The Performance of Freestyle Libre Pro Flash Continuous Glucose Monitoring in Hospitalized Patients Treated with an Intravenous Insulin Infusion for Acute Prednisolone-Induced Hyperglycemia.

Few studies have evaluated the performance of flash glucose monitoring in hospitalized patients requiring intravenous insulin therapy. In this prospective study, an intravenous insulin infusion was adjusted hourly using flash glucose monitoring in hospitalized adults with prednisolone-associated hyperglycemia. The difference in paired point of care (POC) and flash glucose measurements and risk of severe hyper- or hypoglycemia (assessed by Clarke error grid analysis) were assessed. Glucose concentration measured by flash glucose monitoring was lower than POC glucose (mean difference 1.5 mmol/L [27 mg/dL], p < 0.001); however, mean POC glucose was within the target range (9.1 ± 4.1 mmol/L [164 ± 72 mg/dL]) and 97.8% of glucose measurements were within Zone A and B on error grid analysis. Flash glucose monitoring could be used in combination with POC glucose monitoring to minimize the frequency of finger prick blood glucose levels in hospitalized patients prescribed an intravenous insulin infusion.

Sodium-Glucose Cotransporter 2 Inhibitors in South Australia: The Magic Before the Fame.

BACKGROUND: Recent clinical trials have demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2i), which were previously only indicated in treatment of type 2 diabetes mellitus (T2DM), can markedly reduce heart failure hospitalisation (HFH), with less striking potential reductions in acute coronary syndromes and cardiac arrhythmias. To evaluate the impact of SGLT2i on cardiovascular outcomes in real-world practice, we performed a retrospective cohort analysis on South Australian (SA) data. METHODS: A total of 842 individuals with T2DM receiving SGLT2i were identified from SA public hospitals between 2011 and 2019. Episodes of care were temporally matched with those of 3,128 individuals with T2DM not receiving SGLT2i (control). Baseline characteristics were adjusted using inverse probability treatment weighting. The incidence of cardiovascular events at 12 and 24 months was evaluated using coded (International Classification of Diseases, Tenth Revision, Australian Modification [ICD-10-AM]) data. RESULTS: The primary outcome of HFH was lower with SGLT2i use at 12 months (adjusted hazard ratio [HRadj] 0.44; 95% confidence interval [CI] 0.29-0.68; p<0.001) and 24 months. There were also lower hospitalisations due to acute myocardial infarction (HRadj 0.42; 95% CI 0.21-0.85; p=0.015) and atrial or ventricular arrhythmias (HRadj 0.29; 95% CI 0.14-0.59; p=0.001), with no difference observed in hospitalisation due to ischaemic cerebrovascular events. There was no difference in all-cause mortality at 12 months but interestingly a higher rate at 24 months (HRadj 2.08; 95% CI 1.59-2.72; p<0.001). Despite this, similar reductions in cardiovascular outcomes were observed at 24 months. CONCLUSION: Use of SGLT2i in patients with T2DM in SA was associated with reductions in cardiovascular events even before their recent Pharmaceutical Benefits Scheme (PBS) listing for heart failure. Furthermore, this analysis supports that SGLT2i play a role not only in HFH reduction but also in reducing coronary and tachyarrhythmic events. This real-world evidence supports the use of SGLT2i as broadly protective cardiovascular drugs.

Clinical determinants of insulin requirements during treatment of prednisolone-induced hyperglycaemia.

