Incident Type 2 Diabetes Cases Research Articles

Long-term exposure to air pollutants (PM2.5and NO2) and incidence of type 2 diabetes in the Mexican Teachers’ Cohort.

Background/Aim: Air pollution is a risk factor for type 2 diabetes (T2D). However, no longitudinal studies have evaluated this association in a low- and middle-income countries, where 80% of the worldwide cases of T2D occur. Our aim was to evaluate the association between incident T2D and long-term exposure to PM2.5 and NO2 in the Mexican Teachers’ Cohort (MTC). Methods: We selected a subsample of female teachers from the MTC who lived and worked in the Mexico City Metropolitan Area, recruited in 2008 and with active follow-up every 3 years (n = 14,194). We assigned the time-weighted exposures (PM2.5 and NO2) in home and work addresses, from 12 months before baseline to failure or censoring. We developed two high resolution (1km x 1km) spatio-temporal predictive Generalized Additive Models of PM2.5 and NO2. We defined incident T2D when teachers self-reported at least two of the following questions: have a medical diagnosis, use of medical treatment, or date of diagnosis. We fitted time-varying Cox models to estimate hazard ratios of the relation between PM2.5 and NO2 and incident T2D; adjusting for confounding variables: age, passive and active smoking status, physical activity, SES, wood smoking and time spent outdoors. Results: Teachers were followed up for 11.5 years. There were 795 incident T2D cases (84 cases per 100,000 person-months). Incident T2D increased by 80% (HR = 1.8[1.6-2.1]) for each 10 μg/m3 increase of PM2.5 and 60% for every 10 ppb of NO2 (HR = 1.6[1.4-1.9]). In two-pollutant models, effects were attenuated. Conclusions: PM2.5 and NO2 increased the risk of T2D in Mexico, in a larger magnitude than previous published studies. Despite improvements in air quality, there are still health risks related to current pollutant levels, arguing for even stricter regulation.

Intentional weight loss as a predictor of type 2 diabetes occurrence in a general adult population

IntroductionObservational and intervention studies have verified that weight loss predicts a reduced type 2 diabetes (T2D) risk. At the population level, knowledge on the prediction of self-report intentional weight loss...

Egg consumption and risk of type 2 diabetes: findings from 3 large US cohort studies of men and women and a systematic review and meta-analysis of prospective cohort studies

Whether egg consumption is associated with the risk of type 2 diabetes (T2D) remains unsettled. We evaluated the association between egg consumption and T2D risk in 3 large US prospective cohorts, and performed a systematic review and meta-analysis of prospective cohort studies. We followed 82,750 women from the Nurses' Health Study (NHS; 1980-2012), 89,636 women from the NHS II (1991-2017), and 41,412 men from the Health Professionals Follow-up Study (HPFS; 1986-2016) who were free of T2D, cardiovascular disease, and cancer at baseline. Egg consumption was assessed every 2-4 y using a validated FFQ. We used Cox proportional hazard models to estimate HRs and 95% CIs. During a total of 5,529,959 person-years of follow-up, we documented 20,514 incident cases of T2D in the NHS, NHS II, and HPFS. In the pooled multivariable model adjusted for updated BMI, lifestyle, and dietary confounders, a 1-egg/d increase was associated with a 14% (95% CI: 7%, 20%) higher T2D risk. In random-effects meta-analysis of 16 prospective cohort studies (589,559 participants; 41,248 incident T2D cases), for each 1 egg/d, the pooled RR of T2D was 1.07 (95% CI: 0.99, 1.15; I2=69.8%). There were, however, significant differences by geographic region (P for interaction=0.01). Each 1 egg/d was associated with higher T2D risk among US studies (RR: 1.18; 95% CI: 1.10, 1.27; I2=51.3%), but not among European (RR: 0.99; 95% CI: 0.85, 1.15; I2=73.5%) or Asian (RR: 0.82; 95% CI: 0.62, 1.09; I2=59.1%) studies. Results from the updated meta-analysis show no overall association between moderate egg consumption and risk of T2D. Whether the heterogeneity of the associations among US, European, and Asian cohorts reflects differences in egg consumption habits warrants further investigation.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019127860.

