Lower Risk Of Type 2 Diabetes Research Articles

Abstract P132: Anti-Müllerian Hormone Levels and Risk of Type 2 Diabetes in Women

Introduction: Given its role in ovarian follicle development, circulating anti-Müllerian hormone (AMH) is correlated with timing of menopause. Accordingly, women with higher AMH levels become menopausal at a higher age. Previous research suggests that a higher age at menopause is associated with a decreased risk of type 2 diabetes (T2D). In contrast, AMH levels are increased in women with polycystic ovary syndrome (PCOS), who have a higher risk of insulin resistance and T2D than women without PCOS. However, it is not clear yet whether AMH actually plays a role in the development of T2D. We aimed to investigate whether plasma AMH levels and age-related AMH trajectories are associated with risk of T2D in women. Hypothesis: Higher age-specific plasma AMH levels are associated with a decreased risk of T2D. Methods: We analyzed longitudinal data from 3104 female participants, aged 20-60 years at recruitment, in the population-based Doetinchem Cohort Study. In total, we analyzed 12460 plasma AMH measurements. We calculated age-specific AMH tertiles, to account for the strong AMH-age correlation. Cox Proportional hazards models adjusted for known risk factors for diabetes were used to assess the relation between age-specific AMH tertiles and T2D. We applied linear mixed models to compare age-related AMH trajectories between T2D cases and non-cases. Results: After a median follow-up of 20 years, 163 incident T2D cases were identified. Higher age-specific AMH levels were associated with a lower risk of T2D (hazard ratio (HR) T2vsT1 = 0.77, 95%CI: 0.53-1.11; HR T3vsT1 =0.62, 95%CI: 0.40-0.94; p for trend = 0.02). These findings were supported by predicted AMH trajectories, which suggested that plasma AMH levels were lower at younger ages and declined at a slower rate in women who were diagnosed with T2D compared to women who were not. However, differences in trajectories between T2D cases and non-cases were not statistically significant. Conclusions: We observed that women with higher age-specific AMH levels were at a lower risk of T2D. In addition, our longitudinal analyses may suggest that AMH is lower in women who develop T2D compared to women who do not. These findings are in line with previous studies that observed that a higher age at menopause was associated with a decreased risk of T2D.

Circulating Very-Long-Chain SFA Concentrations Are Inversely Associated with Incident Type 2 Diabetes in US Men and Women

Background:Very-long-chain SFAs (VLCSFAs), such as arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have demonstrated inverse associations with cardiometabolic conditions, although more evidence is needed to characterize their relation with risk of type 2 diabetes (T2D). In addition, little is known regarding their potential dietary and lifestyle predictors. Objective:We aimed to examine the association of plasma and erythrocyte concentrations of VLCSFAs with incident T2D risk. Methods:We used existing measurements of fatty acid concentrations in plasma and erythrocytes among 2854 and 2831 participants in the Nurses´ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS), respectively. VLCSFAs were measured using GLC, and individual fatty acid concentrations were expressed as a percentage of total fatty acids. Incident T2D cases were identified by self-reports and confirmed by a validated supplementary questionnaire. Cox proportional hazards regression was used to evaluate the association between VLCSFAs and T2D, adjusting for demographic, lifestyle, and dietary variables. Results:During 39,941 person-years of follow-up, we documented 243 cases of T2D. Intakes of peanuts, peanut butter, vegetable fat, dairy fat, and palmitic/stearic (16:0–18:0) fatty acids were significantly, albeit weakly, correlated with plasma and erythrocyte VLCSFA concentrations (|rs| = 0.19). Comparing the highest with the lowest quartiles of plasma concentrations, pooled HRs (95% CIs) were 0.51 (0.35, 0.75) for arachidic acid, 0.43 (0.28, 0.64) for behenic acid, 0.40 (0.27, 0.61) for lignoceric acid, and 0.41 (0.27, 0.61) for the sum of VLCSFAs, after multivariate adjustments for demographic, lifestyle, and dietary factors. For erythrocyte VLCSFAs, only arachidic acid and behenic acid concentrations were inversely associated with T2D risk. Conclusions:Our findings suggest that, in US men and women, higher plasma concentrations of VLCSFAs are associated with lower risk of T2D. More research is needed to understand the mechanistic pathways underlying these associations.