AIMS: The optimal treatment of prednisolone-associated hyperglycaemia is unclear, but guidelines recommend using a body weight-based daily insulin dose. This study evaluated how clinical variables were associated with insulin requirements in hospitalised patients with prednisolone-associated hyperglycaemia. METHODS: In this prospective study, fifty adult inpatients who were taking prednisolone ≥20 mg/day and experienced hyperglycaemia were prescribed a 24-h intravenous insulin infusion. The daily insulin dose required to attain a mean glucose of 8 mmol/L was calculated. The associations between daily insulin dose and clinical variables were assessed. RESULTS: The participants age was 69 ± 10 years, daily prednisolone dose was 34 ± 10 mg, HbA1c was 7.7 ± 2.0 % (61 ± 10 mmol/mol), 77 % had known type 2 diabetes and 30 % were female. In univariate analysis, weight was associated with daily insulin dose (r2 = 0.11, p = 0.024). A multivariate model comprising sex, HbA1c, a prior diagnosis of diabetes, diabetes treatment and weight explained nearly-two thirds of the variability in daily insulin dose (r2 = 0.65, p < 0.001). CONCLUSIONS: In patients with prednisolone-associated hyperglycaemia, calculating insulin doses based on sex, HbA1c, diabetes status and regular diabetes treatment and weight may improve glycaemic control compared to weight-based dosing.

Management of type 2 diabetes in young adults aged 18-30 years: ADS/ADEA/APEG consensus statement.

INTRODUCTION: Type 2 diabetes in young adults (nominally, 18-30 years of age) is a more aggressive condition than that seen in older age, with a greater risk of major morbidity and early mortality. This first Australian consensus statement on the management of type 2 diabetes in young adults considers areas where existing type 2 diabetes guidance, directed mainly towards older adults, may not be appropriate or relevant for the young adult population. Where applicable, recommendations are harmonised with current national guidance for type 2 diabetes in children and adolescents (aged < 18 years). The full statement is available at https://www.diabetessociety.com.au, https://www.adea.com.au and https://www.apeg.org.au. MAIN RECOMMENDATIONS: Advice is provided on important aspects of care including screening, diabetes type, psychological care, lifestyle, glycaemic targets, pharmacological agents, cardiovascular disease risk management, comorbidity assessment, contraception and pregnancy planning, and patient-centred education. Special considerations for Aboriginal and Torres Strait Islander Australians are highlighted separately. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Management recommendations for young adults, which differ from those for adults, include: ▪screening for diabetes in young adults with overweight or obesity and additional risk factors, including in utero exposure to type 2 diabetes or gestational diabetes mellitus; ▪more stringent glucose targets (glycated haemoglobin ≤ 6.5% [≤ 48 mmol/mol]); ▪in the context of obesity or higher cardio-renal risk, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors are preferred second line agents; ▪ß-cell decline is more rapid, so frequent review, early treatment intensification and avoidance of therapeutic inertia are indicated; ▪a blood pressure target of < 130/80 mmHg, as the adult target of ≤ 140/90 mmHg is too high; ▪absolute cardiovascular disease risk calculators are not likely to be accurate in this age group; early statin use should therefore be considered; and ▪a multidisciplinary model of care including an endocrinologist and a certified diabetes educator.

Driving with Type 1 Diabetes: Real-World Evidence to Support Starting Glucose Level and Frequency of Monitoring During Journeys.

There is limited evidence supporting the recommendation that drivers with insulin-treated diabetes need to start journeys with glucose >90 mg/dL. Glucose levels of drivers with type 1 diabetes were monitored for 3 weeks using masked continuous glucose monitoring (CGM). Eighteen drivers (median [IQR] age 40 [35, 51] years; 11 men) undertook 475 trips (duration 15 [13, 21] min). Hypoglycemia did not occur in any trip starting with glucose >90 mg/dL (92%; n = 436). Thirteen drivers recorded at least one trip (total n = 39) starting with glucose <90 mg/dL. Among these, driving glucose was <70 mg/dL in five drivers (38%) during 10 trips (26%). Among five drivers (28%), a ≥ 36 mg/dL drop was observed within 20 min of starting their journey. Journey duration was positively associated with maximum glucose change. These findings support current guidelines to start driving with glucose >90 mg/dL, and to be aware that glucose levels may change significantly within 20 min. A CGM-based, in-vehicle display could provide glucose information and alerts that are compatible with safe driving. Clinical Trial Registration number: ACTRN12617000520336.

Meal-time glycaemia in adults with type 1 diabetes using multiple daily injections vs insulin pump therapy following carbohydrate-counting education and bolus calculator provision.

