Clinical significance of an elevated on-admission beta-hydroxybutyrate in acutely ill adult patients without diabetes.

OBJECTIVE: To determine the relationship between point-of-care ß-hydroxybutyrate (BHB) concentration and outcomes in adult patients without diabetes admitted through ED. METHODS: This was a prospective study from 10 March to 2 July 2021. Admitted patients without diabetes had capillary BHB sampled in ED. Outcomes of length-of-stay (LOS), composite mortality/ICU admission rates and clinical severity scores (Quick Sepsis Organ Failure Assessment score/National Early Warning Score [qSOFA/NEWS]) were measured. BHB was assessed as a continuous variable and between those with BHB above and equal to 1.0 mmol/L and those below 1.0 mmol/L. RESULTS: A total of 311 patients were included from 2377 admissions. Median length-of-stay was 4.1 days (IQR 2.1-9.8), 18 (5.8%) died and 37 (11.8%) were admitted to ICU. Median BHB was 0.2 mmol/L (IQR 0.1-0.4). Twenty-five patients had BHB ≥1.0 mmol/L and five were >3.0 mmol/L. There was no significant difference in median LOS for patients with BHB ≥1.0 mmol/L compared to non-ketotic patients, 5.3 days (IQR 2.2-7.5) versus 4.1 days, respectively (IQR 2.0-9.8) (P = 0.69). BHB did not correlate with LOS (Spearman ρ = 0.116, 95% confidence interval: 0.006-0.223). qSOFA and NEWS also did not differ between these cohorts. For those 25 patients with BHB ≥1.0 mmol/L, an infective/inflammatory diagnosis was present in 11 (44%), at least 2 days of fasting in 10 (40%) and ethanol intake >40 g within 48 h in 4 (16%). CONCLUSIONS: Routine BHB measurement in patients without diabetes does not add to clinical bedside assessment and use should be limited to when required to confirm a clinical impression.

Decreased rates of hospital-acquired infection after introduction of an active surveillance, virtual glucose management system.

Addition of an active surveillance virtual glucose management (VGM) system to usual consultation-based diabetes inpatient care at our hospital was associated with a decrease in hospital-acquired infection from 8.7% (17/196) to 3.5% (6/172) with an adjusted odds ratio of 0.17 (95%CI: 0.05-0.61), and a reduction in hypoglycemic and hyperglycemic patient-stay days.

What is the utility of blood beta-hydroxybutyrate measurements in emergency department in patients without diabetes: a systematic review.

BACKGROUND: Ketones are synthesised as an alternative fuel source during times of energy restriction. In the absence of a hyperglycemic emergency, ketosis in patients presenting to the emergency department (ED) may indicate reduced carbohydrate intake. In the perioperative setting, excess fasting with ketosis is associated with worse outcomes; however, whether ketosis in patients without diabetes presenting to ED is also associated with worse outcomes is unclear. This systematic review aims to examine the evidence for ketosis in predicting the need for hospital admission in patients without diabetes, presenting to the ED. METHODS: A systematic review was performed using PRISMA guidelines. We searched electronic bases (OVID-Medline, OVID-EMBASE, Scopus and PubMed) up to December 2022. Eligible studies included children or adults without diabetes presenting to the ED where a point-of-care capillary beta-hydroxybutyrate (BHB) was measured and compared to outcomes including the need for admission. Outcome measures included need for admission and length of stay. Content analysis was performed systematically; bias and certainty assessed using standard tools. RESULTS: The literature search found 17,133 citations, 14,965 papers were subjected to title and abstract screening. The full text of 62 eligible studies were reviewed. Seven articles met the inclusion criteria. Six studies were conducted solely in the paediatric population, and of these, four were limited to children presenting with gastroenteritis symptoms. Median BHB was higher in children requiring hospital admission with an AUC of 0.64-0.65 across two studies. There was a weak correlation between BHB and dehydration score or duration of symptoms. The single study in adults, limited to stroke presentations, observed no relationship between BHB and neurological deficit at presentation. All studies were at risk of bias using the Newcastle-Ottawa Scale and was assessed of "very low" to "low" quality due to their study design in the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Heterogeneity amongst selected studies precluded meta-analysis. CONCLUSION: The evidence for any utility of BHB measurement in the ED in absence of diabetes is limited to the paediatric population, specifically children presenting with symptoms of gastroenteritis. Any role in adults remains unexplored.