Prospective associations between a food-based Indian Diet Quality Score and type 2 diabetes risk among South Indian adults (CURES-154)

Background: Asian Indians are culturally different and have diverse dietary and culinary habits. Further, there are potential biological differences in metabolism due to genetic or cultural factors. This warrants the development of a unique population-specific food-based diet score for prevention of noncommunicable disorders. Materials and Methods: Dietary intake was assessed using a validated food frequency questionnaire in 1033 adults who participated in the 10-year follow-up study of Chennai Urban Rural Epidemiological Study (CURES). The diet score was developed considering eight food groups and one major cooking oil that were either significantly associated with a higher or lower risk of incident type 2 diabetes (T2D). The foods that showed a protective effect was assigned higher scores and vice versa for foods that increased the risk of diabetes assigned the lower. We further assessed the effect of Indian Diet Quality score (IDQS) and three popular diet quality indices: the Healthy Eating Index-2015 (HEI), the Dietary Approach to Stop Hypertension (DASH), and Diabetes Diet Score (DDS) in relation to the risk of incidence of diabetes among Indian population. Results: Higher IDQS is associated with a significant lower risk of diabetes incidence; however, no such significant association was observed with diet quality indices (DASH, HEI-2015, and DDS) and diabetes incidence. This warrants the need for population-specific diet score for Indians. Conclusion: Higher IDQS was associated with a lower risk of T2D among South Indian adults. Thus, IDQS can be a suitable tool to identify the diet–disease relationship especially in a population with diverse dietary intakes.

Biomarkers of Vascular Injury and Type 2 Diabetes: A Prospective Study, Systematic Review and Meta-Analysis.

Data on biomarkers of vascular injury and type 2 diabetes (T2D) risk from prospective studies are lacking. We evaluated seven biomarkers of vascular injury in relation to T2D. Additionally, a meta-analysis was performed. From the EPIC–Heidelberg cohort, 2224 participants were followed-up from baseline for 16 (median) years. E-Selectin, P-Selectin, intercellular adhesion molecule 3 (ICAM3), thrombomodulin, thrombopoietin, glycoprotein IIb/IIIa and fibrinogen levels were measured in baseline blood samples. The systematic review and meta-analysis included prospective studies identified through MEDLINE and Web of Science that investigated the association between mentioned biomarkers and T2D. The study population included 55% women, median age was 50 years, and 163 developed T2D. ICAM3 was associated with lower T2D risk (fully adjusted HRhighest vs. lowest tertile 0.62 (95% CI: 0.43, 0.91)), but no other studies on ICAM3 were identified. Overall, fifteen studies were included in the systematic review and meta-analysis (6,171 cases). E-Selectin was associated with higher T2D risk HRper SD: 1.34 (95% CI: 1.16, 1.54; I2 = 63%, n = 9 studies), while thrombomodulin was associated with lower risk HRper SD: 0.82 (95% CI: 0.71, 0.95; I2 = 0%, n = 2 studies). In the EPIC–Heidelberg, ICAM3 was associated with lower T2D risk. The meta-analysis showed a consistent positive association between E-Selectin and T2D. It was also suggestive of an inverse association between thrombomodulin and T2D, although further studies are needed to corroborate this finding.

Changes in dairy product consumption and risk of type 2 diabetes: results from 3 large prospective cohorts of US men and women

Whether changes in dairy product consumption are related to subsequent risk of type 2 diabetes (T2D) remains unknown. We evaluated the association of long-term changes in dairy product consumption with subsequent risk of T2D among US men and women. We followed up 34,224 men in the Health Professionals Follow-Up Study (1986-2012), 76,531 women in the Nurses' Health Study (1986-2012), and 81,597 women in the Nurses' Health Study II (1991-2013). Changes in dairy consumption were calculated from consecutive quadrennial FFQs. Multivariable Cox proportional regression models were used to calculate HRs for T2D associated with changes in dairy product consumption. Results of the 3 cohorts were pooled using an inverse variance-weighted, fixed-effect meta-analysis. During 2,783,210 person-years, we documented 11,906 incident T2D cases. After adjustment for initial and changes in diet and lifestyle covariates, decreasing total dairy intake by >1.0 serving/d over a 4-y period was associated with an 11% (95% CI: 3%, 19%) higher risk of T2D in the subsequent 4 y compared with maintaining a relatively stable consumption (i.e., change in intake of ±1.0 serving/wk). Increasing yogurt consumption by >0.5 serving/d was associated with an 11% (95% CI: 4%, 18%) lower T2D risk, whereas increasing cheese consumption by >0.5 serving/d was associated with a 9% (95% CI: 2%, 16%) higher risk compared with maintaining stable intakes. Substituting 1 serving/d of yogurt or reduced-fat milk for cheese was associated with a 16% (95% CI: 10%, 22%) or 12% (95% CI: 8%, 16%) lower T2D risk, respectively. Increasing yogurt consumption was associated with a moderately lower risk of T2D, whereas increasing cheese consumption was associated with a moderately higher risk among US men and women. Our study suggests that substituting yogurt or reduced-fat milk for cheese is associated with a lower risk of T2D.

The Impact of Dairy Products in the Development of Type 2 Diabetes: Where Does the Evidence Stand in 2019?

