Persistent disparities in insulin pump uptake despite a universal pump programme for type 1 diabetes in Ontario, Canada.

AIM: To evaluate associations between social disadvantage and insulin pump use among adults with type 1 diabetes (T1D) in the context of a universal publicly funded insulin pump programme in Ontario, Canada, and to ascertain whether social disparities in insulin pump programme enrolment have decreased over time. METHODS: Population-based cross-sectional studies were conducted using administrative healthcare data in Ontario, Canada. First, among adults aged older than 18 years diagnosed with T1D before 31 March 2021, logistic regression was used to assess the association between neighbourhood social disadvantage (Ontario marginalization index quintiles) and insulin pump use. Second, among all paediatric and adult applicants to the insulin pump programme from 1 September 2006 to 31 March 2022, ordinal logistic regression was used to evaluate associations between year of insulin pump initiation and social disadvantage. RESULTS: Among 27 453 adults with T1D, 60% used insulin pumps. Greater social disadvantage was associated with lower odds of insulin pump use (adjusted odds ratio [OR] 0.44 [95% confidence interval {CI} 0.39-0.48] for greatest vs. lowest social disadvantage quintile). Among 21 002 paediatric and adult applicants to the insulin pump programme, social disparities in pump use decreased in the first 3 years of the programme, plateaued until 2020, then increased from 2020 to 2022, with no change in the odds of being in a higher social deprivation quintile for 2022 relative to 2007 (OR 1.09 [95% CI 0.83-1.44]). CONCLUSIONS: Despite a universal pump programme for individuals with T1D, disparities by social disadvantage persist. Residual financial and non-financial barriers must be addressed to promote equitable insulin pump uptake.

Glycaemic control in transition-aged versus early adults with type 1 diabetes and the effect of a government-funded insulin pump programme.

AIM: To compare glycaemic control and adverse outcomes between transition-aged and early adults with type 1 diabetes, and the impact of continuous subcutaneous insulin infusion (CSII) therapy funded through a government Assisted Devices Program. METHODS: This retrospective cohort study using healthcare administrative databases from Ontario, Canada included adults aged 18-35 with type 1 diabetes between 1 April 2011 and 31 March 2014. Mean HbA1c was compared between transition-aged (18-24 years) and early adults (25-35 years), overall and stratified by whether or not they received government-funded CSII therapy (CSII vs. non-CSII). Secondary outcomes included rates of hospitalizations/emergency department visits for hyperglycaemia and hypoglycaemia over a 3-year follow-up. Comparisons were adjusted for relevant covariates. RESULTS: Among 7157 participants with type 1 diabetes, mean HbA1c was significantly higher for transition-aged compared to early adults (71 mmol/mol [8.68%] vs. 64 mmol/mol [8.04%], p < 0.0001). This difference was smaller among CSII compared to non-CSII users (p = 0.02 for interaction between age group and CSII use). The transition-age group were more likely to experience a hyperglycaemic event compared to early adults (adjusted risk ratio, aRR: 1.56, 95% confidence interval [CI]: 1.25-1.96), which was attenuated by CSII use (aRR: 1.13, 95% CI: 0.7-1.69). CONCLUSIONS: Transition-aged adults with type 1 diabetes had a significantly higher mean HbA1c and risk of hyperglycaemic events compared to early adults. This difference was attenuated for CSII users, indicating that a government-funded CSII programme is associated with narrowing of the gap in glycaemic control and associated adverse outcomes for this population.

Reporting and variability of constructing medication treatment episodes in pharmacoepidemiology studies: A methodologic systematic review using the case study of DPP-4 inhibitors and cardiovascular outcomes.

