Publications

With the release of this issue, our editorial team is now at the 3.5-year mark in our tenure of overseeing the scientific aspects of Diabetes Care.During this time, we have done our best to keep you up to date on all changes, innovations, progress, and successes of the journal.We realize that with each issue we are responsible for providing new information to help health care professionals care for people with diabetes and to stimulate the research community in its quest for new discoveries and new treatment paradigms.At this time last year, our editorial on the status of Diabetes Care was titled "It Just Doesn't Get Any Better . . .or Does It?" (1).We also questioned whether in another 12 months we would "still be asking, 'Can it possibly get any better than this?'"With this report, we feel that question has clearly been answered in the affirmative.A new norm for excellence has been established at Diabetes Care.Over the last year, the number of new submissions reached record levels and the quality of the published articles (our primary metric) has never been higher.Moreover, the range of topics our journal covers is unlike that of any other.In the last year, we presented reports on new medications, new combinations of medications, critical reviews of safety of commercially available agents, extended outcomes of bariatric surgery, new data on the microbiome, latest developments in the artificial pancreas, staggering data on economic costs and analysis, emerging ideas on the pathogenesis of type 2 diabetes, functional imaging studies, cognitive outcomes, and corneal nerve morphology, just to name a fewdthe list goes on and on!The journal also disseminates Scientific Statements, Consensus Reports, and Position Statements carefully prepared by the American Diabetes Association (ADA) (see Table 1 for highlighted articles).This past year, we were honored to publish the Position Statements "Type 1 Diabetes Through the Life Span," "Care of Young Children With Diabetes in the Child Care Setting," and "BMI Cut Points to Identify At-Risk Asian Americans for Type 2 Diabetes Screening" (2-4), as well as the joint Position Statement of the ADA and the European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes (5).Accompanying the update from the ADA/European Association for the Study of Diabetes was a report that examined the ADA Standards of Medical Care in Diabetes recommendations and trends in the quality of evidence supporting the recommendations (6).Over the 9-year period spanning from 2005 to 2014, the proportion of recommendations per year that were based on higher-level evidence increased from 39 to 51% (6).As we stated in the January 2015 update, the process for review from the ADA is working to the benefit of clinicians (7).In addition to the position statements, in October 2014, the journal published a Scientific Statement from the American Heart Association and ADA "Type 1 Diabetes Mellitus and Cardiovascular Disease" (8), and in April 2015, we published an incredibly comprehensive statement on insulin pump risks and benefits (9).A report from an ADA Consensus Conference on diabetic kidney disease was published in October 2014 (10).In addition to contributions from the ADA, we are privileged to feature noteworthy lectures from recent Scientific Sessions, and this year we published Dr. Seaquist's 2014

In this paper, we identify the Young's modulus and residual stress state of a free-standing thin aluminum membrane, used in MEMS radio-frequency (rf) s

Abstract Objectives To evaluate the individual and combined associations of five modifiable risk factors with risk of type 2 diabetes among women with a history of gestational diabetes mellitus and examine whether these associations differ by obesity and genetic predisposition to type 2 diabetes. Design Prospective cohort study. Setting Nurses’ Health Study II, US. Participants 4275 women with a history of gestational diabetes mellitus, with repeated measurements of weight and lifestyle factors and followed up between 1991 and 2009. Main outcome measure Self-reported, clinically diagnosed type 2 diabetes. Five modifiable risk factors were assessed, including not being overweight or obese (body mass index <25.0), high quality diet (top two fifths of the modified Alternate Healthy Eating Index), regular exercise (≥150 min/week of moderate intensity or ≥75 min/week of vigorous intensity), moderate alcohol consumption (5.0-14.9 g/day), and no current smoking. Genetic susceptibility for type 2 diabetes was characterised by a genetic risk score based on 59 single nucleotide polymorphisms associated with type 2 diabetes in a subset of participants (n=1372). Results Over a median 27.9 years of follow-up, 924 women developed type 2 diabetes. Compared with participants who did not have optimal levels of any of the risk factors for the development of type 2 diabetes, those who had optimal levels of all five factors had >90% lower risk of the disorder. Hazard ratios of type 2 diabetes for those with one, two, three, four, and five optimal levels of modifiable factors compared with none was 0.94 (95% confidence interval 0.59 to 1.49), 0.61 (0.38 to 0.96), 0.32 (0.20 to 0.51), 0.15 (0.09 to 0.26), and 0.08 (0.03 to 0.23), respectively (P trend <0.001). The inverse association of the number of optimal modifiable factors with risk of type 2 diabetes was seen even in participants who were overweight/obese or with higher genetic susceptibility (P trend <0.001). Among women with body mass index ≥25 (n=2227), the hazard ratio for achieving optimal levels of all the other four risk factors was 0.40 (95% confidence interval 0.18 to 0.91). Among women with higher genetic susceptibility, the hazard ratio of developing type 2 diabetes for having four optimal factors was 0.11 (0.04 to 0.29); in the group with optimal levels of all five factors, no type 2 diabetes events were observed. Conclusions Among women with a history of gestational diabetes mellitus, each additional optimal modifiable factor was associated with an incrementally lower risk of type 2 diabetes. These associations were seen even among individuals who were overweight/obese or were at greater genetic susceptibility.