ABSTRACTThe prevalence of type 2 diabetes (T2D) has increased rapidly. Adopting a heathy diet is suggested as one of the effective behaviors to prevent or delay onset of T2D. Dairy consumption has been recommended as part of a healthy diet, but there remains uncertainty in both the scientific community and the public about the effect of different dairy products on T2D risk. In a recent workshop, the evidence on dairy products and T2D risk was presented and discussed by a group of experts. The main conclusions from the workshop are presented in this position paper and are as follows. 1) Available evidence from large prospective cohort studies and limited randomized controlled trials (RCTs) suggests that total dairy consumption has a neutral or moderately beneficial effect on T2D risk. 2) Increasing evidence from prospective cohort studies indicates that yogurt is most strongly associated with a lower T2D risk, but evidence from RCTs is scarce. 3) Fatty acids from dairy (medium-chain, odd, and very long-chain SFAs as well as trans-palmitoleic acid) are associated with lower T2D risk and improved metabolic health, but more research is needed on studies that explore cause and effect relations to exclude the possibility that the dairy fatty acids simply serve as markers of overall dairy consumption. 4) The food matrix can be a stronger determinant of health effects than SFA content. This review further identifies research gaps in the existing knowledge and highlights key research questions that need to be addressed to better understand the impact of dairy consumption on future T2D risk.

A Dietary Pattern Derived from Reduced Rank Regression and Fatty Acid Biomarkers Is Associated with Lower Risk of Type 2 Diabetes and Coronary Artery Disease in Chinese Adults

Combinations of circulating fatty acids may affect the risk of type 2 diabetes (T2D) and coronary artery disease (CAD). No previous studies have identified a dietary pattern predicting fatty acid profiles using reduced rank regression (RRR) and evaluated its associations with the risk of T2D and CAD. The aim of this study was to derive a dietary pattern to explain variation in plasma fatty acid concentrations using RRR and evaluate these in relation to risk of T2D and CAD. We derived a dietary pattern using fatty acid concentrations from 711 controls of a nested case-control study in the Singapore Chinese Health Study using RRR with 36 food and beverages as predictors and 19 fatty acid biomarkers as responses. Dietary pattern scores were then calculated for the full cohort of men and women (mean age: 56 y). We followed up 45,411 and 58,065 participants for incident T2D and CAD mortality, respectively. Multivariable Cox regression models were used to estimate HRs and 95% CIs. We identified a dietary pattern high in soy, vegetables, fruits, tea, tomato products, bread, fish, margarine and dairy, and low in rice, red meat, coffee, alcohol, sugar-sweetened beverages, and eggs. This pattern predicted higher circulating n-3 (ω-3) PUFAs (18:3n-3, 20:3n-3, 20:5n-3), odd-chain fatty acids (15:0, 17:0), 18:2n-6 and 20:1, and lower 20:4n-6 and 16:1. During a mean follow-up of 11 y and 19 y, 5207 T2D and 3016 CAD mortality events, respectively, were identified. Higher dietary pattern scores were associated with a lower risk of T2D [multivariable-adjusted HR comparing extreme quintiles, 0.86 (95% CI: 0.79, 0.95); P-trend<0.001] and CAD mortality [HR, 0.76 (95% CI: 0.68, 0.86); P-trend<0.001]. Dietary patterns reflecting higher circulating n-3 PUFAs, odd-chain fatty acids, and linoleic acid may be associated with lower T2D and CAD risk in Chinese adults. This trial was registered at www.clinicaltrials.gov as NCT03356340.

Legume Consumption and Cardiometabolic Health

Legumes are key components of several plant-based diets and are recognized as having a wide range of potential health benefits. Previous systematic reviews and meta-analyses have summarized the evidence regarding different cardiometabolic outcomes, such as cardiovascular disease (CVD) and type 2 diabetes (T2D), and legume consumption. However, those studies did not differentiate between nonsoy and soy legumes, which have different nutritional profiles. The aim of the present updated review, therefore, was to summarize and meta-analyze the published evidence regarding legume consumption (making a distinction between nonsoy and soy legumes) and cardiometabolic diseases. In addition, we reviewed randomized clinical trials assessing the effect of legume consumption on CVD risk factors in order to understand their associations. The results revealed a prospective, significant inverse association between total legume consumption and CVD and coronary heart disease risk, whereas a nonsignificant association was observed with T2D and stroke. In the stratified analysis by legume subtypes, only nonsoy legumes were associated with lower risk of T2D. Unfortunately, owing to the paucity of studies analyzing legumes and CVD, it was not possible to stratify the analysis for these outcomes. Because of the high degree of heterogeneity observed for most of the outcomes and the few studies included in some analyses, further prospective studies are warranted to determine the potential role of legume consumption on CVD and T2D.