Epigenetic Changes in Islets of Langerhans Preceding the Onset of Diabetes.

The identification of individuals with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention. Here, we used a translational approach and prediction criteria to identify changes in DNA methylation visible before the development of T2D. Islets of Langerhans were isolated from genetically identical 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and in liver fat content. The application of a semiexplorative approach identified 497 differentially expressed and methylated genes (P = 6.42e-09, hypergeometric test) enriched in pathways linked to insulin secretion and extracellular matrix-receptor interaction. The comparison of mouse data with DNA methylation levels of incident T2D cases from the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort, revealed 105 genes with altered DNA methylation at 605 cytosine-phosphate-guanine (CpG) sites, which were associated with future T2D. AKAP13, TENM2, CTDSPL, PTPRN2, and PTPRS showed the strongest predictive potential (area under the receiver operating characteristic curve values 0.62–0.73). Among the new candidates identified in blood cells, 655 CpG sites, located in 99 genes, were differentially methylated in islets of humans with T2D. Using correction for multiple testing detected 236 genes with an altered DNA methylation in blood cells and 201 genes in diabetic islets. Thus, the introduced translational approach identified novel putative biomarkers for early pancreatic islet aberrations preceding T2D.

Development and validation of a model for predicting incident type 2 diabetes using quantitative clinical data and a Bayesian logistic model: A nationwide cohort and modeling study.

Obesity is closely related to the development of insulin resistance and type 2 diabetes (T2D). The prevention of T2D has become imperative to stem the rising rates of this disease. Weight loss is highly effective in preventing T2D; however, the at-risk pool is large, and a clinically meaningful metric for risk stratification to guide interventions remains a challenge. The objective of this study is to predict T2D risk using full-information continuous analysis of nationally sampled data from white and black American adults age ≥45 years. A sample of 12,043 black (33%) and white individuals from a population-based cohort, REasons for Geographic And Racial Differences in Stroke (REGARDS) (enrolled 2003-2007), was observed through 2013-2016. The mean participant age was 63.12 ± 8.62 years, and 43.7% were male. Mean BMI was 28.55 ± 5.61 kg/m2. Risk factors for T2D regularly recorded in the primary care setting were used to evaluate future T2D risk using Bayesian logistic regression. External validation was performed using 9,710 participants (19% black) from Atherosclerotic Risk in Communities (ARIC) (enrolled 1987-1989), observed through 1996-1998. The mean participant age in this cohort was 53.86 ± 5.65 years, and 44.6% were male. Mean BMI was 27.15 ± 4.92 kg/m2. Predictive performance was assessed using the receiver operating characteristic (ROC) curves and area under the curve (AUC) statistics. The primary outcome was incident T2D. By 2016 in REGARDS, there were 1,602 incident cases of T2D. Risk factors used to predict T2D progression included age, sex, race, BMI, triglycerides, high-density lipoprotein, blood pressure, and blood glucose. The Bayesian logistic model (AUC = 0.79) outperformed the Framingham risk score (AUC = 0.76), the American Diabetes Association risk score (AUC = 0.64), and a cardiometabolic disease system (using Adult Treatment Panel III criteria) (AUC = 0.75). Validation in ARIC was robust (AUC = 0.85). Main limitations include the limited generalizability of the REGARDS sample to black and white, older Americans, and no time to diagnosis for T2D. Our results show that a Bayesian logistic model using full-information continuous predictors has high predictive discrimination, and can be used to quantify race- and sex-specific T2D risk, providing a new, powerful predictive tool. This tool can be used for T2D prevention efforts including weight loss therapy by allowing clinicians to target high-risk individuals in a manner that could be used to optimize outcomes.

Profiles of Polyphenol Intake and Type 2 Diabetes Risk in 60,586 Women Followed for 20 Years: Results from the E3N Cohort Study.

