Baricitinib and ß-Cell Function in Patients with New-Onset Type 1 Diabetes.

BACKGROUND: Janus kinase (JAK) inhibitors, including baricitinib, block cytokine signaling and are effective disease-modifying treatments for several autoimmune diseases. Whether baricitinib preserves ß-cell function in type 1 diabetes is unclear. METHODS: In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with type 1 diabetes diagnosed during the previous 100 days to receive baricitinib (4 mg once per day) or matched placebo orally for 48 weeks. The primary outcome was the mean C-peptide level, determined from the area under the concentration-time curve, during a 2-hour mixed-meal tolerance test at week 48. Secondary outcomes included the change from baseline in the glycated hemoglobin level, the daily insulin dose, and measures of glycemic control assessed with the use of continuous glucose monitoring. RESULTS: A total of 91 patients received baricitinib (60 patients) or placebo (31 patients). The median of the mixed-meal-stimulated mean C-peptide level at week 48 was 0.65 nmol per liter per minute (interquartile range, 0.31 to 0.82) in the baricitinib group and 0.43 nmol per liter per minute (interquartile range, 0.13 to 0.63) in the placebo group (P = 0.001). The mean daily insulin dose at 48 weeks was 0.41 U per kilogram of body weight per day (95% confidence interval [CI], 0.35 to 0.48) in the baricitinib group and 0.52 U per kilogram per day (95% CI, 0.44 to 0.60) in the placebo group. The levels of glycated hemoglobin were similar in the two trial groups. However, the mean coefficient of variation of the glucose level at 48 weeks, as measured by continuous glucose monitoring, was 29.6% (95% CI, 27.8 to 31.3) in the baricitinib group and 33.8% (95% CI, 31.5 to 36.2) in the placebo group. The frequency and severity of adverse events were similar in the two trial groups, and no serious adverse events were attributed to baricitinib or placebo. CONCLUSIONS: In patients with type 1 diabetes of recent onset, daily treatment with baricitinib over 48 weeks appeared to preserve ß-cell function as estimated by the mixed-meal-stimulated mean C-peptide level. (Funded by JDRF International and others; BANDIT Australian New Zealand Clinical Trials Registry number, ACTRN12620000239965.).

Automated insulin delivery among adults with type 1 diabetes for up to 2 years: a real-world, multicentre study.

BACKGROUND AND AIMS: Automated insulin delivery (AID) improves glycaemia among people with type 1 diabetes in clinical trials and overseas real-world studies. Whether improvements are sustained beyond 12 months in the real world, and whether they occur in the Australian context, has not yet been established. We aimed to observe, up to 2 years, the effectiveness of initiating first-generation AID for type 1 diabetes management. METHODS: Retrospective, real-world, observational study using medical records, conducted across five sites in Australia. Adults with type 1 diabetes, who had AID initiated between February 2019 and December 2021, were observed for 6-24 months after initiation (until June 2022). Outcomes examined included glucose metrics assessed by glycated haemoglobin (HbA1c ) and continuous glucose monitoring (CGM), safety and therapy continuation. RESULTS: Ninety-four adults were studied (median age 39 years (interquartile range, IQR: 31-51); pre-initiation HbA1c 7.8% (7.2-8.6)). After AID initiation, HbA1c decreased by mean 0.5 percentage points (95% confidence interval (CI): -0.7 to -0.2) at 3 months (P < 0.001); CGM time in range 3.9-10.0 mmol/L increased by 11 percentage points (9-14) at 1 month (P < 0.001); these improvements were maintained up to 24 months (all P < 0.02). Median CGM time below 3.9 mmol/L was <1.5% pre- and post-AID initiation. The subgroup with pre-initiation HbA1c above 8.5% had the greatest HbA1c improvement (-1.4 percentage points (-1.8 to -1.1) at 3 months). Twelve individuals (13%) discontinued AID, predominantly citing difficulties with CGM. During the 150 person-years observed, four diabetes-related emergencies were documented: three severe hypoglycaemic events and one hyperglycaemic event without ketoacidosis. CONCLUSIONS: Early glucose improvements were observed after real-world AID initiation, sustained up to 2 years, without excess adverse events. The greatest benefits were observed among individuals with highest glycaemia before initiation. Future-generation systems with increased user-friendliness may enhance therapy continuation.

