Modifiable factors to prevent severe hypoglycaemic and diabetic ketoacidosis presentations in people with type 1 diabetes.

AIMS: In tackling rising diabetes-related emergencies, the need to understand and address emergency service usage by people with type 1 diabetes is vital. This review aimed to quantify current trends in presentations for type 1 diabetes-related emergencies and identify public health strategies that reduce the frequency of diabetes-related emergencies and improve glycaemic management. METHODS: Medline (OVID), Cochrane and CINAHL were searched for studies published between 2000 and 2023, focusing on people with type 1 diabetes, severe hypoglycaemia and/or diabetic ketoacidosis, and ambulance and/or emergency department usage. There were 1313 papers identified, with 37 publications meeting review criteria. RESULTS: The incidence of type 1 diabetes-related emergencies varied from 2.4 to 14.6% over one year for hypoglycaemic episodes, and between 0.07 and 11.8 events per 100 person-years for hyperglycaemic episodes. Notably, our findings revealed that ongoing diabetes education and the integration of diabetes technology, such as continuous glucose monitoring and insulin pump therapy, significantly reduced the incidence of these emergencies. However, socio-economic disparities posed barriers to accessing these technologies, subsequently shifting the cost to emergency healthcare and highlighting the need for governments to consider subsidising these technologies as part of preventative measures. CONCLUSIONS: Improving access to continuous glucose monitoring and insulin pump therapy, in combination with ongoing diabetes education focusing on symptom recognition and early management, will reduce the incidence of diabetes-related emergencies. Concurrent research assessing emergency healthcare usage patterns during the implementation of such measures is essential to ensure these are cost-effective.

Health-related quality of life assessment in health economic analyses involving type 2 diabetes.

AIM: Incorporating health-related quality of life (HRQoL) measures into health economic analyses can help to provide evidence to inform decisions about how to improve patient outcomes in the most cost-effective manner. The aim of this narrative review was to assess which HRQoL instruments have been used in economic evaluations of type 2 diabetes management including in Indigenous communities. METHOD: MEDLINE (Ovid), Embase (Ovid) and Cochrane were searched from inception to June 2022. Studies included patients with type 2 diabetes; economic evaluations, derived scores from direct questioning of individuals; and were in English. Records were assessed for bias using the JBI critical appraisal tools. RESULTS: A total of 3737 records were identified, with 22 publications meeting the criteria for inclusion. Across those 22 articles, nine HRQoL instruments had been utilised. Generic tools were most frequently used to measure HRQoL, including EQ-5D (-3 L and -5 L) (n = 10, 38%); SF-12 (n = 5, 19%); and SF-36 (n = 4, 15%). Two tools addressing the specific stressors faced by people with type 2 diabetes were utilised: Problem Areas In Diabetes tool (n = 1, 4%) and Diabetes Distress Scale (n = 1, 4%). Two publications reported whether the study population included Indigenous peoples. CONCLUSION: A wide range of HRQoL instruments are used in economic evaluations of type 2 diabetes management, with the most frequent being varying forms of the EQ-5D. Few economic evaluations noted whether Indigenous peoples were featured in the study population. More research into HRQoL in people living with type 2 diabetes is urgently needed to improve evidence on effectiveness and cost-effectiveness of interventions.

Potential kidney protective effects of glucagon-like peptide-1 receptor agonists.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes (T2DM) with chronic kidney disease (CKD). This class of medication has demonstrated promising results in reducing albuminuria, preserving estimated glomerular filtration rate (eGFR), and mitigating cardiovascular (CV) risk, making them potential therapeutic options for individuals with CKD. The kidney protective effects of GLP-1RAs extend beyond glycaemic control, and are thought to be attributed to their anti-inflammatory, antioxidant, and natriuretic properties. Despite these promising findings, the use of GLP-RAs has yet to be definitively shown to slow progression to chronic kidney failure, or reduce CV and kidney related death in people with T2DM and CKD. The Research Study to See How Semaglutide (a once weekly subcutaneous administered GLP-1RA) Works Compared to Placebo in People with Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) was recently stopped because of efficacy. The primary end point for the FLOW trial consists of a composite endpoint of (i) onset of chronic kidney failure; (ii) death from kidney failure; (iii) cardiovascular death; and (iv) onset of a persistent ≥50% reduction in eGFR from baseline. It has also been reported by the sponsors of the trial that the primary end point of the trial was reduced by 24% with both CKD and CV outcomes contributing to risk reduction. In anticipation of the results of the FLOW trial being published, we review the current evidence surrounding kidney outcomes and proposed kidney protective pathways associated with GLP-1RA use.