PURPOSE: In pharmacoepidemiologic studies, estimating medication adherence, persistence, and exposure patterns is critical. Constructing medication treatment episodes from prescription claims data involves assumptions related to grace period, carry-over, and lag effect, but there are no guidelines for these assumptions. We evaluated reporting and variability of these parameters in pharmacoepidemiology studies, using a case study of antihyperglycemic medications and major adverse cardiovascular events (MACE). METHODS: We conducted a systemic review using MEDLINE and EMBASE for studies published prior to January 2, 2020 comparing the risk of MACE between dipeptidyl peptidase 4 (DPP-4) inhibitors and active comparators. We extracted study characteristics and results, including grace period, carry-over, and lag effect. Risk of bias was assessed by the Newcastle-Ottawa scale, and assessments for prevalent user, immortal time, time lag, and time window biases. RESULTS: A total of 14/1850 studies identified were included. Grace period was not reported in 5 (35.7%) studies and ranged from 0 days to 180 days when reported. Carry-over was not reported in 10 studies (71.4%). Lag effect was not reported in nine (71.4%) studies and ranged from 0 days to 180 days when reported. No studies conducted sensitivity analyses examining the effects of these assumptions on study findings. Predominant biases were inadequate follow-up time, comparability of cohorts, prevalent use, and lag time bias. CONCLUSIONS: Use of grace period, carry-over, and lag effect were poorly reported and highly variable. Future pharmacoepidemiology studies should improve reporting, justify ranges for these parameters, and conduct sensitivity analyses to evaluate effects of these assumptions.

Renal Hemodynamic Function and RAAS Activation Over the Natural History of Type 1 Diabetes.

RATIONALE & OBJECTIVE: The renin-angiotensin-aldosterone system (RAAS) is associated with renal and cardiovascular disease in diabetes. Unfortunately, early RAAS blockade in patients with type 1 diabetes mellitus (T1DM) does not prevent the development of complications. We sought to examine the role of hyperfiltration and RAAS activation across a wide range of T1DM duration to better understand renal hemodynamic status in patients with T1DM. STUDY DESIGN: Post hoc analysis of blood samples. SETTING & PARTICIPANTS: 148 Canadian patients with T1DM: 28 adolescents (aged 16.2±2.0 years), 54 young adults (25.4±5.6 years), and 66 older adults (65.7±7.5 years) studied in a clinical investigation unit. EXPOSURE: Angiotensin II infusion (1ng/kg/min; a measure of RAAS activation) during a euglycemic clamp. OUTCOMES: Glomerular filtration rate measured using inulin clearance, effective renal plasma flow measured using para-aminohippurate, afferent (RA) and efferent (RE) arteriolar resistances, and glomerular hydrostatic pressure estimated using the Gomez equations. RESULTS: In a stepwise fashion, glomerular filtration rate, effective renal plasma flow, and glomerular hydrostatic pressure were higher, while renal vascular resistance and RA were lower in adolescents versus young adults versus older adults. RE was similar in adolescents versus young adults but was higher in older adults. Angiotensin II resulted in blunted renal hemodynamic responses in older adults (renal vascular resistance increase of 3.3% ± 1.6% vs 4.9% ± 1.9% in adolescents; P<0.001), suggesting a state of enhanced RAAS activation. LIMITATIONS: Homogeneous study participants limit the generalizability of findings to other populations. Studying older adult participants with T1DM may be associated with a survivorship bias. CONCLUSIONS: A state of relatively low RAAS activity and predominant afferent dilation rather than efferent constriction characterize early adolescents and young adults with T1DM. This state of endogenous RAAS inactivity in early T1DM may explain why pharmacologic blockade of this neurohormonal system is often ineffective in reducing kidney disease progression in this setting. Older adults with long-standing T1DM who have predominant afferent constriction and RAAS activation may experience renoprotection from therapies that target the afferent arteriole. Further work is required to understand the potential role of non-RAAS pharmacologic agents that target RA in patients with early and long-standing T1DM.

Association between allopurinol and cardiovascular outcomes and all-cause mortality in diabetes: A retrospective, population-based cohort study.