Lived experience of older adults with type 1 diabetes using closed-loop automated insulin delivery in a randomised trial.

AIM: To explore the lived experience of older adults with type 1 diabetes using closed-loop automated insulin delivery, an area previously receiving minimal attention. METHODS: Semi-structured interviews were conducted with adults aged 60 years or older with long-duration type 1 diabetes who participated in a randomised, open-label, two-stage crossover trial comparing first-generation closed-loop therapy (MiniMed 670G) versus sensor-augmented pump therapy. Interview recordings were transcribed, thematically analysed and assessed. RESULTS: Twenty-one older adults participated in interviews after using closed-loop therapy. Twenty were functionally independent, without frailty or major cognitive impairment; one was dependent on caregiver assistance, including for diabetes management. Quality of life benefits were identified, including improved sleep and reduced diabetes-related psychological burden, in the context of experiencing improved glucose levels. Gaps between expectations and reality of closed-loop therapy were also experienced, encountering disappointment amongst some participants. The cost was perceived as a barrier to continued closed-loop access post-trial. Usability issues were identified, such as disruptive overnight alarms and sensor inaccuracy. CONCLUSIONS: The lived experience of older adults without frailty or major cognitive impairment using first-generation closed-loop therapy was mainly positive and concordant with glycaemic benefits found in the trial. Older adults' lived experience using automated insulin delivery beyond trial environments requires exploration; moreover, the usability needs of older adults should be considered during future device development.

Diabetes IN hospital - Glucose and Outcomes in the COVID-19 pandemic (DINGO COVID-19): the 2020 Melbourne hospital experience prior to novel variants and vaccinations.

BACKGROUND AND AIMS: A relationship between diabetes, glucose and COVID-19 outcomes has been reported in international cohorts. This study aimed to assess the relationship between diabetes, hyperglycaemia and patient outcomes in those hospitalised with COVID-19 during the first year of the Victorian pandemic prior to novel variants and vaccinations. DESIGN, SETTING: Retrospective cohort study from March to November 2020 across five public health services in Melbourne, Australia. PARTICIPANTS: All consecutive adult patients admitted to acute wards of participating institutions during the study period with a diagnosis of COVID-19, comprising a large proportion of patients from residential care facilities and following dexamethasone becoming standard-of-care. Admissions in patients without known diabetes and without inpatient glucose testing were excluded. RESULTS: The DINGO COVID-19 cohort comprised 840 admissions. In 438 admissions (52%), there was no known diabetes or in-hospital hyperglycaemia, in 298 (35%) patients had known diabetes, and in 104 (12%) patients had hyperglycaemia without known diabetes. ICU admission was more common in those with diabetes (20%) and hyperglycaemia without diabetes (49%) than those with neither (11%, P < 0.001 for all comparisons). Mortality was higher in those with diabetes (24%) than those without diabetes or hyperglycaemia (16%, P = 0.02) but no difference between those with in-hospital hyperglycaemia and either of the other groups. On multivariable analysis, hyperglycaemia was associated with increased ICU admission (adjusted odds ratio (aOR) 6.7, 95% confidence interval (95% CI) 4.0-12, P < 0.001) and longer length of stay (aOR 173, 95% CI 11-2793, P < 0.001), while diabetes was associated with reduced ICU admission (aOR 0.55, 95% CI 0.33-0.94, P = 0.03). Neither diabetes nor hyperglycaemia was independently associated with in-hospital mortality. CONCLUSIONS: During the first year of the COVID-19 pandemic, in-hospital hyperglycaemia and known diabetes were not associated with in-hospital mortality, contrasting with published international experiences. This likely mainly relates to hyperglycaemia indicating receipt of mortality-reducing dexamethasone therapy. These differences in published experiences underscore the importance of understanding population and clinical treatment factors affecting glycaemia and COVID-19 morbidity within both local and global contexts.

