Publications

Abstract Background People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings. Hypothesis Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers. Design Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years. Entry criteria South Asian, men or women, age 40–70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0–6.4% inclusive). Exclusion criteria: known type 1 or 2 diabetes, normal or underweight (body mass index < 22 kg/m 2 ); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness. Endpoints The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance. Intervention Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker. Results We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 ( SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). Conclusion The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB approval 16/WM/0171 Trial registration EudraCT 2016-001350-18 . Registered on 14 April 2016. ClinicalTrials.gov NCT02949739 . Registered on 31 October 2016, First posted on 31/10/2016.

<i><u>Background</u></i> Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted. <p><i><u>Purpose</u></i><i> </i>To conduct an updated systematic review and meta-analysis of plasma, serum, or urine metabolite markers and incident type 2 diabetes.</p> <p><i><u>Data Sources</u></i><i> </i>PubMed and Embase. </p> <p><i><u>Study Selection</u></i><i> </i>Prospective observational studies investigating the relationship between plasma, serum, or urine metabolites using high throughput techniques and incident type 2 diabetes. </p> <p><i><u>Data Extraction</u></i> Baseline metabolites per-standard deviation risk estimates and 95% confidence intervals for incident type 2 diabetes were extracted from all eligible studies.</p> <p><i><u>Data Synthesis</u></i> Sixty-one reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Overall, 412 metabolites were meta-analyzed, of which 123 were statistically significantly associated (FDR-P<0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, pyruvate), acylcarnitines (C4DC, C4OH, C5, C5OH, C8:1), the majority of meta-analyzed glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides were associated with higher risk of type 2 diabetes (hazard ratio [HR] 1.07-2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (HR 0.69-0.90).</p> <p><i><u>Limitations</u></i><i> </i>Substantial heterogeneity <a>(I<sup>2</sup>>50%, </a>t<sup>2</sup>>0.1) was observed for some of the metabolites.</p> <p><i><u>Conclusions</u></i> Several plasma and serum metabolites, including amino acids, lipids, and carbohydrates are associated with type 2 diabetes risk. </p>

Introduction: Various forms of psychological distress, such as depression and anxiety, have been identified as risk factors for diabetes. However, there is limited evidence from population-based, epidemiologic studies investigating potential molecular mechanisms (e.g., metabolic dysregulation) linking psychological distress and diabetes development. Hypothesis: We assessed the hypothesis that a metabolite score reflecting psychological distress-related metabolic dysregulation is predictive of future diabetes risk in women. Methods: We conducted a nested case-control study of plasma metabolomics and diabetes risk in the Nurses’ Health Study, including 728 women (mean age: 55.2 years) with incident diabetes and 728 controls matched on age, race, fasting status, and time/date of blood collection. Blood samples were collected between 1989-1990 and incident diabetes was diagnosed between 1990-2012. Based on the metabolomic signature of chronic psychological distress we previously identified and validated in women (including coefficient estimates for individual metabolite associations), we calculated a weighted plasma metabolomic score of psychological distress comprised of 19 metabolites (e.g., serotonin, threonine, hippurate, biliverdin, glutamine, etc.). We used conditional logistic regression accounting for matching factors and other diabetes risk factors to estimate odds ratios (OR) and 95% CI for diabetes risk across quintiles of the distress-related metabolite score. Results: After adjusting for sociodemographic factors, family history of diabetes and health behaviors, the OR (95% CI) for diabetes risk across quintiles of the distress-related metabolite score was 1.00 (reference) for Q1, 1.11 (0.77, 1.61) for Q2, 1.64 (1.14, 2.35) for Q3, 2.07 (1.42, 3.01) for Q4, and 2.35 (1.60, 3.47) for Q5. Each 1-unit increase in the score was associated with 26% higher diabetes risk (95% CI: 1.15, 1.38; p-trend<0.0001). This association was moderately attenuated after additional adjustment for baseline body mass index (OR per 1-unit increase: 1.13; 95% CI: 1.02, 1.25; p-trend=0.02). Further, psychological distress assessed via self-report (defined as presence of depression or anxiety) was associated with modestly increased diabetes risk in the same sample (OR: 1.25; 95% CI: 1.01, 1.55). The metabolite score mediated 20.7% (95% CI: 5.1, 56.1) of the association between psychological distress and diabetes risk (p=0.0065). Conclusions: Our results suggest that the distress-related metabolite score was significantly associated with diabetes risk in women and partly mediated the association between self-reported psychological distress and diabetes risk. These findings provide supporting evidence that metabolic dysregulation may be an important mechanism underlying the observed association between psychological distress and diabetes risk.

