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.

Urinary Amino-Terminal Pro-C-Type Natriuretic Peptide: A Novel Marker of Chronic Kidney Disease in Diabetes.

BACKGROUND: Chronic renal inflammation and fibrosis are common sequelae in diabetes mellitus (DM) and are major causes of premature mortality. Although upregulation of NPPC expression occurs in response to renal inflammation in experimental animals, nothing is known of the molecular forms of C-type natriuretic peptide (CNP) products in urine of people with DM or links with renal function. METHODS: ProCNP products in urine were characterized with HPLC and a range of antisera directed to specific epitopes of amino-terminal proCNP (NTproCNP). The 5-kDa intact peptide was quantified in spot urine samples from healthy adults and 202 participants with DM selected to provide a broad range of renal function. RESULTS: The predominant products of proCNP in urine were consistent with the 2-kDa fragment (proCNP 3-20) and a smaller peak of intact (5-kDa) fragment (proCNP 1-50, NTproCNP). No peaks consistent with bioactive forms (proCNP 82-103, 50-103) were identified. The urine NTproCNP to creatinine ratio (NCR) was more reproducible than the albumin to creatinine ratio (ACR) and strongly associated with the presence of chronic kidney disease. In models predicting independence, among 10 variables associated with renal function in DM, including plasma NTproCNP, only 3 (sex, ACR, and plasma creatinine) contributed to NCR. CONCLUSIONS: Characterization of the products of proCNP in urine confirmed the presence of NTproCNP. In spot random urine from study participants with DM, NCR is inversely associated with estimated glomerular filtration rate. In contrast to ACR, NCR reflects nonvascular factors that likely include renal inflammation and fibrosis.

Electronic informed consent: the need to redesign the consent process for the digital age.

The delivery of healthcare, which includes the informed consent process, is moving to a digital environment. This change in informed consent delivery will be associated with opportunities, risks and also unintentional consequences. Physicians are well placed to contribute to the ongoing dialogue about what is needed to make the informed consent process fit for purpose, in the digital age.

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.

Extreme urinary betaine losses in type 2 diabetes combined with bezafibrate treatment are associated with losses of dimethylglycine and choline but not with increased losses of other osmolytes.

PURPOSE: Betaine deficiency is a probable cardiovascular risk factor and a cause of elevated homocysteine. Urinary betaine excretion is increased by fibrate treatment, and is also often elevated in diabetes. Does fibrate further increase betaine excretion in diabetes, and does it affect the plasma concentrations and excretions of related metabolites and of other osmolytes? METHODS: Samples from a previous study of type 2 diabetes were selected if participants were taking bezafibrate (n = 32). These samples were compared with participants matched for age and gender and not on a fibrate (comparator group, n = 64). Betaine, related metabolites, and osmolytes were measured in plasma and urine samples from these 96 participants. RESULTS: Median urinary betaine excretion in those on bezafibrate was 5-fold higher than in the comparator group (p < 0.001), itself 3.5-fold higher than the median reported for healthy populations. In the bezafibrate group, median dimethylglycine excretion was higher (9-fold, p < 0.001). Excretions of choline, and of the osmolytes myo-inositol, taurine and glycerophosphorylcholine, were not significantly different between groups. Some participants excreted more betaine than usual dietary intakes. Several betaine fractional clearances were >100 %. Betaine excretion correlated with excretions of the osmolytes myo-inositol and glycerophosphorylcholine, and also with the excretion of choline and N,N-dimethylglycine, but it was inconclusive whether these relationships were affected by bezafibrate therapy. CONCLUSIONS: Increased urinary betaine excretions in type 2 diabetes are further increased by fibrate treatment, sometimes to more than their dietary intake. Concurrent betaine supplementation may be beneficial.

Understanding the additional impact of prediabetes and type 2 diabetes mellitus on vitamin C requirements in people living with obesity.

