New tools for applying force to animals, tissues, and cells are critically needed in order to advance the field of mechanobiology, as few existing tools enable simultaneous imaging of tissue and cell deformation as well as cellular activity in live animals. Here, we introduce a novel microfluidic device that enables high-resolution optical imaging of cellular deformations and activity while applying precise mechanical stimuli to the surface of the worm’s cuticle with a pneumatic pressure reservoir. To evaluate device performance, we compared analytical and numerical simulations conducted during the design process to empirical measurements made with fabricated devices. Leveraging the well-characterized touch receptor neurons (TRNs) with an optogenetic calcium indicator as a model mechanoreceptor neuron, we established that individual neurons can be stimulated and that the device can effectively deliver steps as well as more complex stimulus patterns. This microfluidic device is therefore a valuable platform for investigating the mechanobiology of living animals and their mechanosensitive neurons.

Given the progressive nature of type 2 diabetes, treatment intensification is usually necessary to maintain glycemic control. However, for a variety of reasons, treatment is often not intensified in a timely manner. The combined use of basal insulin and a glucagon-like peptide-1 receptor agonist is recognized to provide a complementary approach to the treatment of type 2 diabetes. This review evaluates the efficacy and safety of two co-formulation products, insulin degludec/liraglutide and insulin glargine/lixisenatide, for the treatment of type 2 diabetes inadequately controlled on either component agent alone. We consider the benefits and limitations of these medications based on data from randomized clinical trials and discuss how they may address barriers to treatment intensification.

Cardiovascular disease (CVD) is a leading cause of death in people with type 2 diabetes (T2D). Recent cardiovascular (CV) outcomes trials have shown CV benefits for several GLP-1 receptor agonists and SGLT2 inhibitors. We aimed to evaluate T2D patients’ awareness, perceptions, and behaviors regarding CVD and cardioprotective T2D drugs. An online survey was completed by 927 T2D patients of diverse socioeconomic backgrounds from an opted-in patient research panel in the U.S. Median respondent age was 64 and median duration of diabetes was 15 years. Half were taking a GLP-1 or SGLT2, a statistically robust sample of patients on these therapies. Questions covered perceptions of CVD disease; awareness of and interest in diabetes drugs that reduce CVD risk; knowledge of their own health metrics; physicians seen and frequency of discussions about CVD; self-assigned ‘grades’ on lifestyle behaviors known to reduce CVD risk. Most patients recognized the link between T2D and CVD: 61% strongly agreed that T2D increases CVD risk. Yet, only 29% think often about their risk of CVD. Awareness of CV benefits from some T2D therapies was also low (34% overall; 42% for those on SGLT2 or GLP-1). Interest in taking an additional cardioprotective diabetes agent aligned with awareness (37% overall; 42% for those on SGLT2 or GLP-1). While almost all knew their HbA1c and blood pressure, over 25% did not know their LDL cholesterol or other lipid levels. In the prior year, 31% of patients had seen a cardiologist and 17% had discussed CVD risk with an endocrinologist. Respondents generally ranked themselves ‘average’ to ‘below average’ on heart-healthy behaviors like exercise, weight, sleep, diet, and stress management. Although a majority of T2D patients are aware of the link between T2D and CVD, most are not actively managing their CV health, and few know that some T2D therapies are cardioprotective. These data suggest a need to better inform T2D patients about their risk for CVD, and steps they can take to reduce that risk. Disclosure K.C. Stoner: Other Relationship; Self; Multiple companies and organizations in the diabetes field (greater than 10). E.N. Fitts: Other Relationship; Self; Various diabetes companies. D. Gopisetty: Other Relationship; Self; Various diabetes companies. A. Carracher: Other Relationship; Self; Other. C.S. Florissi: Other Relationship; Self; dQ&A has several clients (>10) in the diabetes field. M.J. Kurian: Other Relationship; Self; Other Company. J. Kwon: Other Relationship; Self; Various diabetes companies. P. Marathe: Consultant; Self; Close Concerns. P. Rentzepis: Other Relationship; Self; Various Diabetes Companies. J.B. Rost: Other Relationship; Self; dQ&A has several clients (>10) in the diabetes field. K.L. Close: Other Relationship; Self; Various diabetes companies. I.B. Hirsch: Consultant; Self; Abbott, Becton, Dickinson and Company, Big Foot, Roche Diabetes Care. Research Support; Self; Medtronic. M.N. Kosiborod: Consultant; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eisai Co., Ltd., GlaxoSmithKline plc., Glytec, LLC, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis AG, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. R. Wood: Other Relationship; Self; Multiple companies in the diabetes field (>10 companies). Funding AstraZeneca