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.

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.

Empagliflozin add-on therapy to closed-loop insulin delivery in type 1 diabetes: a 2 × 2 factorial randomized crossover trial.

There is a need to optimize closed-loop automated insulin delivery in type 1 diabetes. We assessed the glycemic efficacy and safety of empagliflozin 25 mg d as add-on therapy to insulin delivery with a closed-loop system. We performed a 2 × 2 factorial randomized, placebo-controlled, crossover two-center trial in adults, assessing 4 weeks of closed-loop delivery versus sensor-augmented pump (SAP) therapy and empagliflozin versus placebo.

Corneal Confocal Microscopy Predicts the Development of Diabetic Neuropathy: A Longitudinal Diagnostic Multinational Consortium Study.

Objective: Corneal nerve fiber length (CNFL) has been shown in research studies to identify diabetic peripheral neuropathy (DPN). In this longitudinal diagnostic study, we assessed the ability of CNFL to predict the development of DPN.

Research Design And Methods: From a multinational cohort of 998 participants with type 1 and type 2 diabetes, we studied the subset of 261 participants who were free of DPN at baseline and completed at least 4 years of follow-up for incident DPN.

Reducing the need for carbohydrate counting in type 1 diabetes using closed-loop automated insulin delivery (artificial pancreas) and empagliflozin: A randomized, controlled, non-inferiority, crossover pilot trial.

Aim: To assess whether adding empagliflozin to closed-loop automated insulin delivery could reduce the need for carbohydrate counting in type 1 diabetes (T1D) without worsening glucose control.

Materials And Methods: In an open-label, crossover, non-inferiority trial, 30 adult participants with T1D underwent outpatient automated insulin delivery interventions with three random sequences of prandial insulin strategy days: carbohydrate counting, simple meal announcement (no carbohydrate counting) and no meal announcement. During each sequence of prandial insulin strategies, participants were randomly assigned empagliflozin (25 mg/day) or not, and crossed over to the comparator.

The Prevalence of Autoimmune Diseases in Longstanding Diabetes: Results from the Canadian Study of Longevity in Adults with Type 1 Diabetes.

Objective: We aimed to determine the prevalence of autoimmune diseases (e.g. thyroid disease, celiac disease, etc) in Canadians with longstanding type 1 diabetes (T1D) and to explore sex-specific differences and the association with complications.

Vasopressin associated with renal vascular resistance in adults with longstanding type 1 diabetes with and without diabetic kidney disease.

Objective: Arginine vasopressin (AVP) and its surrogate, copeptin, have been implicated in diabetic kidney disease (DKD) pathogenesis, which develops in a subset of people with longstanding type 1 diabetes, but not in others (DKD Resistors). We hypothesized that patients with DKD would exhibit higher copeptin concentrations vs. DKD Resistors.

Sex differences in neuropathy & neuropathic pain: A brief report from the Phase 2 Canadian Study of Longevity in Type 1 Diabetes.

To evaluate previous results from a questionnaire-based study, we studied objective neuropathy measures to determine sex differences in the prevalence of neuropathy and neuropathic pain in longstanding type 1 diabetes. Despite better neuropathy measures in females compared to males, we confirmed a trend towards higher neuropathic pain in females.

Analysis of Prevalence, Magnitude and Timing of the Dawn Phenomenon in Adults and Adolescents With Type 1 Diabetes: Descriptive Analysis of 2 Insulin Pump Trials.

Objectives: To better understand the dawn phenomenon in type 1 diabetes, we sought to determine its prevalence, timing and magnitude in studies specifically designed to assess basal insulin requirements in patients using insulin pumps.

Methods: Thirty-three participants from 2 sensor-augmented insulin pump studies were analyzed. Twenty participants were obtained from a methodologically ideal semiautomated basal analysis trial in which basal rates were determined from repeated fasting tests (the derivation set) and 13 from an artificial pancreas trial in which duration of fasting was variable (the "confirmation" set).

Estimating GFR by Serum Creatinine, Cystatin C, and β2-Microglobulin in Older Adults: Results From the Canadian Study of Longevity in Type 1 Diabetes.

