Identifying predictors of sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide 1 receptor agonist use in hospital among adults with diabetes.

Aims: To identify factors associated with use of novel diabetes medications among patients hospitalized under general internal medicine.

Methods: We conducted a cohort study of patients with type 2 diabetes mellitus (T2DM) hospitalized in Ontario, Canada between 2015 and 2020. We evaluated the patient- and physician-level factors associated with sodium-glucose cotransporter 2 inhibitor (SGLT2) and glucagon-like peptide 1 receptor agonist (GLP1R) use using a multivariable logistic regression model.

Assessing corneal dendritic cells in glucose dysregulation small-fibre neuropathy.

Background And Aims: Small-fibre neuropathy (SFN) is associated with glucose dysregulation, including impaired glucose tolerance (IGT) and type 2 diabetes (T2D). Corneal confocal microscopy (CCM) offers a non-invasive tool to assess corneal nerve damage and dendritic cell density (DCD). In this study, we investigated corneal DCD in patients with SFN and glucose dysregulation, defined as IGT or T2D.

Glucagon-like Peptide-1 Receptor Agonist Use in Hospital: A Multicentre Observational Study.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective medications for type 2 diabetes mellitus (T2DM) and obesity, yet their uptake among patients most likely to benefit has been slow.

Methods: We conducted a cross-sectional analysis of medication exposure in adults hospitalized at 16 hospitals in Ontario, Canada, between 2015 and 2022. We estimated the proportions of those with T2DM, obesity, and cardiovascular disease.

Insulin Pump Use and Diabetic Ketoacidosis Risk in Type 1 Diabetes: Secular Trends over Four Decades.

Continuous subcutaneous insulin infusion (CSII) in type 1 diabetes has been regarded as a major diabetic ketoacidosis (DKA) risk factor. We aimed to determine secular trends in risk since CSII implementation in the 1980s. We assessed the relationship between time-varying CSII use and DKA events from 1983 to 2017 and by each decade in the 1441 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study participants using crude and adjusted Cox proportional hazards models.

Applying technologies to simplify strategies for exercise in type 1 diabetes.

Challenges and fears related to managing glucose levels around planned and spontaneous exercise affect outcomes and quality of life in people living with type 1 diabetes. Advances in technology, including continuous glucose monitoring, open-loop insulin pump therapy and hybrid closed-loop (HCL) systems for exercise management in type 1 diabetes, address some of these challenges. In this review, three research or clinical experts, each living with type 1 diabetes, leverage published literature and clinical and personal experiences to translate research findings into simplified, patient-centred strategies.

Prognostic Implications of Diabetic Ketoacidosis in Adults on Long-term Mortality and Diabetes-Related Complications.

Objectives: Diabetic ketoacidosis (DKA) occurring after diabetes diagnosis is often associated with risk factors for other diabetes-related complications. In this study, we aimed to determine the prognostic implications of DKA on all-cause mortality and complications in type 1 diabetes (T1D).

Methods: Previously collected data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study were obtained through the the National Institute of Diabetes and Digestive and Kidney Diseases Central Repository.

Effect of hyperglycemia and empagliflozin on markers of cardiorenal injury and inflammation in patients with type 1 diabetes.

Aims: To investigate the effect of hyperglycemia and empagliflozin on cardiorenal injury and inflammation in patients with uncomplicated type 1 diabetes (T1D).

Methods: Serum cardiac (sST2, Gal-3, cTnT), kidney injury (KIM-1, NGAL), inflammatory (sTNFR1, sTNFR2), and hemodynamic (NT-proBNP, EPO) markers were assessed post-hoc in two separate T1D cohorts. The glycemic clamp trial (NCT02344602) evaluated 49 adults with T1D and 27 controls under euglycemic and acute hyperglycemic conditions.

Longitudinal Trajectories of Biomarkers of Kidney Tubular Function in Type 1 Diabetes.