Review of potential biomarkers of inflammation and kidney injury in diabetic kidney disease.

Diabetic kidney disease is expected to increase rapidly over the coming decades with rising prevalence of diabetes worldwide. Current measures of kidney function based on albuminuria and estimated glomerular filtration rate do not accurately stratify and predict individuals at risk of declining kidney function in diabetes. As a result, recent attention has turned towards identifying and assessing the utility of biomarkers in diabetic kidney disease. This review explores the current literature on biomarkers of inflammation and kidney injury focussing on studies of single or multiple biomarkers between January 2014 and February 2020. Multiple serum and urine biomarkers of inflammation and kidney injury have demonstrated significant association with the development and progression of diabetic kidney disease. Of the inflammatory biomarkers, tumour necrosis factor receptor-1 and -2 were frequently studied and appear to hold most promise as markers of diabetic kidney disease. With regards to kidney injury biomarkers, studies have largely targeted markers of tubular injury of which kidney injury molecule-1, beta-2-microglobulin and neutrophil gelatinase-associated lipocalin emerged as potential candidates. Finally, the use of a small panel of selective biomarkers appears to perform just as well as a panel of multiple biomarkers for predicting kidney function decline.

Insulin antibodies are prevalent in adults with type 1 diabetes referred for islet cell transplantation and are modified by islet transplantation and immunosuppression: an Australian experience.

We have analysed insulin antibodies in 149 adults with type 1 diabetes and 2859 people without diabetes. We have determined that insulin antibody levels are higher in adults with, versus without, diabetes and that the levels are falling, and more patients are becoming antibody-negative post islet cell transplantation.

Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease.

Accumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal renal function and stages 2 to 4 chronic kidney disease (CKD), to identify which AGE has the greatest progressive change with decline in renal function and change in diabetes. We performed a cross-sectional study of patients with stages 2-4 CKD, with and without diabetes, and healthy controls (n = 135). Nine protein-bound and free adduct AGEs were quantified in serum. Most protein-bound AGEs increased moderately through stages 2-4 CKD whereas AGE free adducts increased markedly. Methylglyoxal-derived hydroimidazolone MG-H1 free adduct was the AGE most responsive to CKD status, increasing 8-fold and 30-fold in stage 4 CKD in patients without and with diabetes, respectively. MG-H1 Glomerular filtration flux was increased 5-fold in diabetes, likely reflecting increased methylglyoxal glycation status. We conclude that serum MG-H1 free adduct concentration was strongly related to stage of CKD and increased in diabetes status. Serum MG-H1 free adduct is a candidate AGE risk marker of non-diabetic and diabetic CKD.

Reducing adverse events associated with the glucagon stimulation test for the assessment of growth hormone deficiency in adults with a high prevalence of pituitary hormone deficiencies.

DESIGN: A retrospective review of the adverse events (AEs) in 78 patients during the glucagon stimulation test (GST) for the assessment of growth hormone deficiency (GHD) before and after protocol amendments which aimed to reduce AEs in a group of patients with a high prevalence of pituitary hormone deficiencies. PATIENTS: Based on our observations of frequent AEs during the standard GST protocol in an initial 25 patients (cohort 1), a modified protocol was introduced to include the routine administration of 20 mg of hydrocortisone pre-GST in a subsequent 53 patients (cohort 2). Post hoc analysis of the effect of glucocorticoid dosing pre-GST on AEs was examined in those receiving <20 mg hydrocortisone (group A, n = 19) vs ≥20 mg hydrocortisone (group B, n = 59). MEASUREMENTS: AEs including hypotension, hypoglycaemia and nausea/vomiting. RESULTS: Of the 78 patients undergoing the GST, 79% had ≥2 hormone deficiencies. Rates of AEs were 41% vs 30% for hypotension, 60% vs 28% for hypoglycaemia (p < .05) and 20% vs 13% for nausea/vomiting in cohort 1 compared with cohort 2, respectively. Post hoc analysis revealed lower rates of AEs in those receiving ≥20 mg hydrocortisone (group B) compared to those receiving <20 mg due to a reduction in hypoglycaemic events (82% vs 26%, p < .001) and hypotension (50% vs 27%, p = .05). Similar numbers of patients in group A and group B met criteria for GHD. CONCLUSIONS: In patients with a high prevalence of pituitary deficiencies, a modified GST protocol of additional stress dose glucocorticoid attenuated the frequency of AEs without appearing to compromise the performance of the GST.