AIM: To assess the association between allopurinol and mortality and cardiovascular outcomes in an allopurinol-treated diabetes cohort. MATERIALS AND METHODS: We conducted a population-based retrospective cohort study in Ontario, Canada. Eligible subjects were ≥ 66 years old with diabetes and a first prescription for allopurinol between 1 April, 2002 and 31 March, 2012 and were followed until 31 March, 2016. The primary outcome was a composite: all-cause mortality, non-fatal cardiovascular event (myocardial infarction, revascularization procedure, or stroke) or congestive heart failure (CHF). Secondary outcomes were components of the primary outcome and pneumonia as a negative tracer. Allopurinol was modelled as time-varying exposed versus unexposed, daily dose category and cumulative dose using sex-specific multivariable Cox proportional hazards models. RESULTS: Over a median follow-up of 4.65 years (interquartile range 1.79-7.81), 16 266/23 103 males and 10 571/15 313 females experienced the primary outcome. Allopurinol was associated with a reduction in the primary outcome [adjusted hazard ratios (aHR) 0.77 (95% confidence interval 0.75-0.80) and 0.81 (0.78-0.84) for males and females, respectively], driven by marked reductions in all-cause mortality and modest reductions in cardiovascular events/CHF. There was no effect of cumulative allopurinol dose on any outcome, and allopurinol was also associated with reduced risk of pneumonia in males [aHR 0.88 (0.83, 0.93)]. CONCLUSIONS: Allopurinol was associated with reduced mortality and cardiovascular outcomes. However, lack of cumulative dose effect and a positive tracer outcome in males suggests residual bias. Future research assessing whether allopurinol prevents vascular complications in diabetes requires a clinical trial.

Association between uric acid, renal haemodynamics and arterial stiffness over the natural history of type 1 diabetes.

AIMS: To examine the relationship between normal plasma uric acid (PUA) levels, renal haemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of type 1 diabetes (T1D) durations in adolescents, young adults and older adults. MATERIALS AND METHODS: PUA, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), and plasma renin and aldosterone were measured during a euglycaemic clamp in people with T1D: 27 adolescents (mean ± SD age 16.8 ± 1.9 years), 52 young adults (mean ± SD age 25.6 ± 5.5 years) and 66 older adults (mean ± SD age 65.7 ± 7.5 years). RESULTS: PUA was highest in patients with the longest T1D duration: 197 ± 44 µmol/L in adolescents versus 264 ± 82 µmol/L in older adults (P < 0.001). Higher PUA correlated with lower GFR only in older adults, even after correcting for age, glycated haemoglobin and sex (ß = -2.12 ± 0.56; P = 0.0003), but not in adolescents or young adults. Higher PUA correlated with lower carotid AIx (ß = -1.90, P = 0.02) in adolescents. In contrast, PUA correlated with higher cfPWV (P = 0.02) and higher plasma renin (P = 0.01) in older adults with T1D. CONCLUSIONS: The relationship between higher PUA with lower GFR, increased arterial stiffness and renin angiotensin aldosterone system (RAAS) activation was observed only in older adults with longstanding T1D. T1D duration may modify the association between PUA, renal haemodynamic function and RAAS activation, leading to renal vasoconstriction and ischaemia. Further work must determine whether pharmacological PUA-lowering prevents or reverses injurious haemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes.

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 m2 and <30 mg/d urine albumin excretion) and 22 had DKD, in addition to 73 control participants. GFRINULIN and ERPFPAH were measured, RVR was calculated, and afferent (RA )/efferent (RE ) areteriolar resistances were derived from Gomez equations. Plasma neutrophil gelatinase-associated lipocalin (NGAL), ß2 microglobulin (B2M), osteopontin (OPN) and uromodulin (UMOD) were measured using immunoassay kits from Meso Scale Discovery. RESULTS: Plasma NGAL, B2M and OPN were higher and UMOD was lower in DKD patients vs DKD resistors and non-diabetic controls. In participants with T1D, plasma NGAL inversely correlated with GFR (r = -0.33; P = 0.006) and ERPF (r = -0.34; P = 0.006), and correlated positively with RA (r = 0.26; P = 0.03) and RVR (r = 0.31; P = 0.01). In participants without T1D, NGAL and B2M inversely correlated with GFR (NGAL r = -0.18; P = 0.13 and B2M r = -0.49; P < 0.0001) and with ERPF (NGAL r = -0.19; P = 0.1 and B2M r = -0.42; P = 0.0003), and correlated positively with RA (NGAL r = 0.19; P = 0.10 and B2M r = 0.3; P = 0.01) and with RVR (NGAL r = 0.20; P = 0.09 and B2M r = 0.34; P = 0.003). Differences were significant after adjusting for age, sex, HbA1c, SBP and LDL. There were statistical interactions between T1D status, B2M and intrarenal haemodynamic function (P < 0.05). CONCLUSIONS: Elevated NGAL relates to intrarenal haemodynamic dysfunction in T1D, whereas elevated NGAL and B2M relate to intrarenal haemodynamic dysfunction in adults without T1D. These data may define a diabetes-specific interplay between tubular injury and intrarenal haemodynamic dysfunction.

