Odds Of Type 2 Diabetes Research Articles

Polygenic Risk for Type 2 Diabetes in African Americans.

African Americans (AAs) have been underrepresented in polygenic risk score (PRS) studies. Herein, we integrated genome-wide data from multiple observational studies on type 2 diabetes (T2D), encompassing a total of 101,987 AAs, to train and optimize an AA focused T2D PRS (PRSAA), using a Bayesian polygenic modeling method (PRS-CS). We further tested the score in three independent studies with a total of 7,275 AAs. We then compared the PRSAA to other published scores. Results show that a 1 standard deviation increase in the PRSAA was associated with 40%-60% increase in the odds of T2D (OR=1.60, 95% CI 1.37-1.88; OR=1.40, 95% CI 1.16-1.70; and OR=1.45, 95% CI 1.30-1.62) across three testing cohorts. These models captured 1.0%-2.6% of the variance (R2) in T2D on the liability scale. The positive predictive values (PPV) for three calculated score thresholds (the top 2%, 5% 10%) ranged from 14% to 35%. The PRSAA, in general, performed similarly to existing T2D PRS. Larger datasets remain needed to continue to evaluate the utility of within-ancestry scores in the AA population.

Antioxidant Minerals Modified the Association between Iron and Type 2 Diabetes in a Chinese Population.

Inconsistent findings exist regarding the relationship between heme iron intake and type 2 diabetes (T2D) among Western and Eastern populations. Easterners tend to consume a plant-based diet which is abundant in antioxidant minerals. To examine the hypothesis that antioxidant mineral may modify the relationship between iron and T2D, we performed a case-control study by measuring the serum mineral levels in 2198 Chinese subjects. A total of 2113 T2D patients and 2458 controls were invited; 502 T2D patients and 1696 controls were finally analyzed. In the total population, high serum iron showed a positive association with T2D odds (odds ratio [OR] = 1.27 [1.04, 1.55]); high magnesium (OR = 0.18 [0.14, 0.22]), copper (OR = 0.27 [0.21, 0.33]), zinc (OR = 0.37 [0.30, 0.46]), chromium (OR = 0.61 [0.50, 0.74]), or selenium concentrations (OR = 0.39 [0.31, 0.48]) were inversely associated with T2D odds. In contrast, in individuals with higher magnesium (>2673.2 µg/dL), zinc (>136.7 µg/dL), copper (>132.1 µg/dL), chromium (>14.0 µg/dL), or selenium concentrations (>16.8 µg/dL), serum iron displayed no association with T2D (p > 0.05). Serum copper and magnesium were significant modifiers of the association between iron and T2D in individuals with different physiological status (p < 0.05). Our findings support the idea that consuming a diet rich in antioxidant minerals is an effective approach for preventing T2D.

Socioeconomic Inequalities in Type 2 Diabetes: Mediation Through Status Anxiety?

Objectives: While status anxiety has received attention as a potential mechanism generating health inequalities, empirical evidence is still limited. Studies have been ecological and have largely focused on mental and not physical health outcomes. Methods: We conducted individual-level analyses to assess status anxiety (feelings of inferiority resulting from social comparisons) and resources (financial difficulties) as mediators of the relationship between socioeconomic status (SES) (education/occupation/employment status) and type 2 diabetes (T2D). We used cross-sectional data of 21,150 participants (aged 18-70years) from the Amsterdam-based HELIUS study. We estimated associations using logistic regression models and estimated mediated proportions using natural effect modelling. Results: Odds of status anxiety were higher among participants with a low SES [e.g., OR = 2.66 (95% CI: 2.06-3.45) for elementary versus academic occupation]. Odds of T2D were 1.49 (95% CI: 1.12-1.97) times higher among participants experiencing status anxiety. Proportion of the SES-T2D relationship mediated was 3.2% (95% CI: 1.5%-7.0%) through status anxiety and 10.9% (95% CI: 6.6%-18.0%) through financial difficulties. Conclusion: Status anxiety and financial difficulties played small but consistent mediating roles. These individual-level analyses underline status anxiety's importance and imply that status anxiety requires attention in efforts to reduce health inequalities.