Cholesteryl Ester Transfer Protein Genetic Variants Associated with Risk for Type 2 Diabetes and Diabetic Kidney Disease in Taiwanese Population.

Cholesteryl ester transfer protein (CETP) plays an important role in lipid metabolism. Low levels of high-density lipoprotein cholesterol (HDL-C) increase the risk of type 2 diabetes (T2D). This study investigated CETP gene variants to assess the risk of T2D and specific complications of diabetic kidney disease (DKD) and diabetic retinopathy. Towards this, a total of 3023 Taiwanese individuals (1383 without T2D, 1640 with T2D) were enrolled in this study. T2D mice (+Leprdb/+Leprdb, db/db) were used to determine CETP expression in tissues. The A-alleles of rs3764261, rs4783961, and rs1800775 variants were found to be independently associated with 2.86, 1.71, and 0.91 mg/dL increase in HDL-C per allele, respectively. In addition, the A-allele of rs4783961 was significantly associated with a reduced T2D risk (odds ratio (OR), 0.82; 95% confidence interval (CI), 0.71–0.96)), and the A-allele of rs1800775 was significantly related to a lowered DKD risk (OR, 0.78; 95% CI, 0.64–0.96). CETP expression was significantly decreased in the T2D mice kidney compared to that in the control mice (T2D mice, 0.16 ± 0.01 vs. control mice, 0.21 ± 0.02; p = 0.02). These collective findings indicate that CETP variants in the promoter region may affect HDL-C levels. Taiwanese individuals possessing an allele associated with higher HDL-C levels had a lower risk of T2D and DKD.

Association Between Clinically Meaningful Posttraumatic Stress Disorder Improvement and Risk of Type 2 Diabetes

Posttraumatic stress disorder (PTSD) is associated with increased risk of type 2 diabetes (T2D). Improvement in PTSD has been associated with improved self-reported physical health and hypertension; however, there is no literature, to our knowledge, on whether PTSD improvement is associated with T2D risk. To examine whether clinically meaningful PTSD symptom reduction is associated with lower risk of T2D. This retrospective cohort study examined Veterans Health Affairs medical record data from 5916 patients who received PTSD specialty care between fiscal years 2008 and 2012 and were followed up through fiscal year 2015. Eligible patients had 1 or more PTSD Checklist (PCL) scores of 50 or higher between fiscal years 2008 and 2012 and a second PCL score within the following 12 months and at least 8 weeks after the first PCL score of 50 or higher. The index date was 12 months after the first PCL score. Patients were free of T2D diagnosis or an antidiabetic medication use for 12 months before the index date and had at least 1 visit after the index date. Data analyses were completed during January 2019. Reduction in PCL scores during a 12-month period was used to define patients as those with a clinically meaningful improvement (≥20-point PCL score decrease) and patients with less or no improvement (<20-point PCL score decrease). Incident T2D diagnosed during a 2- to 6-year follow-up. Medical records from a total of 1598 patients (mean [SD] age, 42.1 [13.4] years; 1347 [84.3%] male; 1060 [66.3%] white) were studied. The age-adjusted cumulative incidence of T2D was 2.6% among patients with a clinically meaningful PCL score decrease and 5.9% among patients without a clinically meaningful PCL score decrease (P = .003). After control for confounding, patients with a clinically meaningful PCL score decrease were significantly less likely to develop T2DM compared with those without a clinically meaningful decrease (hazard ratio, 0.51; 95% CI, 0.26-0.98). The findings suggest that clinically meaningful reductions in PTSD symptoms are associated with a lower risk of T2D. A decrease in PCL score, whether through treatment or spontaneous improvement, may help mitigate the greater risk of T2D in patients with PTSD.

Change in Cardiovascular Health and Incident Type 2 Diabetes and Impaired Fasting Glucose: The Whitehall II Study.

Most previous studies on cardiovascular health (CVH) and incident type 2 diabetes (T2D) have used a single measure of CVH, and none have investigated the association with impaired fasting glucose (IFG). We examined the association between changes in CVH and incident T2D and IFG. Within the Whitehall II study, CVH was examined every 5 years from 1991/93 until 2015/16. Subjects with 0-2, 3-4, and 5-6 ideal metrics of CVH from the American Heart Association were categorized as having low, moderate, or high CVH, respectively. There were 6,234 participants (mean age 49.8 ± 6.0 years, 70% male) without prior cardiovascular disease and T2D, including 5,015 who were additionally free from IFG at baseline. Over a median follow-up of 24.8 (interquartile range 24.0-25.2) years, 895 and 1,703 incident cases of T2D and IFG occurred, respectively. Change in CVH between 1991/93 and 2002/04 was calculated among 4,464 participants free from CVD and T2D and among 2,795 participants additionally free from IFG. In multivariate analysis, compared with those with stable low CVH, risk of T2D was lower in those with initially high CVH (hazard ratio [HR] 0.21; 95% CI 0.09, 0.51), those who had persistently moderate CVH or changed from moderate to high CVH (moderate-moderate/high; HR 0.53; 95% CI 0.41, 0.69), low-moderate/high (HR 0.62; 95% CI 0.45, 0.86), and moderate-low (HR 0.74; 95% CI 0.56, 0.98). Results were similar for IFG, but the effect sizes were smaller. Compared with stable low CVH, other patterns of change in CVH were associated with lower risk of T2D and IFG.