AIMS: To compare meal-time glycaemia in adults with type 1 diabetes mellitus (T1D) managed with multiple daily injections (MDI) vs. insulin pump therapy (IPT), using self-monitoring blood glucose (SMBG), following diabetes education. METHODS: Adults with T1D received carbohydrate-counting education and a bolus calculator: MDI (Roche Aviva Expert) and IPT (pump bolus calculator). All then wore 3-weeks of masked-CGM (Enlite, Medtronic). Meal-times were assessed by two approaches: 1) Set time-blocks (breakfast 06:00-10:00hrs; lunch 11:00-15:00hrs; dinner 17:00-21:00hrs) and 2) Bolus-calculator carbohydrate entries signalling meal commencement. Post-meal masked-CGM time-in-range (TIR) 3.9-10.0 mmol/L was the primary outcome. RESULTS: MDI(n = 61) and IPT (n = 59) participants were equivalent in age, sex, diabetes duration and HbA1c. Median (IQR) education time provided did not differ (MDI: 1.1 h (0.75, 1.5) vs. IPT: 1.1 h (1.0, 2.0); p = 0.86). Overall, daytime (06:00-24:00hrs), lunch and dinner TIR did not differ for MDI vs. IPT participants but was greater for breakfast with IPT in both analyses with a mean difference of 12.8%, (95 CI 4.8, 20.9); p = 0.002 (time-block analysis). CONCLUSION: After diabetes education, MDI and IPT use were associated with similar day-time glycemia, though IPT users had significantly greater TIR during the breakfast period. With education, meal-time glucose levels are comparable with use of MDI vs. pumps.

Less Nocturnal Hypoglycemia but Equivalent Time in Range Among Adults with Type 1 Diabetes Using Insulin Pumps Versus Multiple Daily Injections.

Background: This prerandomization analysis from the Australian HCL-Adult trial (registration number: ACTRN12617000520336) compared masked continuous glucose monitoring (CGM) metrics among adults using insulin pumps versus multiple daily injections (MDIs), who were all self-monitoring blood glucose (SMBG). Methods: Adults with type 1 diabetes, using an insulin pump or MDIs without real-time CGM (and entering a trial of closed-loop technology), were eligible. MDI users were given an insulin dosage calculator. All participants received diabetes and carbohydrate-counting education, then wore masked CGM sensors for 3 weeks. Ethics Approval: HREC-D 088/16 Results: Adults using MDIs (n = 61) versus pump (n = 59) did not differ by age, sex, diabetes duration, insulin total daily dose, or HbA1c at baseline. After education, median (interquartile range) CGM time in range (TIR) 70-180 mg/dL (3.9-10.0 mmol/L) was 54% (47, 62) for those using MDIs and 56% (48, 66) for those using pump (P = 0.40). All CGM metrics were equivalent for 24 h/day for MDI and pump users. Overnight, those using MDIs (vs. pump) spent more time with glucose <54 mg/dL (<3.0 mmol/L): 1.4% (0.1, 5.1) versus 0.5% (0.0, 2.0), respectively (P = 0.012). They also had more CGM hypoglycemia episodes (121 vs. 54, respectively; incidence rate ratio [95% confidence interval] 2.48 [1.51, 4.06]; P < 0.001). Conclusions: Adults with type 1 diabetes using pumps versus MDIs in conjunction with SMBG experienced less nocturnal hypoglycemia, measured by masked CGM, after equivalent diabetes and dietary education in conjunction with insulin dosage calculator provision to all. However, both groups had equivalent TIR. This observation may reflect advantages afforded by flexibility in basal insulin delivery provided by pumps.

Six Months of Hybrid Closed-Loop Versus Manual Insulin Delivery With Fingerprick Blood Glucose Monitoring in Adults With Type 1 Diabetes: A Randomized, Controlled Trial.