Obesity and diabetes are known to negatively affect vitamin C status. However, whether the presence of diabetes, in addition to obesity, contributes an additional impact on vitamin C status is currently uncertain. In a cohort of 152 adults living with obesity, we assessed metabolic and nutrient parameters in participants without diabetes (n = 92), and with prediabetes (n = 22) and type 2 diabetes mellitus (T2DM; n = 35). Vitamin C concentrations were measured in plasma and leukocytes using HPLC and vitamin C intakes were assessed using 24-hour dietary recall. Metabolic severity scores were derived using gender, ethnicity, height, weight, waist circumference, systolic blood pressure, fasting glucose, HDL, and triglyceride values. In people living with obesity, those with prediabetes and T2DM had increased metabolic dysregulation and decreased vitamin C status relative to those without diabetes (P < .05). Vitamin C deficiency was observed in a high proportion (23%-32%) of participants with prediabetes and T2DM and ≥50% had hypovitaminosis C. However, there was no difference in vitamin C intake between those without diabetes and those with prediabetes or T2DM (P > .05). There was a significant inverse correlation between plasma vitamin C status and metabolic severity score (r = -0.290, P < .001). Linear regression indicated that for every 1-unit increase in metabolic severity score, there was a 6.5 µmol/L decrease in vitamin C status. Thus, the enhanced metabolic dysregulation observed with prediabetes and T2DM is associated with an increased demand for vitamin C in people living with obesity.

Patient perceptions of barriers to attending annual diabetes review and foot assessment in general practice: a qualitative study.

Introduction Regular diabetic foot checks, at least annually, are important for early identification of risk factors and prevention of ulceration and amputation. To ensure this, most general practices in Aotearoa New Zealand (NZ) offer free annual diabetes reviews (ADRs) which include a comprehensive foot evaluation. However, attendance rates at these ADRs are low. Aim To explore patients' perspectives on the barriers to attending ADRs and foot checks. Methods Semi-structured interviews with people with type 2 diabetes who were overdue their ADR (n = 13; 7 women, 6 Maori) from two urban practices were conducted. Interviews were audio recorded and transcribed verbatim and then analysed using an inductive thematic analysis approach. Results We identified three key themes demonstrating barriers to attendance: healthcare-associated factors (suboptimal clinician-patient relationship, not having a consistent general practitioner (GP)); patient-related factors (co-morbid health conditions, issues surrounding identity, and logistical issues); and systemic factors (COVID-19 pandemic, travel distance to the practice, unawareness of available foot care services). Participants' feedback focused on patient-centred approaches for improvements to service delivery, for example using online educational materials, and utilising culturally appropriate models of health including Te Whare Tapa Wha and Whanau Ora approach. Discussion We identified several barriers to attendance, some of which are potentially modifiable. Addressing modifiable barriers and incorporating suggestions made by participants may improve access to the ADR and reduce non-attendance. Further participatory action research could explore these insights in ways that facilitate tino rangatiratanga (self-determination) and palpable action.

Estimating Vitamin C Intake Requirements in Diabetes Mellitus: Analysis of NHANES 2017-2018 and EPIC-Norfolk Cohorts.

Vitamin C is an essential enzyme cofactor and antioxidant with pleiotropic roles in human physiology. Circulating vitamin C concentrations are lower in people with diabetes mellitus, suggesting a higher dietary requirement for the vitamin. We interrogated the NHANES 2017-2018 and EPIC-Norfolk datasets to compare vitamin C requirements between those with and without diabetes mellitus using dose-concentration relationships fitted with sigmoidal (four-parameter logistic) curves. The NHANES cohort (n = 2828 non-supplementing adults) comprised 488 (17%) participants with diabetes (self-reported or HbA1c ≥ 6.5%). The participants with diabetes had a lower vitamin C status (median [IQR]) than those without (38 [17, 52] µmol/L vs. 44 [25, 61] µmol/L, p < 0.0001), despite comparable dietary intakes between the two groups (51 [26, 93] mg/d vs. 53 [24, 104] mg/d, p = 0.5). Dose-concentration relationships indicated that the group without diabetes reached adequate vitamin C concentrations (50 µmol/L) with an intake of 81 (72, 93) mg/d, whilst those with diabetes required an intake of 166 (126, NA) mg/d. In the EPIC-Norfolk cohort, comprising 20692 non-supplementing adults, 475 (2.3%) had self-reported diabetes at baseline. The EPIC cohort had a lower BMI than the NHANES cohort (26 [24, 28] kg/m2 vs. 29 [25, 34] kg/m2, p < 0.0001). Correspondingly, the EPIC participants without diabetes required a lower vitamin C intake of 64 (63, 65) mg/d while those with diabetes required 129 (104, NA) mg/d to reach adequate circulating vitamin C status. C-reactive protein concentrations were strongly correlated with body weight and BMI and provided a surrogate biomarker for vitamin C requirements. In conclusion, people with diabetes had 1.4 to 1.6 fold higher requirements for vitamin C than those without diabetes. This corresponds to additional daily vitamin C intake requirements of ~30-40 mg for people with diabetes, equating to a total daily intake of at least 125 mg/d.

