Detecting dysglycaemia in compensated liver cirrhosis: Comparison of oral glucose tolerance test and glycated haemoglobin, with continuous glucose monitoring.

AIMS: Liver cirrhosis increases the risk of developing dysglycaemia (pre-diabetes and diabetes), thus people with cirrhosis should undergo regular screening for dysglycaemia. The utility of screening using the laboratory glycated haemoglobin (HbA1c ) test has been questioned in this setting. This study examines the relationship between different potential screening modalities: 75 g oral glucose tolerance test (OGTT) and HbA1c , using continuous glucose monitoring (CGM) as a comparator. METHODS: Participants ≥18 years with no known diabetes, were recruited from a gastroenterology cirrhosis surveillance register. Study measurements included a 75 g OGTT, laboratory HbA1c and two weeks of 'blinded' CGM (Freestyle Libre Pro). The possibility of intravascular haemolysis affecting HbA1c interpretation was also assessed. RESULTS: All 20 participants had compensated cirrhosis. OGTT tended to diagnose more dysglycaemia (N = 7) than did HbA1c (N = 4). Bland-Altman analysis showed laboratory and CGM-estimated HbA1c were broadly comparable, with a difference of 4mmol/mol (95% CI -3 to 12), or 0.4% (95% CI -0.3 to 1.1). Laboratory HbA1c tended to be higher than the CGM-estimated HbA1c , perhaps reflecting positive lifestyle changes in participants during their two weeks of wearing 'blinded' CGM (Hawthorne effect). In the population studied, there was no evidence that haemolysis affected interpretation of HbA1c results. CONCLUSIONS: In the setting of compensated cirrhosis, the OGTT and HbA1c remain standard screening test for diabetes, but multiple studies show the OGTT diagnoses more people with dysglycaemia than does the HbA1c . Blinded CGM in an ambulatory, real world setting provides additional insights into glycaemic excursions but cannot be used to diagnose dysglycaemia.

Insulin degludec overdose in an adolescent with type 1 diabetes: proactive management including monitoring using the Freestyle Libre flash glucose monitoring system.

An adolescent with type 1 diabetes and a history of self-harm, which included intentional overdoses and insulin omission, presented with an insulin degludec overdose. She had been commenced on the ultra-long-acting insulin, degludec, with the aim of reducing ketoacidosis episodes in response to intermittent refusal to take insulin. Insulin degludec was administered under supervision as an outpatient. Because it was anticipated that she would attempt a degludec overdose at some stage, the attending clinicians implemented a proactive management plan for this (and related) scenarios. This included long-term monitoring of interstitial glucose using the Abbott Freestyle Libre flash glucose monitor. The patient took a witnessed overdose of 242 units of degludec (usual daily dose, 32 units). She was hospitalised an hour later. Inpatient treatment was guided primarily by interstitial glucose results, with capillary and venous glucose tests used as secondary measures to assess the accuracy of interstitial glucose values. Four days of inpatient treatment was required. The patient was managed with high glycaemic loads of food and also intermittent intravenous dextrose. No hypoglycaemia was documented during the admission. In summary, while a degludec overdose may require several days of inpatient management, in situations where proactive management is an option and the dose administered is relatively modest, it may be possible to avoid significant hypoglycaemia. In addition, this case demonstrates that inpatient interstitial glucose monitoring may have a role in managing insulin overdose, especially in situations where the effect of the insulin overdose on glucose levels is likely to be prolonged. LEARNING POINTS: Degludec overdoses have a prolonged effect on blood glucose levels, but if the clinical situation allows for early detection and management, treatment may prove easier than that which is typically needed following overdoses of a similar dose of shorter acting insulins.Inpatient real-time interstitial monitoring helped guide management, which in this context included the prescription of high dietary carbohydrate intake (patient led) and intravenous 10% dextrose (nurse led).Use of inpatient interstitial glucose monitoring to guide therapy might be considered 'off label' use, thus, both staff and also patients should be aware of the limitations, as well as the benefits, of interstitial monitoring systems.The Libre flash glucose monitor provided nurses with low cost, easy-to-use interstitial glucose results, but it is nevertheless advisable to check these results against conventional glucose tests, for example, capillary 'finger-stick' or venous glucose tests.

Plasma glucose measurement in diabetes: impact and implications of variations in sample collection procedures with a focus on the first hour after sample collection.

BACKGROUND: Previous studies of participants with plasma glucose concentrations at or near the glucose reference range demonstrate glucose loss following delayed separation and extraction of plasma from the cellular components of blood, of ≤7% per hour. We aimed to assess pre-analytical glucose loss in diabetic subjects, focusing on the first hour after sample collection. METHODS: Venous blood was collected from diabetes clinic attendees, into a series of lithium heparin PST™ (plasma separator tube) and fluoride oxalate Vacutainers™. Baseline (reference) plasma glucose measurements were undertaken on samples prepared under refrigerated conditions. The remaining samples underwent a series of controlled pre-analytical delays in sample preparation, at room temperature. Plasma glucose was measured using the hexokinase method. RESULTS: Median baseline glucose (mmol/L) for the 62 participants was 10.6 (range 3.4-31.1). Using lithium heparin PST™ tubes, mean glucose loss (95% CI) was 0.16 (0.09-0.23) after 30 min delay in plasma preparation and 0.28 (0.21-0.34) after 60 min delay. Glucose loss was independent of both baseline glucose and also individual cellular count. Fluoride failed to inhibit glucose loss within the first hour after sample collection. Immediate plasma centrifugation of PST™ tubes, followed by delayed plasma extraction (median delay 92 min), produced a mean glucose loss of 0.02 mmol/L (-0.05-0.09). CONCLUSIONS: Samples collected into lithium heparin PST™ tubes show pre-analytical glucose loss at 1 h that is independent of baseline glucose and cellular count. Furthermore, immediate plasma separation using these tubes attenuates glucose loss across a wide range of glucose concentrations.

A glucose meter evaluation co-designed with both health professional and consumer input.

Health consumer's input into assessment of medical device safety is traditionally given either as part of study outcome (trial participants) or during post marketing surveillance. Direct consumer input into the methodological design of device assessment is less common. We discuss the difference in requirements for assessment of a measuring device from the consumer and clinician perspectives, using the example of hand held glucose meters. Around 80,000 New Zealanders with diabetes recently changed their glucose meter system, to enable ongoing access to PHARMAC subsidised meters and strips. Consumers were most interested in a direct comparison of their 'old' meter system (Accu-Chek Performa) with their 'new' meter system (CareSens brand, including the CareSens N POP), rather than comparisons against a laboratory standard. This direct comparison of meter/strip systems showed that the CareSens N POP meter read around 0.6 mmol/L higher than the Performa system. Whilst this difference is unlikely to result in major errors in clinical decision making such as major insulin dosing errors, this information is nevertheless of interest to consumers who switched meters so that they could maintain access to PHARMAC subsidised meters and strips. We recommend that when practical, the consumer perspective be incorporated into study design related to medical device assessment.