OBJECTIVE: To investigate glycemic and psychosocial outcomes with hybrid closed-loop (HCL) versus user-determined insulin dosing with multiple daily injections (MDI) or insulin pump (i.e., standard therapy for most adults with type 1 diabetes). RESEARCH DESIGN AND METHODS: Adults with type 1 diabetes using MDI or insulin pump without continuous glucose monitoring (CGM) were randomized to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was masked CGM time in range (TIR; 70-180 mg/dL) during the final 3 weeks. RESULTS: Participants were randomized to HCL (n = 61) or control (n = 59). Baseline mean (SD) age was 44.2 (11.7) years, HbA1c was 7.4% (0.9%) (57 [10] mmol/mol), 53% were women, and 51% used MDI. HCL TIR increased from (baseline) 55% (13%) to (26 weeks) 70% (10%) with the control group unchanged: (baseline) 55% (12%) and (26 weeks) 55% (13%) (difference 15% [95% CI 11, 19]; P < 0.0001). For HCL, HbA1c was lower (median [95% CI] difference -0.4% [-0.6, -0.2]; -4 mmol/mol [-7, -2]; P < 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 [95% CI 0.4, 1.9]; P < 0.0048) without a deterioration in diabetes distress, perceived sleep quality, or cognition. Seventeen (9 device-related) versus 13 serious adverse events occurred in the HCL and control groups, respectively. CONCLUSIONS: In adults with type 1 diabetes, 26 weeks of HCL improved TIR, HbA1c, and their sense of satisfaction from managing their diabetes compared with those continuing with user-determined insulin dosing and self-monitoring of blood glucose. For most people living with type 1 diabetes globally, this trial demonstrates that HCL is feasible, acceptable, and advantageous.

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.

Relative Hyperglycemia Is an Independent Determinant of In-Hospital Mortality in Patients With Critical Illness.

OBJECTIVES: To determine whether relative hyperglycemia was associated with in-hospital mortality in critically ill patients independent of other prognostic variables and whether this association is affected by background glycemia. DESIGN: Prospective observational study. SETTING: Mixed medical-surgical ICU in a metropolitan teaching hospital. PATIENTS: From 2,617 admissions to ICU between January 27, 2016, and March 30, 2017, 1,262 consecutive patients who met inclusion and exclusion criteria were studied. INTERVENTIONS: Glycosylated hemoglobin was used to estimate average glucose concentration over the prior 3 months. Glucose concentration on ICU admission was divided by estimated average glucose concentration to calculate the stress hyperglycemia ratio, an index of relative glycemia. Risk of death score was calculated using data submitted to the Australia and New Zealand Intensive Care Society. MEASUREMENTS AND MAIN RESULTS: In this study, there were 186 deaths (14.7%). Admission glucose was significantly associated with mortality in univariate analysis (odds ratio = 1.08 per mmol/L glucose increment; p < 0.001) but not after adjustment for risk of death score (odds ratio = 1.01; p = 0.338). In contrast, stress hyperglycemia ratio was significantly associated with mortality both in univariate analysis (odds ratio = 1.09 per 0.1 stress hyperglycemia ratio increment; p < 0.001) and after adjustment for risk of death score (odds ratio = 1.03; p = 0.014). Unlike admission glucose concentration, stress hyperglycemia ratio was significantly associated with mortality in patients with glycosylated hemoglobin less than 6.5% (odds ratio = 1.08 per 0.1 stress hyperglycemia ratio increment; p < 0.001) and glycosylated hemoglobin greater than or equal to 6.5% (48 mmol/mol) (odds ratio = 1.08 per 0.1 stress hyperglycemia ratio increment; p = 0.005). CONCLUSIONS: Unlike absolute hyperglycemia, relative hyperglycemia, as assessed by the stress hyperglycemia ratio, independently predicts in-hospital mortality in critically ill patients across the glycemic spectrum. Future studies should investigate whether using measures of relative hyperglycemia to determine individualized glycemic treatment targets improves outcomes in ICU.

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol.

