,557 men from the Health Professionals Follow-Up Study), who were free of CVD and cancer at the time of diabetes diagnosis. Diet and lifestyle factors before and after T2D diagnosis were repeatedly assessed every 2 to 4 years.

Results: There were 2,311 incident CVD cases and 858 CVD deaths during an average of 13.3 years of follow-up. After multivariate adjustment of covariates, the low-risk lifestyle factors after diabetes diagnosis were each associated with a lower risk of CVD incidence and CVD mortality. The multivariate-adjusted hazard ratios for participants with 3 or more low-risk lifestyle factors compared with 0 were 0.48 (95% confidence interval [CI]: 0.40 to 0.59) for total CVD incidence, 0.53 (95% CI: 0.42 to 0.66) for incidence of coronary heart disease, 0.33 (95% CI: 0.21 to 0.51) for stroke incidence, and 0.32 (95% CI: 0.22 to 0.47) for CVD mortality (all p trend <0.001). The population-attributable risk for poor adherence to the overall healthy lifestyle (<3 low-risk factors) was 40.9% (95% CI: 28.5% to 52.0%) for CVD mortality. In addition, greater improvements in healthy lifestyle factors from pre-diabetes to post-diabetes diagnosis were also significantly associated with a lower risk of CVD incidence and CVD mortality. For each number increment in low-risk lifestyle factors there was a 14% lower risk of incident total CVD, a 12% lower risk of coronary heart disease, a 21% lower risk of stroke, and a 27% lower risk of CVD mortality (all p < 0.001). Similar results were observed when analyses were stratified by diabetes duration, sex/cohort, body mass index at diabetes diagnosis, smoking status, and lifestyle factors before diabetes diagnosis.

Conclusions: Greater adherence to an overall healthy lifestyle is associated with a substantially lower risk of CVD incidence and CVD mortality among adults with T2D. These findings further support the tremendous benefits of adopting a healthy lifestyle in reducing the subsequent burden of cardiovascular complications in patients with T2D.
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http://dx.doi.org/10.1016/j.jacc.2018.04.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052788PMC
June 2018

Lifestyle of women before pregnancy and the risk of offspring obesity during childhood through early adulthood.

Int J Obes (Lond) 2018 07 3;42(7):1275-1284. Epub 2018 Mar 3.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: In women, adhering to an overall healthy lifestyle is associated with a dramatically reduced risk of cardio-metabolic disorders. Whether such a healthy lifestyle exerts an intergenerational effects on child health deserves examination.

Methods: We included 5701 children (9-14 years old at baseline) of the Growing Up Today Study 2, and their mothers, who are participants in the Nurses' Health Study II. Pre-pregnancy healthy lifestyle was defined as a normal body mass index, no smoking, physical activity ≥150 min/week, and diet in the top 40% of the Alternative Healthy Eating Index-2010. Obesity during childhood and adolescence was defined using the International Obesity Task Force age- and sex-specific cutoffs. Multivariable log-binominal regression models with generalized estimating equations were used to evaluate the association of pre-pregnancy healthy lifestyle and offspring obesity.

Results: We identified 520 (9.1%) offspring who became obese during follow-up. A healthy body weight of mothers and no smoking before pregnancy was significantly associated with a lower risk of obesity among offspring: the relative risks [RRs; 95% confidence intervals (CIs)] were 0.37 (0.31-0.43) and 0.64 (0.49-0.84), respectively. Eating a healthy diet and regular moderate-to-vigorous physical activities were inversely related to offspring obesity risk, but these relations were not statistically significant. Compared to children of mothers who did not meet any low-risk lifestyle factors, offspring of women who adhered to all four healthy lifestyle factors had 75% lower risk of obesity (RR: 0.25, 95% CI: 0.14-0.43).

Conclusion: Adherence to an overall healthy lifestyle before pregnancy is strongly associated with a low risk of offspring obesity in childhood, adolescence, and early adulthood. These findings highlight the importance of an overall healthy lifestyle before pregnancy as a potential strategy to prevent obesity in future generations.
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http://dx.doi.org/10.1038/s41366-018-0052-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727198PMC
July 2018

Monounsaturated fats from plant and animal sources in relation to risk of coronary heart disease among US men and women.

