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Aims: To compare the level of ketones and bicarbonate in inpatients treated with sodium-glucose linked cotransporter 2 inhibitors (SGLT2i) and those treated with dipeptidyl peptidase-4 inhibitors (DPP4i)., Methods: We conducted an electronic medical records-based cohort study. We identified patients with type 2 diabetes, with ketone measurements available, who received SGLT2i (n = 82) or DPP4i (n = 308) during admission. We compared ketone levels between those who received SGLT2i or DPP4i using mixed ordinal logistic regression. The primary outcome was level of ketosis (<0.6, 0.6-1.5, 1.6-3.0, >3 mmol/L). Secondary outcomes included bicarbonate levels, hospital complications, ICU admission, and death., Results: SGLT2i use was not associated with greater ketosis than DPP4i use, after adjusting for age, weight, Charlson Comorbidity Index, HbA1c, estimated glomerular filtration rate, principal diagnosis category, admission type and insulin administration (OR 4.52 95 % CI (0.33, 61.82)). After adjustment, there was no difference in complications (p = 0.14), ICU admissions (p = 0.64), mortality (p = 0.30), or bicarbonate levels (p = 0.97)., Conclusion: Ketone levels were not greater in patients who received SGLT2i than those who received DPP4i. There were no differences in bicarbonate levels, complications, ICU admissions, or mortality, implying that, in inpatients, SGLT2i use is neither associated with ketosis nor adverse clinical outcomes., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: To compare levels of renal hypoxia measured by Blood Oxygen Level Dependent (BOLD) magnetic resonance imaging (MRI) with measured transverse relaxation rate (R2*) and renal structural changes including apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in patients with type 1 diabetes and healthy controls., Methods: Cohort study comparing MRI metrics in type 1 diabetes (n = 32, GFR 105 (77, 120) ml/min.1.73m 2 ) and controls (n = 10). Renal function and selected inflammatory renal biomarkers were also measured., Results: For BOLD, we found reduced cortical [14.7 (13.7,15.8) (1/s) vs 15.7 (15.1,16.6) (1/s), p < 0.001] and medullary [24.8 (21.8,28.2) (1/s) vs. 29.3 (24.3,32.4) (1/s), p < 0.001] R2*, indicating more oxygenated parenchyma, in type 1 diabetes vs. controls, respectively. We observed reduced cortical FA, indicating decreased structural integrity in type 1 diabetes -0.04 (-0.07, -0.01), (p = 0.02). We found reduced cortical ADC, reflecting reduced water diffusion, in non-hyperfiltering [2.40 (2.29,2.53) (10 3 mm 2 /s)] versus hyperfiltering [2.61 (2.53,2.74) (10 3 mm 2 /s)] type 1 diabetes patients. MRI parameters correlated with renal function and inflammatory renal biomarkers., Conclusions: MRI derived indices of renal function and structure differed between (i) type 1 diabetes and healthy controls, and (ii) between non-hyperfiltering and hyperfiltering type 1 diabetes patients, providing insight into the role of hypoxia and renal structural, and functional changes in DKD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To compare the outcomes of sodium glucose linked cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase 4 inhibitors (DPP4i) in hospitalized patients., Research Design and Methods: Electronic medical records-based cohort study. Identification of patients with type 2 diabetes and treatment with SGLT2i (n = 466) or DPP4i (n = 1541). Outcomes compared between those who received SGLT2i and those who received DPP4i. The primary outcome: adjusted percentage of blood glycemia within 4-10 mmol/L., Results: After adjustment, SGLT2i use had a statistically equivalent percentage of glycemia within range (coefficient: 4.55, 95% CI -3.23 to 12.32, p = 0.25) or <4 mmol/L (coefficient -0.17, 95% CI -0.71 to 3.72, p = 0.54). There were no significant differences in hospital length of stay (p = 0.22), complications, (p = 0.11) or mortality (p = 0.57). When measured, ketone levels were higher in the SGLT2i group on admission, but lower on days 3, 4 and 5 (p < 0.001 for interaction). Bicarbonate levels were not statistically different between groups. Finally, 54% of patients whose SGLT2i was ceased during admission, were