Glycaemic outcomes in hospital with IDegAsp versus BIAsp30 premixed insulins.

BACKGROUND AND AIMS: IDegAsp (Ryzodeg 70/30), a unique premixed formulation of long-acting insulin degludec and rapid-acting insulin aspart, is increasing in use. Management of IDegAsp during hospitalisation is challenging because of degludec's ultra-long duration of action. We investigated inpatient glycaemia in patients treated with IDegAsp compared to biphasic insulin aspart (BIAsp30; Novomix30). METHODS: We performed a retrospective observational study at two hospitals assessing inpatients with type 2 diabetes treated with IDegAsp or BIAsp30 prior to and during hospital admission. Standard inpatient glycaemic outcomes were analysed based on capillary blood glucose (BG) measurements. RESULTS: We assessed 88 individuals treated with IDegAsp and 88 HbA1c-matched individuals treated with BIAsp30. Patient characteristics, including insulin dose at admission, were well matched, but the IDegAsp group had less frequent twice-daily insulin dosing than the BIAsp30 group (49% vs 87%, P < 0.001). Patient-days with BG <4 mmol/L were not different (10.6% vs 9.9%, P = 0.7); however, the IDegAsp group had a higher patient-day mean BG (10.4 (SD 3.4) vs 10.0 (3.4) mmol/L, P < 0.001), and more patient-days with mean BG >10 mmol/L (48% vs 38%, P < 0.001) compared to the BIAsp30 group. Glucose was higher in the IDegAsp group in the evening (4 PM to midnight) (11.6 (SD 4.0) vs 10.9 (4.6) mmol/L, P = 0.004), but not different at other times during the day. CONCLUSIONS: Inpatients treated with IDegAsp compared to BIAsp30 had similar hypoglycaemia incidence, but higher hyperglycaemia incidence, potentially related to less frequent twice-daily dosing. With the increasing use of IDegAsp in the community, development of hospital management guidelines for this insulin formulation is needed.

The experience of an adult diabetic foot unit continuing face-to-face consults during the COVID-19 pandemic.

BACKGROUND AND AIMS: The COVID-19 pandemic significantly disrupted lower limb diabetes care. We aimed to map trends in diabetes-related lower limb amputation and hospitalisation rates through the COVID-19 pandemic. METHODS: We performed a retrospective cohort study of all individuals who underwent a lower limb amputation for a diabetes-related foot complication from 2018 to 2021 at the Royal Melbourne Hospital, a quaternary hospital in Australia. Hospitalisation rates with a diabetes-related foot complication were collected for comparison. The start of the COVID-19 epoch was defined as 16 March 2020, when a state of emergency was declared in Melbourne. RESULTS: During the study period, 360 lower limb amputations for diabetes-related foot complications were performed in 247 individuals. The median monthly number of amputations remained stable prior to and during the COVID-19 epoch; there was a median of 8.0 amputations per month (interquartile range (IQR) = 6.5-11) before COVID-19, compared to 6.5 amputations (IQR = 5.0-8.3) during the COVID-19 epoch (P = 0.23). Hospitalisation with a diabetes-related foot complication significantly increased from a median monthly rate of 11 individuals (IQR = 9.0-14) before COVID-19 to 19 individuals (IQR = 14-22) during the COVID-19 epoch (p < 0.001). CONCLUSIONS: Despite increased hospitalisations for diabetes-related foot complications during COVID-19, there was not a corresponding increase in amputation rates. Face-to-face care of diabetes-related foot complications was prioritised at this centre and may have contributed to stable amputation rates during the pandemic.

Predictors and outcomes of dose reduction of methotrexate and cyclosporin graft-versus-host disease prophylaxis following allogeneic haemopoietic cell transplantation.