Am J Clin Nutr 2018 03;107(3):445-453

Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, MA.

Background: Monounsaturated fatty acids (MUFAs) improve blood lipid profiles in intervention studies, but prospective evidence with regard to MUFA intake and coronary heart disease (CHD) risk is limited and controversial.

Objective: We investigated the associations of cis MUFA intake from plant (MUFA-P) and animal (MUFA-A) sources with CHD risk separately among 63,442 women from the Nurses' Health Study (1990-2012) and 29,942 men from the Health Professionals Follow-Up Study (1990-2012).

Design: Intakes of MUFA-Ps and MUFA-As were calculated by using validated food-frequency questionnaires collected every 4 y. Incident nonfatal myocardial infarction and fatal CHD cases (n = 4419) were confirmed by medical record review.

Results: During follow-up, MUFA-Ps and MUFA-As contributed 5.8-7.9% and 4.2-5.4% of energy on average, respectively. When MUFA-Ps were modeled to isocalorically replace other macronutrients, HRs (95% CIs) of CHD were 0.83 (0.68, 1.00) for saturated fatty acids (SFAs; 5% of energy), 0.86 (0.76, 0.97) for refined carbohydrates (5% of energy), and 0.80 (0.70, 0.91) for trans fats (2% of energy) (P = 0.05, 0.01, and 0.001, respectively). For MUFA-As, corresponding HRs (95% CIs) for the same isocaloric substitutions were 1.04 (0.79, 1.38) for SFAs, 1.11 (0.91, 1.35) for refined carbohydrates, and 0.88 (0.77, 1.01) for trans fats (P = 0.76, 0.31, and 0.08, respectively). Given the common food sources of SFAs and MUFA-As (Spearman correlation coefficients of 0.81-0.83 between these groups of fatty acids), we further estimated CHD risk when the sum of MUFA-As and SFAs (5% of energy) was replaced by MUFA-Ps, and found that the HR was 0.81 (95% CI: 0.73, 0.90; P < 0.001) for this replacement.

Conclusions: The largely different associations of MUFA-Ps and MUFA-As with CHD risk suggest that plant-based foods are the preferable sources of MUFAs for CHD prevention. These findings are observational and warrant confirmation in intervention settings. This study was registered at clinicaltrials.gov as NCT00005152 and NCT00005182.
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http://dx.doi.org/10.1093/ajcn/nqx004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875103PMC
March 2018

Meat Cooking Methods and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies.

Diabetes Care 2018 05 12;41(5):1049-1060. Epub 2018 Mar 12.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA

Objective: To examine open-flame and/or high-temperature cooking (grilling/barbecuing, broiling, or roasting) and doneness preferences (rare, medium, or well done) for red meat, chicken, and fish in relation to type 2 diabetes (T2D) risk among U.S. adults who consumed animal flesh regularly (≥2 servings/week).

Research Design And Methods: The prospective studies included 52,752 women from the Nurses' Health Study (NHS) (followed during 1996-2012), 60,809 women from NHS II (followed during 2001-2013), and 24,679 men from the Health Professionals Follow-Up Study (HPFS) (followed during 1996-2012) who were free of diabetes, cardiovascular disease, and cancer at baseline. Incident cases of T2D were confirmed by validated supplementary questionnaires.

Results: We documented 7,895 incident cases of T2D during 1.74 million person-years of follow-up. After multivariate adjustments including baseline BMI and total consumption of red meat, chicken, and fish, higher frequency of open-flame and/or high-temperature cooking was independently associated with an elevated T2D risk. When comparing open-flame and/or high-temperature cooking >15 times/month with <4 times/month, the pooled hazard ratio (HR) (95% CI) of T2D was 1.28 (1.18, 1.39; <0.001). When comparing the extreme quartiles of doneness-weighted frequency of high-temperature cooking, the pooled HR (95% CI) of T2D was 1.20 (1.12, 1.28; <0.001). These associations remained significant when red meat and chicken were examined separately. In addition, estimated intake of heterocyclic aromatic amines was also associated with an increased T2D risk.