Old Drugs for New Indications in Cardiovascular Medicine.

Inflammation participates in the initiation and progression of atherosclerotic cardiovascular disease, and it is a critical inciting factor leading to acute ischemic events. Evidence has shown that certain anti-inflammatory medications used to treat non-atherosclerotic inflammatory diseases reduce cardiovascular events. This article reviews evidence that commonly used anti-inflammatory therapies (colchicine, allopurinol, methotrexate), reduce cardiovascular events. We discuss potential mechanisms of action, efficacy, and safety of these therapies and propose a clinical trials design to investigate their efficacy.

Trends in the Association Between Diabetes and Cardiovascular Events, 1994-2019.

This study uses administrative health care data from Ontario, Canada, to assess whether changes in diabetes management practices have affected trends in the association between diabetes vs prior cardiovascular disease and risk of cardiovascular events from 1994 to 2019 among adults aged 20 to 84 years.

Cardiovascular disease guideline adherence and self-reported statin use in longstanding type 1 diabetes: results from the Canadian study of longevity in diabetes cohort.

BACKGROUND: Older patients with longstanding type 1 diabetes have high cardiovascular disease (CVD) risk such that statin therapy is recommended independent of prior CVD events. We aimed to determine self-reported CVD prevention guideline adherence in patients with longstanding diabetes. RESEARCH DESIGN AND METHODS: 309 Canadians with over 50 years of type 1 diabetes completed a medical questionnaire for presence of lifestyle and pharmacological interventions, stratified into primary or secondary CVD prevention subgroups based on absence or presence of self-reported CVD events, respectively. Associations with statin use were analyzed using multivariable logistic regression. RESULTS: The 309 participants had mean ± SD age 65.7 ± 8.5 years, median diabetes duration 54.0 [IQR 51.0, 59.0] years, and HbA1c of 7.5 ± 1.1 % (58 mmol/mol). 159 (52.7 %) participants reported diet adherence, 296 (95.8 %) smoking avoidance, 217 (70.5 %) physical activity, 218 (71.5 %) renin-angiotensin-system inhibitor use, and 220 (72.1 %) statin use. Physical activity was reported as less common in the secondary prevention subgroup, and current statin use was significantly lower in the primary prevention subgroup (65.5 % vs. 84.8 %, p = 0.0004). In multivariable logistic regression, the odds of statin use was 0.38 [95 % CI 0.15-0.95] in members of the primary compared to the secondary prevention subgroup, adjusting for age, sex, hypertension history, body mass, HbA1c, cholesterol, microvascular complications, acetylsalicylic acid use, and renin-angiotensin system inhibitor use. CONCLUSION: Despite good self-reported adherence to general CVD prevention guidelines, against the principles of these guidelines we found that statin use was substantially lower in those without CVD history. Interventions are needed to improve statin use in older type 1 diabetes patients without a history of CVD.

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. Diabetes type was categorized as type 2 diabetes (T2D) not prescribed insulin, T2D prescribed insulin, and type 1 diabetes (T1D). Covariates were age, sex, income quintile, province, rural/urban location, estimated glomerular filtration rate, medications, and insulin pump use. Associations between predictors and the outcome (glycated hemoglobin [A1C] of ≤7.0%) were assessed by multivariable logistic regressions. RESULTS: Among 122,106 adults, consisting of 91,366 with T2D not prescribed insulin, 25,131 with T2D prescribed insulin, and 5,609 with T1D, attainment of an A1C of ≤7.0% was 60%, 25%, and 23%, respectively. Proportions with an A1C of ≤7.5% and ≤8.0% were 75% and 84% for those with T2D not prescribed insulin, 41% and 57% for those with T2D prescribed insulin, and 37% and 53% for those with T1D. Highest vs lowest income quintile was associated with greater odds of meeting the A1C target (adjusted odds ratio [95% confidence interval] for each diabetes category: 1.15 [1.10 to 1.21], 1.21 [1.10 to 1.33], and 1.29 [1.04 to 1.60], respectively). Individuals in Alberta and Manitoba had less antihyperglycemic medication use and attainment of A1C target than other provinces. CONCLUSIONS: Attainment of glycemic targets among adults with diabetes was poor and differed by income and geographic location, which must be addressed in national diabetes strategies.