Acceptance and Effect of Continuous Glucose Monitoring on Discharge From Hospital in Patients With Type 2 Diabetes: Open-label, Prospective, Controlled Study.

BACKGROUND: Continuous glucose monitors (CGM) can provide detailed information on glucose excursions. There is little information on safe transitioning from hospital back to the community for patients who have had diabetes therapies adjusted in hospital and it is unclear whether newer technologies may facilitate this process. OBJECTIVE: Our aim was to determine whether offering CGM on discharge would be acceptable and if CGM initiated on hospital discharge in people with type 2 diabetes (T2DM) would reduce hospital re-presentations at 1 month. METHODS: This was an open-label study. Adult inpatients with T2DM, who were to be discharged home and required postdischarge glycemic stabilization, were offered usual care consisting of clinic review at 2 weeks and at 3 months. In addition to usual care, participants in the intervention arm were provided with a Libre flash glucose monitoring system (Abbott Australia). An initial run-in phase for the first 20 participants was planned, where all consenting participants were enrolled in an active arm. Subsequently, all participants were to be randomized to the active arm or usual care control group. RESULTS: Of 237 patients screened during their hospital admission, 34 had comorbidities affecting cognition that prevented informed consent and affected their ability to learn to use the CGM device. In addition, 21 were not able to be approached as the material was only in English. Of 101 potential participants who fulfilled eligibility criteria, 19 provided consent and were enrolled. Of the 82 patients who declined to participate, 31 advised that the learning of a new task toward discharge was overwhelming or too stressful and 26 were not interested, with no other details. Due to poor recruitment, the study was terminated without entering the randomization phase to determine whether CGM could reduce readmission rate. CONCLUSIONS: These results suggest successful and equitable implementation of telemedicine programs requires that any human factors such as language, cognition, and possible disengagement be addressed. Recovery from acute illness may not be the ideal time for introduction of newer technologies or may require more novel implementation frameworks.

Continuous glucose monitoring to assess glucose variability in type 3c diabetes.

AIM: The effectiveness of continuous glucose monitoring (CGM) in maintaining glycaemic control in type 1 diabetes mellitus and type 2 diabetes mellitus has been well demonstrated. However, the degree of glycaemic variability (GV) in people with type 3c diabetes mellitus has not been fully explored using CGM. This study aims to evaluate GV in type 3c diabetes mellitus participants and compare it to type 1 diabetes mellitus and type 2 diabetes mellitus. METHODS: Participants were grouped according to type of diabetes. GV, defined as percentage coefficient of variation (%CV), and other glycaemic indices were obtained using CGM (FreeStyle Libre, Abbott, Australia) from 82 participants across all three cohorts over a 14-day period. Comparison of baseline characteristics and GV were performed across all groups. Correlation of GV with C-peptide values, and whether pancreatic supplementation had an effect on GV were also assessed in the type 3c diabetes mellitus cohort. RESULTS: GV of type 3c diabetes mellitus participants was within the recommended target of less than %CV 36% (p = 0.004). Type 3c diabetes mellitus participants had the lowest GV among the three groups (p = 0.001). There was a trend for lower C-peptide levels to be associated with higher GV in type 3c diabetes mellitus participants (p = 0.22). Pancreatic enzyme supplementation in type 3c diabetes mellitus participants did not have an effect on GV (p = 0.664). CONCLUSIONS: Although type 3c diabetes mellitus participants were the least variable, they had the highest mean glucose levels and estimated HbA1c , which suggests that the concept of 'brittle' diabetes in type 3c diabetes mellitus is not supported by the results of CGM in this study and may be leading to poorer glycaemic control.

The relationship between admission glucose and lactate with critical illness amongst adult patients presenting to the emergency department.