Most studies on dietary polyphenol intake and type 2 diabetes (T2D) risk have focused on total or specific subclasses of polyphenols. Since polyphenols are often consumed simultaneously, the joint effect of an intake of multiple subclasses should be explored. We aimed to identify profiles of the dietary polyphenol subclasses intake associated with T2D. A total of 60,586 women from the Etude Epidémiologique auprès de femmes de l’Education Nationale (E3N) cohort study were followed for 20 years between 1993 and 2014. T2D cases were identified and validated. The individual energy-adjusted daily intakes of 15 subclasses of polyphenols were estimated at baseline using a food frequency questionnaire and the PhenolExplorer database. We used Bayesian profile regression to perform the clustering of the covariates by identifying exposure profiles of polyphenol intakes and, simultaneously, link these to T2D risk by using multivariable Cox regression models. We validated 2740 incident T2D cases during follow-up, and identified 15 distinct clusters with different intake profiles and T2D risk. When compared to the largest cluster (n = 6298 women), higher risks of T2D were observed in three of those clusters, which were composed of women with low or medium intakes of anthocyanins, dihydroflavonols, catechins, flavonols, hydroxybenzoic acids, lignans, and stilbenes. One cluster (n = 4243), characterized by higher intakes of these polyphenol subclasses, exhibited lower T2D risk when compared to the reference cluster. These results highlight the importance of a varied diet of polyphenol-rich foods such as nuts, fruits, and vegetables to prevent T2D risk.

Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

BackgroundDe novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D).Methods and findingsSeventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors.ConclusionsConcentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.

1373-P: Adherence to Healthy Lifestyle on Subsequent Risk of Type 2 Diabetes (T2D) among Women with a History of Gestational Diabetes Mellitus (GDM): A Prospective Cohort Study

Background: Women with a history of GDM are at exceptionally high risk of T2D but adopting a healthy lifestyle may mitigate this risk. Methods: We analyzed 4,287 women with a prior clinician diagnosis of GDM from the Nurses’ Health Study II cohort as part of the Diabetes and Women’s Health Study. Healthy lifestyle factors, which were assessed every 2-4 years, included no current smoking, normal body mass index (&amp;lt;25 kg/m2), regular moderate-to-vigorous physical activity (&amp;gt;500 MET-min/week), high-quality diet (above median for the Alternative Healthy Eating Index), and moderate alcohol consumption (&amp;gt;0-15 g/day). Self-reported incident T2D was confirmed via validated supplementary questionnaire (98% concordance with medical records). Multivariate-adjusted Cox models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI), adjusting for demographic, reproductive, and clinical characteristics. Results: We ascertained 835 incident T2D cases during a median 27.9 years of follow-up. Compared to women reporting no healthy lifestyle factors, HR (95% CI) for risk of T2D among those with 1, 2, 3, 4, or 5 factors were 0.91 (0.64, 1.30), 0.62 (0.44, 0.87), 0.45 (0.31, 0.64), 0.33 (0.22, 0.48), and 0.13 (0.06, 0.28), respectively (P&amp;lt;trend&amp;lt;0.001) (Table 1). When number of health lifestyle factors was modeled continuously, each additional factor was associated with a 29% lower risk of T2D, HR (95% CI): 0.71 (0.67, 0.76). In addition, &amp;gt;86% (population attributable risk [PAR]%: 86.3%; 95% CI: 70.6%, 93.7%) of T2D cases were theoretically preventable if participants had adherence to all 5 healthy lifestyle factors. Conclusion: Adherence to healthy lifestyle factors was associated with a substantially lower likelihood of progressing to T2D in women with a history of GDM, and strategies to improve long-term adherence are warranted. Disclosure F. Qian: None. J.E. Chavarro: None. S.H. Ley: None. D. Tobias: None. E. Yeung: None. M. Li: None. A. Liu: None. J. Mills: None. Q. Sun: None. F. Hu: None. C. Zhang: None.