Methyl Donor Nutrient Intake and Risk of Type 2 Diabetes: Results from 3 Large US Cohorts (OR15-02-19)

ObjectivesDNA methylation may play a role in the development of type 2 diabetes (T2D). DNA methylation can be influenced by methyl donor nutrients such as vitamins B2, B6, B12, folate, and methionine, which are all central to one carbon metabolism. Using 3 large cohorts of US health professionals, we examined whether intake of these nutrients from food or supplements is associated with T2D risk. MethodsWe included 69,949 women from the Nurses’ Health Study (1984–2012), 90,239 women from the Nurses’ Health Study II (1991–2011), and 40,539 men from the Health Professionals Follow-Up Study (1986–2010). Dietary data were collected every 2–4 years using a validated semi-quantitative FFQ, from which dietary intakes of vitamin B2, vitamin B6, vitamin B12, folate, and methionine were calculated. We used Cox proportional hazards model with time-varying covariates and adjusted for several sociodemographic and lifestyle variables. We also adjusted for cereal fiber, animal protein, polyunsaturated and saturated fatty acids ratio. Food sources of vitamins were additionally adjusted for multivitamin use while supplemental sources of vitamins were adjusted for a measure of overall diet quality. ResultsDuring 1763,428 years of follow-up, we documented 8141 T2D cases. In pooled multivariable-adjusted analyses, compared to those in the lowest quintile, those in the highest quintile of vitamins B2 and B6 had a 10% (95% CI 3%–16%) and 11% (95% CI 3%–16%) lower T2D risk, respectively. Total vitamin B12 intake was not associated with T2D. However, when analyses were stratified by source, vitamin B12 from food sources was associated with a higher T2D risk (HR [95% CI] = 1.11 [1.02–1.19]). On the other hand, supplemental vitamin B12 was associated with lower T2D risk (HR [95% CI] for Q5 vs Q1 = 0.92 [0.85–0.98]). We found no evidence for an association between intakes of folate and methionine and T2D risk. ConclusionsOur study suggests that higher intakes of vitamin B2 and vitamin B6 are associated with a lower T2D risk. A higher vitamin B12 intake from food seems to be associated with a higher T2D risk, which may be due to consumption of animal products. Funding SourcesThe analysis was supported by grants from the National Institutes of Health.

159-OR: Changes in Dairy Product Consumption and Risk of Type 2 Diabetes among U.S. Men and Women

Background: The relationship between changes in dairy product consumption and risk of type 2 diabetes (T2D) has not been evaluated. Objective: We evaluated the association of 4-year changes in dairy product consumption with subsequent 4-year risk of T2D among U.S. men and women. Methods: We followed-up 35,148 men in the Health Professionals Follow-up Study (1986-2012), 78,357 women in the Nurses’ Health Study (1986-2012), and 82,937 women in the Nurses’ Health Study II (1991-2013). Diet was assessed using validated food frequency questionnaires every 4 years. Cox proportional regression models were used to calculate hazard ratios (HRs) for T2D associated with 4-year changes in dairy product consumption, with adjustment for initial dairy intake and multiple T2D risk factors including BMI and diet quality. Results of the 3 cohorts were pooled using an inverse variance-weighted, fixed-effect meta-analysis. Results: During 2,849,389 person-years of follow-up, we documented 12,007 incident T2D cases. Changes in milk consumption during a 4-year period were not associated with T2D risk in the following 4 years. Increasing yogurt consumption by &amp;gt;0.5 serving/day was associated with a 13% (95% CI: 6%, 19%) lower risk of T2D compared with maintaining a stable consumption. Increasing cheese consumption by &amp;gt;0.5 serving/day was associated with an 8% (95% CI: 2%, 16%) higher risk of T2D. Substituting reduced-fat milk for whole milk or low-fat cheese for high-fat cheese was not associated with subsequent T2D risk. However, increasing intake of yogurt or reduced-fat milk by 1 serving/day and concomitantly decreasing cheese intake by 1 serving/day was associated with a 16% (95% CI: 10%, 22%) and 11% (95% CI: 7%, 15%) lower risk of T2D, respectively. Conclusion: Increasing yogurt consumption was associated with a moderately lower risk of T2D, while increasing cheese consumption was associated with a moderately higher risk. Substituting yogurt or reduced-fat milk for cheese was associated with lower risk of T2D. Disclosure J. Drouin-Chartier: Other Relationship; Self; Dairy Farmers of Canada. Y. Li: None. A.V. Ardisson Korat: None. M. Ding: None. B. Lamarche: Advisory Panel; Self; Dairy Farmers of Canada. J.E. Manson: None. E. Rimm: Advisory Panel; Self; Take C/O, US Highbush Blueberry Council/USDA. W.C. Willett: None. F. Hu: None. Funding National Institutes of Health (UM1CA186107, UM1CA176726, UM1CA167552, DK112940, HL60712, HL118264); Canadian Institutes of Health Research (BPF-156628)