Recent Improvements in Attainment of the Hemoglobin A1c Target of ≤7.0% Among Adults with Type 1 Diabetes in Ontario: A Retrospective Cohort Study.

Aims: We evaluated attainment of the hemoglobin A1c (HbA1c) target of ≤7.0%, its temporal trends, and associated factors among adults with type 1 diabetes in Ontario, Canada, using administrative data. Methods: We conducted a retrospective cohort study, including Ontarians with type 1 diabetes ≥18 years old with ≥1 HbA1c test between April 1, 2012 (fiscal year 2013), and March 31, 2023. Generalized estimating equations were used to determine probabilities of meeting the HbA1c target, as well as associations between fiscal year and individual-, physician-, and system-level factors on odds of meeting the target. Results: Among 28,827 adults with type 1 diabetes [14,385 (49.9%) female, 17,998 (62.4%) pump users], with median age at index of 25 years [interquartile range (IQR) 18-37] and median diabetes duration of 12 years [6-18], there were 474,714 HbA1c tests [median 2/individual/year (IQR: 1-3)]. The model-estimated probability of meeting the HbA1c target of ≤7.0% was 22.1% (95% confidence interval, CI: 21.6 to 22.5) in 2013, remained stable until 2020, and increased to 34.7% (95% CI: 34.3 to 35.2) in 2023. The age- and sex-adjusted odds ratio for meeting the target in 2023 versus 2013 was 1.87 (95% CI: 1.79 to 1.96). Young adults (18-25 years), diabetic ketoacidosis, greater comorbidity, and receiving diabetes care from a nonspecialist physician were associated with reduced odds of meeting the HbA1c target. Conclusions: One-third of adults with type 1 diabetes in Ontario met the recommended HbA1c target of ≤7.0% in 2023, with improvement noted since 2021, which may be due to advanced technologies or effects of the COVID-19 pandemic.

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. Using Cox proportional hazards models with time-dependent covariates, we examined age- and sex-adjusted, glycated hemoglobin-adjusted, and fully adjusted associations of DKA with all-cause mortality, cardiovascular disease, microvascular, and acute complications over 34 years. RESULTS: Of the 1,441 study participants, 297 had 488 DKA events. Prior DKA was associated with a higher risk of age- and sex-adjusted all-cause mortality (hazard ratio [HR] 8.28, 95% confidence interval [CI] 3.74 to 18.32, p<0.001), major adverse cardiovascular events (MACEs) (HR 2.05, 95% CI 1.34 to 3.13, p<0.001), and all advanced microvascular and acute complications compared with no prior DKA. Most associations except retinopathy were significant even after adjustment for covariates. In our fully adjusted analysis, prior DKA was associated with a significantly higher risk of subsequent all-cause mortality (HR 9.13, 95% CI 3.87 to 21.50, p<0.001), MACEs (HR 1.66, 95% CI 1.07 to 2.59, p=0.03), advanced kidney disease (HR 2.10, 95% CI 1.00 to 4.22, p=0.049), advanced neuropathy (HR 1.49, 95% CI 1.05 to 2.13, p=0.03), severe hypoglycemia (HR 1.53, 95% CI 1.28 to 1.81, p<0.001), and recurrent DKA (HR 3.24, 95% CI 2.41 to 4.36, p<0.001) compared with person-time without DKA. CONCLUSIONS: DKA is a prognostic marker for diabetes complications, including excess all-cause mortality. Intensified clinical interventions, such as cardiovascular prevention strategies, may be warranted after diagnosis of DKA.