discharged home without it., Conclusion: Among inpatients with type 2 diabetes, SGLT2i use was associated with equivalent within-target glycaemia and no significant increase in hypoglycemia, ketonemia, or lower bicarbonate levels. These hypothesis-generating findings support further investigation of SGLT2i therapy in inpatients., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To assess the association between glycaemic status prior to the first hospital presentation with developing adverse renal outcomes overtime in patients with multiple hospital re-admissions., Design: A prospective observational cohort study., Participants: All inpatients aged ≥54 years admitted between 2013 and 16 to a tertiary hospital., Main Outcomes: We prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013 and 16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30 ml/min/1·73m 2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR; (b) rapid decline in renal function (eGFR decline >5 mL/min/1·73m 2 /year) and (c) final eGFR<30 ml/min/1·73m 2 ., Results: Of 4126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR = 1·42;95% CI:1·18-1·70;p < 0·001); (b) rapid decline in renal function (OR = 1·40;95%CI:1·20-1·63;p < 0·001), and (c) reaching eGFR<30 ml/min/1.73m 2 (OR = 1·25;95%CI:1·03-1·53;p < 0·05). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR = 1·07;95% CI:1·01-1·4;p < 0·05) and (b) rapid decline in renal function (OR = 1·11;95% CI:1·05-1·18;p < 0·001)., Conclusions: In patients with ≥two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Glomerular hyperfiltration is not able to be detected in clinical practice. We assessed whether hyperfiltration is associated with albuminuria progression among Indigenous Australians at high risk of diabetes and kidney disease to determine its role in kidney disease progression., Methods: Longitudinal observational study of Indigenous Australians aged ≥18 years recruited from >20 sites, across diabetes and/or kidney function strata. At baseline, iohexol clearance was used to measure glomerular filtration rate (mGFR) and hyperfiltration was defined as (i) a mGFR of ≥125 mL/min/1.73 m 2 , and (ii) an age-adjusted definition, with the top 10% of the mGFR for each 10 year age group at baseline. Baseline and follow-up urine albumin-to-creatinine ratio (uACR) was collected, and linear regression was used to assess the associations of hyperfiltration and uACR at follow up., Results: 407 individuals (33% men, mean age 47 years) were followed-up for a median of 3 years. At baseline, 234 had normoalbuminuria and 173 had albuminuria. Among participants with normoalbuminuria, those with mGFR ≥125 mL/min/1.73 m 2 had 32% higher uACR at follow-up (p = 0.08), and those with age-adjusted hyperfiltration had 60% higher uACR (p = 0.037) compared to those who had normofiltration. These associations were independent of uACR at baseline, but attenuated by HbA 1c . Associations were stronger among those without than those with albuminuria at baseline., Conclusions: Although not available for assessment in current clinical practice, hyperfiltration may represent a marker of subsequent albuminuria progression among individuals who have not yet developed albuminuria., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Diabetes is a major risk factor for stroke. We aimed to investigate the prevalence of diabetes and pre-diabetes within a stroke cohort and examine the association of glycaemia status with mortality and morbidity., Methods: Inpatients aged ≥54 who presented with a diagnosis of stroke had a routine HbA1c measurement as part of the Austin Health Diabetes Discovery Initiative. Additional data were attained from hospital databases and Australian Stroke Clinical Registry. Outcomes included diabetes and pre-diabetes prevalence, length of stay, 6-month and in-hospital mortality, 28-day readmission rates, and 3-month modified Rankin scale score., Results: Between July 2013 and December 2015, 610 patients were studied. Of these, 31% had diabetes while 40% had pre-diabetes. Using multivariable regression analyses, the presence of diabetes was associated with higher odds of 6-month mortality (OR = 1.90, p = 0.022) and higher expected length of stay (IRR = 1.29, p = 0.004). Similarly, a