The Insulinemic, Inflammatory, and Glycemic Potential of the Diet in Relation to Risk of Type 2 Diabetes

Abstract Objectives Dietary patterns that promote chronic systemic inflammation, hyperinsulinemia, or hyperglycemia may influence type 2 diabetes (T2D) risk. We evaluated an empirical dietary index for hyperinsulinemia (EDIH), empirical dietary inflammatory pattern (EDIP), glycemic index (GI), and glycemic load (GL), and risk of T2D among US postmenopausal women. EDIH and EDIP assess the insulinemic or inflammatory potential of habitual diets, irrespective of macronutrient content, and are based on plasma concentrations of insulin response or inflammatory biomarkers, respectively. The GI and GL assess postprandial glycemic potential based on carbohydrate content of the diet. Methods We calculated dietary scores from baseline food frequency questionnaires among 73,495 participants aged 50–79 years in the Women's Health Initiative Observational Study and Clinical Trials. We used multivariable-adjusted Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for risk of T2D according to quintiles of dietary scores. Results There were 11,009 incident cases of T2D during a median 13.3 years of follow-up. In multivariable-adjusted analyses, participants in the highest dietary score quintiles (consuming the most hyperinsulinemic, proinflammatory, or hyperglycemic diets) were at highest risk of T2D compared to those in the lowest quintiles: EDIH: HR, 1.54(1.37, 1.74); Ptrend &amp;lt; .0001; EDIP: HR, 1.45 (1.29, 1.64); Ptrend &amp;lt; .0001). GI and GL were not associated with T2D risk: GI: HR, 0.99 (0.88, 1.12); Ptrend = 0.94; GL: HR, 0.98 (0.85, 1.12); Ptrend = 0.32. In subgroup analyses, associations of EDIH and EDIP with T2D risk were stronger among overweight or obese than normal-weight women (Pinteraction: EDIH = 0.02, EDIP = 0.003), and findings did not significantly vary by race/ethnicity. Conclusions In this large sample of postmenopausal women, hyperinsulinemic, and pro-inflammatory dietary patterns were associated with higher risk of T2D, more so among overweight and obese women, whereas dietary glycemic potential was not associated with T2D risk. Funding Sources NCI grant # R00CA207736 and the WHI program is funded by NHLBI grant #s HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C.

Dietary Copper-Zinc Ratio and Type 2 Diabetes Risk in Women: The E3N Cohort Study

Abstract Objectives Trace elements are essential minerals that are required for a variety of biological processes. Zinc (Zn) is a trace element involved in many biological processes including regulation of insulin and glycaemia. It has been suggested that the serum copper (Cu) to Zn ratio could be of importance towards risk of diabetes. However, little is known about the effect of suboptimal intakes of these two competitive trace elements. We aimed to investigate the association between type 2 diabetes (T2D) incidence and the dietary Cu-Zn, ratio. Methods A total of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort study were followed for 20 years. The individual daily energy-adjusted intakes of Cu and Zn were estimated at baseline using a validated food frequency questionnaire. T2D cases were identified and validated using diabetes-specific questionnaires and drug reimbursement insurance databases. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) between dietary Cu-Zn ratio intakes and T2D risk. Interactions were tested between Cu-Zn ratio and smoking status and BMI on incident T2D. Results A total of 3292 incident T2D cases were identified during follow-up. A lower Cu-Zn ratio was associated with a lower risk of T2D. Compared to the 1st quintile group, women from the 2nd (HR 0.87 [95% CI 0.78, 0.97]) and 3rd (HR 0.89 [95% CI 0.79, 0.99]) quintile groups had a lower risk of T2D. Spline analysis showed that a Cu-Zn ratio intake &amp;lt; 0.30 was associated with a lower risk of T2D and that there was no departure from a linear association (P = 0.1180). There was an interaction between the Cu-Zn ratio and BMI on T2D risk (pInteraction = 0.0010) but not smoking status (pInteraction = 0.6956). Cu-Zn ratio was positively associated with T2D only in obese women, but not in normal-weight or overweight women. Conclusions Our findings suggest that a lower dietary Cu-Zn ratio intake is associated with a lower T2D risk, especially among obese women. Further studies are warranted to validate our results and determine whether the associations are similar in men. Funding Sources This work was supported by a grant for the E4N study project by the Agence Nationale de Recherche and by a grant for the Nutriperso Project (IDEX Paris Saclay).