Severe acute respiratory syndrome coronavirus 2 as a potential cause of type 1 diabetes facilitated by spike protein receptor binding domain attachment to human islet cells: An illustrative case study and experimental data.

AIMS: Aim of this study is to report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, responsible for coronavirus disease 2019 (COVID-19), as a possible cause for type 1 diabetes by providing an illustrative clinical case of a man aged 45 years presenting with antibody-negative diabetic ketoacidosis post-recovery from COVID-19 pneumonia and to explore the potential for SARS-CoV-2 to adhere to human islet cells. METHODS: Explanted human islet cells from three independent solid organ donors were incubated with the SARS-CoV-2 spike protein receptor biding domain (RBD) fused to a green fluorescent protein (GFP) or a control-GFP, with differential adherence established by flow cytometry. RESULTS: Flow cytometry revealed dose-dependent specific binding of RBD-GFP to islet cells when compared to control-GFP. CONCLUSIONS: Although a causal basis remains to be established, our case and in vitro data highlight a potential mechanism by which SARS-CoV-2 infection may result in antibody-negative type 1 diabetes.

The effect of preventative cardiovascular therapies on coronary artery disease in people with and without type 2 diabetes: a propensity-matched score study.

BACKGROUND: Although it is known that patients with Type 2 Diabetes Mellitus (T2DM) are at an increased risk of coronary artery disease (CAD), the actual coronary artery burden of atherosclerotic disease in patients with and without T2DM in a real-world setting and its possible modification by preventative therapies has not been extensively documented. METHODS: Merged coronary angiography and hospital discharge data between 2013 and 2019 were obtained for analysis and a random sub-sample of patient charts were reviewed for medication use. Propensity scores were estimated using logistic regression models and used to match patients, looking at the effect of severity of CAD over time in years in an ordinal logistic regression model. A separate propensity score was estimated and used to inverse probability weight the ordinal logistic regression looking at the effect of medication use on CAD severity in patients with and without T2DM. RESULTS: From 3,016 patients in the coronary angiography database, 1421 with T2DM and 1421 without T2DM were matched on propensity score. T2DM patients had more extensive CAD in 2018 compared to 2013 ((adjusted odds ratio) adjOR: 2.06 95% C.I. 1.38, 2.07), but this risk appeared to be attenuated in 2019. In contrast, there was no effect of time on CAD burden in patients without diabetes. In the sub-sample of 760 patients who underwent a chart review of their medication use, there were 367 (48%) with T2DM. For patients with T2DM 69.8% reported taking statins, 64.0% RAS inhibitors and 64.0% anti-platelet drugs. This was significantly higher than patients without diabetes of whom 46.6% reported taking statins, 49.0% RAS inhibitors and 49.9% anti-platelet drugs. As in the full matched sample, patients with diabetes had more extensive CAD (adjOR: 1.32 95% CI: 1.01, 1.74). However, after adjustment for the use of RAS inhibitors, statins and anticoagulants there was no difference in extent of CAD between patients with and without diabetes (adjOR: 1.14 95% CI: 0.85, 1.53). CONCLUSIONS: Although patients with diabetes have a greater extent of CAD in comparison to those without T2DM, preventative medication use decreases this CAD burden significantly.