Adherence to diet with higher dietary diabetes risk reduction score is associated with reduced risk of type 2 diabetes incident in Iranian adults

BackgroundThe Dietary diabetes risk reduction score (DDRRS) has recently been considered by researchers as a diet quality index to predict the risk of chronic diseases, such as type 2 diabetes (T2D). In this study, we aimed to assess the association of DDRRS with T2D risk in Iranian adults.MethodsSubjects aged ≥ 40 years without T2D (n = 2081) were selected for the current study from participants of the Tehran Lipid and Glucose Study (2009–2011) and followed for a mean of 6.01 years. We used the food frequency questionnaire to determine the DDRRS that is characterized by eight components, including higher consumption of nuts, cereal fiber, coffee, and polyunsaturated to saturated fat ratio and lower consumption of red or processed meats, trans fats, sugar-sweetened beverages, and high glycemic index foods. The multivariable logistic regression analysis was used to determine the odds ratio (ORs) and 95% confidence interval (CI) of T2D across the DDRRS tertiles.ResultsThe mean ± SD age of individuals was 50.4 ± 8.2 years at baseline. The Median (25–75 interquartile range) DDRRS of the study population was 24(22–27). During the study follow-up, 233(11.2%) new cases of T2D were ascertained. In the age and sex-adjusted model, the odds of T2D were decreased across tertiles of DDRRS (OR = 0.68; 95%CI: 0.48–0.97, P for trend = 0.037). Based on the multivariable-adjusted model, after controlling all potential confounders, the risk of T2D is reduced across tertiles of DDRRS (OR = 0.66; 95%CI: 0.44–0.98, P for trend = 0.047). Also, higher scores (lower consumption) of red and processed meat (OR = 0.59; 95%CI: 0.39–0.88, P = 0.012) and sugar-sweetened beverages (OR = 0.49; 95%CI: 0.32–0.76, P = 0.002) as DDRRS components were associated with decreased T2D incident.ConclusionsOur findings suggested that a diet with a higher score of DDRRS may be related to reducing the risk of T2D in Iranian adults.

Genetic study of type 2 diabetes risk in diverse populations of survivors of childhood cancer: A report from the St. Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS).

10029 Background: Type 2 diabetes (T2D) is an established late effect of cancer treatment among long-term survivors of childhood cancer. Genetic factors underpinning T2D in diverse populations of survivors have not been well studied. Methods: We conducted a multi-ancestry genome-wide association study (GWAS) for clinically ascertained T2D among survivors of European (EUR; N = 3,102 with 261 cases) and African (AFR; N = 574 with 43 cases) ancestry from SJLIFE. Replication analyses were performed between ancestries in SJLIFE and in EUR survivors in CCSS (N = 5,965; 270 self-reported cases). Two published T2D polygenic risk scores (PRSs) were assessed in survivors: a 338-variant multi-ancestry PRS (N~1.4 million; 49% non-EUR descent) and a ~6.9 million-variant EUR-only PRS (N~160K; DIAGRAM Consortium and UK Biobank Study). Treatment-related T2D risk effect modification was evaluated for abdominal irradiation and alkylating agents. Results: In SJLIFE AFR survivors, one novel locus with suggestive significance was identified (5p15.2: OR = 10.19, P = 5.1x10-7), replicating in both SJLIFE EUR (P = 0.011) and CCSS EUR survivors (P = 0.021). A EUR-specific genome-wide significant association at 8q11.21 ( SNTG1 intronic variant; OR = 1.99; P = 4.4x10-8) was replicated in CCSS (P = 8.1x10-3). Two other loci with suggestive associations (P &lt; 5x10-6) in SJLIFE EUR survivors replicated in SJLIFE AFR survivors (P &lt; 0.05), achieving genome-wide significance in multi-ancestry meta-analysis (2p25.3: OR = 2.05, P = 4.5x10-8; 19p12: OR = 2.43 P = 5.7x10-9). Each of the three novel trans-ancestral loci overlapped putative Polycomb-repressed regions, i.e., chromatin-based gene regulation elements, in pancreatic cells and displayed treatment-related effect heterogeneity across ancestry groups. Notably, AFR survivors with risk alleles experienced disproportionately greater T2D risk if treated with alkylating agents (2p25.3: OR = 3.95; 19p12: OR = 5.74; 5p15.2: OR = 17.81). Increases in the T2D odds per multi-ancestry PRS standard deviation were consistent in survivors across ancestries (SJLIFE EUR: OR = 1.84, P = 1.1x10-16; SJLIFE AFR: OR = 1.80, P = 2.8x10-3, CCSS EUR: OR = 1.60, P = 8.4x10-13). However, T2D risk association with the EUR-only PRS was absent in AFR survivors (OR = 0.97, P = 0.95). Conclusions: Multi-ancestry genetic analyses revealed three novel T2D risk alleles associated with disproportionately greater alkylating agent-related risk among African-ancestry survivors. Furthermore, an external multi-ancestry T2D PRS was associated with increased risk in diverse ancestry survivors, whereas a EUR-only PRS was not useful for African-ancestry survivors. This study supports precision diabetes surveillance and survivorship care for all childhood cancer survivors, including those in minority ancestry groups.