Introduction: Tubular biomarkers may shed insight into progression of kidney tubulointerstitial pathology complementary to traditional measures of glomerular function and damage.

Methods: We examined trajectories of tubular biomarkers in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC Study) of type 1 diabetes (T1D). Biomarkers were measured in a subset of 220 participants across 7 time points over 26 years.

Associations of Kidney Tubular Biomarkers With Incident Macroalbuminuria and Sustained Low eGFR in DCCT/EDIC.

Objective: Tubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D).

Research Design And Methods: We performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning ∼30 years, with incident macroalbuminuria ("severely elevated albuminuria," urinary albumin excretion rate [AER] ≥300 mg/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR <60 mL/min/1.

Neuropathic Pain With and Without Diabetic Peripheral Neuropathy in Type 1 Diabetes.

Objective: Diabetic peripheral neuropathy (DPN) is common; however, the features and burden of neuropathic pain (NP) in type 1 diabetes (T1D) are poorly understood. We evaluated the incidence of first occurrence, annual prevalence, remission, and risk factors for NP during long-term follow-up of participants with T1D.

Research Design And Methods: The Michigan Neuropathy Screening Instrument (MNSI) was administered annually (1994-2020) for 1,324 participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

Modeling multiple correlated end-organ disease trajectories: A tutorial for multistate and joint models with applications in diabetes complications.

State-of-the-art biostatistics methods allow for the simultaneous modeling of several correlated non-fatal disease processes over time, but there is no clear guidance on the optimal analysis in most settings. An example occurs in diabetes, where it is not known with certainty how microvascular complications of the eyes, kidneys, and nerves co-develop over time. In this article, we propose and contrast two general model frameworks for studying complications (sequential state and parallel trajectory frameworks) and review multivariate methods for their analysis, focusing on multistate and joint modeling.

Ketone production and excretion even during mild hyperglycemia and the impact of sodium-glucose co-transporter inhibition in type 1 diabetes.

Aims: We aimed to determine if ketone production and excretion are increased even at mild fasting hyperglycemia in type 1 diabetes (T1D) and if these are modified by ketoacidosis risk factors, including sodium-glucose co-transporter inhibition (SGLTi) and female sex.

Methods: In secondary analysis of an 8-week single-arm open-label trial of empagliflozin (NCT01392560) we evaluated ketone concentrations during extended fasting and clamped euglycemia (4-6 mmol/L) and mild hyperglycemia (9-11 mmol/L) prior to and after treatment. Plasma and urine beta-hydroxybutyrate (BHB) concentrations and fractional excretion were analyzed by metabolomic analysis.

Interactive Effects of Empagliflozin and Hyperglycemia on Urinary Amino Acids in Individuals With Type 1 Diabetes.

Optimizing energy use in the kidney is critical for normal kidney function. Here, we investigate the effect of hyperglycemia and sodium-glucose cotransporter 2 (SGLT2) inhibition on urinary amino acid excretion in individuals with type 1 diabetes (T1D). The open-label ATIRMA trial assessed the impact of 8 weeks of 25 mg empagliflozin orally once per day in 40 normotensive normoalbuminuric young adults with T1D.

Fasted C-Peptide Distribution and Associated Clinical Factors in Adults With Longstanding Type 1 Diabetes: Analysis of the Canadian Study of Longevity in Type 1 Diabetes.

Objective: Although insulin production is reportedly retained in many people with longstanding type 1 diabetes (T1D), the magnitude and relevance of connecting peptide (C-peptide) production are uncertain. In this study, we aimed to define fasted C-peptide distributions and associated clinical factors.

Methods: In a cross-sectional analysis of the Canadian Study of Longevity, fasted serum and urinary C-peptide was measured in 74 patients with longstanding T1D (duration ≥50 years) and 75 age- and sex-matched controls.

Factors Associated With Attainment of Glycemic Targets Among Adults With Type 1 and Type 2 Diabetes in Canada: A Cross-sectional Study Using Primary and Specialty Care Electronic Medical Record Data.