The impact of botanical fermented foods on metabolic syndrome and type 2 diabetes: a systematic review of randomised controlled trials.

Our systematic review assessed the impact of botanical fermented food (BFF) consumption on glucose, lipid, anthropometric, inflammatory and gut microbiota parameters, in adults with metabolic syndrome (MetS), MetS components or type 2 diabetes mellitus (T2DM). Embase, MEDLINE, Cochrane CENTRAL and Google Scholar were searched with no language limits, from inception to 31 August 2022, for eligible randomised controlled trials (RCTs). Two independent reviewers screened 6873 abstracts and extracted relevant data. Risk of bias (ROB) was assessed using the Cochrane Collaboration's ROB2 tool. The final review included twenty-six RCTs, with thirty-one reports published between 2001 and 2022. Significant (p < 0·05) within-group and between-group changes in cardiometabolic outcome means were reported in twenty-three and nineteen studies, respectively. Gut microbiota composition was assessed in four studies, with two finding significant between-group differences. No significant difference between groups of any measured outcomes was observed in five studies. There were fourteen studies at low ROB; ten were of some concern; and two were at high ROB. In 73% of included studies, BFF consumption by participants with obesity, MetS or T2DM led to significant between-group improvements in discrete cardiometabolic outcomes, including fasting blood glucose, lipid profile, blood pressure, waist circumference, body fat percentage and C-reactive protein. BFF consumption increased the abundance of beneficial gut bacteria, such as Bifidobacterium and LAB, whilst reducing potential pathogens such as Bacteroides. To determine the clinical significance of BFFs as therapeutic dietary adjuncts, their safety, tolerability and affordability must be balanced with the limited power and magnitude of these preliminary findings.

Improved metabolic parameters of people with diabetes attending an Aboriginal health service in regional Victoria.

BACKGROUND: Aboriginal and Torres Strait Islander people have higher rates of diabetes and its complications than non-Aboriginal people. Rumbalara Aboriginal Co-operative is the major primary healthcare provider for Aboriginal people in the Greater Shepparton region. AIMS: To evaluate the baseline metabolic parameters and presence of diabetes complications in people with type 2 diabetes attending Rumbalara Aboriginal Co-operative in 2017 and compare it with other Aboriginal and Torres Strait Islander studies and Australian specialist diabetes services. METHODS: Clinical and biochemical characteristics, including diabetes type, age, weight, body mass index (BMI), blood pressure, micro- and macrovascular complications, glycosylated haemoglobin (HbA1c), haemoglobin, renal function, lipid profile, urine albumin:creatinine ratio, diabetes medications, renin angiotensin system inhibition therapies, HMG-CoA reductase inhibitors and antiplatelet agents, were determined. RESULTS: One hundred and twenty-six individuals had diabetes, 121 had type 2 diabetes. One hundred and thirteen identified as Aboriginal and/or Torres Strait Islander. Median age was 57.5 (48-68) years, median HbA1c was 7.8% (6.8-9.6) and median BMI was 33.4 kg/m2 (29-42.3). Compared with other Australian Aboriginal and Torres Strait Islander populations, this population was older and had more obesity, but with better glycaemia management. Compared with specialist diabetes services, this population was of similar age, with greater BMI but comparable HbA1c. CONCLUSIONS: Aboriginal people living with type 2 diabetes attending this regional Aboriginal health service have comparable glycaemic management to specialist diabetes services in Australia, managed largely by primary care physicians with limited access to specialist care for the past 5 years.

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.

