Genetic predisposition to macronutrient preference and workplace food choices.

Prior research identified genetic variants influencing macronutrient preference, but whether genetic differences underlying nutrient preference affect long-term food choices is unknown. Here we examined the associations of polygenic scores for carbohydrate, fat, and protein preference with 12 months' workplace food purchases among 397 hospital employees from the ChooseWell 365 study. Food purchases were obtained retrospectively from the hospital's cafeteria sales data for the 12 months before participants were enrolled in the ChooseWell 365 study. Traffic light labels, visible to employees when making purchases, measured the quality of workplace purchases. During the 12-month study period, there were 215,692 cafeteria purchases. Each SD increase in the polygenic score for carbohydrate preference was associated with 2.3 additional purchases/month (95%CI, 0.2 to 4.3; p = 0.03) and a higher number of green-labeled purchases (ß = 1.9, 95%CI, 0.5-3.3; p = 0.01). These associations were consistent in subgroup and sensitivity analyses accounting for additional sources of bias. There was no evidence of associations between fat and protein polygenic scores and cafeteria purchases. Findings from this study suggest that genetic differences in carbohydrate preference could influence long-term workplace food purchases and may inform follow-up experiments to enhance our understanding of the molecular mechanisms underlying food choice behavior.

Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans.

Nontargeted metabolomics methods have increased potential to identify new disease biomarkers, but assessments of the additive information provided in large human cohorts by these less biased techniques are limited. To diversify our knowledge of diabetes-associated metabolites, we leveraged a method that measures 305 targeted or "known" and 2,342 nontargeted or "unknown" compounds in fasting plasma samples from 2,750 participants (315 incident cases) in the Jackson Heart Study (JHS)-a community cohort of self-identified African Americans-who are underrepresented in omics studies. We found 307 unique compounds (82 known) associated with diabetes after adjusting for age and sex at a false discovery rate of <0.05 and 124 compounds (35 known, including 11 not previously associated) after further adjustments for BMI and fasting plasma glucose. Of these, 144 and 68 associations, respectively, replicated in a multiethnic cohort. Among these is an apparently novel isomer of the 1-deoxyceramide Cer(m18:1/24:0) with functional geonomics and high-resolution mass spectrometry. Overall, known and unknown metabolites provided complementary information (median correlation ρ = 0.29), and their inclusion with clinical risk factors improved diabetes prediction modeling. Our findings highlight the importance of including nontargeted metabolomics methods to provide new insights into diabetes development in ethnically diverse cohorts.

The SLC16A11 risk haplotype is associated with decreased insulin action, higher transaminases and large-size adipocytes.

Objective A haplotype at chromosome 17p13 that reduces expression and function of the solute carrier transporter SLC16A11 is associated with increased risk for type 2 diabetes in Mexicans. We aim to investigate the detailed metabolic profile of SLC16A11 risk haplotype carriers to identify potential physiological mechanisms explaining the increased type 2 diabetes risk. Design Cross-sectional study. Methods We evaluated carriers (n = 72) and non-carriers (n = 75) of the SLC16A11 risk haplotype, with or without type 2 diabetes. An independent sample of 1069 subjects was used to replicate biochemical findings. The evaluation included euglycemic-hyperinsulinemic clamp, frequently sampled intravenous glucose tolerance test (FSIVGTT), dual-energy X-ray absorptiometry (DXA), MRI and spectroscopy and subcutaneous abdominal adipose tissue biopsies. Results Fat-free mass (FFM)-adjusted M value was lower in carriers of the SLC16A11 risk haplotype after adjusting for age and type 2 diabetes status (ß = -0.164, P = 0.04). Subjects with type 2 diabetes and the risk haplotype demonstrated an increase of 8.76 U/L in alanine aminotransferase (ALT) (P = 0.02) and of 7.34 U/L in gamma-glutamyltransferase (GGT) (P = 0.05) compared with non-carriers and after adjusting for gender, age and ancestry. Among women with the risk haplotype and normal BMI, the adipocyte size was higher (P < 0.001). Conclusions Individuals carrying the SLC16A11 risk haplotype exhibited decreased insulin action. Higher serum ALT and GGT levels were found in carriers with type 2 diabetes, and larger adipocytes in subcutaneous fat in the size distribution in carrier women with normal weight.