Introduction: Glomerular filtration rate (GFR) is routinely used for clinical assessment of kidney function. However, the accuracy of estimating equations in older adults is uncertain.

Methods: In 66 adults with ≥50 years type 1 diabetes (T1D) duration and 73 nondiabetic controls from age/sex-matched subgroups (65 ± 8 years old and 77[55%] were women) we evaluated the performance of estimated GFR (eGFR) by creatinine (Modification of Diet and Renal Disease [MDRD], Chronic Kidney Disease-Epidemiology [CKD-EPI]), cystatin C (CKD-EPI, CKD-EPI), and β-microglobulin (β2M) compared with measured GFR by inulin clearance (mGFR).

Elevated plasma cyclic guanosine monophosphate may explain greater efferent arteriolar tone in adults with longstanding type 1 diabetes: A brief report.

Cyclic guanosine monophosphate (cGMP) influences intrarenal hemodynamics in animal models, but the relationship between cGMP and renal function in adults with type 1 diabetes (T1D) remains unclear. In this study, plasma cGMP correlated with efferent arteriolar resistance, effective renal plasma flow, and renal vascular resistance in adults with T1D.

Risk factors for diabetic kidney disease in adults with longstanding type 1 diabetes: results from the Canadian Study of Longevity in Diabetes.

Diabetic kidney disease (DKD) is an independent predictor of cardiovascular morbidity and mortality in type 1 diabetes (T1D). We aimed to explore clinical and biochemical factors, including the achievement of American Diabetes Association (ADA) recommended targets associated with DKD in people living with T1D for ≥50 years. This was a post hoc analysis of a cross-sectional study of 75 participants enrolled in the Canadian Study of Longevity in T1D.

Retinopathy and RAAS Activation: Results From the Canadian Study of Longevity in Type 1 Diabetes.

Objective: The importance of renin-angiotensin-aldosterone system (RAAS) activation in retinopathy for long-standing diabetes is not well understood. We determined retinopathy stage and evaluated associations with other vascular complications before and after physiological RAAS activation in adults with long-standing (≥50 years duration) type 1 diabetes.

Research Design And Methods: Participants underwent retinal examination by digital funduscopic photography and optical coherence tomography and were classified as having nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), or no diabetic retinopathy (NDR) with or without diabetic macular edema (DME).

The relationships between markers of tubular injury and intrarenal haemodynamic function in adults with and without type 1 diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes.

Objective: Our aim was to define the relationships between plasma biomarkers of kidney injury and intrarenal haemodynamic function (glomerular filtration rate [GFR], effective renal plasma flow [ERPF], renal vascular resistance [RVR]) in adults with type 1 diabetes (T1D).

Methods: The study sample comprised patients with longstanding T1D (duration ≥50 years), among whom 44 were diabetic kidney disease (DKD) resistors (eGFR >60 mL/min/1.73 m and <30 mg/d urine albumin excretion) and 22 had DKD, in addition to 73 control participants.

Atherosclerosis and Microvascular Complications: Results From the Canadian Study of Longevity in Type 1 Diabetes.

Objective: Type 1 diabetes carries a significant risk for cardiovascular mortality, but it is unclear how atherosclerosis associates with microvascular complications. We aimed to determine the relationships between atherosclerotic burden and neuropathy, retinopathy, and diabetic kidney disease (DKD) in adults with a ≥50-year history of type 1 diabetes.

Research Design And Methods: Adults with type 1 diabetes ( = 69) underwent coronary artery calcification (CAC) volume scoring by wide-volume computerized tomography.

Sex differences in neuropathic pain in longstanding diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes.

Aim: Neuropathy and neuropathic pain are common complications of type 1 diabetes (T1D). We aimed to determine if sex-specific differences in neuropathic pain are present in adults with longstanding T1D.

Methods: Canadians with ≥50 years of T1D (n = 361) completed health history questionnaires that included assessment of neuropathy (defined by Michigan Neuropathy Screening Instrument questionnaire components ≥3; NEUROPATHY) and neuropathic pain.

Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy: a pooled multinational consortium study.