Body mass index is inversely associated with capillary ketones at the time of colonoscopy: Implications for SGLT2i use.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been associated with diabetic ketoacidosis at the time of colonoscopy. This study aimed to identify factors associated with ketone concentrations in SGLT2i-treated type 2 diabetes compared with non-SGLT2i-treated diabetes, and those with impaired fasting glycaemia (IFG) and normoglycaemia. DESIGN: Cross-sectional, multicentre, observational study June-December 2020 in four Australian tertiary hospitals. PARTICIPANTS: Capillary glucose and ketones were measured in people undergoing colonoscopy: 37 SGLT2i-treated and 105 non-SGLT2i-treated type 2 diabetes, 65 IFG and 151 normoglycaemia. MEASUREMENTS: Body mass index (BMI), age, glucose, fasting duration and where relevant, HbA1c and time since last SGLT2i dose. RESULTS: In SGLT2i-treated diabetes, BMI (ρ = -0.43 [95% confidence interval: -0.67, -0.11]) and duration since last SGLT2i dose (ρ = -0.33 [-0.60, 0.00]) correlated negatively with increasing ketones, but there was no correlation with fasting duration. In non-SGLT2i-treated diabetes, BMI correlated negatively (ρ = -0.24 [-0.42, -0.05]) and fasting duration positively (ρ = 0.26 [0.07, 0.43]) with ketones. In IFG participants, only fasting duration correlated with ketones (ρ = 0.28 [0.03, 0.49]). In normoglycaemic participants, there were negative correlations with BMI (ρ = -0.20 [-0.35, -0.04]) and fasting glucose (ρ = -0.31 [-0.45, -0.15]) and positive correlations with fasting duration (ρ = 0.20 [0.04, 0.35]) and age (ρ = 0.19 [0.03, 0.34]). Multiple regression analysis of the entire cohort showed BMI, age and fasting glucose remained independently associated with ketones, but in SGLT2i-treated participants only BMI remained independently associated. CONCLUSIONS: In SGLT2i-treated diabetes, lower BMI was a novel risk factor for higher ketones precolonoscopy. Pending larger confirmatory studies, extra vigilance for ketoacidosis is warranted in these people.

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.

An overview of COVID-19 in people with diabetes: Pathophysiology and considerations in the inpatient setting.

INTRODUCTION: The coronavirus disease (COVID-19) pandemic has continued to have a devastating impact on health worldwide. There has been a rapid evolution of evidence, establishing an increased risk of morbidity and mortality associated with diabetes and concurrent COVID-19. The objective of this review is to explore the current evidence for inpatient assessment and management of diabetes during the COVID-19 pandemic and highlight areas requiring further exploration. METHODS: A literature search of databases was conducted to November 2020 using variations on keywords SARS-CoV-2, COVID-19, SARS, MERS and diabetes. Information relating to the impact of diabetes on severity of COVID-19 infection, the impact of COVID-19 infection on diabetes management and diabetes-related complications was integrated to create a narrative review. DISCUSSION: People with diabetes and COVID-19 are at an increased risk of morbidity and mortality. It is important that people with both known and previously unrecognised diabetes and COVID-19 be promptly identified and assessed during acute illness, with close monitoring for clinical deterioration or complications. People with diabetes may require titration or alteration of their glycaemic management due to the potential for worse outcomes with hyperglycaemia and COVID-19 infection. Comprehensive discharge planning is vital to optimise ongoing glycaemic management. CONCLUSION: Further understanding of the risk of adverse outcomes and optimisation of glycaemic management for people with diabetes during COVID-19 is required to improve outcomes. Increased glucose and ketone monitoring, substitution of insulin for some oral anti-hyperglycaemic medications and careful monitoring for complications of diabetes such as diabetic ketoacidosis should be considered.

DNA methylation profiling identifies epigenetic differences between early versus late stages of diabetic chronic kidney disease.

BACKGROUND: We investigated a cross-sectional epigenome-wide association study of patients with early and late diabetes-associated chronic kidney disease (CKD) to identify possible epigenetic differences between the two groups as well as changes in methylation across all stages of diabetic CKD. We also evaluated the potential of using a panel of identified 5'-C-phosphate-G-3' (CpG) sites from this cohort to predict the progression of diabetic CKD. METHODS: This cross-sectional study recruited 119 adults. DNA was extracted from blood using the Qiagen QIAampDNA Mini Spin Kit. Genome-wide methylation analysis was performed using Illumina Infinium MethylationEPIC BeadChips (HM850K). Intensity data files were processed and analysed using the minfi and MissMethyl packages for R. We examined the degree of methylation of CpG sites in early versus late diabetic CKD patients for CpG sites with an unadjusted P-value <0.01 and an absolute change in methylation of 5% (n = 239 CpG sites). RESULTS: Hierarchical clustering of the 239 CpG sites largely separated the two groups. A heat map for all 239 CpG sites demonstrated distinct methylation patterns in the early versus late groups, with CpG sites showing evidence of progressive change. Based on our differentially methylated region (DMR) analysis of the 239 CpG sites, we highlighted two DMRs, namely the cysteine-rich secretory protein 2 (CRISP2) and piwi-like RNA-mediated gene silencing 1 (PIWIL1) genes. The best predictability for the two groups involved a receiver operating characteristics curve of eight CpG sites alone and achieved an area under the curve of 0.976. CONCLUSIONS: We have identified distinct DNA methylation patterns between early and late diabetic CKD patients as well as demonstrated novel findings of potential progressive methylation changes across all stages (1-5) of diabetic CKD at specific CpG sites. We have also identified associated genes CRISP2 and PIWIL1, which may have the potential to act as stage-specific diabetes-associated CKD markers, and showed that the use of a panel of eight identified CpG sites alone helps to increase the predictability for the two groups.