INTRODUCTION: Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months' closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes. METHODS AND ANALYSIS: This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users. ETHICS AND DISSEMINATION: The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications. TRIAL REGISTRATION NUMBER: ACTRN12617000520336; Pre-results.

Treatment of prednisolone-induced hyperglycaemia in hospitalized patients: Insights from a randomized, controlled study.

AIM: Prednisolone causes hyperglycaemia predominantly between midday and midnight. Consequently, glargine-based basal-bolus insulin regimens may under treat daytime hyperglycaemia and cause nocturnal hypoglycaemia. We investigated whether an isophane-based insulin regimen is safer and more effective than a glargine-based regimen in hospitalized patients. MATERIALS AND METHODS: Fifty inpatients prescribed ≥20 mg/day prednisolone acutely with (1) finger prick blood glucose level (BGL) ≥15 mmol/L or (2) BGLs ≥10 mmol/L within the previous 24 hours were randomized to either insulin isophane or glargine before breakfast and insulin aspart before meals. The initial daily insulin dose was 0.5 U/kg bodyweight or 130% of the current daily insulin dose. Glycaemic control was assessed using a continuous glucose monitoring system. RESULTS: On Day 1, there were no significant differences in percentage of time outside a target glucose range of 4 to 10 mmol/L (41.3% ± 5.5% vs 50.0% ± 5.7%, P = .28), mean daily glucose (10.2 ± 0.7 vs 10.8 ± 0.8 mmol/L, P = .57) or glucose <4 mmol/L (2.2% ± 1.1% vs 2.0% ± 1.3%, P = .92) in patients randomized to isophane and glargine. In patients treated for 3 days, the prednisolone dose was reduced ( P = .02) and the insulin dose was increased over time ( P = .02), but the percentage of time outside the 4 to 10 mmol/L glucose range did not differ over time ( P = .45) or between groups ( P = .24). CONCLUSIONS: There were no differences in the efficacy or safety of the isophane and glargine-based insulin regimens. We recommend an initial daily insulin dose of 0.5 units/kg bodyweight if not on insulin, a greater than 30% increase in pre-prednisolone insulin dose and larger insulin dose adjustments in patients with prednisolone-induced hyperglycaemia.

Relationship between Vitamin D Status and Autonomic Nervous System Activity.

Vitamin D deficiency is associated with increased arterial stiffness. However, the mechanisms underlying this association have not been clarified. The aim was to investigate whether changes in autonomic nervous system activity could underlie an association between 25 hydroxy vitamin D and arterial stiffness. A total of 49 subjects (age = 60 ± 8 years, body mass index = 26.7 ± 4.6 kg/m², 25 hydroxy vitamin D = 69 ± 22 nmol/L) underwent measurements of pulse wave velocity (PWV) and augmentation index (AIx), spontaneous baroreflex sensitivity, plasma metanephrines and 25 hydroxy vitamin D. Subjects with 25 hydroxy vitamin D ≤ 50 nmol/L were restudied after 200,000 International Units 25 hydroxy vitamin D. Plasma metanephrine was positively associated with AIx (p = 0.02) independent of age, sex, smoking and cholesterol and negatively associated with 25 hydroxy vitamin D (p = 0.002) independent of age, sex and season. In contrast, there was no association between baroreflex sensitivity and 25 hydroxy vitamin D (p = 0.54). Treatment with vitamin D increased 25 hydroxy vitamin D from 43 ± 5 to 96 ± 24 nmol/L (p < 0.0001) but there was no significant change in plasma metanephrine (115 ± 25 vs. 99 ± 39 pmol/L, p = 0.12). We conclude that as plasma metanephrine was negatively associated with 25 hydroxy vitamin D and positively with AIx, it could mediate an association between these two variables. This hypothesis should be tested in larger interventional studies.

Relative Hyperglycemia, a Marker of Critical Illness: Introducing the Stress Hyperglycemia Ratio.