Conclusions: Independent of consumption amount, open-flame and/or high-temperature cooking for both red meat and chicken is associated with an increased T2D risk among adults who consume animal flesh regularly.
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http://dx.doi.org/10.2337/dc17-1992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911789PMC
May 2018

Plasma Concentrations of Perfluoroalkyl Substances and Risk of Type 2 Diabetes: A Prospective Investigation among U.S. Women.

Environ Health Perspect 2018 03 1;126(3):037001. Epub 2018 Mar 1.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Background: Emerging evidence suggests that perfluoroalkyl substances (PFASs) are endocrine disruptors and may contribute to the etiology of type 2 diabetes (T2D), but this hypothesis needs to be clarified in prospective human studies.

Objectives: Our objective was to examine the associations between PFAS exposures and subsequent incidence of T2D in the Nurses' Health Study II (NHSII). In addition, we aimed to evaluate potential demographic and lifestyle determinants of plasma PFAS concentrations.

Methods: A prospective nested case-control study of T2D was conducted among participants who were free of diabetes, cardiovascular disease, and cancer in 1995-2000 [(mean±SD): 45.3±4.4 y) of age]. We identified and ascertained 793 incident T2D cases through 2011 (mean±SD) years of follow-up: 6.7±3.7 y). Each case was individually matched to a control (on age, month and fasting status at sample collection, and menopausal status and hormone replacement therapy). Plasma concentrations of five major PFASs, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonate, perfluorononanoic acid, and perfluorodecanoic acid were measured. Odds ratios (ORs) of T2D by PFAS tertiles were estimated by conditional logistic regression.

Results: Shorter breastfeeding duration and higher intake of certain foods, such as seafood and popcorn, were significantly associated with higher plasma concentrations of PFASs among controls. After multivariate adjustment for T2D risk factors, including body mass index, family history, physical activity, and other covariates, higher plasma concentrations of PFOS and PFOA were associated with an elevated risk of T2D. Comparing extreme tertiles of PFOS or PFOA, ORs were 1.62 (95% CI: 1.09, 2.41; =0.02) and 1.54 (95% CI: 1.04, 2.28; =0.03), respectively. Other PFASs were not clearly associated with T2D risk.

Conclusions: Background exposures to PFASs in the late 1990s were associated with higher T2D risk during the following years in a prospective case-control study of women from the NHSII. These findings support a potential diabetogenic effect of PFAS exposures. https://doi.org/10.1289/EHP2619.
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http://dx.doi.org/10.1289/EHP2619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071816PMC
March 2018

Persistent organic pollutants and risk of type 2 diabetes: A prospective investigation among middle-aged women in Nurses' Health Study II.

Environ Int 2018 05 22;114:334-342. Epub 2018 Feb 22.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States. Electronic address:

Background: Exposure to persistent organic pollutants (POPs) may predispose to the development of type 2 diabetes (T2D), but prospective human evidence is scarce.

Objectives: We investigated the association between plasma-POP concentrations in the late 1990s and incident T2D over 11 years of follow-up in the Nurses' Health Study II.

Discussion: Three organochlorine pesticides and 20 polychlorinated biphenyls (PCBs) were measured in banked plasma from 793 case-control pairs of T2D. In a multiviarate-adjusted model, T2D ORs (95%CIs) comparing extreme POP tertiles (high vs. low) were 1.67 (1.24, 2.23; P < 0.001) for hexachlorobenzene (HCB), 3.62 (2.57, 5.11; P < 0.001) for β-hexachlorocyclohexane (β-HCH), 1.55 (1.13, 2.13; P = 0.05) for p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and 1.95 (1.42, 2.69; P < 0.001) for total dioxin-like PCBs (DL-PCBs) which included 5 mono-ortho congeners, PCB-105, 118, 156, 157, and 167. Adjustment for previous weight change and body mass index (BMI) at blood draw attenuated these associations, but that for DL-PCBs remained (OR[95% CI] = 1.78[1.14, 2.76]; P = 0.006). Age, breastfeeding history, previous weight change and BMI at blood draw were significant predictors of plasma POP concentrations. In addition, we found significant interactions of POPs and weight change before blood draw on T2D risk. ORs (95%CIs) of T2D comparing extreme (high vs. low) POP groups were 2.00 (1.02, 3.92; P = 0.01) for HCB, 2.69 (1.34, 5.40; P < 0.001) for β-HCH, and 2.41 (1.22, 4.77; P < 0.001) for DL-PCBs in the lowest weight gain group, whereas these values were 1.29 (0.73, 2.28; P = 0.46; P = 0.04) for HCB, 1.41 (0.77, 2.60; P = 0.24; P = 0.003) for β-HCH, and 0.90 (0.50, 1.63; P = 0.61; P = 0.01) for DL-PCBs in the highest weight-gain group.