Geometric Distortion Correction of Renal Diffusion Tensor Imaging Using the Reversed Gradient Method.

ABSTRACT: Renal echo planar diffusion tensor imaging (DTI) has clinical potential but suffers from geometric distortion. We evaluated feasibility of reversed gradient distortion correction in 10 diabetic patients and 6 volunteers. Renal area, apparent diffusion coefficient, fractional anisotropy, and tensor eigenvalues were measured on uncorrected and distortion-corrected DTI. Corrected DTI correlated better than uncorrected DTI (r = 0.904 vs 0.840, P = 0.002) with reference anatomic T2-weighted imaging, with no significant difference in DTI metrics.

Treatment implications of a delayed diagnosis of maturity-onset diabetes of the young.

Maturity-onset diabetes of the young (MODY) is a rare form of monogeneic diabetes that classically presents as non-insulin requiring diabetes with evidence of autosomal dominant inheritance in individuals who are typically young and lean. However, these criteria do not capture all cases and can also overlap with other types of diabetes. The hepatocyte nuclear factor-1 alpha (HNF1A) mutation is a common cause of MODY and is highly sensitive to sulphonylureas, which should be first-line therapy. Our case represents the diagnostic challenges of HNF1A MODY and the implications of a delayed diagnosis, which can lead to reduced success of sulphonylurea treatment.

Feasibility of once weekly exenatide-LAR and enhanced diabetes care in Indigenous Australians with type 2 diabetes (Long-acting-Once-Weekly-Exenatide laR-SUGAR, 'Lower SUGAR' study).

BACKGROUND: Diabetes is 3-4 times more prevalent in Indigenous Australians with blood glucose levels often above target range. Once weekly formulations of exenatide(exenatide-LAR) have demonstrated significantly greater improvements in glycaemic management with no increased risk of hypoglycaemia and with reductions in bodyweight but have not been studied in Indigenous Australians. AIMS: To assess the feasibility and metabolic effects of once weekly supervised injection of exenatide-LAR in addition to standard care in Indigenous Australians with type 2 diabetes. METHODS: Two communities in Central Australia with longstanding specialist clinical outreach services were allocated by random coin toss to receive once-weekly exenatide-LAR injection with weekly nurse review and adjustment of medication for 20 weeks (community with exenatide-LAR) or to weekly nurse review in addition to standard care over 20 weeks (community without exenatide-LAR). The primary outcome was the feasibility of an intensive diabetes management model of care with and without weekly supervised exenatide-LAR. Secondary outcomes included change in HbA1c. RESULTS: Thirteen participants from the community with exenatide-LAR and nine participants from the community without exenatide-LAR were analysed. Eighty-five percent of individuals in the community with exenatide-LAR and 67% in the community without exenatide-LAR attended more than half of clinic visits. Median difference in the change in HbA1c from baseline to final visit, adjusted for baseline HbA1c, between the community with exenatide-LAR and the community without exenatide-LAR was -3.1%, 95% CI (-5.80%, -0.38%; P = 0.03). CONCLUSIONS: Weekly exenatide-LAR combined with weekly nurse review demonstrated greater improvements in HbA1c, highlighting its potential for use in remote communities.

Risk factors for pregnancy outcomes in Type 1 and Type 2 diabetes.