CONTEXT: Hyperglycemia in hospitalized patients is associated with increased morbidity and mortality. OBJECTIVE: We examined whether critical illness is more strongly associated with relative or absolute hyperglycemia. DESIGN: The study was an observational cohort study. PATIENTS AND SETTING: A total of 2290 patients acutely admitted to a tertiary hospital. MAIN OUTCOME MEASURE: The relative hyperglycemia (stress hyperglycemia ratio [SHR]) was defined as admission glucose divided by estimated average glucose derived from glycosylated hemoglobin. The relationships between glucose and SHR with critical illness (in-hospital death or critical care) were examined. RESULTS: In univariable analyses, SHR (odds ratio, 1.23 per 0.1 increment [95% confidence interval, 1.18-1.28]; P < .001) and glucose (odds ratio, 1.18 per mmol/L [1.13-1.23]; P < .001) were associated with critical illness. In multivariable analysis, the association was maintained for SHR (odds ratio, 1.20 per 0.1 increment [1.13-1.28]; P < .001), but not glucose (odds ratio, 1.03 per mmol/L [0.97-1.11]; P = .31). Background hyperglycemia affected the relationship between glucose (P = .002) and critical illness, but not SHR (P = .35) and critical illness. In patients with admission glucose ≤ 10 mmol/L, the odds ratio for critical illness was higher in the fourth (2.4 [1.4-4.2]; P = .001) and fifth (3.9 [2.3-6.8]; P < .001) SHR quintiles than in the lowest SHR quintile. CONCLUSIONS: SHR controls for background glycemia and is a better biomarker of critical illness than absolute hyperglycemia. SHR identifies patients with relative hyperglycemia at risk of critical illness. Future studies should explore whether basing glucose-lowering therapy on relative, rather than absolute, hyperglycemia improves outcomes in hospitalized patients.

Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial.

BACKGROUND: When patients with type 2 diabetes start their first injectable therapy, clinicians can choose between glucagon-like peptide-1 (GLP-1) receptor agonists and basal insulins. In DURATION-3, exenatide once weekly was compared with insulin glargine (henceforth, glargine) as first injectable therapy. Here, we report the results of the final 3-year follow-up. METHODS: DURATION-3 was an open-label randomised trial done between May 13, 2008, and Jan 30, 2012. Patients with type 2 diabetes aged 18 years or older were enrolled at 72 sites worldwide. They were eligible when they had suboptimum glycaemic control (HbA1c 7.1-11.0% [54-97 mmol/mol]) despite maximum tolerated doses of metformin alone or with a sulfonylurea for at least 3 months, a stable bodyweight for at least 3 months, and a BMI of 25-45 kg/m(2) (23-45 kg/m(2) in South Korea and Taiwan). Patients were randomly assigned (1:1) by computer-generated random sequence with an interactive voice-response system (block size four, stratified by country and concomitant therapy) to once-weekly exenatide (2 mg subcutaneous injection) or once-daily glargine (titrated to target) to be given in addition to their existing oral glucose-lowering regimens. The primary efficacy measure at 3 years was change in HbA1c from baseline in patients given at least one dose of the assigned drug (ie, analyses by modified intention to treat). Patients, investigators, and data analysts were not masked to treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT00641056. FINDINGS: 456 patients underwent randomisation and received at least one dose of the assigned drug (233 given exenatide, 223 glargine). At 3 years, least-squares mean HbA1c change was -1.01% (SE 0.07) in the exenatide group versus -0.81% (0.07) in the glargine group (least-squares mean difference -0.20%, SE 0.10, 95% CI -0.39 to -0.02; p=0.03). Transient gastrointestinal adverse events characteristic of GLP-1 receptor agonists were more frequent with exenatide than glargine (nausea: 36 [15%] of 233 patients vs five [2%] of 223; vomiting: 15 [6%] vs six [3%]; diarrhoea: 32 [14%] vs 15 [7%]), although frequency of these events did decrease after week 26 in the exenatide group. The proportion of patients who reported serious adverse events in the exenatide group (36 patients [15%]) was the same as that in the glargine group (33 [15%]). The exposure-adjusted rate of overall hypoglycaemia was three times higher in patients given glargine (0.9 events per patient per year) than in those given exenatide (0.3 events per patient per year). INTERPRETATION: Efficacy of once-weekly exenatide is sustained for 3 years. GLP-1 receptor agonists could be a viable long-term injectable treatment option in patients with type 2 diabetes who have not yet started taking insulin. FUNDING: Amylin Pharmaceuticals and Eli Lilly.