BACKGROUND: Concern regarding dose-related toxicities of methotrexate (MTX) and cyclosporin (CYA) graft-versus-host disease (GVHD) prophylaxis occasionally leads to dose alterations post allogeneic haemopoietic cell transplant (alloHCT). AIMS: To clarify causes of MTX and CYA dose alteration and assess impact on patient outcomes, including GVHD, relapse, non-relapse mortality (NRM) and overall survival (OS). METHODS: Analysis of retrospective data was performed in a single tertiary centre of patients who underwent alloHCT for any indication and who received GVHD prophylaxis with CYA and MTX between the years 2011 and 2015. Univariate analysis was conducted using the log-rank test for OS and using competing risk regression for NRM, relapse and GVHD. Fisher exact tests were used to determine if an association existed between each of the pre-transplant variables and MTX alteration. Multivariate models for OS and NRM were constructed using Cox proportional hazards modelling and competing risk regression respectively. RESULTS: Fifty-four (28%) of 196 had MTX alterations and 61/187 (33%) had CYA alterations. Reasons for MTX alteration included mucositis, renal or liver impairment, fluid overload and sepsis. Causes of CYA alteration were numerous, but most commonly due to acute kidney impairment. MTX alteration was associated with inferior OS (hazard ratio 2.4; P = <0.001) and higher NRM (odds ratio (OR) 4.6; P < 0.001) at 6 years post-landmark. CYA alteration was associated with greater NRM (OR 2.7; P = 0.0137) at 6 years. GVHD rates were unaffected by dose alteration. CONCLUSIONS: Our findings suggest dose alteration in MTX and CYA GVHD prophylaxis is associated with adverse survival outcomes in alloHCT, without a significant impact on GVHD rates.

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.

The Canadian Hypoglycemia During Hospitalization Score Is Externally Valid in the Australian Diabetes IN-hospital: Glucose & Outcomes (DINGO) Cohort.

OBJECTIVES: The Hypoglycemia During Hospitalization (HyDHo) score predicts hypoglycemia in a population of Canadian inpatients by assigning various weightings to 5 key clinical criteria known at the time of admission, in particular age, recent presentation to an emergency department, insulin use, use of oral hypoglycemic agents, and chronic kidney disease. Our aim in this study was to externally validate the HyDHo score by applying this risk calculator to an Australian population of inpatients with diabetes. METHODS: This study was a retrospective data analysis of a subset of the Diabetes IN-hospital: Glucose & Outcomes (DINGO) cohort. The HyDHo score was applied based on clinical information known at the time of admission to stratify risk of inpatient hypoglycemia. RESULTS: The HyDHo score was applied to 1,015 patients, generating a receiver-operating characteristic c-statistic of 0.607. A threshold of ≥9, as per the original study, generated a sensitivity of 83% and a specificity of 20%. A threshold of ≥10, to better suit this Australian population, generated a sensitivity of 90% and a specificity of 34%. The HyDHo score has been externally valid in a geographically different population; in fact, it outperformed the original study after accounting for local hypoglycemia rates. CONCLUSIONS: Our findings support the external validity of the HyDHo score in a geographically different population. Application of this simple and accessible tool can serve as an adjunct to predict an inpatient's risk of hypoglycemia and guide more appropriate glucose monitoring and diabetes management.

Cardiovascular and Metabolic Risk Incidence Among Adult Allogeneic Stem Cell Transplant Recipients: A Narrative Review.

Advances in allogeneic hematopoietic stem cell transplantation (alloHSCT) and supportive care over the past decade have reduced transplant and relapse-related mortality, leading to a greater number of long-term survivors. However, transplant-related late effects, such as cardiovascular disease (CVD) and metabolic diseases, are becoming significant concerns for this group. This review aims to address several key questions regarding cardiovascular late effects in alloHSCT recipients, including the long-term incidence of CVD-related events, the prevalence of risk factors, screening and management recommendations, and evidence for screening and prevention strategies. A literature search was conducted in PubMed Central using the National Library of Medicine search engine, covering all relevant research from inception to 2023. The initial search identified 751 research records, of which 41 were shortlisted based on specific criteria (≥18 years of age at the time of transplant, allogeneic transplant, and inclusion of more than 30 patients). Our review highlights published evidence confirming the increased CVD risk among alloHSCT recipients. This risk is especially pronounced among individuals who have developed traditional and modifiable risk factors or have been exposed to transplant-specific risk factors. Evidence of the use of traditional cardiac risk factor calculators in the alloHSCT population is limited, in addition, there is emerging evidence that general population calculators potentially underestimate CVD risk given the increased risk of CVD in the allogeneic group as a whole. Studies that develop and validate transplant recipient-specific CVD risk stratification tools appear to be severely lacking and the field's focus needs to be shifted here in the coming years. To improve patient engagement and adherence to CVD risk factor measures, we recommend that a multidisciplinary model involving both specialists and primary care physicians is crucial in ensuring regular follow-up in the community and to potentially improve adherence.