Effects of residential greenness and genetic predisposition on hemoglobin A1c and type 2 diabetes: Gene-environment interaction analysis from a nationwide study

BackgroundCurrent evidence on the relations of residential greenness with glucose homeostasis and type 2 diabetes (T2D) remained largely uncertain. Most importantly, no prior studies have investigated whether genetic predisposition modifies the above associations. MethodsWe leveraged data from the UK Biobank prospective cohort study, with participants enrolled between 2006 and 2010. Residential greenness was assessed by using the Normalized Difference Vegetation Index, and the weighting T2D-specific genetic risk score (GRS) was constructed based on previously published genome-wide association studies. Linear regression models and logistic regression models were used to investigate associations of residential greenness with glycated hemoglobin (HbA1c) and T2D prevalence, respectively. Interaction models explored whether genetic predisposition modifies greenness-HbA1c/T2D associations. ResultsAmong 315,146 individuals (mean [SD] age, 56.59 [8.09] years), each one-unit increase in residential greenness was associated with reduction in HbA1c (β: −0.87, 95% CI: −1.16 to −0.58) and a 12% decrease in odds of T2D (OR: 0.88, 95% CI: 0.79 to 0.98), respectively. Additionally, interaction analyses further demonstrated that residential greenness and genetic risk had cumulative effects on HbA1c and T2D. Compared with individuals who were exposed to low greenness and had high GRS, participants with low GRS and high greenness had a significant decline in HbA1c (β: −2.96, 95% CI: −3.10 to −2.82, P for interaction = 0.04) and T2D (OR: 0.47, 95% CI: 0.45 to 0.50, P for interaction = 0.09). ConclusionsWe add novel evidence that residential greenness has protective effects on glucose metabolism and T2D, and those beneficial effects can be amplified by low genetic risk. Our findings may facilitate the improvement of the living environment and the development of prevention strategies by considering genetic susceptibility to T2D.

Abstract P164: Most Non-invasive Diabetes Risk Scores Identify Type 2 Diabetes Due To Insulin Resistance But Not β-cell Failure: The Africans In America Study

Background: Five of the most important Type 2 Diabetes (T2D) prediction scores are: Cambridge, Finnish Diabetes Risk Score (FINDRISC), Rotterdam, Kuwaiti and Omani. These scores are based on the premise that Insulin Resistance (IR) is the primary cause of T2D. Yet, data in Africans suggest β-cell-failure without obesity is the most common cause of T2D. It is unknown whether these scores can identify undiagnosed T2D when the cause is β-cell-failure. Aims: Our aim was to compare in 514 African-born Blacks (age 38±10 (mean±SD); 68% male; BMI 28±5 kg/m 2 ) the ability of Cambridge, FINDRISC, Rotterdam, Kuwait and Omani scores to identify previously undiagnosed T2D due to either IR or β-cell-failure. Methods: Diabetes was diagnosed by OGTT. Insulin resistance was defined by the lowest quartile of the Matsuda index (≤2.97). Beta-cell failure was defined as T2D diagnosis in the absence of IR. Body mass index (BMI), waist circumference (WC) and visceral adipose tissue (VAT) was measured. Area under the Receiver Operator Characteristic curve (AROC) estimated sensitivity, specificity, and criteria for AROC were: 0.70-0.79=acceptable; 0.80-0.89=excellent; &gt;0.90=outstanding. Logistic regression determined odds of T2D at the optimal cut-point for each score. Results: The prevalence of T2D was 7% (38/514). Of the T2D cases, IR occurred in 61% (23/38) and β-cell failure in 39% (15/38). Age did not differ by group, but the IR group had higher BMI (31±5 vs 27±4 kg/m 2 P &lt;0.001) and WC (101±10 vs 91±10 cm P &lt;0.001). This is supported by the higher VAT in the IR group (161±73 vs 106±62 cm 2 P &lt;0.001), an important physiological correlate of insulin resistance. All scores showed acceptable to outstanding predictability for T2D due to IR, ranging from Cambridge at AROC=0.75, to the FINDRISC with AROC=0.92. Only weak to moderate predictability for all scores were shown in β-cell-failure (Cambridge at AROC=0.48 to FINDRISC with AROC=0.63). All models predicted significant odds of T2D due to IR, with FINDRISC≥10 OR=6.8 (95%CI, 2.6, 17.8) P&lt;0 .001; Rotterdam≥7 OR=8.5 (95%CI, 3.1, 23.2) P&lt;0 .001; Cambridge≥23 OR=11.4 (95%CI, 2.6, 50.0) P =0.001) proving most effective. Only the Cambridge score significantly predicted odds of T2D in β-cell-failure (OR=5.7 (95%CI 1.58, 20.54) P =0.001). Conclusions: All 5 diabetes risk scores effectively predicted undiagnosed T2D in Africans when the etiology was IR, but only the Cambridge score predicted T2D when the cause was β-cell failure. The Cambridge risk score rates overweight status, not just obesity status, which might explain why it was successful in predicting T2D in β-cell failure and the others were not. Existing scores which predict T2D might be modified, to effectively assess T2D risk when β-cell failure is the primary cause.