Growing Income-Related Disparities in Cardiovascular Hospitalizations Among People With Diabetes, 1995-2019: A Population-Based Study.

OBJECTIVE: Cardiovascular risk reduction is an important focus in the management of people with diabetes. Although event rates have been declining over the long term, they have been observed to plateau or reverse in recent years. Furthermore, the impact of income-related disparities in cardiovascular events is unknown. The objective of this study is to evaluate age-, sex-, and income-related trends in cardiovascular hospitalization rates among people with diagnosed diabetes. RESEARCH DESIGN AND METHODS: We calculated rates of hospitalization for acute myocardial infarction, stroke, heart failure, and lower-extremity amputation in annual cohorts of the entire population of Ontario, Canada, with diagnosed diabetes, from 1995 to 2019. Event rates were stratified by age, sex, and income level. RESULTS: We studied nearly 1.7 million people with diabetes. The rate of acute myocardial infarction declined throughout the 25-year study period (P < 0.0001), such that the rate in 2019 was less than half the rate in 1995. Rates of stroke (P < 0.0001), heart failure (P < 0.0001), and amputation (P < 0.0001) also changed over time, but hospitalization rates stabilized through the 2010s. This apparent stabilization concealed a growing income-related disparity: wealthier patients showed continued declines in rates of these outcomes during the decade, whereas rates for lower-income patients increased (P for interaction < 0.0001 for all four outcomes). CONCLUSIONS: During a quarter-century of follow-up, cardiovascular hospitalization rates among people with diabetes fell. However, the apparent stabilization in rates of stroke, heart failure, and amputation in recent years masks the fact that rates have risen for lower-income individuals.

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. RESULTS: DKA events occurred in 12 of 484 participants at a median of 105 (interquartile range 43, 199) days. Maximum ketone levels were higher in patient cases compared with in control patients (0.8 [0.6, 1.2] vs. 0.3 [0.2, 0.7] mmol/L; P = 0.002), with a nonparametric area under the receiver operating characteristic curve of 0.77 (95% CI 0.66-0.88). Ketone levels ≥0.8 mmol/L had a sensitivity of 64%, a specificity of 78%, and positive and negative likelihood ratios of 2.9 and 0.5, respectively. CONCLUSIONS: This proof of concept that routine capillary ketone surveillance can identify individuals at high risk of future DKA implies a role for future technologies including continuous ketone monitoring.

Improving diagnosis and treatment of knee osteoarthritis in persons with type 2 diabetes: development of a complex intervention.

BACKGROUND: Symptomatic knee osteoarthritis (OA) commonly co-occurs in people with type 2 diabetes (T2DM) and increases the risk for diabetes complications, yet uptake of evidence-based treatment is low. We combined theory, stakeholder involvement and existing evidence to develop a multifaceted intervention to improve OA care in persons with T2DM. This was done in partnership with Arthritis Society Canada to leverage the existing infrastructure and provincial funding for community arthritis care. METHODS: Each step was informed by a User Advisory Panel of stakeholder representatives, including persons with lived experience. First, we identified the target groups and behaviours through consulting stakeholders and current literature. Second, we interviewed persons living with T2DM and knee OA (n = 18), health professionals (HPs) who treat people with T2DM (n = 18) and arthritis therapists (ATs, n = 18) to identify the determinants of seeking and engaging in OA care (patients), assessing and treating OA (HPs) and considering T2DM in OA treatment (ATs), using the Theoretical Domains Framework (TDF). We mapped the content to behavioural change techniques (BCTs) to identify the potential intervention components. Third, we conducted stakeholder meetings to ascertain the acceptability and feasibility of intervention components, including content and modes of delivery. Fourth, we selected intervention components informed by prior steps and constructed a programme theory to inform the implementation of the intervention and its evaluation. RESULTS: We identified the barriers and enablers to target behaviours across a number of TDF domains. All stakeholders identified insufficient access to resources to support OA care in people with T2DM. Core intervention components, incorporating a range of BCTs at the patient, HP and AT level, sought to identify persons with knee OA within T2DM care and refer to Arthritis Society Canada for delivery of evidence-based longitudinal OA management. Diverse stakeholder input throughout development allowed the co-creation of an intervention that appears feasible and acceptable to target users. CONCLUSIONS: We integrated theory, evidence and stakeholder involvement to develop a multifaceted intervention to increase the identification of knee OA in persons with T2DM within diabetes care and improve the uptake and engagement in evidence-based OA management. Our partnership with Arthritis Society Canada supports future spread, scalability and sustainability. We will formally assess the intervention feasibility in a randomized pilot trial.