Hyperglycemia in hospital: an independent marker of infection, acute kidney injury & stroke for hospital inpatients.

CONTEXT: Hyperglycemia in hospital inpatients without pre-existing diabetes is associated with increased mortality. However, the independent contribution of hyperglycemia to healthcare-associated infection (HAI), acute kidney injury (AKI), and stroke is unclear. OBJECTIVE: To investigate the relationship between hyperglycemia and adverse clinical outcomes in hospital for patients with and without diabetes. DESIGN: Diabetes IN-hospital: Glucose and Outcomes (DINGO) was a 26-week (October 2019 - March 2020) prospective cohort study. Clinical and glucose data were collected up to the 14th day of admission. Primary stratification was by hyperglycemia, defined as ≥2 random capillary blood glucose (BG) measurements ≥11.1 mmol/L (≥200 mg/dL). Propensity weighting for nine clinical characteristics, was performed to allow interrogation of causality. To maintain the positivity assumption, patients with HbA1c > 12.0% were excluded and pre-hospital treatment not adjusted for. SETTING: The Royal Melbourne Hospital, a quaternary referral hospital in Melbourne, Australia. PATIENTS: Admissions with at least two capillary glucose values and length of stay >24 hours were eligible, with half randomly sampled. OUTCOME MEASURES: HAI, AKI, stroke, and mortality. RESULTS: Of 2,558 included admissions, 1,147 (45%) experienced hyperglycemia in hospital. Following propensity-weighting and adjustment, hyperglycemia in hospital was found to, independently of nine covariables, contribute an increased risk of in-hospital HAI (130 [11.3%] vs.100 [7.1%], adjusted odds ratio [aOR] 1.03, 95% confidence interval [95%CI] 1.01-1.05, p = 0.003), AKI (120 [10.5%] vs. 59 [4.2%], aOR 1.07, 95%CI 1.05-1.09, p < 0.001), and stroke (10 [0.9%] vs. 1 [0.1%], aOR 1.05, 95%CI 1.04-1.06, p < 0.001). CONCLUSIONS: In hospital inpatients (HbA1c ≤ 12.0%), irrespective of diabetes status and pre-hospital glycaemia, hyperglycemia increases the risk of in-hospital HAI, AKI, and stroke compared with those not experiencing hyperglycemia.

The Specialist Treatment of Inpatients: Caring for Diabetes in Surgery (STOIC-D Surgery) Trial: A Randomized Controlled Trial of Early Intervention With an Electronic Specialist-Led Model of Diabetes Care.

OBJECTIVE: To investigate the effect of early intervention with an electronic specialist-led "proactive" model of care on glycemic and clinical outcomes. RESEARCH DESIGN AND METHODS: The Specialist Treatment of Inpatients: Caring for Diabetes in Surgery (STOIC-D Surgery) randomized controlled trial was performed at the Royal Melbourne Hospital. Eligible participants were adults admitted to a surgical ward during the study with either known diabetes or newly detected hyperglycemia (at least one random blood glucose result ≥11.1 mmol/L). Participants were randomized 1:1 to standard diabetes care or the intervention consisting of an early consult by a specialist inpatient diabetes team using electronic tools for patient identification, communication of recommendations, and therapy intensification. The primary outcome was median patient-day mean glucose (PDMG). The key secondary outcome was incidence of health care-associated infection (HAI). RESULTS: Between 12 February 2021 and 17 December 2021, 1,371 admissions met inclusion criteria, with 680 assigned to early intervention and 691 to standard diabetes care. Baseline characteristics were similar between groups. The early intervention group achieved a lower median PDMG of 8.2 mmol/L (interquartile range [IQR] 6.9-10.0 mmol/L) compared with 8.6 mmol/L (IQR 7.2-10.3 mmol/L) in the control group for an estimated difference of -0.3 mmol/L (95% CI -0.4 to -0.2 mmol/L, P < 0.0001). The incidence of HAI was lower in the intervention group (77 [11%] vs. 110 [16%]), for an absolute risk difference of -4.6% (95% CI -8.2 to -1.0, P = 0.016). CONCLUSIONS: In surgical inpatients, early diabetes management intervention with an electronic specialist-led diabetes model of care reduces glucose and HAI.