Branched and hyperbranched nanowire structures were synthesized via a multistep nanocluster-catalyzed vapor−liquid−solid approach. Scanning electron microscopy studies of silicon nanowire structures prepared in this way confirmed the formation of branched nanostructures and showed that the branch density could be controlled by the nanocluster catalyst concentration. This same approach was also used to grow branched gallium nitride nanowires. High-resolution transmission electron microscopy studies of the branched silicon nanowire structures revealed that the branches grew epitaxially as single-crystal nanowires from the silicon nanowire backbone. In addition, hyperbranched silicon nanowire structures were prepared in a controlled manner by repeating the catalyst deposition and nanowire growth steps. The ability to prepare rationally branched and hyperbranched nanowires should open up new opportunities for both fundamental research and applications, including three-dimensional nanoelectronics.

OBJECTIVE Whether dietary habits early in life can affect risk of type 2 diabetes (T2DM) in adulthood is unknown. We evaluated the relationship between dietary patterns during adolescence and risk of T2DM in midlife. RESEARCH DESIGN AND METHODS We examined the 7-year incidence of T2DM in relation to dietary patterns during high school among 37,038 participants in the Nurses’ Health Study II cohort, who completed a food-frequency questionnaire about their diet during high school. Dietary patterns were derived by factor analysis. Cox proportional hazards regression was used to estimate relative risk (RR) and 95% CI. RESULTS The prudent pattern, characterized by healthy foods, was not associated with risk of T2DM. The Western pattern, characterized by desserts, processed meats, and refined grains, was associated with 29% greater risk of T2DM (RR 1.29; 95% CI 1.00–1.66; P trend 0.04), after adjusting for high school and adult risk factors comparing extreme quintiles, but was attenuated after adjusting for adult weight change (1.19; 0.92–1.54). Women who had high Western pattern scores in high school and adulthood had an elevated risk of T2DM compared with women who had consistent low scores (1.82; 1.35–2.45), and this association was partly mediated by adult BMI (1.15; 0.85–1.56). CONCLUSIONS A Western dietary pattern during adolescence may increase risk of T2DM in later life, partly through adult weight gain. Preventive measures should be aimed at developing healthy dietary habits that begin in early life and continue through adulthood.

Improved diet quality over 12 years was consistently associated with a decreased risk of death. (Funded by the National Institutes of Health.).

Integration of compound semiconductors with silicon (Si) has been a long-standing goal for the semiconductor industry, as direct band gap compound semiconductors offer, for example, attractive photonic properties not possible with Si devices. However, mismatches in lattice constant, thermal expansion coefficient, and polarity between Si and compound semiconductors render growth of epitaxial heterostructures challenging. Nanowires (NWs) are a promising platform for the integration of Si and compound semiconductors since their limited surface area can alleviate such material mismatch issues. Here, we demonstrate facet-selective growth of cadmium sulfide (CdS) on Si NWs. Aberration-corrected transmission electron microscopy analysis shows that crystalline CdS is grown epitaxially on the {111} and {110} surface facets of the Si NWs but that the Si{113} facets remain bare. Further analysis of CdS on Si NWs grown at higher deposition rates to yield a conformal shell reveals a thin oxide layer on the Si{113} facet. This observation and control experiments suggest that facet-selective growth is enabled by the formation of an oxide, which prevents subsequent shell growth on the Si{113} NW facets. Further studies of facet-selective epitaxial growth of CdS shells on micro-to-mesoscale wires, which allows tuning of the lateral width of the compound semiconductor layer without lithographic patterning, and InP shell growth on Si NWs demonstrate the generality of our growth technique. In addition, photoluminescence imaging and spectroscopy show that the epitaxial shells display strong and clean band edge emission, confirming their high photonic quality, and thus suggesting that facet-selective epitaxy on NW substrates represents a promising route to integration of compound semiconductors on Si.

This article describes a prototype system for quantifying bioassays and for exchanging the results of the assays digitally with physicians located off-site. The system uses paper-based microfluidic devices for running multiple assays simultaneously, camera phones or portable scanners for digitizing the intensity of color associated with each colorimetric assay, and established communications infrastructure for transferring the digital information from the assay site to an off-site laboratory for analysis by a trained medical professional; the diagnosis then can be returned directly to the healthcare provider in the field. The microfluidic devices were fabricated in paper using photolithography and were functionalized with reagents for colorimetric assays. The results of the assays were quantified by comparing the intensities of the color developed in each assay with those of calibration curves. An example of this system quantified clinically relevant concentrations of glucose and protein in artificial urine. The combination of patterned paper, a portable method for obtaining digital images, and a method for exchanging results of the assays with off-site diagnosticians offers new opportunities for inexpensive monitoring of health, especially in situations that require physicians to travel to patients (e.g., in the developing world, in emergency management, and during field operations by the military) to obtain diagnostic information that might be obtained more effectively by less valuable personnel.