A Randomized Trial Comparing Inhaled Insulin Plus Basal Insulin Versus Usual Care in Adults With Type 1 Diabetes.

Objective: To evaluate a regimen of inhaled Technosphere insulin (TI) plus insulin degludec in adults with type 1 diabetes, who prestudy were predominately using either an automated insulin delivery (AID) system or multiple daily insulin injections (MDI) with continuous glucose monitoring.

Research Design And Methods: At 19 sites, adults with type 1 diabetes were randomly assigned to TI plus insulin degludec (N = 62) or usual care (UC) with continuation of prestudy insulin delivery method (N = 61) for 17 weeks.

Results: Prestudy, AID was used by 48% and MDI by 45%.

Results From a Randomized Trial of Intensive Glucose Management Using CGM Versus Usual Care in Hospitalized Adults With Type 2 Diabetes: The TIGHT Study.

Objective: To evaluate whether continuous glucose monitoring (CGM) could assist providers in intensifying glycemic management in hospitalized patients with type 2 diabetes.

Research Design And Methods: At six academic hospitals, adults with type 2 diabetes hospitalized in a non-intensive care setting were randomly assigned to either standard therapy with glucose target 140-180 mg/dL (standard group) or intensive therapy with glucose target 90-130 mg/dL guided by CGM (intensive group). The primary outcome was mean glucose measured with CGM (blinded in standard group), and the key secondary outcome was CGM glucose <54 mg/dL.

A genome-wide association study identifies genetic determinants of hemoglobin glycation index with implications across sex and ethnicity.

Introduction: We investigated the genetic determinants of variation in the hemoglobin glycation index (HGI), an emerging biomarker for the risk of diabetes complications.

Methods: We conducted a genome-wide association study (GWAS) for HGI in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial ( = 7,913) using linear regression and additive genotype encoding on variants with minor allele frequency greater than 3%. We conducted replication analyses of top findings in the Atherosclerosis Risk in Communities (ARIC) study with inverse variance-weighted meta-analysis.

Upscaling biodiversity monitoring: Metabarcoding estimates 31,846 insect species from Malaise traps across Germany.

Mitigating ongoing losses of insects and their key functions (e.g. pollination) requires tracking large-scale and long-term community changes.

High-dimensional Iterative Causal Forest (hdiCF) for Subgroup Identification Using Health Care Claims Data.

We recently developed a machine-learning subgrouping algorithm, iterative causal forest (iCF), to identify subgroups with heterogeneous treatment effects (HTEs) using predefined covariates. However, such predefined covariates may miss or poorly define important features leading to inaccurate subgrouping. To address such limitations, we developed a new semi-automatic subgrouping algorithm, hdiCF, which adapts methodology from high-dimensional propensity score for feature recognition in claims data.

A Systematic Approach to Evaluating Instrumental Variable Assumptions: Applied Example of Glucose-lowering Medications and Risk for Hospitalized Heart Failure in Older Adults.

One obstacle to adopting instrumental variable (IV) methods in pharmacoepidemiology is their reliance on strong, unverifiable assumptions. We can falsify IV assumptions by leveraging the causal structure, which can strengthen or refute their plausibility and increase the validity of effect estimates. We illustrate a systematic approach to evaluate calendar time IV assumptions in estimating the known effect of thiazolidinediones on hospitalized heart failure.

An orally administered glucose-responsive polymeric complex for high-efficiency and safe delivery of insulin in mice and pigs.

Contrary to current insulin formulations, endogenous insulin has direct access to the portal vein, regulating glucose metabolism in the liver with minimal hypoglycaemia. Here we report the synthesis of an amphiphilic diblock copolymer comprising a glucose-responsive positively charged segment and polycarboxybetaine. The mixing of this polymer with insulin facilitates the formation of worm-like micelles, achieving highly efficient absorption by the gastrointestinal tract and the creation of a glucose-responsive reservoir in the liver.

Effect of SARS-CoV-2 Infection on Incident Diabetes by Viral Variant: Findings From the National COVID Cohort Collaborative (N3C).

Objective: The coronavirus 2019 (COVID-19) pandemic has evolved over time by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, disease severity, treatment, and prevention. There is evidence of an elevated risk of incident diabetes after COVID-19; our objective was to evaluate whether this association is consistent across time and with contemporary viral variants.

Research Design And Methods: We conducted a retrospective cohort study using National COVID Cohort Collaborative (N3C) data to evaluate incident diabetes risk among COVID-positive adults compared with COVID-negative patients or control patients with acute respiratory illness (ARI).

Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial.

Aim: The decline in estimated glomerular filtration rate (eGFR), a significant predictor of cardiovascular disease (CVD), occurs heterogeneously in people with diabetes because of various risk factors. We investigated the role of eGFR decline in predicting CVD events in people with type 2 diabetes in both primary and secondary CVD prevention settings.