Longitudinal Digital Glucometric Benchmarking to Evaluate the Impact of Institutional Diabetes Care Initiatives in Adults With Diabetes Mellitus Over the 2016-2020 Period.

BACKGROUND: While glucometric benchmarking has been used to compare glucose management between institutions, the value of longitudinal intra-institution benchmarking to assess quality improvement changes is not established. METHODS: A prospective six-month observational study (October 2019-March 2020 inclusive) of inpatients with diabetes or newly detected hyperglycemia admitted to eight medical and surgical wards at the Royal Melbourne Hospital. Networked blood glucose (BG) meters were used to collect capillary BG levels. Outcomes were measures of glycemic control assessed by mean and threshold glucometric measures and comparison with published glucometric benchmarks. Intra-institution comparison was over the 2016-2020 period. RESULTS: In all, 620 admissions (588 unique individuals) met the inclusion criteria, contributing 15 164 BG results over 4023 admission-days. Compared with the 2016 cohort from the same institution, there was increased BG testing (3.8 [SD = 2.2) vs 3.3 [SD = 1.7] BG measurements per patient-day, P < .001), lower mean patient-day mean glucose (PDMG; 8.9 mmol/L [SD = 3.2] vs 9.5 mmol/L [SD = 3.3], P < .001), and reduced mean and threshold measures of hyperglycemia (P < .001 for all). Comparison with institutions across the United States revealed lower incidence of mean PDMG >13.9 or >16.7 mmol/L, and reduced hypoglycemia (<3.9, <2.8, and <2.2 mmol/L), when compared with published benchmarks from an earlier period (2009-2014). CONCLUSIONS: Comprehensive digital-based glucometric benchmarking confirmed institutional quality improvement changes were followed by reduced hyperglycemia and hypoglycemia in a five-year comparison. Longitudinal glucometric benchmarking enables evaluation and validation of changes to institutional diabetes care management practices.

In-hospital hyperglycemia but not diabetes mellitus alone is associated with increased in-hospital mortality in community-acquired pneumonia (CAP): a systematic review and meta-analysis of observational studies prior to COVID-19.

The objective of this review was to quantify the association between diabetes, hyperglycemia, and outcomes in patients hospitalized for community-acquired pneumonia (CAP) prior to the COVID-19 pandemic by conducting a systematic review and meta-analysis. Two investigators independently screened records identified in the PubMed (MEDLINE), EMBASE, CINAHL, and Web of Science databases. Cohort and case-control studies quantitatively evaluating associations between diabetes and in-hospital hyperglycemia with outcomes in adults admitted to hospital with CAP were included. Quality was assessed using the Newcastle-Ottawa Quality Assessment Scale, effect size using random-effects models, and heterogeneity using I2 statistics. Thirty-eight studies met the inclusion criteria. Hyperglycemia was associated with in-hospital mortality (adjusted OR 1.28, 95% CI 1.09 to 1.50) and intensive care unit (ICU) admission (crude OR 1.82, 95% CI 1.17 to 2.84). There was no association between diabetes status and in-hospital mortality (adjusted OR 1.04, 95% CI 0.72 to 1.51), 30-day mortality (adjusted OR 1.13, 95% CI 0.77 to 1.67), or ICU admission (crude OR 1.91, 95% CI 0.74 to 4.95). Diabetes was associated with increased mortality in all studies reporting >90-day postdischarge mortality and with longer length of stay only for studies reporting crude (OR 1.50, 95% CI 1.11 to 2.01) results. In adults hospitalized with CAP, in-hospital hyperglycemia but not diabetes alone is associated with increased in-hospital mortality and ICU admission. Diabetes status is associated with increased >90-day postdischarge mortality. Implications for management are that in-hospital hyperglycemia carries a greater risk for in-hospital morbidity and mortality than diabetes alone in patients admitted with non-COVID-19 CAP. Evaluation of strategies enabling timely and effective management of in-hospital hyperglycemia in CAP is warranted.

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN: Network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES: Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS: 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153180.