Brief report: Comparison of continuous glucose monitoring and finger-prick blood glucose levels in hospitalized patients administered basal-bolus insulin.

BACKGROUND: Previous studies have assessed the efficacy of basal-bolus insulin (BBI) in hospitalized patients by measuring four finger-prick blood glucose levels (BGLs) per day. The aim of this study was to investigate whether this BGL monitoring regimen provides an accurate reflection of glycemia in hospitalized patients administered BBI. We hypothesized that, as three of four readings are preprandial, finger-prick BGLs would underestimate the mean glucose concentration. SUBJECTS AND METHODS: Twenty-six consecutive consenting subjects with type 1 (n=3) or type 2 (n=23) diabetes mellitus admitted to the hospital and administered insulin glargine once daily and rapid-acting insulin before meals underwent continuous glucose monitoring for up to 72 h. Finger-prick BGLs were performed before each main meal (0700, 1200, and 1700 h) and at 2100 h. RESULTS: Mean daily glucose concentration was not significantly different when assessed by continuous glucose monitoring and finger-prick BGLs (9.6±2.4 vs. 9.6±2.7 mmol/L, P=0.84). A Bland-Altman plot revealed some variability but no bias between the two methods of measurement of glucose concentration. There were 88 postprandial hyperglycemic excursions recorded on continuous glucose monitoring; 61 (69%) were identified by finger-prick BGL monitoring. There were 10 glucose excursions <4 mmol/L during continuous glucose monitoring; only one was detected by finger-prick BGL monitoring. CONCLUSIONS: Traditional finger-prick BGL monitoring provides a reasonable approximation of mean daily glucose concentration in the majority of hospitalized patients receiving BBI but underestimates the prevalence of postprandial hyperglycemia and hypoglycemia.

Basal-bolus insulin versus sliding-scale insulin for inpatient glycaemic control: a clinical practice comparison.

OBJECTIVE: To determine if the improvement in inpatient glycaemic control observed with basal-bolus insulin (BBI) over sliding-scale insulin (SSI) in the formal study setting translates to routine clinical conditions. DESIGN, SETTING AND PATIENTS: Cross-sectional study in which capillary blood glucose levels (BGLs) were prospectively measured four times daily for up to 8 days in 124 patients with type 2 diabetes admitted to a tertiary teaching hospital and treated with BBI between November 2008 and May 2010. Data from the BBI treatment group were compared with retrospective data from 96 patients treated with SSI between June 2001 and May 2006. MAIN OUTCOME MEASURES: Mean daily BGL; independent effect of insulin regimen on mean daily BGL. RESULTS: Mean baseline BGL was not significantly different in patients receiving BBI and SSI (mean ± SD, 11.3 ± 4.1 v 10.6 ± 4.3 mmol/L; P = 0.23). After the first full day of therapy, mean daily BGL for patients receiving BBI was 1.6 ± 3.7 mmol/L lower than baseline BGL, and it remained 1.6-2.4 mmol/L lower than baseline throughout the study (P < 0.001). In contrast, there was no significant change in BGL for patients receiving SSI. Random effects regression analysis indicated that BBI was associated with a significantly lower mean daily BGL than SSI, independent of other variables (P < 0.001). The incidence of hypoglycaemia (BGL < 4 mmol/L) was significantly greater in patients receiving BBI than SSI (3.3% v 1.4%; P < 0.001), but there was no significant difference for severe hypoglycaemia (BGL < 2.8 mmol/L) (0.3 v 0.5%; P = 0.3). CONCLUSIONS: Under routine clinical conditions, BBI is effective and safe across a range of patients and appears to be superior to SSI. Clinical improvements reflected those seen in a strict formal study setting.

