Richard J. Macisaac

Objective: This study assessed the concordance and misclassification of chronic kidney disease (CKD) stages between directly measured glomerular filtration rate (mGFR) and estimates of GFR (eGFR) using the creatinine-based CKD-EPI-2009 and the CKD-EPI-2021 equations in individuals with diabetes. Methods: Data from 5,177 individuals across six international diabetes cohorts included mGFR measurements using exogenous filtration markers. We calculated an intra-class correlation coefficient (ICC), bias, precision and accuracy between mGFR and CKD-EPI estimates using a four-level mixed-effect linear variance component model. Results: The pooled cohort included people with type 1 (n = 1,748, median age: 33 years [IQR: 27, 40], mGFR = 104.2 ml/min per 1.73 m2) and type 2 diabetes (n = 3,429, median age: 66 years [IQR: 58, 73], mGFR = 58.4 ml/min per 1.73 m2). Both CKD-EPI equations showed good agreement (2009 ICC: 0.90; 2021 ICC: 0.87) but substantial bias (2009: 3.7 ml/min/1.73 m2; 2021: 8.6 ml/min/1.73 m2), low precision (2009: 12.4 ml/min/1.73 m2; 2021: 13.91 ml/min/1.73 m2), and limited accuracy (2009 p30: 77 %; 2021 p30: 70 %) compared to mGFR. Conclusions: The use of CKD-EPI equations has the potential for misdiagnosis and suboptimal CKD management in people with diabetes. Alternative methods of estimating kidney function for people with diabetes are needed to optimally manage diabetes-related kidney disease.

Delayed identification of impending diabetic ketoacidosis (DKA) often results in hospitalizations. We describe a case where continuous ketone monitor (CKM) use facilitated prompt identification and intervention for impending DKA, avoiding hospitalization. A 55-year-old male (total daily insulin dose of 0.5 units/kg/day; HbA1c 6.9% [51.9 mmol/mol]) with type 1 diabetes using automated insulin delivery (AID) wore a CKM (Abbott) and was educated in responses to ketone information as part of a clinical trial (ACTRN12624000448549). Insulin pump cannula dislodgement resulted in a rapid rise in ketone levels. Initial CKM alarm notification for elevated ketones >1.0 mmol/L prompted initiation of management, including cannula replacement and additional insulin administration. Ketosis resolved following a rise to >3.1 mmol/L without need for hospitalization. He remained asymptomatic throughout. This case highlights the potential for CKM to act as an early warning system to facilitate timely intervention for ketonemia and reduce the risk of DKA and associated hospitalizations.

Recent trials underscore the cardiovascular (CV), renal, and metabolic benefits of semaglutide in individuals with and without type 2 diabetes (T2D). In T2D, semaglutide enhances glycemic control, reduces major adverse CV events (MACE), and slows chronic kidney disease (CKD) progression. The SUSTAIN-6 trial demonstrated a 26% MACE reduction (HR 0.74; 95% CI: 0.58-0.95; p = 0.02) in high CV-risk patients with T2D using semaglutide (0.5 or 1.0 mg weekly). Similarly, the FLOW trial showed a 24% reduction in major kidney disease events (HR 0.76; 95% CI: 0.66-0.88; p = 0.002) with weekly 1.0 mg semaglutide in individuals with T2D with CKD. Beyond T2D, the SELECT trial highlighted semaglutide's efficacy in reducing MACE by 20% (HR 0.80; 95% CI: 0.72-0.90; p < 0.001) and slowing kidney function loss in overweight or obese individuals with preexisting CV disease using 2.4 mg weekly. Additionally, semaglutide alleviates heart failure symptoms and reduces hospitalizations in obese individuals regardless of T2D status. These findings underscore semaglutide's role in improving kidney, CV, and survival outcomes among high-risk patients. This review highlights the cardio-kidney-metabolic benefits of semaglutide in individuals with and without T2D to inform cardiologists about its potential to enhance patient care.

Sodium-glucose co-transporter (SGLT) inhibitors have been evaluated for use in people with type 1 diabetes (T1D). Despite evidence for glycaemic and non-glycaemic benefits in people with T1D as discussed in the accompanying review (Part A), the increased risk of diabetic ketoacidosis (DKA) with this class of medication remains a barrier limiting its widespread use in this population. DKA is a serious and life-threatening complication of diabetes and the excess risk associated with SGLT inhibitor use needs to be addressed before this medication could be considered as part of glycaemia and complications management in people with T1D. Understanding factors that increase DKA risk in the setting of SGLT inhibitors, as well as an appreciation of general DKA risk factors, may facilitate the development of strategies that allow for an acceptable risk versus benefit ratio to permit the use of SGLT inhibitors in people with T1D.

Objective: This study assessed the concordance and misclassification of chronic kidney disease (CKD) stages between directly measured glomerular filtration rate (mGFR) and estimates of GFR (eGFR) using the creatinine-based CKD-EPI-2009 and the CKD-EPI-2021 equations in individuals with diabetes. Methods: Data from 5,177 individuals across six international diabetes cohorts included mGFR measurements using exogenous filtration markers. We calculated an intra-class correlation coefficient (ICC), bias, precision and accuracy between mGFR and CKD-EPI estimates using a four-level mixed-effect linear variance component model. Results: The pooled cohort included people with type 1 (n = 1,748, median age: 33 years [IQR: 27, 40], mGFR = 104.2 ml/min per 1.73 m2) and type 2 diabetes (n = 3,429, median age: 66 years [IQR: 58, 73], mGFR = 58.4 ml/min per 1.73 m2). Both CKD-EPI equations showed good agreement (2009 ICC: 0.90; 2021 ICC: 0.87) but substantial bias (2009: 3.7 ml/min/1.73 m2; 2021: 8.6 ml/min/1.73 m2), low precision (2009: 12.4 ml/min/1.73 m2; 2021: 13.91 ml/min/1.73 m2), and limited accuracy (2009 p30: 77 %; 2021 p30: 70 %) compared to mGFR. Conclusions: The use of CKD-EPI equations has the potential for misdiagnosis and suboptimal CKD management in people with diabetes. Alternative methods of estimating kidney function for people with diabetes are needed to optimally manage diabetes-related kidney disease.

A Phase 2, Randomised, Placebo Controlled Study Investigating the Efficacy of Baricitinib in New Onset Type 1 Diabetes Mellitus