Conclusions: Our findings suggest that elevated POP exposure may have diabetogenic potential. These data also highlight the impact of lifestyle factors, especially history of weight gain, on circulating POP concentrations and their associations with subsequent T2D risk.
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http://dx.doi.org/10.1016/j.envint.2017.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899920PMC
May 2018

Perfluoroalkyl substances and changes in body weight and resting metabolic rate in response to weight-loss diets: A prospective study.

PLoS Med 2018 02 13;15(2):e1002502. Epub 2018 Feb 13.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Background: The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs) have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown. This study aimed to examine the associations of PFAS exposure with changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting.

Methods And Findings: In the 2-year POUNDS Lost randomized clinical trial based in Boston, Massachusetts, and Baton Rouge, Louisiana, that examined the effects of energy-restricted diets on weight changes, baseline plasma concentrations of major PFASs were measured among 621 overweight and obese participants aged 30-70 years. Body weight was measured at baseline and 6, 12, 18, and 24 months. RMR and other metabolic parameters, including glucose, lipids, thyroid hormones, and leptin, were measured at baseline and 6 and 24 months. Participants lost an average of 6.4 kg of body weight during the first 6 months (weight-loss period) and subsequently regained an average of 2.7 kg of body weight during the period of 6-24 months (weight regain period). After multivariate adjustment, baseline PFAS concentrations were not significantly associated with concurrent body weight or weight loss during the first 6 months. In contrast, higher baseline levels of PFASs were significantly associated with a greater weight regain, primarily in women. In women, comparing the highest to the lowest tertiles of PFAS concentrations, the multivariate-adjusted mean weight regain (SE) was 4.0 (0.8) versus 2.1 (0.9) kg for perfluorooctanesulfonic acid (PFOS) (Ptrend = 0.01); 4.3 (0.9) versus 2.2 (0.8) kg for perfluorooctanoic acid (PFOA) (Ptrend = 0.007); 4.7 (0.9) versus 2.5 (0.9) kg for perfluorononanoic acid (PFNA) (Ptrend = 0.006); 4.9 (0.9) versus 2.7 (0.8) kg for perfluorohexanesulfonic acid (PFHxS) (Ptrend = 0.009); and 4.2 (0.8) versus 2.5 (0.9) kg for perfluorodecanoic acid (PFDA) (Ptrend = 0.03). When further adjusted for changes in body weight or thyroid hormones during the first 6 months, results remained similar. Moreover, higher baseline plasma PFAS concentrations, especially for PFOS and PFNA, were significantly associated with greater decline in RMR during the weight-loss period and less increase in RMR during the weight regain period in both men and women. Limitations of the study include the possibility of unmeasured or residual confounding by socioeconomic and psychosocial factors, as well as possible relapse to the usual diet prior to randomization, which could have been rich in foods contaminated by PFASs through food packaging and also dense in energy.

Conclusions: In this diet-induced weight-loss trial, higher baseline plasma PFAS concentrations were associated with a greater weight regain, especially in women, possibly explained by a slower regression of RMR levels. These data illustrate a potential novel pathway through which PFASs interfere with human body weight regulation and metabolism. The possible impact of environmental chemicals on the obesity epidemic therefore deserves attention.

Trial Registration: ClinicalTrials.gov NCT00072995.
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http://dx.doi.org/10.1371/journal.pmed.1002502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810983PMC
February 2018

Bisphenol A substitutes and obesity in US adults: analysis of a population-based, cross-sectional study.

Lancet Planet Health 2017 Jun;1(3):e114-e122

Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.