Safety and efficacy of once-weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes over 84 weeks.

OBJECTIVE: We recently reported that after 26 weeks, exenatide once weekly (EQW) resulted in superior A1C reduction, reduced hypoglycemia, and progressive weight loss compared with daily insulin glargine (IG) in patients with type 2 diabetes who were taking metformin alone or with sulfonylurea. This 84-week extension study assessed the long-term safety and efficacy of EQW versus IG. RESEARCH DESIGN AND METHODS: This multicenter, open-label, randomized, two-arm, parallel trial assessed change in A1C, proportions of patients achieving A1C <7.0 and ≤6.5%, body weight, incidence of hypoglycemia, and overall safety. RESULTS: Of 415 patients who completed 26 weeks, 390 (194 EQW and 196 IG patients) entered the extension study. At 84 weeks, A1C decreased from baseline (8.3%) by -1.2% for EQW vs. -1.0% for IG (P = 0.029). The proportions of patients who achieved end point A1C targets <7.0 and ≤6.5% were 44.6% for EQW patients vs. 36.8% for IG patients (P = 0.084) and 31.3% for EQW patients vs. 20.2% for IG patients (P = 0.009), respectively. Patients taking EQW lost 2.1 kg of body weight, whereas those taking IG gained 2.4 kg (P < 0.001). Among patients taking metformin plus sulfonylurea, the incidence of minor hypoglycemia was 24% for EQW patients vs. 54% for IG patients (P < 0.001); among patients taking metformin alone, it was 8% for EQW patients vs. 32% for IG patients (P < 0.001). Among adverse events occurring in ≥5% of patients, diarrhea and nausea occurred more frequently (P < 0.05) in the EQW group than in the IG group (12 vs. 6% and 15 vs. 1%, respectively). CONCLUSIONS: After 84 weeks, patients treated with EQW continued to experience better glycemic control with sustained overall weight loss and a lower risk of hypoglycemia than patients treated with IG.

Screening for diabetes in patients with inflammatory rheumatological disease administered long-term prednisolone: a cross-sectional study.

OBJECTIVE: The aim of the study was to assess the effect of long-term prednisolone on fasting and post-glucose load glucose concentration in patients with inflammatory rheumatological disease. We hypothesized that prednisolone would predominantly increase post-glucose load glucose concentration and that fasting glucose would have poor sensitivity as a screening test for diabetes in patients receiving chronic prednisolone therapy. METHODS: In a cross-sectional study of subjects with inflammatory rheumatological disease but without known diabetes, 60 subjects [age = 70 (±10) years, 62% female] who were receiving chronic (>6 months) prednisolone [6.5 (±2.1) mg/day] (Group 1) and 58 controls [age = 70 (±11) years, 62% female] who had not received oral glucocorticoids for at least 6 months (Group 2) underwent an oral glucose tolerance test. RESULTS: Fasting glucose was significantly lower [5.0 (±0.1) vs. 5.3 (±0.1) mmol/l, P = 0.02) and post-glucose load glucose concentration significantly higher [8.0 (±0.4) vs. 6.8 (±0.3) mmol/l, P = 0.02] in Group 1 than in Group 2. In a multiple regression analysis, glucocorticoid use (P = 0.004) and log CRP (P = 0.02) were independently associated with fasting glucose, while waist circumference (P = 0.01), but not glucocorticoid use, was independently associated with post-glucose load glucose concentration. A fasting glucose ≥5.6 mmol/l had 33 and 83% sensitivity for diabetes in Groups 1 and 2, respectively. CONCLUSION: There is discordance between a reduced fasting and increased post-glucose load glucose concentration in rheumatological patients on long-term prednisolone. Therefore fasting glucose has poor sensitivity to screen for diabetes in prednisolone-treated patients. Treatment of prednisolone-induced hyperglycaemia should be directed at the postprandial period. Trial registration. Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au/, ACTRN12607000540415.