Utility of adrenocorticotropic hormone in adrenal vein sampling despite the occurrence of discordant lateralization.

BACKGROUND: Adrenal vein sampling (AVS) is crucial for accurate lateralization of aldosterone excess but it is technically challenging due to the difficulty of adrenal vein cannulation. The use of adrenocorticotropic hormone (ACTH) to improve cannulation success is controversial and can lead to discordant lateralization outcomes. OBJECTIVE: To evaluate the utility of ACTH in two centres with different levels of AVS expertise and formulate a strategy for interpreting discordant results. DESIGN: A retrospective cross-sectional analysis of AVS results and postoperative patient outcomes. SETTING: Two large tertiary hospitals with harmonized AVS protocols where adrenal venous samples are collected both before and after ACTH stimulation. MEASUREMENTS: Cannulation success (measured by selectivity index, SI), lateralization (measured by lateralization index, LI) and postoperative biochemical cure. RESULTS: Number of AVS procedures judged to have successful bilateral adrenal vein cannulation increased from 53% pre- to 73% post-ACTH. The increase in cannulation success was significantly higher in centre where AVS was performed by multiple radiologists with a lower basal success rate. In both centres, the proportion of cases deemed to display lateralization significantly decreased with the use of ACTH (70% pre- to 52% post-ACTH). Based on postoperative outcomes of patients with discordant results who underwent unilateral adrenalectomy, the combination of LI >3 pre-ACTH and LI >2 post-ACTH was predictive of a biochemical cure. CONCLUSION: Adrenocorticotropic hormone can increase the rate of cannulation success during AVS at the expense of reduced lateralization. The criteria for lateralization should be carefully determined based on local data when ACTH is used.

Reducing glucose variability with continuous subcutaneous insulin infusion is associated with reversal of axonal dysfunction in type 1 diabetes mellitus.

INTRODUCTION: We assess whether improvement in control of type 1 diabetes mellitus (T1DM) with continuous subcutaneous insulin infusion (CSII) can protect peripheral nerve function. METHODS: Twelve patients with T1DM treated with multiple daily insulin injections were assessed with nerve excitability testing prior to and 3 months after initiation of CSII. RESULTS: Although commencing treatment with CSII for 3 months improved mean glycosylated hemoglobin, it did not significantly alter nerve excitability or glycemic variability (GV). In four patients, some deterioration in GV was observed, while eight patients had improvement in SD and mean amplitude of glycemic excursions. For these eight patients, there was normalization of depolarizing and hyperpolarizing threshold electrotonus and recovery cycle superexcitablity. DISCUSSION: When CSII initiation is able to reduce glycemic variability in T1DM, reversal of axonal dysfunction is seen, likely due to normalization of sodium-potassium pump function and restoration of transaxonal membrane potential.

Baseline liver function tests and full blood count indices and their association with progression of chronic kidney disease and renal outcomes in Aboriginal and Torres Strait Islander people: the eGFR follow- up study.