AIM: Our aim was to determine the relationship between glucose and lactate amongst adult patients admitted to hospital via the emergency department. METHOD: We performed a cross-sectional observational study of 2541 patients admitted via the emergency department who had an admission glucose and lactate measurement available. RESULTS: 23% of the whole cohort had a diagnosis of diabetes. Glucose and lactate were predictors of the primary outcome of critical illness defined as composite of intensive care unit (ICU) admission or in-hospital death. In the multivariable analysis, lactate but not glucose remained an independent predictor of ICU/in hospital death in the group without diabetes. In the diabetes group, both glucose and lactate remained independent predictors of ICU admission/ in-hospital death. CONCLUSIONS: Hyperglycaemia and hyperlactataemia are part of the metabolic response to critical illness. Lactate and a diagnosis of diabetes modify the relationship between glycaemia and critical illness.

Diabetes-related outcomes after pancreatic surgery.

BACKGROUND: The development of pancreatogenic diabetes mellitus (PDM) is a common complication post-pancreatectomy; however, its prevalence has not been described in Australia. We aimed to describe the glycaemic status pre- and post-pancreatectomy, compare patients' clinical characteristics, group according to pre- and post-pancreatectomy diabetes mellitus (DM) status and identify predictors of post-operative PDM. METHODS: We retrospectively reviewed the medical records of patients admitted for pancreatic resection at a single institution from 2011 to 2017. Post-operative DM status was determined at the time of discharge or at 30 days post-operation. Longer term DM onset was as documented in medical record subsequent to admission for pancreatic surgery. RESULTS: A total of 137 cases were analysed; 13.3% and 24.8% of patients developed post-operative PDM within 30 days and at median of 1 year (range 1-4 years) follow-up, respectively. All patients with pre-existing DM continued to have DM post-operatively. Patients with pre-existing DM were older (P = 0.004) and had a family history of DM (P = 0.020); 8.3% of patients who had undergone pancreaticoduodenectomy versus 17.1% of patients who had undergone distal pancreatectomy developed PDM (P = 0.318). A lower estimated glomerular filtration rate (P = 0.033) was significantly associated with post-operative PDM development. No independent predictors for post-operative PDM were identified. CONCLUSIONS: The new development of DM within 30 days post-pancreatectomy occurs in approximately one in seven persons. No patients with pre-existing DM demonstrated a remission of DM post-pancreatectomy. These findings suggest that all patients should be screened for DM pre-operatively and followed up post-operatively, particularly those with pre-existing impaired renal function.

Routine glucose assessment in the emergency department for detecting unrecognised diabetes: a cluster randomised trial.

OBJECTIVE: To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow-up plans. DESIGN, SETTING: Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 - 31 December 2012; outcomes follow-up to 31 March 2016. PARTICIPANTS: Patients aged 18 years or more admitted to hospital from EDs. INTERVENTION: Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA1c ) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more. MAIN OUTCOME MEASURE: New diagnoses of diabetes and documented follow-up plans for patients with admission blood glucose levels of 14 mmol/L or more. RESULTS: Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow-up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26%; adjusted odds ratio [aOR], 0.83; 95% CI 0.42-1.7; P = 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31%; control, 86/278, 31%; aOR, 1.51; 95% CI, 0.83-2.80; P = 0.18). 30-day re-admission (31% v 22%; aOR, 1.34; 95% CI, 0.86-2.09; P = 0.21) and post-hospital mortality rates (24% v 22%; aOR, 1.07; 95% CI, 0.74-1.55; P = 0.72) were also similar for patients in intervention and control hospitals. CONCLUSION: Glucose and HbA1c screening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.

The Significance of an Increased Beta-Hydroxybutyrate at Presentation to the Emergency Department in Patients with Diabetes in the Absence of a Hyperglycemic Emergency.