Dietary habits are associated with the prevalence of type 2 diabetes: a study among a middle eastern population.

Worldwide type 2 diabetes (T2D) prevalence is increasing dramatically. The present study aimed to evaluate the association between dietary habits and T2D in an Iranian adult population using a cross-sectional analysis of the Shahedieh cohort study. Participants were adults aged 35-70 years (n 9261) from Zarch and Shahedieh, Yazd, Iran, who attended the baseline phase of the Shahedieh cohort study. Dietary habits including meal frequency, fried-food consumption, adding salt to prepared meals and grilled-food consumption were assessed by a standard questionnaire. T2D was defined as fasting plasma glucose (FPG) ≥126 mg/dl according to the American Diabetes Association. Multiple logistic regression assessed the association between dietary habits and T2D. Individuals who consumed a meal more than six times per day compared to three times per day had greater odds for T2D (OR 2⋅503, 95 % CI 1⋅651, 3⋅793). These associations remained significant in a fully adjusted model. There was a significant association between greater intakes of fried foods and prevalence of T2D (OR 1⋅294, 95 % CI 1⋅004, 1⋅668) in the adjusted model. No significant associations were observed between other dietary habits (adding salt to prepared meals and grilled-food consumption) and odds of T2D in all crude and adjusted models. In conclusion, we have highlighted the association between meal and fried-food consumption frequencies with risk of T2D. Large longitudinal studies in different ethnicities are needed to confirm these associations.

325-OR: Genetic and Socioeconomic Factors Are Independently Associated with Type 2 Diabetes

Genetics and socioeconomic status (SES) are key drivers of increased type 2 diabetes (T2D) risk, but the extent to which they impact disease in an additive or non-additive manner is unknown. We examined T2D prevalence using cross-sectional electronic health record (EHR) data from 27,771 participants of European ancestry in the Mass General Brigham Biobank. A polygenic score for T2D was derived using a previously published globally expanded score (gePS). Multiple area-based socioeconomic risk estimates were evaluated (including deprivation indices and a machine learning model incorporating hundreds of census variables) with similar impact on T2D risk; here, an individual’s estimated SES risk was defined as the percent of residents in their census tract with less than high school education. T2D status was derived using a machine-learning algorithm validated by expert chart review to have 90% positive predictive value. The age and sex-adjusted odds of T2D was 1.72 (95% CI 1.63-1.81, p&amp;lt;0.001) per SD increase of T2D gePS and 1.36 (95% CI 1.31-1.42, p&amp;lt;0.001) per SD increase in socioeconomic risk. In a combined model of gePS and socioeconomic risk, these associations persisted, with no evidence of interaction. Persons in the highest quintile of both genetic and socioeconomic risk had an almost 3-fold risk of T2D compared to those of middle quintile risk for both (OR 2.67, 95% CI 2.08-3.44, p&amp;lt;0.001). Notably, the T2D risk of individuals in the highest quintile of genetic risk but lowest quintile of socioeconomic risk was indistinguishable from that of those in the middle quintile for both risk factors (OR 1.13, 95% CI 0.85-1.51). These data provide evidence for the independent associations of genetic risk and SES with T2D and suggest that living in a community with high SES is associated with reduced T2D risk, even among those at increased genetic risk. Our findings raise the hypothesis that interventions targeted at specific elements of SES, such as education, may reduce risk of T2D in those with high genetic risk. Disclosure S. Cromer: Employee; Spouse/Partner; Johnson &amp; Johnson Medical Devices Companies. C. M. Lakhani: Consultant; Self; xy. ai. J. M. Mercader: None. T. Majarian: None. J. C. Florez: Consultant; Self; Goldfinch Bio, Inc., Other Relationship; Self; Novo Nordisk. A. Manning: Employee; Spouse/Partner; Emulate, Inc, Stock/Shareholder; Spouse/Partner; Invitae. J. Merino: None. M. Udler: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007028)

Diabetes and Composition of Weight Lifting and Cardio in Exercise.

