Publications

We identified two novel SNPs (rs599839 and rs16996148) at newly identified lipid-associated loci that were significantly associated with CHD susceptibility in a Chinese Han population.

Introduction We investigated whether network analysis revealed clusters of coregulated metabolites associated with prevalent type 2 diabetes (T2D) among Puerto Rican adults. Research design and methods We used liquid chromatography-mass spectrometry to measure fasting plasma metabolites (>600) among participants aged 40–75 years in the Boston Puerto Rican Health Study (BPRHS; discovery) and San Juan Overweight Adult Longitudinal Study (SOALS; replication), with (n=357; n=77) and without (n=322; n=934) T2D, respectively. Among BPRHS participants, we used unsupervised partial correlation network-based methods to identify and calculate metabolite cluster scores. Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D at the baseline blood draw in the BPRHS, and significant associations were replicated in SOALS. Inverse-variance weighted random-effect meta-analysis was used to combine cohort-specific estimates. Results Six metabolite clusters were significantly associated with prevalent T2D in the BPRHS and replicated in SOALS (false discovery rate (FDR) <0.05). In a meta-analysis of the two cohorts, the OR and 95% CI (per 1 SD increase in cluster score) for prevalent T2D were as follows for clusters characterized primarily by glucose transport (0.21 (0.16 to 0.30); FDR <0.0001), sphingolipids (0.40 (0.29 to 0.53); FDR <0.0001), acyl cholines (0.35 (0.22 to 0.56); FDR <0.0001), sugar metabolism (2.28 (1.68 to 3.09); FDR <0.0001), branched-chain and aromatic amino acids (2.22 (1.60 to 3.08); FDR <0.0001), and fatty acid biosynthesis (1.54 (1.29 to 1.85); FDR <0.0001). Three additional clusters characterized by amino acid metabolism, cell membrane components, and aromatic amino acid metabolism displayed significant associations with prevalent T2D in the BPRHS, but these associations were not replicated in SOALS. Conclusions Among Puerto Rican adults, we identified several known and novel metabolite clusters that associated with prevalent T2D.

Polymer-based electronics with low bending stiffnesses and high flexibility, including recently reported macroporous syringe-injectable mesh electronics, have shown substantial promise for chronic studies of neural circuitry in the brains of live animals. A central challenge for exploiting these highly flexible materials for in vivo studies has centered on the development of efficient input/output (I/O) connections to an external interface with high yield, low bonding resistance, and long-term stability. Here we report a new paradigm applied to the challenging case of injectable mesh electronics that exploits the high flexibility of nanoscale thickness two-sided metal I/O pads that can deform and contact standard interface cables in high yield with long-term electrical stability. First, we describe the design and facile fabrication of two-sided metal I/O pads that allow for contact without regard to probe orientation. Second, systematic studies of the contact resistance as a function of I/O pad design and mechanical properties demonstrate the key role of the I/O pad bending stiffness in achieving low-resistance stable contacts. Additionally, computational studies provide design rules for achieving high-yield multiplexed contact interfacing in the case of angular misalignment such that adjacent channels are not shorted. Third, the in vitro measurement of 32-channel mesh electronics probes bonded to interface cables using the direct contact method shows a reproducibly high yield of electrical connectivity. Finally, in vivo experiments with 32-channel mesh electronics probes implanted in live mice demonstrate the chronic stability of the direct contact interface, enabling consistent tracking of single-unit neural activity over at least 2 months without a loss of channel recording. The direct contact interfacing methodology paves the way for scalable long-term connections of multiplexed mesh electronics neural probes for neural recording and modulation and moreover could be used to facilitate a scalable interconnection of other flexible electronics in biological studies and therapeutic applications.

Studies of delayed conception and risk of gestational diabetes (GDM) are sparse, although common underlying mechanisms are plausible, including insulin resistance and inflammation. The association between a history of infertility and GDM was assessed prospectively among 40,773 eligible pregnancies in the US Nurses' Health Study II cohort (1989-2001). Biennial questionnaires provided updated information on infertility and several lifestyle and health-related characteristics. Multivariable log-binomial models with generalized estimating equations were used to compute risk ratios and 95% confidence intervals, adjusting for age, prepregnancy body mass index (weight (kg)/height (m)(2)), and additional potential confounders. GDM occurred among 1,405 (5.2%) women. A prepregnancy history of infertility was reported by 5,497 (20.5%) participants and was significantly associated with a 39% greater risk of GDM (risk ratio (RR) = 1.39, 95% confidence interval (CI): 1.24, 1.57; P < 0.001). Underlying reasons for infertility associated with GDM included ovulation disorders (RR = 1.52, 95% CI: 1.23, 1.87; P < 0.001) and tubal blockage (RR = 1.83, 95% CI: 1.20, 2.77; P = 0.005). The association of cervical mucus disorder with GDM was of borderline significance (RR = 1.70, 95% CI: 0.88, 3.30; P = 0.11). Endometriosis (RR = 1.27, 95% CI: 0.70, 2.31; P = 0.43) and male factor infertility (RR = 1.12, 95% CI: 0.78, 1.61; P = 0.55) were not associated with GDM risk. These novel findings suggest that infertility, particularly from ovulation disorders and tubal blockage, is associated with an increased GDM risk. Further research is needed to identify mechanisms or common underlying metabolic dysfunction explaining these observations.