152-OR: Changes in Consumption of Sugary Beverages and Artificially Sweetened Beverages and Risk of Type 2 Diabetes among U.S. Women and Men

Background: Whether changes in consumption of sugary beverages or artificially sweetened beverages (ASBs) are associated with type 2 diabetes (T2D) risk has never been evaluated. Objective: We evaluated the association of changes in sugary beverage and ASB consumption over a 4-year period with subsequent 4-year risk of T2D among U.S. women and men. Methods: We followed-up 78,357 women in the Nurses’ Health Study (1986-2012), 82,937 women in the Nurses’ Health Study II (1991-2013) and 35,148 men in the Health Professionals Follow-up Study (1986-2012). Beverage intakes were assessed using validated food frequency questionnaires every 4 years. Cox proportional regression models were used to calculate hazard ratios (HRs) for T2D regarding 4-year changes in beverage consumption, adjusted for initial beverage intake and BMI. Results of the 3 cohorts were pooled using an inverse variance-weighted, fixed-effect meta-analysis. Results: During 2,849,389 person-years of follow-up, we documented 12,007 incident cases of T2D. Increasing sugary beverage intake by &amp;gt;0.5 serving/day over a 4-year period was associated with a 14% (95% CI: 7%, 21%) higher T2D risk compared with maintaining a stable consumption. Both beverages with added sugars (e.g., soft drinks) and 100% fruit juices were associated with higher T2D risk. Increasing ASB consumption by &amp;gt;0.5 serving/day was associated with a 19% (95% CI: 12%, 27%) higher T2D risk. Substituting ASB for sugary beverages was not associated with subsequent T2D risk (HR: 0.99, 95% CI: 0.96, 1.02). However, decreasing sugary beverage consumption and increasing water, coffee or tea intake by 1 serving/day was associated with a 3% to 11% lower risk of T2D. Conclusion: Increasing consumption of sugary beverages or ASBs was associated with a higher risk of T2D compared with maintaining a stable consumption of these beverages. Substituting water, coffee or tea but not ASB for sugary beverages was associated with lower T2D risk. Disclosure J. Drouin-Chartier: Other Relationship; Self; Dairy Farmers of Canada. Y. Zheng: None. Y. Li: None. V. Malik: None. A. Pan: None. J.E. Manson: None. W.C. Willett: None. F. Hu: None. Funding National Institutes of Health (UM1CA186107, UM1CA176726, UM1CA167552, DK112940, HL60712, HL118264); Canadian Institutes of Health Research (BPF-156628)

240-LB: Angiotensin-Converting Enzyme and Type 2 Diabetes Risk: A Mendelian Randomization Study

The causal relationship between angiotensin-converting enzyme (ACE) inhibition and protection from type 2 diabetes (T2D) remains uncertain. While three large randomized control trials (RCTs) suggested a protective effect of ACE inhibitors compared to placebo, three other RCTs failed to observe an effect, including the only trial dedicated to this question. We hypothesized that ACE concentration-lowering genetic variants could be used to infer the pharmacological effect of ACE inhibitors on T2D risk using a Mendelian Randomization (MR) approach. We first assessed the association between T2D prevalence and ACE serum level in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial (N=8,197). We next investigated whether genetically lowered ACE level was causally linked to the risk of T2D using (i) a two-sample MR analysis applied to the DIAbetes Genetics Replication And Meta-analysis consortium (n=26,676 T2D cases; 132,532 controls), and (ii) an ACE concentration-lowering genetic risk score in the UK Biobank cohort (N=341,872). We then compared the genetically determined effect of lower ACE level on T2D risk to the pharmacological inhibition of ACE vs. placebo, which was evaluated through a meta-analysis of six RCTs (N=31,200). Lower ACE serum level was associated with reduced T2D prevalence (OR, 0.89; 95% CI, 0.82-0.96; P=3.50x10-3) in the ORIGIN trial. Through MR analyses, a 1 SD lower genetically determined ACE level predicted a lower risk of T2D (OR, 0.92; 95% CI, 0.89-0.95; P=1.79x10-7). This result was replicated in the UK Biobank (OR, 0.97; 95% CI, 0.96-0.99, P=8.73x10-4). RCT meta-analysis showed a reduction in T2D incidence on ACE inhibitors vs. placebo (OR, 0.76; 95% CI, 0.60-0.97; P=2.59x10-2), which was consistent with the findings from MR analyses (P for comparison=0.95). Our results support a protective effect of long-term ACE inhibition on T2D risk and suggest to consider patient's risk for T2D when prescribing blood-pressure lowering drugs. Disclosure M. Pigeyre: None. J. Sjaarda: None. M. Chong: None. S. Hess: None. J. Bosch: Advisory Panel; Self; Bayer AG. S. Yusuf: None. H. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Sanofi. G. Pare: Consultant; Self; Amgen Inc., Bristol-Myers Squibb Company, Lexicomp, Sanofi. Research Support; Self; Canada Research Chair in Genetic and Molecular Epidemiology, CISCO Professorship in Integrated Health Biosystems, Sanofi. Funding Sanofi; Canadian Institutes of Health Research