The prevalence of type-2 diabetes(T2D) has increased globally. This has led to greater mortality, morbidity and disability in the general population. It is thus crucial to identify methods to prevent its onset among the healthy, and to also discover solutions to adequately manage the complications among those affected. Most research in this area has focused on the role of diet and exercise. More recently, different exercise types and their relationship with T2D has received considerable attention. In our work, we investigate the association between T2D (primary outcome) and two types of exercises: cardio (CR) and weight lifting (WL). Specifically, the relationship between duration of time spent in the two exercises and the odds of T2D is explored. Data are obtained from the Behavioural Risk Factor Surveillance System (BRFSS) survey, USA. Three ethnic populations are considered: White American, Black American and Hispanic American. Both WL and CR are found to be associated with negative log-odds of diabetes across all three ethnicities (WL: p <; 0.0001 and CR: p=0.00431). The association between WL and T2D is found to be modified for females (interaction-term coefficient: -0.096 (p=0.0115)).

The Relationship Between Household Food Insufficiency and Development of Type 2 Diabetes over 10 Years in a Sample of U.S. Black and White Adults

Abstract Objectives Household food insufficiency (HFI) is associated with type 2 diabetes (T2D) but longitudinal studies are scarce. Our objectives were to test the relationship of 1) HFI during young-to-middle adulthood with risk of T2D 10 years (y) later; and 2) transient (1 time) or persistent (2 times) HFI with odds of T2D. Methods We used data from 3672 black and white adults (32–49y) from Year 15, 20, and 25 follow-up exams of the Coronary Artery Risk Development in Young Adults (CARDIA) Study (2000–2011). Participants with missing HFI or T2D data, prevalent T2D at Year 15 (and Year 20 for objective 2), or reported pregnancy were excluded (n = 720), for a total of n = 2952. At each exam, a screener question captured HFI over the past 12 months. Participants reporting that the food they had to eat was not always what they wanted, sometimes not enough, or often not enough were categorized with HFI. Participants with enough of the kinds of food they wanted were categorized with household food sufficiency. T2D was defined as fasting serum glucose ≥126 mg/dL or hemoglobin A1c ≥6.5%. Multivariable-adjusted repeated-measures and logistic regression models tested the relationships between HFI at Year 15 with risk of T2D at Year 25, and between transient or persistent HFI from Years 15 to 20 with odds of T2D at Year 25, respectively. Results T2D prevalence was 4.7% at Year 20 and 9.7% at Year 25. At Year 15, 13.2% reported HFI, and 14.6% and 5.2% were categorized with transient or persistent HFI, respectively. Adjusted for age, sex, and race, HFI at Year 15 was associated with 36% higher risk of T2D by Year 25 (Risk Ratio (95% Confidence Interval (RR (95% CI)): 1.36 (1.02, 1.80); P &amp;lt; 0.05), though the relationship was attenuated after adjustment for education (1.28 (0.96, 1.71)). Compared to no HFI at Years 15 and 20, participants with persistent, but not transient, HFI had higher odds of T2D at Year 25 in fully-adjusted models (Odds Ratio (OR (95% CI)): persistent HFI: 2.06 (1.09, 3.67), P &amp;lt; 0.05; transient HFI: 1.26 (0.76, 2.01)). Conclusions Transient or persistent exposure to HFI in young-to-middle adulthood may be a risk factor for developing T2D among black and white adults. Preventing and reducing HFI may be a strategy to reduce socioeconomic and racial disparities in T2D prevalence in the U.S. Funding Sources SDSU University Grants Program; NIH NHLBI K01.

Abstract P462: Myosteatosis: Differences in Association With Type 2 Diabetes by Anatomical Location

Background: CT-derived muscle density (MD) reflects the degree of adiposity in muscle (i.e., myosteatosis) with lower MD indicating greater adiposity. Previous research indicates lower MD is associated with increased risk of type 2 diabetes (T2D). However, few studies have compared the association of simultaneously measured MD by anatomic location. The relationship between myosteatosis and cardiometabolic health may differ by body site and influence which location(s) is most useful for risk assessment. We investigated potential differential relationships between T2D and MD of the locomotor muscles of the abdomen (psoas), thigh, and calf among 539 African Caribbean men from Tobago. Methods: Men were aged 50-91 years (mean 64.4 years, mean BMI 27.5 kg/m 2 ). Calf MD was measured at 66% of calf length using peripheral quantitative CT; calf MD was defined as the ratio of muscle mass to cross-sectional muscle area. Psoas MD was measured in the abdomen (between L3/L4) and thigh MD was measured in the mid-thigh using CT; for these, MD was defined as the average muscle attenuation across each site. MDs were converted to per-SD units for comparability. T2D was defined as a fasting serum glucose level of ≥126 mg/dL or currently taking antidiabetic medication. Results: Psoas and thigh MDs were more highly correlated (r = 0.70) than psoas and calf (r = 0.33) or thigh and calf (r = 0.53) MDs, and calf MD was moderately correlated with BMI (r = -0.38) compared to lower BMI correlations for thigh (r = -0.18) or psoas (r = -0.16) MDs (all significant p &lt; 0.05). After age and lifestyle factor adjustment (Table), a 1-SD lower MD of the thigh or calf was significantly associated with higher odds of T2D. Additional adjustment for BMI completely attenuated the association with T2D for thigh MD, but not calf MD. Conclusion: In our study of African Ancestry men, only calf MD was associated with higher odds of T2D independent of BMI and other muscle groups. Longitudinal studies are needed to better characterize specific muscle myosteatosis and metabolic abnormalities.

Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis

Background: Globally, 1 in 11 adults has diabetes mellitus, and most of these cases are type 2 diabetes (T2D). The risk of T2D is influenced by many factors, including diet. The synthesis of long-chain n-6 polyunsaturated fatty acids (LC n-6 PUFA) has been posited as a risk factor for T2D; however, its causal role is uncertain. Aim: To test the causal effect of LC n-6 PUFA synthesis on insulin resistance and transgenerational T2D risk in a large cohort of men and women. Methods: Two-sample mendelian randomization (MR) was conducted to evaluate the effect of low or high levels of LC n-6 PUFA synthesis on glycemia and development of T2D in the UK Biobank (n = 463,010) and Meta-Analysis of Glucose- and Insulin-Related Traits Consortium (MAGIC; n = 5,130) cohorts. The increased likelihood of a predisposition to low or high LC n-6 PUFA synthesis and the risk of T2D was also investigated using the participants’ siblings and parents. In MR-Base, 4 genetic variants associated with LC n-6 PUFA synthesis were found (p < 10^–8). After pruning, 1 variant (rs174547) on the FADS1 gene was retained. Results: Lower LC n-6 PUFA synthesis and abundance (per % unit decrease) are associated with small reductions in the insulin disposition index (–0.038 ± 0.012 mM^–1; p = 0.002) within MAGIC. In the UK Biobank, we report negligible effects of low n-6 PUFA synthesis on the odds of T2D (OR <1%; p < 0.05). Additionally, reduced LC n-6 PUFA synthesis does not appear to be a contributor to familial T2D risk. No significant association was observed between LC n-6 PUFA synthesis and BMI. Conclusion: In a primarily white European population, LC n-6 PUFA synthesis is not a major contributor to T2D risk.

Plasma Strontium and Interactions between Calcium and Strontium for Type 2 Diabetes—A Hospital-Based Case-Control Study

Objective: Strontium and calcium play an essential role in bone metabolism but a paucity of epidemiological or experimental studies referring the role of strontium in the development type 2 diabetes (T2D). Prior studies have reported conflicting results for the relationships between plasma strontium and T2D. We therefore investigated the association between plasma strontium as well as the ratio of calcium to strontium (Ca/Sr) and newly diagnosed T2D. Methods: After propensity score matching for age and sex, 2,5newly-diagnosed T2D patients and 2,5controls with normal glucose tolerance were recruited in the case-control study. Plasma strontium and calcium levels were determined by inductively coupled plasma mass spectrometry (ICP-MS). Multivariate logistic regression analysis was used to evaluate the independent association of plasma strontium levels and Ca/Sr values with the likelihood of T2D. Results: Compared with the middle quintile, the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals of T2D associated with the lowest quintile and the highest quintile of plasma strontium were 2.01 (1.66, 2.44) and 2.01 (1.65, 2.44), of plasma Ca/Sr were 2.11 (1.75, 2.54) and 2.01 (1.66, 2.43), respectively. In spline analysis, the U-shaped associations were consistently indicated, with the lowest odds of T2D at the plasma strontium concentration of 42.52 μg/L, and Ca/Sr value of 1500 approximately. We also discovered the pattern of high plasma calcium and low strontium level was associated with the highest odds of T2D, while the pattern of high plasma calcium and moderate to high strontium level was associated with the lowest odds of T2D. Conclusions: Our results suggested U-shaped associations between plasma strontium, Ca/Sr and T2D; both low and high levels of plasma strontium and Ca/Sr were associated with higher odds of newly diagnosed T2D. We should not only pay attention to calcium, but also to strontium and the homeostasis of the both. Disclosure L. Chen: None. Q. Wang: None. X. Hu: None. X. Wang: None. T. Sun: None. W. Bao: None. L. Liu: None.