Materials And Methods: Bayesian joint modelling of repeated measures of eGFR and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to examine the association between the eGFR slope and the incidence of major adverse CV event/hospitalization for heart failure (MACE/hHF) (non-fatal myocardial infarction, non-fatal stroke, CV death, or hospitalization for heart failure).

A Randomized Comparison of Postprandial Glucose Excursion Using Inhaled Insulin Versus Rapid-Acting Analog Insulin in Adults With Type 1 Diabetes Using Multiple Daily Injections of Insulin or Automated Insulin Delivery.

Objective: To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin.

Research Design And Methods: A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61).

Results: The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference -12 mg/dL, 95% CI -22 to -2, P = 0.

Study protocol for a prospective, multicentre study of hypercortisolism in patients with difficult-to-control type 2 diabetes (CATALYST): prevalence and treatment with mifepristone.

Introduction: Even with recent treatment advances, type 2 diabetes (T2D) remains poorly controlled for many patients, despite the best efforts to adhere to therapies and lifestyle modifications. Although estimates vary, studies indicate that in >10% of individuals with difficult-to-control T2D, hypercortisolism may be an underlying contributing cause. To better understand the prevalence of hypercortisolism and the impact of its treatment on T2D and associated comorbidities, we describe the two-part Hyper ortisolism in P ients with Difficult to Control Type 2 Di betes Despite Receiving Standard-of-Care Therapies: Preva ence and Treatment with Korl m (Mifepri one) (CATALYST) trial.

Glucagon-like Peptide 1 Receptor Agonists and Asthma Exacerbations: Which Patients Benefit Most?

Although recent evidence suggested that glucagon-like peptide 1 receptor agonists (GLP1RAs) might reduce the risk of asthma exacerbations, it remains unclear which subpopulations might derive the most benefit from GLP1RA treatment. To identify characteristics of patients with asthma that predict who might benefit the most from GLP1RA treatment using real-world data. We implemented an active-comparator, new-user design analysis using commercially ensured patients 18-65 years of age from MarketScan data for 2007-2019 and identified two cohorts: GLP1RAs versus thiazolidinediones and GLP1RAs versus sulfonylureas.

Polygenic subtype identified in ACCORD trial displays a favorable type 2 diabetes phenotype in the UKBiobank population.

Introduction: We previously identified a genetic subtype (C4) of type 2 diabetes (T2D), benefitting from intensive glycemia treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Here, we characterized the population of patients that met the C4 criteria in the UKBiobank cohort.

Research Design And Methods: Using our polygenic score (PS), we identified C4 individuals in the UKBiobank and tested C4 status with risk of developing T2D, cardiovascular disease (CVD) outcomes, and differences in T2D medications.

Skeletal muscle density performance for screening frailty in older adults with cancer and the impact of diabetes: The CARE Registry.

Introduction: Skeletal muscle density (SMD) measurements from imaging scans identify myosteatosis and could screen patients for geriatric assessment. We assessed SMD performance as a screening tool to identify older adults with cancer likely to be frail and who could benefit from in-depth assessment; we compared performance by sex and diabetes status.

Materials And Methods: We analyzed patients in the Cancer & Aging Resilience Evaluation (CARE) Registry.

Understanding the Pharmacokinetics and Glucodynamics of Once Weekly Basal Insulins to Inform Dosing Principles: An Introduction to Clinicians.

Objective: A new generation of basal insulin analogs enabling once-weekly administration is currently under development. Weekly basal insulins have the potential to overcome limitations exhibited by current daily basal insulins. The pharmacokinetic and glucodynamic characteristics differ significantly between weekly and daily basal insulins and will require paradigm shifts in how basal insulins are dosed.

Recent Progress in Glucose-Responsive Insulin.

Insulin replacement therapy is indispensable in the treatment of type 1 and advanced type 2 diabetes. However, insulin's clinical application is challenging due to its narrow therapeutic index. To mitigate acute and chronic risks of glucose excursions, glucose-responsive insulin (GRI) has long been pursued for clinical application.

Risk of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Among Patients with Type 2 Diabetes Mellitus on Anti-Hyperglycemic Medications.

Background: Observed activity of metformin in reducing the risk of severe COVID-19 suggests a potential use of the anti-hyperglycemic in the prevention of post-acute sequelae of SARS-CoV-2 infection (PASC). We assessed the 3-month and 6-month risk of PASC among patients with type 2 diabetes mellitus (T2DM) comparing metformin users to sulfonylureas (SU) or dipeptidyl peptidase-4 inhibitors (DPP4i) users.

Methods: We used de-identified patient level electronic health record data from the National Covid Cohort Collaborative (N3C) between October 2021 and April 2023.