Serum 25-hydroxyvitamin D3 and risk of type 2 diabetes among Japanese adults: the Hitachi Health Study

Increasing evidence has suggested a protective role of vitamin D on diabetes, but epidemiologic evidence is scarce among Asian populations. Here we prospectively examined the association between serum 25-hydroxyvitamin D3 (25[OH]D3) and type 2 diabetes (T2D) risk in Japanese individuals. A nested case-control study was conducted in a biomarker cohort of 4754 employees (baseline age 34-69 years) who had attended in a comprehensive health checkup and donated a blood sample. Diabetes diagnosis was based on plasma glucose, glycated hemoglobin, and self-reporting during the 5-year follow-up. Using density sampling, two controls were randomly matched to each case by sex, age, and date of checkup; 336 cases and 668 controls had serum 25(OH)D3 data. Association between serum 25[OH]D3 and the risk of T2D was assessed using conditional logistic regression analysis. Serum 25(OH)D3 was significantly and inversely associated with T2D risk after adjustment for known risk factors other than BMI (OR [highest vs. lowest serum 25(OH)D3 quartile]=0.58, 95% CI=0.36-0.92; P for trend=0.03). This association was somewhat attenuated after additional adjustment for BMI (OR=0.65, 95% CI=0.40-1.08; P for trend=0.08). The inverse association was more evident among individuals whose blood samples were taken during the darker season (OR=0.45; P for trend=0.01). In the highest quartile of 25(OH)D3, progression from prediabetes to T2D was about 37% lower than in the lowest quartile. Higher circulating 25(OH)D3 was associated with a lower risk of T2D, and this association was stronger among individuals whose blood was taken during the darker season and among those with prediabetes.

Associations of marital status with diabetes, hypertension, cardiovascular disease and all-cause mortality: A long term follow-up study.

BackgroundTo investigate the associations of marital status with major clinical outcomes including type 2 diabetes (T2D), hypertension, cardiovascular disease (CVD) and all-cause mortality.MethodsThe study cohort (1999–2014) included 9,737 (45% male) Iranian adults with a mean age of 47.6 years. Marital status was defined as married versus never married, divorced and widowed. The relationship between marital status and the four above mentioned outcomes were investigated using Cox regression models adjusted for the main confounders, specific to each outcome.ResultsAfter more than 12 years of follow-up, 1,889 (883 men) individuals developed hypertension, 1,038 (468 men) T2D, 1015 (597 men) CVD and 668 (409 men) all-cause mortality. Compared with married, being never married in men was associated with higher risk of hypertension [hazard ratio (HR): 1.55; 95% confidence interval (CI), 1.11–2.16] and all-cause mortality (2.17; 0.95–5.00; p-value = 0.066) after adjusting for confounders. Among women, compared with married status, widowed status was associated with a lower risk of T2D (0.74; 0.56–0.97) in the confounders adjusted model. Moreover, never married women had a lower risk of hypertension (0.58; 0.37–0.90) compared to married ones in the age adjusted model, a finding that did not achieve significance, after further adjustment for confounders.ConclusionWe found that the relationship between marital status and health outcomes varied by gender. Being never married was an important risk factor for hypertension and tended to be a significant risk factor for mortality in men. However, among women, being widowed was associated with a lower risk of T2D.

Developmental pathways and programming of diabetes: epidemiological aspects.