The significance of hyperketonemia in adults with diabetes presenting to the emergency department with acute illness, not due to a diabetic hyperglycemic emergency, has not been well characterized. Adult patients with diabetes presenting to the emergency department who had venous blood gas and beta-hydroxybutyrate levels measured whilst in the emergency department were retrospectively evaluated for the relationship between BHB and clinical outcomes. Over 6 months, 404 patients with diabetes had at least one beta-hydroxybutyrate level measured in the emergency department. There were 23 admissions for diabetic ketoacidosis (DKA) or hyperosmolar state. Of the remainder, 58 patients had a beta-hydroxybutyrate ≥ 1 mmol/L; this group had a higher glucose at presentation (19.0 (8.8) versus 10.4 (9.9) mmol/L), higher HbA1c (8.8 (5.4) versus 8.0 (3.3)%), lower bicarbonate (22.6 (6.2) versus 24.8 (4.7) mmol/L), and higher anion gap (14.8 (6.1) versus 12.6 (4.2)) than had those with BHB < 1 mmol/L. There was no association between the presence of ketosis and the length of stay (4.2 (7.3) versus (3.0) (7.2) days). Acute illness in those with diabetes associated with ketosis in the absence of DKA is associated with worse glycaemic control than in those without ketosis. Ketosis may represent an intermediate state of metabolic dysregulation rather than being associated with a more severe acute illness, as suggested by no relationship between BHB and length of stay.

A high ankle-brachial index is associated with obesity and low serum 25-hydroxyvitamin D in patients with diabetes.

Peripheral artery disease (PAD), when present with diabetes, is associated with significant morbidity and mortality. The spectrum of PAD in diabetes includes atherosclerosis with stenotic disease; and diffuse medial calcification with non-compliant arteries, as reflected by high ankle brachial index. The clinical characteristics of a high ABI are less well characterized than that of low ABI. The aim of this study was to determine the unique clinical phenotype of patients with diabetes who have high ankle brachial index (ABI) reading. We performed a cross sectional observational study including 360 patients. Subjects were grouped according to normal (≥ 0.8 ≤ 1.3), low (<0.8) or high ABI (>1.3) result. Subjects with high ABI were characterised by higher BMI, higher waist/height ratio (WHtR), and lower serum lower vitamin D. Although reduced renal function and neuropathy was present more frequently in those with high ABI, this was also the case in those with low ABI. Similarly to those with low ABI result, a high ABI result was associated with increased risk of diabetic foot complications including amputation. When adjusted for known risk factors for PAD, higher WHtR and lower vitamin D were significant predictors of high ABI. These results suggest an association between increased WHtR and low vitamin D with high ABI; whether there is a causal relationship requires further exploration.

The Effect of Different Glycaemic States on Renal Transplant Outcomes.

Background. Optimal glycaemic targets following transplantation are unknown. Understanding the impact of DM and posttransplant diabetes mellitus (PTDM) may improve patient and graft survival in transplant recipients. Aim. To determine the perioperative and one-year outcomes after renal transplantation and whether these outcomes are affected by preexisting DM, PTDM, or glycaemia during transplant admission. Method. Adult recipients of renal transplants from a single centre over 5.5 years were retrospectively reviewed. Measured outcomes during transplant admission included glycaemia and complications (infective complications, acute rejection, and return to dialysis) and, at 12 months, glycaemic control and complications (cardiovascular complication, graft failure). Results. Of 148 patients analysed, 29 (19.6%) had DM and 27 (18.2%) developed PTDM. Following transplantation, glucose levels were higher in patients with DM and PTDM. DM patients had a longer hospital stay, had more infections, and were more likely return to dialysis. PTDM patients had increased rates of acute rejection and return to dialysis. At 1 year after transplant, there were more cardiovascular complications in DM patients compared to those without DM. Conclusions. Compared to patients without DM, patients with DM or PTDM are more likely to suffer from complications perioperatively and at 12 months. Perioperative glycaemia is associated with graft function and may be a modifiable risk.

Urine albumin-creatinine ratio in women with gestational diabetes: its link with glycaemic status.

BACKGROUND: Micro-albuminuria has been established as a marker for micro-vascular disease. Spot urine albumin-to-creatinine ratio (UACR), even in the high normal range, predicts future cardiovascular events. The value of UACR in women with gestational diabetes mellitus (GDM) during pregnancy is uncertain. AIM: The objectives of this study were to assess the associations between UACR (performed at the time of GDM diagnosis) and various maternal parameters and to evaluate its correlation with pregnancy outcomes. MATERIALS AND METHODS: We conducted a retrospective review of women with GDM who attended antenatal clinics at a single centre between March 2010 and September 2013. RESULTS: Among 1015 women included in this study, high UACR levels were associated with advancing maternal age, maternal obesity, gestational hypertension, elevated glycosylated haemoglobin (HbA1c) and high fasting glucose level. After adjustments for various maternal factors, only advancing age, HbA1c and fasting glucose level were associated with UACR. In terms of pregnancy outcomes, elevated UACR was not associated with adverse events, but was a predictor for pre-eclampsia. CONCLUSIONS: The finding that UACR was associated with glycaemic status in women with GDM suggests early micro-vascular disease may be present in women who had greater degree of hyperglycaemia. This raises the question of whether women with GDM and elevated UACR may be at higher risk of developing cardiovascular disease in the future. Long-term follow-up of this subgroup of women would be worthwhile.