Amino acid and lipid metabolism in post-gestational diabetes and progression to type 2 diabetes: A metabolic profiling study.

BackgroundWomen with a history of gestational diabetes mellitus (GDM) have a 7-fold higher risk of developing type 2 diabetes (T2D) during midlife and an elevated risk of developing hypertension and cardiovascular disease. Glucose tolerance reclassification after delivery is recommended, but fewer than 40% of women with GDM are tested. Thus, improved risk stratification methods are needed, as is a deeper understanding of the pathology underlying the transition from GDM to T2D. We hypothesize that metabolites during the early postpartum period accurately distinguish risk of progression from GDM to T2D and that metabolite changes signify underlying pathophysiology for future disease development.Methods and findingsThe study utilized fasting plasma samples collected from a well-characterized prospective research study of 1,035 women diagnosed with GDM. The cohort included racially/ethnically diverse pregnant women (aged 20–45 years—33% primiparous, 37% biparous, 30% multiparous) who delivered at Kaiser Permanente Northern California hospitals from 2008 to 2011. Participants attended in-person research visits including 2-hour 75-g oral glucose tolerance tests (OGTTs) at study baseline (6–9 weeks postpartum) and annually thereafter for 2 years, and we retrieved diabetes diagnoses from electronic medical records for 8 years. In a nested case–control study design, we collected fasting plasma samples among women without diabetes at baseline (n = 1,010) to measure metabolites among those who later progressed to incident T2D or did not develop T2D (non-T2D). We studied 173 incident T2D cases and 485 controls (pair-matched on BMI, age, and race/ethnicity) to discover metabolites associated with new onset of T2D. Up to 2 years post-baseline, we analyzed samples from 98 T2D cases with 239 controls to reveal T2D-associated metabolic changes. The longitudinal analysis tracked metabolic changes within individuals from baseline to 2 years of follow-up as the trajectory of T2D progression. By building prediction models, we discovered a distinct metabolic signature in the early postpartum period that predicted future T2D with a median discriminating power area under the receiver operating characteristic curve of 0.883 (95% CI 0.820–0.945, p < 0.001). At baseline, the most striking finding was an overall increase in amino acids (AAs) as well as diacyl-glycerophospholipids and a decrease in sphingolipids and acyl-alkyl-glycerophospholipids among women with incident T2D. Pathway analysis revealed up-regulated AA metabolism, arginine/proline metabolism, and branched-chain AA (BCAA) metabolism at baseline. At follow-up after the onset of T2D, up-regulation of AAs and down-regulation of sphingolipids and acyl-alkyl-glycerophospholipids were sustained or strengthened. Notably, longitudinal analyses revealed only 10 metabolites associated with progression to T2D, implicating AA and phospholipid metabolism. A study limitation is that all of the analyses were performed with the same cohort. It would be ideal to validate our findings in an independent longitudinal cohort of women with GDM who had glucose tolerance tested during the early postpartum period.ConclusionsIn this study, we discovered a metabolic signature predicting the transition from GDM to T2D in the early postpartum period that was superior to clinical parameters (fasting plasma glucose, 2-hour plasma glucose). The findings suggest that metabolic dysregulation, particularly AA dysmetabolism, is present years prior to diabetes onset, and is revealed during the early postpartum period, preceding progression to T2D, among women with GDM.Trial registrationClinicalTrials.gov Identifier: NCT01967030.

Contributions of amino acid, acylcarnitine and sphingolipid profiles to type 2 diabetes risk among South-Asian Surinamese and Dutch adults

IntroductionPeople of South Asian origin are at high risk of type 2 diabetes (T2D), but the underpinning mechanisms are not fully understood. We determined ethnic differences in acylcarnitine, amino acid...