The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 × 10−4) and higher plasma cotinine levels (p = 7.0 × 10−5). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking.

Background: Whether dietary quality modifies genetic association with body mass index (BMI) is unknown. Methods: We examined the interactions prospectively of a genetic risk score (GRS) based on 97 BMI-associated variants with three diet quality scores (alternative healthy eating index 2010 (AHEI-2010), Alternative Mediterranean Diet score (AMED) and Dietary Approach to Stop Hypertension (DASH) diet score) on BMI in 30,904 participants from three large US cohorts. According to the enrichment of genes near the BMI-associated loci in the central nervous system (CNS), we further created two subsets of GRSs: CNS GRS based on 54 variants and non-CNS GRS based on 43 variants. Findings: We found significant interactions between total GRS and all three diet scores on BMI assessed after 2 to 3 years, with an attenuated genetic effect observed in individuals with healthier diets (AHEI: P for interaction = 0.003; AMED: P = 0.001; DASH: P = 0.004). For example, the difference in BMI per 10 unit increment of the GRS was smaller among participants in the highest tertile of AHEI score compared to those in the lowest tertile (0.84 [95% CI: 0.72, 0.96] vs. 1.14 [0.99, 1.29] kg/m 2 ). Results were consistent across the three cohorts with no significant heterogeneity. The interactions with diet scores on BMI appeared more significant for CNS GRS (AHEI: P = 0.009; AMED and DASH: P < 0.001) than for non-CNS GRS (AHEI: P = 0.10; AMED: P = 0.50; DASH: P = 0.68). Among individual components of diet scores, higher consumption of red/processed meat, sugar-sweetened beverages, and trans fat accentuated genetic associations with BMI (P <0.01), while higher consumption of fruit and moderate alcohol attenuated genetic associations with BMI (P < 0.01). Interpretation: A higher diet quality may mitigate genetic predisposition to obesity. These findings provide insights into complex interplays between diet and genetic influences and underscore the importance of adopting a healthful diet for the prevention of obesity, particularly those individuals with a strong genetic predisposition to obesity.

Earlier studies have associated smoking with a higher rate of dental caries, periodontal disease and tooth loss. The aim of this cross‐sectional study was to determine whether smoking is associated with tooth loss among young adults. The data consist of the 1966 birth cohort of Northern Finland, which is an unselected general population birth cohort ( n = 12 058). The data were collected using a postal questionnaire in 1997–98 ( n = 8690). Prevalence odds ratios and confidence intervals were estimated by applying a logistic regression model. It was found that smoking was associated with tooth loss in an exposure‐dependent manner. The odds for those who smoked 16 or more pack‐years were 5.30 (CI = 2.35–11.2) after adjustment for socio‐economic and behavioral factors. Differences in socio‐economic or health behavior are not likely to explain the findings since an exposure‐response pattern was seen even when data was stratified according to sex, education and health‐oriented lifestyle. A possible explanation for this association is a combination of treatment decisions and dental diseases, which are most likely associated with smoking in an exposure‐dependent manner.

Significance We describe several noncontact methods of orienting objects in three-dimensional (3D) space using Magnetic Levitation (MagLev), and report the discovery of a sharp geometry-dependent transition of the orientation of levitating objects. An analytical theory of the orientation of arbitrary objects in MagLev explains this transition. MagLev is capable of manipulating and orienting hard and soft objects, and objects of irregular shape. Because controlling the orientation of objects in space is a prerequisite for assembling complex structures from simpler components, this paper extends MagLev into 3D self-assembly, robotic assembly, and noncontact (stiction-free) orientation of hard and soft objects for applications in biomimetics, soft robotics, and stimulus-responsive materials, among others.

When sandwich panels with prismatic cores are impulsively loaded, the stresses imposed by the core on the front face, as well as those transmitted through the core govern the response metrics, especially the center displacement, resistance to tearing, and loads transmitted to the supports.This article presents a basic study of the dynamic response with emphasis on the I-core.A prior assessment revealed bucklewaves induced because of inertial phenomena accompanying the rapid compression of the members.The development of these waves is an integral aspect of the dynamic response.One objective of this investigation is to ascertain the characteristics governing such waves in I-core configurations through a combined experimental and numerical study.A particular emphasis is on the influence of manufacturing imperfections in the core members on the formation and propagation of the buckles.A second goal is to examine the stresses associated with the dynamic compression of the core, again through a combined experimental and numerical investigation.The investigation is conducted for stainless steel I-core panels supported at the back face and subjected to a constant velocity at the front.Imperfections to be included in the numerical study have been ascertained by comparing buckle patterns with those found experimentally over the relevant velocity range.The simulations reveal that the stresses induced differ on the front and back faces.On the front they are higher and velocity dependent.On the rear they are velocity invariant and scale with the relative density and material yield strength.The duration of the stress pulses, which is essentially the same on both faces, scales linearly with the core height.It correlates with the time needed for bucklewaves to propagate through the core to the back face.After the pulse terminates, the core continues to compress at a stress level about an order of magnitude smaller.

Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides.We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)).We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.

Abstract The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. We conducted a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 was associated with gestational duration; the association was replicated in 9,291 additional infants (combined P = 3.96 × 10 −14 ). Analysis of 15,536 mother-child pairs showed that the association was driven by fetal rather than maternal genotype. Functional experiments showed that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.