Diabetic retinopathy screening integrated in a multidisciplinary diabetes care clinic: a pilot project.

OBJECTIVE: To characterize patients referred for diabetic retinopathy (DR) screening in a unique multidisciplinary diabetes care clinic at a tertiary care centre. METHODS: A retrospective study was conducted involving patients who were referred to the Cardiac and Renal Endocrine Clinic at a tertiary care centre (University Health Network) for DR screening between April 2019-March 2020 and November 2020-August 2021. Patients' demographics; micro- and macrovascular disease measurements; visual acuity, intraocular pressure, fundus imaging, and optical coherence tomography results were collected and analyzed. RESULTS: Of the 64 patients who attended the clinic, 21 patients (33%) with type 2 diabetes had on-site DR screening. The remaining 43 patients had DR screening within 6 months of the appointment or were under ophthalmology care with annual screening visits elsewhere. Of the 21 patients who underwent retinopathy screening, 7 patients (33%) had DR: 4 had mild nonproliferative DR, 2 had moderate nonproliferative DR, 1 had proliferative DR, and 1 had macular edema. Patients with DR had a significantly longer diabetes duration than patients without DR (24.5 ± 10.2 years vs 12.5 ± 5.8 years; p = 0.0247). No significant differences were observed in glycemic control, blood pressure, lipid profiles, kidney function, visual acuity, or intraocular pressure. CONCLUSIONS: Our analysis suggests a potential benefit of integrated DR screening in patients with long-standing diabetes as part of a multidisciplinary diabetes care clinic to diagnose and manage DR. Future work is needed to further develop such clinics and investigate their long-term effect on patient outcomes.

A Unique Multi- and Interdisciplinary Cardiology-Renal-Endocrine Clinic: A Description and Assessment of Outcomes.

BACKGROUND: Patients with diabetes and co-existing chronic kidney disease and/or cardiovascular disease have complex medical needs with multiple indications for different guideline-directed medical therapies and require high health care resource utilization. The Cardiac and Renal Endocrine Clinic (C.a.R.E. Clinic) is a multi- and interdisciplinary clinic offering a unique care model to this population to overcome barriers to optimal care. OBJECTIVE: To describe the patient characteristics and clinical data of consecutive patients seen in the C.a.R.E. Clinic between 2014 and 2020, with a focus on the feasibility, strengths, and challenges of this outpatient care model. DESIGN: Single-center retrospective cohort study. SETTING: The C.a.R.E. Clinic is a multi- and interdisciplinary clinic at Toronto General Hospital in Toronto, Canada. PATIENTS: We reviewed the charts of all 118 patients who had been referred to the C.a.R.E. Clinic with type 2 diabetes mellitus, co-existing renal disease, and/or cardiovascular disease. MEASUREMENTS: Demographic data, medication data, clinic blood pressure measurements, and laboratory data were assessed at the first and last available clinic visit. METHODS: Data were extracted via manual chart review of paper and electronic medical records. RESULTS: First and last attended clinic visit data were available for descriptive analysis in 74 patients. There was a significant improvement in low-density lipoprotein (LDL) cholesterol (1.9 mmol/L vs 1.5 mmol/L, P < .01), hemoglobin A1C (7.5% vs 7.1%, P = .02), and the proportion of patients with blood pressure at target (52.7% vs 36.5%, P = .04), but not body mass index (29.7 kg/m² vs 29.6 kg/m², P = .15) between the last and first available clinic visits. There was higher uptake in evidence-based medication use including statins (93.2% vs 81.1%, P = .01), SGLT-2i (35.1% vs 4.1%, P < .01), and GLP-1 receptor agonists (13.5% vs 4.1%, P = .02), while RAAS inhibitor use was already high at baseline (81.8% vs 78.4%, P = .56). There remains a significant opportunity for therapy with sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. LIMITATIONS: This is a retrospective chart review lacking a control group, therefore clinical improvements cannot be causally attributed to the clinic alone. New evidence and changes to guideline-recommended therapies also contributed to practice changes during this time period. CONCLUSIONS: A multi- and interdisciplinary clinic is a feasible and potentially effective way to improve evidence-based and patient-centered care for patients with diabetes, kidney, and cardiovascular disease.