Type 2 diabetes (T2D) is a major, rapidly increasing global public health challenge. The major risk factors for T2D include overweight and obesity, lifestyle related factors and genetic factors. Early life exposures shape the developmental trajectories and alter susceptibility to T2D. Based on epidemiological studies it has been suggested that fetal undernutrition plays a role in the etiology of T2D. A low birth weight has been considered a proxy for fetal undernutrition. A meta-analysis reported that a 1 kg increase in birth weight is associated with a roughly 20% lower risk of T2D. Although fetal life is of major importance for future health, the period spanning the first 1 000 days of life, is characterized by great plasticity and largely influencing later health. Different growth trajectories during this time period have also been associated with an increased risk of T2D. Studies assessing the association between age at BMI rebound in childhood and later risk for T2D have reported a 5-fold difference in T2D according to age at BMI rebound. Developmental and epidemiological cohort studies focusing on T2D have major public health implications supporting a paradigm shift; a shift from focusing upon risk factor modification in adult life to adopting a life course perspective when studying T2D. This paradigm shift will not only help us in getting a better understanding of the pathophysiology underlying T2D, but it will also open new possibilities and opportunities in the prevention of T2D and related disorders.

Abstract MP43: Monounsaturated Fatty Acids From Plant or Animal Sources and Risk of Type 2 Diabetes in Three Large Prospective Cohorts of Men and Women

Background: Existing evidence on the relationship between intakes of monounsaturated fatty acids (MUFAs) and risk of developing type 2 diabetes (T2D) is conflicting. Few studies have examined whether MUFAs from plant or animal sources exhibit differential associations with T2D. Aims: To examine the association of intake of total, plant-based (MUFA-Ps), and animal-based MUFAs (MUFA-As) with T2D risk. Methods: We used data from three prospective cohorts which included 54,518 women in Nurses’ Health Study (1990-2012), 88,613 women in Nurses’ Health Study II (1991-2013), and 29,520 men in Health Professionals Follow-up Study (1990-2012). Using validated food-frequency questionnaires and food composition tables, we calculated the average MUFA-Ps and MUFA-As intake in every 4-year period and modeled their association with T2D using Cox regression models. Results: During 3,682,622 person-years of follow-up, we documented 13,077 incident cases of T2D. After multivariate adjustment, total MUFA intake was not associated with risk of T2D. In contrast, MUFA-Ps were associated with a lower risk of T2D, whereas MUFA-As were associated with a higher risk. In iso-caloric substitution analyses, the pooled hazard ratios (HRs) and 95% confidence intervals (CI) were 0.99 (0.88, 1.12; P =0.89) for saturated fat (SFAs, 5% of energy), 0.91 (0.85, 0.98; P =0.01) for refined carbohydrates (5% of energy), and 0.87 (0.80, 0.94; P =0.0006) for trans fats (2% of energy), when replaced by MUFA-Ps ( Table 1 ). Additionally, the HRs (95% CIs) were 0.67 (0.61, 0.73; P &lt;0.0001) and 0.78 (0.73, 0.83; P &lt;0.0001), respectively, for replacing 5% of energy in MUFA-As or the sum of SFAs and MUFA-As with MUFA-Ps. Conclusion: In three large prospective cohort studies, higher intakes of MUFA-Ps were associated with a lower risk of T2D, whereas increased intakes of MUFA-As was associated with higher risk. Replacing refined carbohydrates, trans fats, and MUFA-As with MUFA-Ps may be beneficial for the prevention of T2D.

Abstract 034: Omega-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-level Pooling Project of 20 Prospective Cohort Studies

Background: Effects of omega-3 fatty acids on the prevention of type 2 diabetes (T2D) are unclear. Relatively few prospective studies have utilized objective omega-3 biomarkers to assess risk. Aims: To assess the prospective relationship between circulating and tissue levels of alpha linoleic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with respect to risk of T2D. Methods: A global consortium of 20 prospective cohort studies from 14 nations with assessments of ALA, EPA, DPA, or DHA in adults (age &gt; 18 years) were identified through July 2017 and included in this investigation. A pre-specified analytic protocol, including definitions for exposures, covariate list, disease outcome definitions, and subgroup analyses was developed and followed in new participant-level cohort analysis. Associations were pooled using inverse variance-weighted meta-analysis. Results: Among 65,147 participants, 16,693 incident cases of T2D occurred during follow-up (median follow-up in the cohorts ranged from 2.5 to 21.2 years). In pooled multivariate analysis, per interquintile range (difference between the midpoints of the first and fifth quintile for each fatty acid), EPA, DPA, DHA, and their sum ( Figure 1 ) were associated with 8%, 21%, 18%, and 19% lower risk of T2D, respectively (all P &lt;0.001). Higher levels of ALA were not significantly associated with T2D. Associations were consistent across different lipid compartments and pre-specified subgroups, including by age, sex, and geographic region, as well as in several sensitivity analyses. Conclusion: Higher circulating and tissue biomarkers of seafood-derived omega-3 fatty acids, EPA, DPA, and DHA, were associated with lower risk of T2D in a global consortium of prospective studies. Plant-derived ALA was not significantly associated with risk.