Acute renal failure and metformin-associated lactic acidosis following colonoscopy.

Two patients with type 2 DM developed acute kidney injury and lactic acidosis following colonoscopy despite withholding metformin. We recommend that DM patients on metformin also withhold ACEI, ARB until their dehydration is reversed after colonoscopy. This should reduce the risk of acute renal failure (ARF) and of lactic acidosis.

Triggers to offering bariatric surgery in the management of type 2 diabetes.

It is unclear how current guidelines suggesting bariatric surgery as a therapeutic option for management of obesity complicated by type 2 diabetes mellitus are utilised in clinical practice. Of 609 patients with T2DM assessed in this study, 147 had a BMI ≥ 35 kg/m2; and of these 147, patients where bariatric surgery had been discussed as compared to those where it had not been discussed, had a higher BMI (44.4 ± 6.8 kg/m2 versus 40.3 ± 5.2 kg/m2, p < 0.005). Diabetes related factors did not differ between the two groups.

Assessing the influences on therapeutic intensification in type 2 diabetes mellitus according to career stage.

AIM: This study was designed to document the factors influencing therapeutic decisions in the management of diabetes in relation to stage of medical career. METHODS: An anonymous survey was distributed among medical students, resident medical officers (RMOs) and general practitioners (GPs) presenting a hypothetical case of a 58 year old patient with sub-optimally controlled diabetes on metfomin and gliclazide. Participants were then asked for their next step in management and about factors that would influence their decision-making. RESULTS: GPs (n=72) were most likely to add pioglitazone (33.3%). RMOs (n=42) were more likely to add insulin (47.6%, p<0.01 vs. GPs). Medical students (n=40) were more likely to review diet and observe (42.5%, p<0.01 vs. GPs). Significant differences were observed between the 3 groups in what influenced their choice of therapy. GPs were most likely to take into account patient related factors such as patient's motivation to improve glycaemic control. CONCLUSION: GPs were less likely to initiate insulin therapy, and our results suggest that this may be due to their greater awareness of patient related barriers to commencing insulin. These results justify support for continuing medical education of GPs that focuses on evidence based guidelines.

Effect of comorbid diabetes on length of stay and risk of death in patients admitted with acute exacerbations of COPD.

BACKGROUND AND OBJECTIVE: Hyperglycaemia during hospital admission is associated with poor outcomes in patients admitted with acute myocardial infarction, stroke and pneumonia. Less evidence exists for effect of diabetes mellitus (DM) on those admitted with an acute exacerbation of COPD (AECOPD). We proposed that comorbidity with DM is associated with an increased length of stay in patients admitted with AECOPD. METHODS: Records of patients admitted with AECOPD during 2007 were reviewed. Data on the presence of diagnosed DM, length of stay and markers of disease severity and other comorbidities were collected. Analysis was performed using generalized estimating equations to adjust for correlation between multiple admissions in some individuals. Log-transformed length of stay and death were the dependent variables. RESULTS: There were 246 admissions in 172 subjects. Diabetes was a comorbid condition in 22% of admissions for AECOPD. There was a trend for increased length of stay and deaths in those with diabetes (geometric mean 7.8 days and 8% mortality respectively) compared with those without diabetes (6.5 days and 4%). However, after adjustment for covariates, the differences were not statistically significant. CONCLUSIONS: Taken together with a previous study that revealed a similar trend, our study suggests that comorbid DM prolongs length of stay and increases risk of death in patients with AECOPD. Further studies are now required to elucidate the reasons for these poorer outcomes, in particular whether premorbid glycaemic control or inpatient control is responsible, as these are potentially modifiable factors.