Glycolysis/gluconeogenesis- and tricarboxylic acid cycle–related metabolites, Mediterranean diet, and type 2 diabetes

Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear. We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions. We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet+extra-virgin olive oil, MedDiet+nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC-tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-one-out cross-validation approach. Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D risk (17-44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1 y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons. We identified a panel of glycolysis/gluconeogenesis-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites.This trial was registered at controlled-trials.com as ISRCTN35739639.

Abstract P442: Periodontal Disease is Associated With Risk of Incident Diabetes Among Non-obese Individuals

Background: Strong evidence suggests that diabetes is a risk factor for periodontal disease and that periodontal disease, once established in the diabetic state, then contributes to worsened glycemic control. Recent studies suggest that periodontal disease is also associated with diabetes development. Hypothesis: Incident Type 2 Diabetes (T2D) rates will be higher among participants with baseline periodontal disease vs. those with periodontal health. The relationship is modified by Body Mass Index (BMI). Methods: We included 5586 diabetes-free eligible participants (aged 52-75 years) from Visit 4 (1996-1999) of The Atherosclerosis Risk in Communities (ARIC) Study. Participants received full-mouth periodontal exams and periodontal disease status was classified using Periodontal Profile Classes (PPC-Stages). T2D was defined based on participant-self report of physician diagnosis during annual telephone follow-ups. Time-to-event was computed from baseline through 2018. Competing risk, multivariable Cox proportional hazard models examined T2D and All-Cause Mortality risk according to baseline periodontal disease status. We tested the interaction with BMI. Multivariable adjustment was performed for race/center, age, gender, smoking and education. Results: Participants were mean age (SD) 62.4 (5.6), 55.0% female, 16.7% African American. During the average 21.1 years of follow-up there were 1,359 incident T2D cases and 1,531 deaths. Cumulative incidence rates were 24.3% and 27.4% for T2D and deaths, respectively. Among underweight participants, the hazard ratios[95%Cis] for incident diabetes among severe periodontitis or severe tooth loss (vs. periodontally healthy) were 1.84[1.14-2.96] and 2.29[1.57-3.33], respectively. Hazard ratios[95%Cis] among normal weight participants were 1.54[1.06-2.23] and 1.88[1.41-2.51], respectively. There were no significant associations with T2D in obese participants (p for interaction = 0.06. Conclusion: Severe periodontal disease was associated with a modestly increased risk for T2D among a multi-racial community-based sample. Two periodontal disease stages in the PPC-Stages index system are significantly associated with increased risk for incident diabetes. This periodontal disease-associated risk is modified by BMI levels and only associated with incident diabetes in study participants with lower BMI.

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.

Glucosamine Use, Inflammation, and Genetic Susceptibility, and Incidence of Type 2 Diabetes: A Prospective Study in UK Biobank.

Glucosamine is a widely used supplement typically taken for osteoarthritis and joint pain. Emerging evidence suggests potential links of glucosamine with glucose metabolism, inflammation, and cardiometabolic risk. We prospectively analyzed the association of habitual glucosamine use with risk of type 2 diabetes (T2D) and assessed whether genetic susceptibility and inflammation status might modify the association. This study analyzed 404,508 participants from the UK Biobank who were free of diabetes, cancer, or cardiovascular disease at baseline and completed the questionnaire on supplement use. Cox proportional hazards models were used to evaluate the association between habitual use of glucosamine and risk of incident T2D. During a median of 8.1 years of follow-up, 7,228 incident cases of T2D were documented. Glucosamine use was associated with a significantly lower risk of T2D (hazard ratio 0.83, 95% CI 0.78-0.89) after adjustment for age, sex, BMI, race, center, Townsend deprivation index, lifestyle factors, history of disease, and other supplement use. This inverse association was more pronounced in participants with a higher blood level of baseline C-reactive protein than in those with a lower level of this inflammation marker (P-interaction = 0.02). A genetic risk score for T2D did not modify this association (P-interaction = 0.99). Our findings indicate that glucosamine use is associated with a lower risk of incident T2D.