Background: Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used to substitute bisphenol A (BPA), a widespread environmental endocrine disruptor and putative obesogen. However, studies on effects of BPF and BPS on obesity in humans are lacking. We examined the associations of BPA, BPF, and BPS exposure with obesity in U.S. adults.

Methods: We included 1,521 participants aged 20 years or older from a cross-sectional study, the National Health and Nutrition Examination Survey 2013-2014. Urinary BPA, BPF, and BPS concentrations were measured using on-line solid phase extraction coupled to high performance liquid chromatography and tandem mass spectrometry. We used body mass index and waist circumference to define general obesity and abdominal obesity, respectively. We used logistic regression with sample weights to estimate the odds ratios (ORs) of obesity and 95% confidence intervals.

Findings: Higher BPA, BPF, and BPS concentrations were observed in obese adults than non-obese adults. After adjustment for demographic, socioeconomic, lifestyle factors, and urinary creatinine concentrations, BPA, but not BPF or BPS, was significantly associated with obesity. The OR of general obesity was 1.78 (1.10-2.89) comparing the highest with lowest quartile of BPA, 1.02 (0.70-1.47) for BPF, and 1.22 (0.81-1.83) for BPS. The corresponding OR for abdominal obesity was 1.55 (1.04-2.32) for BPA, 1.05 (0.68-1.63) for BPF, and 1.16 (0.72-1.88) for BPS.

Interpretation: Whereas there were significant associations of BPA exposure with general and abdominal obesity, BPF or BPS, at current exposure level, was not significantly associated with obesity in U.S. adults. Continued biomonitoring of these bisphenols in populations and further investigations on their health effects in humans are warranted.
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http://dx.doi.org/10.1016/S2542-5196(17)30049-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751959PMC
June 2017

Exposure to perchlorate, nitrate and thiocyanate, and prevalence of diabetes mellitus.

Int J Epidemiol 2017 12;46(6):1913-1923

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: It is known that perchlorate, nitrate and thiocyanate have the property of inhibiting sodium iodide symporter. Animal studies have suggested that these compounds, especially perchlorate, might also interfere with insulin secretion. However, the association between their exposure and diabetes risk is largely unknown in humans.

Methods: Among 11 443 participants (mean age 42.3 years) from the National Health and Nutritional Examination Survey 2001-14, urinary perchlorate, nitrate and thiocyanate were measured by using ion chromatography coupled with electrospray tandem mass spectrometry. Diabetes was defined as self-reported doctor diagnosis, use of oral hypoglycaemic medication or insulin, fasting plasma glucose ≥ 126 mg/dl or glycated haemoglobin A1c (HbA1c) ≥ 6.5%.

Results: The median (interquartile range) levels of urinary perchlorate, nitrate and thiocyanate were 3.32 (1.84, 5.70) μg/l, 46.4 (27.9, 72.0) mg/l and 1.23 (0.59, 2.78) mg/l, respectively. Higher levels of urinary perchlorate were associated with elevated levels of fasting glucose, HbA1c, insulin and homeostatic model assessment of insulin resistance (all Ptrend < 0.001). After multivariate adjustment including urinary creatinine, smoking status and body mass index (BMI), higher urinary perchlorate, but not nitrate or thiocyanate, was associated with an increased prevalence of diabetes mellitus. Comparing extreme quintiles, the odds ratio (95% confidence interval) of diabetes was 1.53 (1.21, 1.93; Ptrend < 0.001) for perchlorate, 1.01 (0.77, 1.32; Ptrend = 0.44) for nitrate and 0.98 (0.73, 1.31; Ptrend = 0.64) for thiocyanate. When urinary perchlorate, nitrate and thiocyanate were further mutually adjusted, the results did not materially change. Similar results were observed when analyses were stratified by smoking status, as well as by age, gender, kidney function and BMI.

Conclusions: Higher urinary perchlorate levels are associated with an increased prevalence of diabetes mellitus, independent of traditional risk factors. Future prospective studies are needed to confirm these findings.
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http://dx.doi.org/10.1093/ije/dyx188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837594PMC
December 2017

Individual and Joint Effects of Early-Life Ambient Exposure and Maternal Prepregnancy Obesity on Childhood Overweight or Obesity.