BACKGROUND: Understanding the risk factors and pregnancy outcomes in women affected by Type 1 and Type 2 diabetes is important for pre-pregnancy counselling. AIM: To explore differences in pregnancy outcomes between women with Type 1 and Type 2 diabetes, and healthy controls, and to examine the relationships between potential adverse risk factors and pregnancy outcomes in this cohort of women. METHODS: This is a 10-year retrospective study of women with Type 1 diabetes (n = 92), Type 2 diabetes (n = 106) and healthy women without diabetes (controls) (n = 119) from a tertiary obstetric centre. Clinical and biochemical characteristics of women with Type 1 and Type 2 diabetes were determined and related to major obstetric outcomes using univariate analysis. RESULTS: Women with pre-existing diabetes had higher adverse pregnancy outcomes (preeclampsia, emergency caesarean section, preterm birth <32 and 37 weeks, large for gestational age, neonatal jaundice, Apgar score < 7 at 5 min, neonatal intensive care admission and neonatal hypoglycaemia) compared to controls. A higher birth weight gestational centile (97.4% vs 72.4%, P = 0.001) and large for gestational age rate (63.4% vs 35.8%, P = 0.001) were observed in Type 1 diabetes compared to Type 2 diabetes. There were no differences in other outcomes between women with Type 1 and 2 diabetes. CONCLUSION: In this exploratory study, risk factors for maternal adverse outcomes differ between Type 1 and Type 2 diabetes. Maternal and foetal adverse outcomes were higher in pregnancies affected by diabetes compared to healthy women but occurred with similar frequency in women with Type 1 and Type 2 diabetes.

Lipoprotein apheresis and PCSK9 inhibitors for severe familial hypercholesterolaemia: Experience from Australia and New Zealand.

INTRODUCTION: Severe familial hypercholesterolaemia (FH) causes premature disability and death due to atherosclerotic cardiovascular disease and is refractory to standard lipid-lowering therapies. Lipoprotein apheresis (LA) has long been a standard of care for patients with severe FH, but is invasive, expensive and time-consuming for patients and their caregivers. Newer drug therapies, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the need for LA. MATERIALS AND METHODS: We audited the records of 16 patients (eight homozygous, eight heterozygous) treated with LA in Australia and New Zealand, 14 of whom subsequently commenced PCSK9 inhibitor therapy. LA was performed by cascade filtration in all centres. RESULTS: LDL-cholesterol was acutely lowered by 69 ± 7% in patients with homozygous FH and by 72 ± 9% in those with heterozygous FH, representing time-averaged reductions of 36 ± 12% and 34 ± 5%, respectively. LA was well-tolerated, and patients reported comparable quality of life to population and disease-related norms. After commencement of PCSK9 inhibitors, four of seven patients with homozygous FH had meaningful biochemical responses, with a reduction in the frequency of LA permitted in one patient and complete cessation in another. Four of seven patients with heterozygous FH were able to be managed without LA after commencing PCSK9 inhibitors. CONCLUSION: While PCSK9 inhibitors have reduced the need for LA, some patients with severe FH continue to require LA, and will require it for the foreseeable future. However, emerging therapies, including angiopoetin-like 3 inhibitors, may further reduce the need for LA.

Older People With Type 2 Diabetes-Individualising Management With a Specialised Community Team (OPTIMISE): Perspectives of Participants on Care.

Despite the high prevalence of diabetes in older people, there is limited information on optimal methods to support their diabetes management, including how to incorporate technology. This article reports on the results of semi-structured interviews with 41 adult participants with type 2 diabetes (mean age 74 ± 7 years) on their perspectives of a new model of care (the Older People With Type 2 Diabetes-Individualising Management With a Specialised Community Team [OPTIMISE] program) for older people with type 2 diabetes. The OPTIMISE program involved telemedicine consultations, home visits by a credentialed diabetes educator, and intermittent flash glucose monitoring. Human connection and relationships were key to the positive perspectives expressed by participants in this program that used technology to enhance the care of older people in their homes.

A safety and pharmacodynamics study of temelimab, an antipathogenic human endogenous retrovirus type W envelope monoclonal antibody, in patients with type 1 diabetes.

AIM: To report the first study of temelimab, a monoclonal antibody neutralizing the pathogenic human endogenous retrovirus type W envelope, in patients with type 1 diabetes (T1D). MATERIALS AND METHODS: This double-blind, placebo-controlled, randomized clinical trial recruited adult patients with T1D within 4 years postdiagnosis and remaining C-peptide secretion. Sixty-four patients were randomized (2:1) to monthly temelimab 6 mg/kg or placebo during 24 weeks followed by a 24-week, open-label extension, during which all patients received temelimab. The primary objective was the safety and tolerability of temelimab. The secondary objective was to assess the pharmacodynamics response such as C-peptide levels, insulin use, HbA1c, hypoglycaemia and autoantibodies. RESULTS: Temelimab was well tolerated without any group difference in the frequency or severity of adverse events. Concerning exploratory endpoints, there was no difference in the levels of C-peptide, insulin use or HbA1c between treatment groups at weeks 24 and 48. The frequency of hypoglycaemia events was reduced with temelimab (P = 0.0004) at week 24 and the level of anti-insulin antibodies was lower with temelimab (P < 0.01); the other autoantibodies did not differ between groups. CONCLUSIONS: Temelimab appeared safe in patients with T1D. Pharmacodynamics signals (hypoglycaemia and anti-insulin antibodies) under temelimab were observed. Markers of ß-cell functions were not modified by treatment. These results need to be further explored in younger patients with T1D with earlier disease onset.