higher HbA1c was associated with higher odds of 6-month mortality (OR = 1.27, p = 0.005) and higher expected length of stay (IRR = 1.08, p = 0.010)., Conclusions: 71% of this cohort had diabetes or pre-diabetes. Presence of diabetes and higher HbA1c were associated with higher 6-month mortality and length of stay. Further research is necessary to determine if improved glycaemic control may improve stroke outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: Renal hyperfiltration is observed prior to the development of diabetic kidney disease (DKD) in patients with type 1 diabetes (T1DM); however its significance remains uncertain. Longitudinal data were used to investigate the association between measured baseline glomerular filtration rate (GFR) and renal function decline in patients with T1DM., Methods: This study included 142 adult patients with T1DM and ≥2 measurements of glomerular filtration rate (mGFR; determined by diethylene-triamine-penta-acetic acid plasma clearance). Median follow up was 19 years. Patients were stratified by baseline mGFR quartile. The relationship between baseline mGFR and rate of renal function decline was assessed using random-effect generalized least squares regression, adjusted for age, duration of diabetes, HbA1c, blood pressure, renin-angiotensin-aldosterone system inhibitor therapy, LDL and BMI., Results: The average rates of decline in renal function for the 2nd (baseline mGFR: 96.4-112.6 ml min-(1) 1.73 m-(2)), 3(rd) (baseline mGFR: 112.6-125.5 ml min- (1) 1.73 m-(2)) and 4th quartiles (baseline mGFR >125.5 ml min-(1) 1.73 m-(2)) were significantly faster than the first quartile (baseline mGFR: 60.9-96.4 ml min-(1) 1.73 m-(2)). In further detail, the average rates of decline in the 2nd (rate of decline 1.25 ml min- (1) 1.73 m-(2) per year, 95% CI: 0.97; 1.52, p=0.008), 3rd (rate of decline 1.35 ml min-(1) 1.73 m-(2) per year, 95% CI: 1.08; 1.62, p= 0.001) and 4th quartiles (rate of decline 1.6 ml min-(1) 1.73 m-(2) per year, 95% CI: 1.34, 1.88, <0.0001) were significantly faster when compared to the first quartile (rate of decline 0.67 ml min-(1) 1.73 m-(2) per year, 95% CI: 0.37; 0.96). Sub-analysis of quartile 4 revealed higher HbA1c measurements throughout follow-up in those with rapid mGFR decline (>3.0 ml min(-1)1.73 m(-2)/year)., Conclusions: In patients with T1DM, higher baseline mGFR is associate ed with more rapid mGFR decline. Patients with high baseline mGFR who developed rapid mGFR decline had higher HbA1c measurements throughout the study. These findings are consistent with the concept that poor glycaemic control over time may be a determining factor for the rapid renal function decline observed in some hyperfiltering patients., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Aims: To assess the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at baseline and longitudinally in people with type 2 diabetes., Methods: Adults with type 2 diabetes attending Austin Health, Melbourne, with≥3 prospective GFR measurements were included in this retrospective study. Plasma disappearance rate of DTPA (diethylene-triamine-penta-acetic acid) was used to calculate measured GFR (mGFR) and compared to estimated GFR (eGFR). The agreement between mGFR and eGFR was estimated using Intraclass Correlation Coefficient (ICC)., Results: 152 patients had a median of 4 (IQR: 3, 5) mGFR measurements over a period of 11years (IQR: 9, 12). The difference between mGFR and eGFR increased proportionally to the magnitude of the GFR, increasing by 0.2ml/min/1.73m(2) for every 1ml/min/1.73m(2) increase in mGFR, indicative of proportional bias. At lower mGFR levels, eGFR overestimated mGFR, and at higher mGFR levels, eGFR underestimated mGFR. There was a significant association between LDL cholesterol, triglycerides, HbA1c, diastolic blood pressure and the difference between mGFR and eGFR., Conclusions: The CKD-EPI formula underestimates mGFR and the rate of decline of mGFR in patients with type 2 diabetes with an mGFR greater than 60ml/min/1.73m(2). The association between LDL cholesterol, triglycerides, HbA1c, diastolic blood pressure and the difference between mGFR and eGFR warrants further study., (Copyright © 2016. Published by Elsevier Inc.)