A new glucose-responsive formulation for self-regulated insulin delivery was constructed by packing insulin, glucose-specific enzymes into pH-sensitive polymersome-based nanovesicles assembled by a diblock copolymer. Glucose can passively transport across the bilayer membrane of the nanovesicle and be oxidized into gluconic acid by glucose oxidase, thereby causing a decrease in local pH. The acidic microenvironment causes the hydrolysis of the pH sensitive nanovesicle that in turn triggers the release of insulin in a glucose responsive fashion. In vitro studies validated that the release of insulin from nanovesicle was effectively correlated with the external glucose concentration. In vivo experiments, in which diabetic mice were subcutaneously administered with the nanovesicles, demonstrate that a single injection of the developed nanovesicle facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 5 days.

Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to “closed-loop” insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels. “Closing the loop” between blood glucose level (BGL) measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed.

BACKGROUND: Coverage for cardiac rehabilitation (CR) for patients with heart failure with reduced ejection fraction was expanded in 2014, but contemporary referral and participation rates remain unknown. METHODS: Patients hospitalized for heart failure with reduced ejection fraction (≤35%) in the American Heart Association Get With The Guidelines–Heart Failure registry from 2010 to 2020 were included, and CR referral status was described as yes, no, or not captured. Temporal trends in CR referral were assessed in the overall cohort. Patient and hospital-level predictors of CR referral were assessed using multivariable-adjusted logistic regression models. Additionally, CR referral and proportional utilization of CR within 1-year of referral were evaluated among patients aged >65 years with available Medicare administrative claims data who were clinically stable for 6-weeks postdischarge. Finally, the association of CR referral with the risk of 1-year death and readmission was evaluated using multivariable-adjusted Cox models. RESULTS: Of 69,441 patients with heart failure with reduced ejection fraction who were eligible for CR (median age 67 years; 33% women; 30% Black), 17,076 (24.6%) were referred to CR, and referral rates increased from 8.1% in 2010 to 24.1% in 2020 ( P trend <0.001). Of 8310 patients with Medicare who remained clinically stable 6-weeks after discharge, the CR referral rate was 25.8%, and utilization of CR among referred patients was 4.1% (mean sessions attended: 6.7). Patients not referred were more likely to be older, of Black race, and with a higher burden of comorbidities. In adjusted analysis, eligible patients with heart failure with reduced ejection fraction who were referred to CR (versus not referred) had a lower risk of 1-year death (hazard ratio, 0.84 [95% CI, 0.70–1.00]; P =0.049) without significant differences in 1-year readmission. CONCLUSIONS: CR referral rates have increased from 2010 to 2020. However, only 1 in 4 patients are referred to CR. Among eligible patients who received CR referral, participation was low, with <1 of 20 participating in CR.