Environ Health Perspect 2017 06 14;125(6):067005. Epub 2017 Jun 14.

Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA

Background: Although previous studies suggest that exposure to traffic-related pollution during childhood increases the risk of childhood overweight or obesity (COWO), the role of early life exposure to fine particulate matter (aerodynamic diameter <2.5 μm; PM) and its joint effect with the mother’s prepregnancy body mass index (MPBMI) on COWO remain unclear.

Objectives: The present study was conducted to examine the individual and joint effects of ambient PM exposures and MPBMI on the risk of COWO.

Methods: We estimated exposures to ambient PM and during the first 2 y of life (F2YL), using data from the U.S. Environmental Protection Agency’s (EPA’s) Air Quality System matched to residential address, in 1,446 mother–infant pairs who were recruited at birth from 1998 and followed up prospectively through 2012 at the Boston Medical Center in Massachusetts. We quantified the individual and joint effects of PM exposure with MPBMI on COWO, defined as the child’s age- and sex-specific BMI -score ≥85th percentile at the last well-child care visit between 2 and 9 y of age. Additivity was assessed by estimating the reduced excess risk due to interaction.

Results: Comparing the highest and lowest quartiles of PM, the adjusted relative risks (RRs) [95% confidence intervals (CIs)] of COWO were 1.3 (95% CI: 1.1, 1.5), 1.2 (95% CI: 1.0, 1.4), 1.2 (95% CI: 1.0, 1.4), 1.3 (95% CI: 1.1, 1.6), 1.3 (95% CI: 1.1, 1.5) and 1.3 (1.1, 1.5) during preconception; the first, second, and third trimesters; the entire period of pregnancy; and F2YL, respectively. Spline regression showed a dose–response relationship between PM levels and COWO after a threshold near the median exposure (10.46 μg/m–10.89 μg/m). Compared with their counterparts, children of obese mothers exposed to high levels of PM had the highest risk of COWO [RR≥2.0, relative excess risk due to interaction (RERI) not significant].

Conclusions: In the present study, we observed that early life exposure to PM may play an important role in the early life origins of COWO and may increase the risk of COWO in children of mothers who were overweight or obese before pregnancy beyond the risk that can be attributed to MPBMI alone. Our findings emphasize the clinical and public health policy relevance of early life PM exposure. https://doi.org/10.1289/EHP261
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http://dx.doi.org/10.1289/EHP261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743454PMC
June 2017

Cooking Methods for Red Meats and Risk of Type 2 Diabetes: A Prospective Study of U.S. Women.

Diabetes Care 2017 08 13;40(8):1041-1049. Epub 2017 Jun 13.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA

Objective: This study examined different cooking methods for red meats in relation to type 2 diabetes (T2D) risk among U.S. women who consumed red meats regularly (≥2 servings/week).

Research Design And Methods: We monitored 59,033 women (1986-2012) aged 30-55 years and free of diabetes, cardiovascular disease, and cancer at baseline when information on frequency of different cooking methods for red meats, including broiling, barbequing, roasting, pan-frying, and stewing/boiling, was collected.

Results: During 1.24 million person-years of follow-up, we documented 6,206 incident cases of T2D. After multivariate adjustment including red meat cooking methods, total red meat and processed red meat intake were both associated with a monotonically increased T2D risk (both trend <0.05). After multivariate adjustment including total red meat intake, a higher frequency of broiling, barbequing, and roasting red meats was each independently associated with a higher T2D risk. When comparing ≥2 times/week with <1 time/month, the hazard ratios (HRs) and 95% CI of T2D were 1.29 (1.19, 1.40; trend <0.001) for broiling, 1.23 (1.11, 1.38; trend <0.001) for barbequing, and 1.11 (1.01, 1.23; trend = 0.14) for roasting. In contrast, the frequency of stewing/boiling red meats was not associated with T2D risk, and an inverse association was observed for pan-frying frequency and T2D risk. The results remained similar after cooking methods were further mutually adjusted.

Conclusions: Independent of total red meat consumption, high-temperature and/or open-flame cooking methods for red meats, especially broiling and barbequing, may further increase diabetes risk among regular meat eaters.
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http://dx.doi.org/10.2337/dc17-0204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521980PMC
August 2017