Objective: Using a new database combining primary and specialty care electronic medical record (EMR) data in Canada, we determined attainment of glycemic targets and associated predictors among adults with diabetes.

Methods: We conducted a cross-sectional observational study combining primary and specialty care EMR data in Canada. Adults with diabetes whose primary care provider contributed to the National Diabetes Repository or who were assessed at a diabetes specialty clinic (LMC Diabetes and Endocrinology) between July 3, 2015, and June 30, 2019, were included.

Point-of-Care Capillary Blood Ketone Measurements and the Prediction of Future Ketoacidosis Risk in Type 1 Diabetes.

Objective: Rather than during illness while diabetic ketoacidosis (DKA) is developing, we aimed to determine if levels of routine point-of-care capillary blood ketones could predict future DKA.

Research Design And Methods: We examined previously collected data from placebo-assigned participants in an adjunct-to-insulin medication trial program that included measurement of fasted capillary blood ketone levels twice per week in a 2-month baseline period. The outcome was 6- to 12-month trial-adjudicated DKA.

Reliability of confocal corneal microscopy for measurement of dendritic cell density in suspected small fiber neuropathy.

Introduction/aims: Dendritic cells (DCs) and their contacts with corneal nerves are described in animal models of nerve damage. Dendritic cell density (DCD) is a potential marker of immune activity in suspected small-fiber neuropathy (SFN). Here, we aim to evaluate the intra- and inter-rater reliability of DCD measurements in suspected SFN.

Estimated glomerular filtration rate calculated by serum creatinine lacks precision and accuracy in adults with type 2 diabetes with preserved renal function.

Aims: We evaluated the performance of creatinine-based equations that are currently used to estimate glomerular filtration rate (GFR) in people with type 2 diabetes compared to measured GFR using gold-standard methods.

Methods: In this post-hoc analysis, 32 participants underwent repeated measurement of GFR by inulin clearance (mGFR). GFR was estimated by serum creatinine using the MDRD (eGFR) and CKD-EPI (eGFR) equations four times over the course of one month.

Cardiovascular Autonomic Neuropathy and Risk of Kidney Function Decline in Type 1 and Type 2 Diabetes: Findings From the PERL and ACCORD Cohorts.

Results of previous studies have suggested that cardiovascular autonomic neuropathy (CAN) may predict rapid kidney function decline among people with diabetes. We analyzed the association between baseline CAN and subsequent glomerular filtration rate (GFR) decline among individuals with type 1 diabetes (T1D) from the Preventing Early Renal Loss in Diabetes (PERL) study (N = 469) and with type 2 diabetes (T2D) from Action to Control Cardiovascular Risk in Diabetes (ACCORD) (N = 7,973). Baseline CAN was ascertained with electrocardiogram-derived heart rate variability indices.

Relationships Between the Cumulative Incidences of Long-term Complications in Type 1 Diabetes: The DCCT/EDIC Study.

Objective: To describe the relationships between the cumulative incidences of long-term complications in individuals with type 1 diabetes (T1D) and assess whether observed associations are independent of age, duration of diabetes, and glycemic levels.

Methods: Proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), reduced estimated glomerular filtration rate (eGFR), amputations, cardiovascular disease (CVD), and mortality were assessed in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study over ∼30 years.

Research Design And Results: The cumulative incidence of complications ranged from 3% (amputations) to 37% (CSME).

Implementation Plan for a High-Frequency, Low-Touch Care Model at Specialized Type 1 Diabetes Clinics: Model Development.

Background: Individuals with type 1 diabetes (T1D) are more likely to achieve optimal glycemic management when they have frequent visits with their health care team. There is a potential benefit of frequent, telemedicine interventions as an effective strategy to lower hemoglobin A1c (HbA1c).

Objective: The objective is this study was to understand the provider- and system-level factors affecting the successful implementation of a virtual care intervention in type 1 diabetes (T1D) clinics.