BACKGROUND: Determination of risks for chronic kidney disease (CKD) progression could improve strategies to reduce progression to ESKD. The eGFR Study recruited a cohort of adult Aboriginal and Torres Strait Islander people (Indigenous Australians) from Northern Queensland, Northern Territory and Western Australia, aiming to address the heavy CKD burden experienced within these communities. METHODS: Using data from the eGFR study, we explored the association of baseline liver function tests (LFTs) (alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin and albumin) and full blood count (FBC) indices (white blood cell and red blood cell counts and haemoglobin) with annual eGFR decline and renal outcomes (first of 30% decline in eGFR with a follow-up eGFR < 60 mL/min/1.73 m2, initiation of renal replacement therapy, or renal death). Comparisons of baseline variables across eGFR categories were calculated using analysis of variance and logistic regression as appropriate. Linear and multivariable regression models were used to estimate the annual change in eGFR for changes in FBC indices and LFTs. Cox proportional hazard models were used to estimate the hazard ratio for developing renal outcome for changes in baseline FBC indices and LFTs. RESULTS: Of 547 participants, 540 had at least one baseline measure of LFTs and FBC indices. The mean age was 46.1 (14.7) years and 63.6% were female. The median follow-up was 3.1 (IQR 2.8-3.6) years. Annual decline in eGFR was associated with low serum albumin (p < 0.001) and haemoglobin (p = 0.007). After adjustment for age, gender, urine albumin/creatinine ratio, diabetes, BMI, CRP, WHR, alcohol consumption, cholesterol and triglycerides, low serum albumin (p < 0.001), haemoglobin (p = 0.012) and bilirubin (p = 0.011) were associated with annual decline in eGFR. Renal outcomes were inversely associated with serum albumin (p < 0.001), bilirubin (p = 0.012) and haemoglobin (p < 0.001) and directly with GGT (p = 0.007) and ALP (p < 0.001). Other FBC indices and LFTs were not associated with annual decline in eGFR or renal outcomes. CONCLUSIONS: GGT, ALP, bilirubin, albumin and haemoglobin independently associate with renal outcomes. Contrary to findings from other studies, no association was found between renal outcomes and other FBC indices. These findings may help focus strategies to prevent disease progression in this high-risk population.

Exercise capacity in diabetes mellitus is predicted by activity status and cardiac size rather than cardiac function: a case control study.

BACKGROUND: The reasons for reduced exercise capacity in diabetes mellitus (DM) remains incompletely understood, although diastolic dysfunction and diabetic cardiomyopathy are often favored explanations. However, there is a paucity of literature detailing cardiac function and reserve during incremental exercise to evaluate its significance and contribution. We sought to determine associations between comprehensive measures of cardiac function during exercise and maximal oxygen consumption ([Formula: see text]peak), with the hypothesis that the reduction in exercise capacity and cardiac function would be associated with co-morbidities and sedentary behavior rather than diabetes itself. METHODS: This case-control study involved 60 subjects [20 with type 1 DM (T1DM), 20 T2DM, and 10 healthy controls age/sex-matched to each diabetes subtype] performing cardiopulmonary exercise testing and bicycle ergometer echocardiography studies. Measures of biventricular function were assessed during incremental exercise to maximal intensity. RESULTS: T2DM subjects were middle-aged (52 ± 11 years) with a mean T2DM diagnosis of 12 ± 7 years and modest glycemic control (HbA1c 57 ± 12 mmol/mol). T1DM participants were younger (35 ± 8 years), with a 19 ± 10 year history of T1DM and suboptimal glycemic control (HbA1c 65 ± 16 mmol/mol). Participants with T2DM were heavier than their controls (body mass index 29.3 ± 3.4 kg/m2 vs. 24.7 ± 2.9, P = 0.001), performed less exercise (10 ± 12 vs. 28 ± 30 MET hours/week, P = 0.031) and had lower exercise capacity ([Formula: see text]peak = 26 ± 6 vs. 38 ± 8 ml/min/kg, P < 0.0001). These differences were not associated with biventricular systolic or left ventricular (LV) diastolic dysfunction at rest or during exercise. There was no difference in weight, exercise participation or [Formula: see text]peak in T1DM subjects as compared to their controls. After accounting for age, sex and body surface area in a multivariate analysis, significant positive predictors of [Formula: see text]peak were cardiac size (LV end-diastolic volume, LVEDV) and estimated MET-hours, while T2DM was a negative predictor. These combined factors accounted for 80% of the variance in [Formula: see text]peak (P < 0.0001). CONCLUSIONS: Exercise capacity is reduced in T2DM subjects relative to matched controls, whereas exercise capacity is preserved in T1DM. There was no evidence of sub-clinical cardiac dysfunction but, rather, there was an association between impaired exercise capacity, small LV volumes and sedentary behavior.