Aims/hypothesis: Small cohort studies raise the hypothesis that corneal nerve abnormalities (including corneal nerve fibre length [CNFL]) are valid non-invasive imaging endpoints for diabetic sensorimotor polyneuropathy (DSP). We aimed to establish concurrent validity and diagnostic thresholds in a large cohort of participants with and without DSP.

Methods: Nine hundred and ninety-eight participants from five centres (516 with type 1 diabetes and 482 with type 2 diabetes) underwent CNFL quantification and clinical and electrophysiological examination.

Validity of a point-of-care nerve conduction device for polyneuropathy identification in older adults with diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes.

Objective: Point-of-care nerve conduction devices (POCD) have been studied in younger patients and may facilitate screening for polyneuropathy in non-specialized clinical settings. However, performance may be impaired with advanced age owing to age-related changes in nerve conduction. We aimed to evaluate the validity of a POCD as a proxy for standard nerve conduction studies (NCS) in older adults with type 1 diabetes (T1D).

Adiposity Impacts Intrarenal Hemodynamic Function in Adults With Long-standing Type 1 Diabetes With and Without Diabetic Nephropathy: Results From the Canadian Study of Longevity in Type 1 Diabetes.

Objective: Central adiposity is considered to be an important cardiorenal risk factor in the general population and in type 1 diabetes. We sought to determine the relationship between central adiposity and intrarenal hemodynamic function in adults with long-standing type 1 diabetes with and without diabetic nephropathy (DN).

Research Design And Methods: Patients with type 1 diabetes ( = 66, duration ≥50 years) and age-/sex-matched control subjects ( = 73) were studied.

Renin-angiotensin-aldosterone system activation in long-standing type 1 diabetes.

Background: In type 1 diabetes (T1D), adjuvant treatment with inhibitors of the renin-angiotensin-aldosterone system (RAAS), which dilate the efferent arteriole, is associated with prevention of progressive albuminuria and renal dysfunction. Uncertainty still exists as to why some individuals with long-standing T1D develop diabetic kidney disease (DKD) while others do not (DKD resistors). We hypothesized that those with DKD would be distinguished from DKD resistors by the presence of RAAS activation.

Diabetes Care Disparities in Long-standing Type 1 Diabetes in Canada and the U.S.: A Cross-sectional Comparison.

Objective: To assess national differences in diabetes care and quality of life (QOL) between individuals with long-standing type 1 diabetes (≥50 years) in Canada and the U.S.

Research Design And Methods: Cross-sectional data from identical surveys administered in the Canadian Study of Longevity in Diabetes and the Joslin Medalist Study, collected in 2013-2016 and 2005-2011, respectively, were compared.

Agreement between automated and manual quantification of corneal nerve fiber length: Implications for diabetic neuropathy research.

Aims: Quantification of corneal nerve fiber length (CNFL) by in vivo corneal confocal microscopy represents a promising diabetic neuropathy biomarker, but applicability is limited by resource-intensive image analysis. We aimed to evaluate, in cross-sectional analysis of non-diabetic controls and patients with type 1 and type 2 diabetes with and without neuropathy, the agreement between manual and automated analysis protocols.

Methods: Sixty-eight controls, 139 type 1 diabetes, and 249 type 2 diabetes participants underwent CNFL measurement (N=456).

Validation of cooling detection threshold as a marker of sensorimotor polyneuropathy in type 2 diabetes.

Aim: We aimed to validate the performance cooling detection thresholds (CDT) to detect diabetic sensorimotor polyneuropathy (DSP) in type 2 diabetes.

Methods: Two hundred and twenty participants with type 2 diabetes underwent clinical and electrophysiological examinations including 3 small fiber function tests: CDT, heart rate variability (HRV) and LDIFLARE. Clinical DSP was defined by consensus criteria whereas preclinical DSP was defined by presence of at least one electrophysiological abnormality.

Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy.

Objective: In vivo Corneal Confocal Microscopy (IVCCM) is a validated, non-invasive test for diabetic sensorimotor polyneuropathy (DSP) detection, but its utility is limited by the image analysis time and expertise required. We aimed to determine the inter- and intra-observer reproducibility of a novel automated analysis program compared to manual analysis.

Methods: In a cross-sectional diagnostic study, 20 non-diabetes controls (mean age 41.