Advances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes.

Treatment options for type 2 diabetes have expanded. While metformin remains the first line treatment in most cases, choices for second line treatment now extend beyond sulfonylureas and include the sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors. SGLT2 inhibitors are recommended for people with atherosclerotic cardiovascular disease, heart failure or kidney disease. Diabetic ketoacidosis is an uncommon but important side effect; its occurrence can be minimised with appropriate patient education and management, especially during perioperative periods and times of illness. GLP1 receptor agonists are recommended for people with atherosclerotic cardiovascular disease. Gastrointestinal side effects are common but are less prominent with the longer acting agents and can be minimised with slow titration of the shorter acting agents. DPP4 inhibitors are generally well tolerated, but alogliptin and saxagliptin should be used with caution in people with risk factors for heart failure. To optimise the management of type 2 diabetes, clinicians need to be aware of the pharmacological characteristics of each class of blood glucose-lowering medications and of the effect on cardiovascular health and renal function, balanced by potential adverse effects. Medications that have cardiovascular or renal benefits should be prescribed for patients with these comorbidities, and this is reflected in recent international guidelines.

Metformin: time to review its role and safety in chronic kidney disease.

■Metformin is recommended as first-line therapy for type 2 diabetes because of its safety, low cost and potential cardiovascular benefits. ■The use of metformin was previously restricted in people with chronic kidney disease (CKD) - a condition that commonly coexists with diabetes - due to concerns over drug accumulation and metformin-associated lactic acidosis. ■There are limited data from observational studies and small randomised controlled trials to suggest that metformin, independent of its antihyperglycaemic effects, may be associated with lower risk of myocardial infarction, stroke and all-cause mortality in people with type 2 diabetes and CKD. ■Research into the risk of metformin-associated lactic acidosis in CKD has previously been limited and conflicting, resulting in significant variation across international guidelines on the safe prescribing and dosing of metformin at different stages of renal impairment. ■Present-day large scale cohort studies now provide supporting evidence for the safe use of metformin in mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73m2 ). However, prescribing metformin in people with severe renal impairment (eGFR < 30 mL/min/1.73m2 ) remains a controversial issue. Due to observed increased risk of lactic acidosis and all-cause mortality in people with type 2 diabetes and severe renal impairment, it is generally recommended that metformin is discontinued if renal function falls below this level or during acute renal deterioration.

Hospital-acquired complications in intensive care unit patients with diabetes: A before-and-after study of a conventional versus liberal glucose control protocol.

BACKGROUND: Critically ill patients with diabetes mellitus (DM) are at increased risk of in-hospital complications and the optimal glycemic target for such patients remains unclear. A more liberal approach to glucose control has recently been suggested for patients with DM, but uncertainty remains regarding its impact on complications. METHODS: We aimed to test the hypothesis that complications would be more common with a liberal glycemic target in ICU patients with DM. Thus, we compared hospital-acquired complications in the first 400 critically ill patients with DM included in a sequential before-and-after trial of liberal (glucose target: 10-14 mmol/L) vs conventional (glucose target: 6-10 mmol/L) glucose control. RESULTS: Of the 400 patients studied, 165 (82.5%) patients in the liberal and 177 (88.5%) in the conventional-control group were coded for at least one hospital-acquired complication (P = 0.09). When comparing clinically relevant complications diagnosed between ICU admission and hospital discharge, we found no difference in the odds for infectious (adjusted odds ratio [aOR] for liberal-control: 1.15 [95% CI: 0.68-1.96], P = 0.60), cardiovascular (aOR 1.40 [95% CI: 0.63-3.12], P = 0.41) or neurological complications (aOR: 1.07 [95% CI: 0.61-1.86], P = 0.81), acute kidney injury (aOR 0.83 [95% CI: 0.43-1.58], P = 0.56) or hospital mortality (aOR: 1.09 [95% CI: 0.59-2.02], P = 0.77) between the liberal and the conventional-control group. CONCLUSION: In this prospective before-and-after study, liberal glucose control was not associated with an increased risk of hospital-acquired infectious, cardiovascular, renal or neurological complications in critically ill patients with diabetes.