CONTEXTE: Les patients diabétiques présentant une néphropathie chronique et/ou maladie cardiovasculaire co-existante ont des besoins complexes avec de multiples indications concernant différents traitements médicaux recommandés par les lignes directrices. En outre, ces patients nécessitent une utilisation élevée des ressources de santé. La clinique C.a.R.E. (Cardiac and Renal Endocrine Clinic) est une clinique interdisciplinaire et multidisciplinaire offrant un modèle de soins unique qui permet de surmonter les obstacles aux soins optimaux pour cette population. OBJECTIF: Décrire les caractéristiques et les données cliniques des patients consécutifs suivis à la clinique C.a.R.E. entre 2014 et 2020, en se concentrant sur la faisabilité et sur les avantages et les défis de ce modèle de soins ambulatoires. TYPE D'ÉTUDE: Étude de cohorte rétrospective menée dans un seul centre. CADRE: La clinique C.a.R.E. est une clinique multidisciplinaire et interdisciplinaire de l'Hôpital général de Toronto (Canada). SUJETS: Nous avons examiné les dossiers des 118 patients diabétiques de type 2 atteints d'une néphropathie et/ou maladie cardiovasculaire qui ont été dirigés vers la clinique C.a.R.E. au cours de la période étudiée. MESURES: Les données démographiques, les données sur les ordonnances, les mesures cliniques de la pression artérielle et les données de laboratoire ont été évaluées pour la première et la dernière visite à la clinique disponibles. MÉTHODOLOGIE: Les données ont été extraites par un examen manuel des dossiers médicaux papier et électronique. RÉSULTATS: Les données d'intérêt pour la première et la dernière visite à la clinique étaient disponibles pour l'analyse descriptive chez 74 patients. Entre la première et la dernière visite disponible, on a observé une amélioration significative du taux de cholestérol LDL (1,9 mmol/L vs 1,5 mmol/L; p < 0,01), de l'hémoglobine A1c (7,5 % vs 7,1 %; p = 0,02) et de la proportion de patients avec une mesure de pression artérielle dans les valeurs cibles (52,7 % vs 36,5 %; p = 0,04) alors que l'indice de masse corporelle est demeuré inchangé (29,7 kg/m² vs 29,6 kg/m²; p = 0,15). Les ordonnances de thérapies fondées sur les données probantes ont été plus fréquentes, notamment pour les statines (93,2 % vs 81,1 %; p = 0,01), le SGLT-2i (35,1 % vs 4,1 %; p < 0,01) et les agonistes des récepteurs GLP-1 (13,5 % vs 4,1 %; p = 0,02); l'utilisation d'inhibiteurs du SRAA était déjà élevée au départ (81,8 % vs 78,4 %; p = 0,56). De grandes possibilités de traitement demeurent pour les inhibiteurs du cotransporteur-2 de sodium-glucose et les agonistes des récepteurs du peptide-1 de type glucagon. LIMITES: Il s'agit d'un examen rétrospectif des dossiers sans groupe témoin; les améliorations cliniques ne peuvent être attribuées de façon causale à la clinique seule. Pendant la période étudiée, de nouvelles données probantes et des changements aux traitements recommandés par les lignes directrices ont également entraîné des changements dans la pratique. CONCLUSION: Une clinique multidisciplinaire et interdisciplinaire est une solution viable et potentiellement efficace pour améliorer les soins axés sur les patients et les traitements fondés sur les données probantes pour les patients diabétiques atteints de néphropathie et/ou de maladies cardiovasculaires.