Intentional weight loss as a predictor of type 2 diabetes occurrence in a general population

AbstractObesity is a major risk factor of type 2 diabetes (T2D). Accordingly, weight loss is being used to reduce this risk. Intervention studies have shown a T2D risk reduction due to weight loss in populations with an elevated risk. Data on the prediction of intentional weight loss (IWL) on diabetes occurrence at population level is, however, sparse. Since in observational studies IWL has been shown to predict later weight gain, possibly leading to adverse consequences, this study examined the prediction of IWL on T2D occurrence in a general population. Data from the representative Finnish Health 2000 Survey conducted in 2000–2001 was used. The study sample consisted of 1962 men and 2308 women, aged 30–69. Information on IWL during the previous year was collected with a questionnaire. Data for the covariates was collected with a health examination, interviews and questionnaires. Incident T2D cases during a 15-year follow-up were drawn from national health registers covering information on medication use, hospitalization, and cause of death. The Cox model was used to estimate strength of association between IWL and T2D occurrence. During the follow-up, 417 individuals developed a T2D. After adjusting for socio-demographic and lifestyle factors and the components of metabolic syndrome, IWL predicted an increased risk of T2D occurrence (HR 1.44; 95% CI 1.11–1.87) compared to individuals without IWL. Moreover, in interaction analyses, the risk in individuals with IWL compared to those without IWL was pronounced in younger age group and in those with the lowest quality diet. Furthermore, an elevated risk was consistently found in persons with IWL and overweight (BMI ≥ 25 kg/m2), also in combination with different aspects of poor health (i.e. mental health, self-perceived health, metabolic health). In the present cohort, IWL predicted an increased subsequent risk of developing T2D. This may be due to that in long-term at population level IWL causes an elevated risk of T2D e.g. by acting as a promotor for weight gain or by causing weight cycling resulting in unfavorable changes in metabolic health indicators. Alternatively, it cannot be excluded, that individuals reporting IWL already are at a greater risk of T2D and pursue IWL in response to that. Greater emphasis should be put on the initial prevention of weight gain and on the support on the weight maintenance after weight loss. Further cohort studies with repeated measurements on dieting behavior and changes in weight are needed.

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.

Estimated Substitution of Tea or Coffee for Sugar-Sweetened Beverages Was Associated with Lower Type 2 Diabetes Incidence in Case–Cohort Analysis across 8 European Countries in the EPIC-InterAct Study

BackgroundBeverage consumption is a modifiable risk factor for type 2 diabetes (T2D), but there is insufficient evidence to inform the suitability of substituting 1 type of beverage for another. ObjectiveThe aim of this study was to estimate the risk of T2D when consumption of sugar-sweetened beverages (SSBs) was replaced with consumption of fruit juice, milk, coffee, or tea. MethodsIn the European Prospective Investigation into Cancer and Nutrition (EPIC)–InterAct case–cohort study of 8 European countries (n = 27,662, with 12,333 cases of incident T2D, 1992–2007), beverage consumption was estimated at baseline by dietary questionnaires. Using Prentice-weighted Cox regression adjusting for other beverages and potential confounders, we estimated associations of substituting 1 type of beverage for another on incident T2D. ResultsMean ± SD of estimated consumption of SSB was 55 ± 105 g/d. Means ± SDs for the other beverages were as follows: fruit juice, 59 ± 101 g/d; milk, 209 ± 203 g/d; coffee, 381 ± 372 g/d; and tea, 152 ± 282 g/d. Substituting coffee for SSBs by 250 g/d was associated with a 21% lower incidence of T2D (95% CI: 12%, 29%). The rate difference was −12.0 (95% CI: −20.0, −5.0) per 10,000 person-years among adults consuming SSBs ≥250 g/d (absolute rate = 48.3/10,000). Substituting tea for SSBs was estimated to lower T2D incidence by 22% (95% CI: 15%, 28%) or −11.0 (95% CI: −20.0, −2.6) per 10,000 person-years, whereas substituting fruit juice or milk was estimated not to alter T2D risk significantly. ConclusionsThese findings indicate a potential benefit of substituting coffee or tea for SSBs for the primary prevention of T2D and may help formulate public health recommendations on beverage consumption in different populations.