OBJECTIVE—To examine dietary fat and meat intake in relation to risk of type 2 diabetes. RESEARCH DESIGN AND METHODS—We prospectively followed 42,504 male participants of the Health Professionals Follow-Up Study who were aged 40–75 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1986. Diet was assessed by a validated food frequency questionnaire and updated in 1990 and 1994. During 12 years of follow-up, we ascertained 1,321 incident cases of type 2 diabetes. RESULTS—Intakes of total fat (multivariate RR for extreme quintiles 1.27, CI 1.04–1.55, P for trend=0.02) and saturated fat (1.34, 1.09–1.66, P for trend=0.01) were associated with a higher risk of type 2 diabetes. However, these associations disappeared after additional adjustment for BMI (total fat RR 0.97, CI 0.79–1.18; saturated fat 0.97, 0.79–1.20). Intakes of oleic acid, trans-fat, long-chain n-3 fat, and α-linolenic acid were not associated with diabetes risk after multivariate adjustment. Linoleic acid was associated with a lower risk of type 2 diabetes in men &amp;lt;65 years of age (RR 0.74, CI 0.60–0.92, P for trend=0.01) and in men with a BMI &amp;lt;25 kg/m2 (0.53, 0.33–0.85, P for trend=0.006) but not in older and obese men. Frequent consumption of processed meat was associated with a higher risk for type 2 diabetes (RR 1.46, CI 1.14–1.86 for ≥5/week vs. &amp;lt;1/month, P for trend &amp;lt;0.0001). CONCLUSIONS—Total and saturated fat intake were associated with a higher risk of type 2 diabetes, but these associations were not independent of BMI. Frequent consumption of processed meats may increase risk of type 2 diabetes.

This paper describes a strategy that uses template-directed self-assembly of micrometer-scale microspheres to fabricate arrays of microlenses for projection photolithography of periodic, quasiperiodic, and aperiodic infrared metasurfaces. This method of "template-encoded microlens projection lithography" (TEMPL) enables rapid prototyping of planar, multiscale patterns of similarly shaped structures with critical dimensions down to ∼400 nm. Each of these structures is defined by local projection lithography with a single microsphere acting as a lens. This paper explores the use of TEMPL for the fabrication of a broad range of two-dimensional lattices with varying types of nonperiodic spatial distribution. The matching optical spectra of the fabricated and simulated metasurfaces confirm that TEMPL can produce structures that conform to expected optical behavior.

Background: If preschool measures of body size routinely collected at preventive health examinations are associated with adult central obesity and metabolic syndrome, a focused use of these data for the identification of high risk children is possible. The aim of this study was to test the associations between preschool weight and body mass index (BMI) and adult BMI, central obesity and metabolic alterations. Methods: The Northern Finland Birth Cohort 1966 (NFBC1966) (N = 4111) is a population-based cohort. Preschool weight (age 5 months and 1 year) and BMI (age 2–5 years) were studied in relation to metabolic syndrome as well as BMI, waist circumference, lipoproteins, blood pressure, and fasting glucose at the age of 31 years. Linear regression models and generalized linear regression models with log link were used. Results: Throughout preschool ages, weight and BMI were significantly linearly associated with adult BMI and waist circumference. Preschool BMI was inversely associated with high-density lipoprotein levels from the age of 3 years. Compared with children in the lower half of the BMI range, the group of children with the 5% highest BMI at the age of 5 years had a relative risk of adult obesity of 6.2(95% CI:4.2–9.3), of adult central obesity of 2.4(95% CI:2.0–2.9), and of early onset adult metabolic syndrome of 2.5(95% CI:1.7–3.8). Conclusions: High preschool BMI is consistently associated with adult obesity, central obesity and early onset metabolic syndrome. Routinely collected measures of body size in preschool ages can help to identify children in need of focused prevention due to their increased risk of adverse metabolic alterations in adulthood.

The association of GDM with offspring obesity from late childhood through early adulthood may differ by sex; a significant association was observed among male but not female offspring.

OBJECTIVE To examine whether proinflammatory and hyperinsulinemic diets are associated with increased risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We prospectively followed 74,767 women from the Nurses’ Health Study (1984–2016), 90,786 women from the Nurses’ Health Study II (1989–2017), and 39,442 men from the Health Professionals Follow-up Study (1986–2016). Using repeated measures of food-frequency questionnaires, we calculated empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores, which are food-based indices that characterize dietary inflammatory or insulinemic potential based on circulating biomarkers of inflammation or C-peptide. Diagnoses of type 2 diabetes were confirmed by validated supplementary questionnaires. RESULTS We documented 19,666 incident type 2 diabetes cases over 4.9 million person-years of follow-up. In the pooled multivariable-adjusted analyses, individuals in the highest EDIP or EDIH quintile had 3.11 times (95% CI 2.96–3.27) and 3.40 times (95% CI 3.23–3.58) higher type 2 diabetes risk, respectively, compared with those in the lowest quintile. Additional adjustment for BMI attenuated the associations (hazard ratio 1.95 [95% CI 1.85–2.05] for EDIP and hazard ratio 1.87 [95% CI 1.78–1.98] for EDIH), suggesting adiposity partly mediates the observed associations. Moreover, individuals in both highest EDIP and EDIH quintiles had 2.34 times higher type 2 diabetes risk (95% CI 2.17–2.52), compared with those in both lowest quintiles, after adjustment for BMI. CONCLUSIONS Higher dietary inflammatory and insulinemic potential were associated with increased type 2 diabetes incidence. Findings suggest that inflammation and hyperinsulinemia are potential mechanisms linking dietary patterns and type 2 diabetes development.