Relationship between urinary sodium-to-potassium ratio and ambulatory blood pressure in patients with diabetes mellitus.

Previous studies investigating the relationship between sodium intake and blood pressure have mostly relied on dietary recall and clinic blood pressure measurement. In this cross-sectional study, we aimed to investigate the relationship between 24 hour urinary sodium and potassium excretion, and their ratio, with 24 hour ambulatory blood pressure parameters including nocturnal blood pressure dipping in patients with type 1 and 2 diabetes. We report that in 116 patients with diabetes, systolic blood pressure was significantly predicted by the time of day, age, the interaction between dipping status with time, and 24 hour urinary sodium-to-potassium ratio (R2  = 0.83) with a relative contribution of 53%, 21%, 20% and 6%, respectively. However, there was no interaction between urinary sodium-to-potassium ratio and dipping status.

Diabetic ketoacidosis in adult patients: an audit of factors influencing time to normalisation of metabolic parameters.

BACKGROUND: Diabetic ketoacidosis (DKA) is an acute life-threatening metabolic complication of diabetes that imposes substantial burden on our healthcare system. There is a paucity of published data in Australia assessing factors influencing time to resolution of DKA and length of stay (LOS). AIMS: To identify factors that predict a slower time to resolution of DKA in adults with diabetes. METHODS: Retrospective audit of patients admitted to St Vincent's Hospital Melbourne between 2010 to 2014 coded with a diagnosis of 'Diabetic Ketoacidosis'. The primary outcome was time to resolution of DKA based on normalisation of biochemical markers. Episodes of DKA within the wider Victorian hospital network were also explored. RESULTS: Seventy-one patients met biochemical criteria for DKA; median age 31 years (26-45 years), 59% were male and 23% had newly diagnosed diabetes. Insulin omission was the most common precipitant (42%). Median time to resolution of DKA was 11 h (6.5-16.5 h). Individual factors associated with slower resolution of DKA were lower admission pH (P < 0.001) and higher admission serum potassium level (P = 0.03). Median LOS was 3 days (2-5 days), compared to a Victorian state-wide LOS of 2 days. Higher comorbidity scores were associated with longer LOS (P < 0.001). CONCLUSIONS: Lower admission pH levels and higher admission serum potassium levels are independent predictors of slower time to resolution of DKA. This may assist to stratify patients with DKA using markers of severity to determine who may benefit from closer monitoring and to predict LOS.

Lipid-lowering therapy use and achievement of cholesterol targets in an Australian diabetes clinic.

We documented temporal changes in the use of lipid-lowering medications and achievement of cholesterol targets in an Australian diabetes clinic. The number of patients using lipid-lowering therapy for primary or secondary cardiovascular prevention increased from 6 to 69% between 1993-1995 and 2014-2016, which corresponded to a decrease in low-density lipoprotein cholesterol levels from 3.7 to 2.4 mmol/L (P < 0.01).

Bone health in chronic kidney disease-mineral and bone disorder: a clinical case seminar and update.

The metabolic abnormalities affecting bone in the setting of chronic kidney disease (CKD) are complex with overlapping and interacting aetiologies and have challenging diagnostic and management strategies. Disturbances in calcium, phosphate, fibroblast growth factor 23, parathyroid hormone concentrations and vitamin D deficiency are commonly encountered and contribute to the clinical syndromes of bone disorders in CKD, including hyperparathyroidism, osteomalacia, osteoporosis and adynamic bone disease. Mineral and bone abnormalities may also persist or arise de novo post-renal transplantation. The Kidney Disease Improving Global Outcomes organisation describes these mineral metabolism derangements and skeletal abnormalities as 'CKD Mineral and Bone Disorder'. Patients with this disorder have an increased risk of fracture, cardiovascular events and overall increased mortality. In light of the recently updated 2017 guidelines from the Kidney Disease Improving Global Outcomes, we present a clinical case-based discussion to highlight the complexities of investigating and managing the bone health of patients with CKD with a focus on these updates.