Abstract MP048: Ectopic Muscle and Liver Adiposity are Independently Associated with Type 2 Diabetes in African Ancestry Men

Although obesity is a major driver of type 2 diabetes (T2D), many obese individuals do not develop T2D. Indeed, fat around and within non-adipose tissue organs (i.e., ectopic fat) is emerging as a strong risk factor for diabetes. The potential differential contribution of ectopic fat depots throughout the body on T2D risk is unclear because studies have mainly focused on visceral and/or liver fat. No study, to our knowledge, has addressed the potential independent association of visceral, liver, and skeletal muscle adiposity with T2D. Such studies are particularly needed among African ancestry populations, as generalized obesity and other risk factors do not appear to explain the high T2D burden in this population segment. To address this knowledge gap, we measured total body fat by DXA, and visceral, liver, and calf skeletal muscle adiposity by computed tomography in 490 Afro-Caribbean men, aged 50-91 years (mean age=64 years, mean BMI=27.5 kg/m 2 ). The prevalence of T2D in this population was 22.3%. We employed multiple logistic regression using total body fat percent and ectopic fat depots as predictors (Table). We found that each 7.9 HU decrease in liver attenuation (indicative of greater liver adiposity) was associated with a 33% increased odds of T2D (p=0.011). Similarly, each 4.2 mg/cm 3 decrease in muscle attenuation (indicative of greater intra-muscular adiposity) was associated with a 31% increased odds of T2D (p=0.04). These associations were independent of total and visceral adiposity. Our results support the “ectopic fat syndrome” theory, as opposed to the “portal theory”, in the pathogenesis of diabetes among African ancestry men. Longitudinal studies are needed to clarify the exact role of specific ectopic fat depots in T2D, particularly in high-risk African ancestry populations.

A Mendelian randomization study of the effect of type-2 diabetes on coronary heart disease.

In observational studies, type-2 diabetes (T2D) is associated with an increased risk of coronary heart disease (CHD), yet interventional trials have shown no clear effect of glucose-lowering on CHD. Confounding may have therefore influenced these observational estimates. Here we use Mendelian randomization to obtain unconfounded estimates of the influence of T2D and fasting glucose (FG) on CHD risk. Using multiple genetic variants associated with T2D and FG, we find that risk of T2D increases CHD risk (odds ratio (OR)=1.11 (1.05–1.17), per unit increase in odds of T2D, P=8.8 × 10−5; using data from 34,840/114,981 T2D cases/controls and 63,746/130,681 CHD cases/controls). FG in non-diabetic individuals tends to increase CHD risk (OR=1.15 (1.00–1.32), per mmol·per l, P=0.05; 133,010 non-diabetic individuals and 63,746/130,681 CHD cases/controls). These findings provide evidence supporting a causal relationship between T2D and CHD and suggest that long-term trials may be required to discern the effects of T2D therapies on CHD risk.

Associations between Breakfast Skipping and Body Mass Index, and Type 2 Diabetes in South Korea

Objective: The purpose of this study was to investigate the associations between breakfast skipping and body mass index (BMI), and type 2 diabetes (T2D) in South Korea. Methods: Data were obtained from the Korea National Health and Nutrition Examination Survey IV (2007–2009) using a rolling sampling design of a complex, stratified, multistage, probability-cluster survey of civilian noninstitutionalized Korean residents. In total, 12,172 of 18,210 subjects were included in this study (subjects with missing variables were excluded). Results: The odds of T2D in individuals who did not consume breakfast was 3.05 (95% confidence interval (CI), 2.46–3.77) than in those who consumed breakfast. The estimated BMI was decreased by 0.19 kg/m2 (p<0.001) in those who did not consume breakfast compared with those who did. Conclusions: Breakfast skipping in South Korea is associated with increased T2D and BMI, similar to research results reported in Western countries.

Dietary patterns and odds of Type 2 diabetes in Beirut, Lebanon: a case–control study

BackgroundIn Lebanon, Type 2 diabetes (T2D) has a major public health impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities. Diet is an important environmental factor in the development and prevention of T2D. Dietary patterns may exert greater effects on health than individual foods, nutrients, or food groups. The objective of this study is to examine the association between dietary patterns and the odds of T2D among Lebanese adults.MethodsFifty-eight recently diagnosed cases of T2D and 116 population-based age, sex, and place of residence matched control participants were interviewed. Data collection included a standard socio-demographic and lifestyle questionnaire. Dietary intake was evaluated by a semi-quantitative 97-item food frequency questionnaire. Anthropometric measurements including weight, height, waist circumference, and percent body fat were also obtained. Dietary patterns were identified by factor analysis. Multivariate logistic regression analysis was used to evaluate the associations of extracted patterns with T2D. Pearson correlations between these patterns and obesity markers, energy, and nutrient intakes were also examined.ResultsFour dietary patterns were identified: Refined Grains & Desserts, Traditional Lebanese, Fast Food and Meat & Alcohol. While scores of the “Refined Grains & Desserts” had the highest correlations with energy (r = 0.74) and carbohydrates (r = 0.22), those of the “Fast Food” had the highest correlation with fat intake (r = 0.34). After adjustment for socio-demographic and lifestyle characteristics, scores of the Refined Grains & Desserts and Fast Food patterns were associated with higher odds of T2D (OR: 3.85, CI: 1.13-11.23 and OR: 2.80, CI: 1.14-5.59; respectively) and scores of the Traditional Lebanese pattern were inversely associated with the odds of T2D (OR: 0.46, CI: 0.22-0.97).ConclusionsThe findings of this study demonstrate direct associations of the Refined Grains & Desserts and Fast Food patterns with T2D and an inverse association between the Traditional Lebanese pattern and the disease among Lebanese adults. These results may guide the development of nutrition interventions for the prevention and management of T2D among Lebanese adults.

Abstract P215: Common Beta-cell-associated Genetic Variants and Hypertension or Anti-hypertensive Drugs do not Interact in Their Positive Associations With Risk for Rising Fasting Glucose or Incident Type 2 Diabetes in Framingham

Background: Hypertension (HTN) and some anti-HTN drugs raise fasting glucose (FG) levels and type 2 diabetes (T2D) risk. We hypothesized that common single nucleotide polymorphisms (SNPs) associated with FG or T2D that influence beta-cell function will interact with hypertension (HTN) or anti-HTN drugs in their positive associations with change over time in FG (ΔFG) or incident T2D. Methods: We studied 3,471 Framingham Offspring Study participants comprising 18,786 person-exams (mean age 49 yr; 54% women), in pooled (7 ∼4-yr periods) age-, sex-adjusted logistic regression models predicting T2D incidence, or age-, sex-, baseline FG-adjusted mixed linear models testing ΔFG (FG end minus beginning of period). T2D cases were excluded at baseline of each period, and people who started T2D treatment within a given period were removed for ΔFG analyses. We defined three HTN exposures: 1) HTN (SBP≥140/DBP≥90 mmHg) vs. no-HTN; 2) treated vs. untreated HTN; 3) five mutually-exclusive anti-HTN drug categories (beta-blockers, thiazides, renin-angiotensin system agents, combination, other) vs. untreated HTN, and two genetic exposures reflecting total beta-cell genetic risk burden: 16 FG-SNP and 33 T2D-SNP (only 8 overlap) additive genetic risk scores. We tested ∼4-year mean ΔFG and odds of T2D by HTN category and per-risk allele change in SNP scores, seeking first-order HTNxSNP significant interaction (P&lt;0.05). Results: Versus no HTN, HTN (n=5,372 p-e) was associated with higher ∼4-year ΔFG (0.14 vs. 0.03 mmol/l; P&lt;0.0001) and ∼3-fold increased odds of T2D (OR 3.3; P&lt;0.0001). Versus untreated HTN, treated HTN (n=2,832 p-e) conferred higher ΔFG (0.18 vs. 0.12 mmol/l; P&lt;0.0001) and 1.5-fold increased odds of T2D (P=0.0006). Versus untreated HTN, beta-blockers (n=676 p-e; OR=1.58), combined (n=499 p-e; OR=1.57) and other (n=569 p-e; OR=1.94) were associated with increased odds of T2D (all P&lt;0.03). Per-SNP score risk allele, ΔFG increased by 0.03 mmol/l (P=2.2x10 −16 ) and odds of T2D increased 17% (P=3.1x10 −08 ). In joint models with interaction terms, all HTN-treatment category-by-SNP score interaction terms were non-significant. In joint models without interaction, HTN (P&lt;0.0001) and HTN treatment (P&lt;0.02), but no specific drugs (all but one P&gt;0.02), and per FG-SNP or T2D-SNP risk allele (highest P value=0.0005), all independently predicted ΔFG or incident T2D. Conclusion: HTN, HTN treatment and common FG- and T2D-SNP genetic scores were independently associated with ΔFG and T2D incidence, but did not modify each other's association with ΔFG or T2D risk. Next, larger samples and individual SNP-by-specific drug category interaction tests might disclose some biological basis for T2D risk associated with anti-HTN therapy.