Comparing Literature- and Subreddit-Derived Laboratory Values in Polycystic Ovary Syndrome (PCOS): Validation of Clinical Data Posted on PCOS Reddit Forums.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous condition that affects 4% to 21% of people with ovaries. Inaccessibility or dissatisfaction with clinical treatment for PCOS has led to some individuals with the condition discussing their experiences in specialized web-based forums. OBJECTIVE: This study explores the feasibility of using such web-based forums for clinical research purposes by gathering and analyzing laboratory test results posted in an active PCOS forum, specifically the PCOS subreddit hosted on Reddit. METHODS: We gathered around 45,000 posts from the PCOS subreddit. A random subset of 5000 posts was manually read, and the presence of laboratory test results was labeled. These labeled posts were used to train a machine learning model to identify which of the remaining posts contained laboratory results. The laboratory results were extracted manually from the identified posts. These self-reported laboratory test results were compared with values in the published literature to assess whether the results were concordant with researcher-published values for PCOS cohorts. A total of 10 papers were chosen to represent published PCOS literature, with selection criteria including the Rotterdam diagnostic criteria for PCOS, a publication date within the last 20 years, and at least 50 participants with PCOS. RESULTS: Overall, the general trends observed in the laboratory test results from the PCOS web-based forum were consistent with clinically reported PCOS. A number of results, such as follicle stimulating hormone, fasting insulin, and anti-Mullerian hormone, were concordant with published values for patients with PCOS. The high consistency of these results among the literature and when compared to the subreddit suggests that follicle stimulating hormone, fasting insulin, and anti-Mullerian hormone are more consistent across PCOS phenotypes than other test results. Some results, such as testosterone, sex hormone-binding globulin, and homeostasis model assessment-estimated insulin resistance index, were between those of PCOS literature values and normal values, as defined by clinical testing limits. Interestingly, other results, including dehydroepiandrosterone sulfate, luteinizing hormone, and fasting glucose, appeared to be slightly more dysregulated than those reported in the literature. CONCLUSIONS: The differences between the forum-posted results and those published in the literature may be due to the selection process in clinical studies and the possibility that the forum disproportionally describes PCOS phenotypes that are less likely to be alleviated with medical intervention. However, the degree of concordance in most laboratory test values implied that the PCOS web-based forum participants were representative of research-identified PCOS cohorts. This validation of the PCOS subreddit grants the possibility for more research into the contents of the subreddit and the idea of undertaking similar research using the contents of other medical internet forums.

People with diabetes and hypovitaminosis C fail to conserve urinary vitamin C.

Background: Hypovitaminosis C has negative health consequences. People with diabetes and hypovitaminosis C may fail to conserve vitamin C in the urine, thereby displaying evidence of inappropriate renal leak of vitamin C. This study describes the relationship between plasma and urinary vitamin C in diabetes, with a focus on the clinical characteristics of participants with renal leak. Methods: Retrospective analysis of paired, non-fasting plasma and urine vitamin C, and also clinical characteristics, from participants with either type 1 or type 2 diabetes, recruited from a secondary care diabetes clinic. Plasma vitamin C thresholds for renal leak have been defined previously as 38.1 µmol/L for men and 43.2 µmol/L for women. Results: Statistically significant differences in clinical characteristics were seen between those with; i) renal leak (N = 77) and; ii) hypovitaminosis C but no renal leak (N = 13) and; iii) normal plasma vitamin C levels (n = 34). Compared to participants with adequate plasma vitamin C levels, participants with renal leak tended to have type 2 (rather than type 1) diabetes, a lower eGFR and a higher HbA1c. Conclusion: In the diabetes population studied, renal leak of vitamin C was common. In some participants, it may have contributed to hypovitaminosis C.

A review of the hormones involved in the endocrine dysfunctions of polycystic ovary syndrome and their interactions.

Polycystic ovary syndrome (PCOS) affects up to 20% of women but remains poorly understood. It is a heterogeneous condition with many potential comorbidities. This review offers an overview of the dysregulation of the reproductive and metabolic systems associated with PCOS. Review of the literature informed the development of a comprehensive summarizing 'wiring' diagram of PCOS-related features. This review provides a justification for each diagram aspect from the relevant academic literature, and explores the interactions between the hypothalamus, ovarian follicles, adipose tissue, reproductive hormones and other organ systems. The diagram will provide an efficient and useful tool for those researching and treating PCOS to understand the current state of knowledge on the complexity and variability of PCOS.

Vitamin C Status in People with Types 1 and 2 Diabetes Mellitus and Varying Degrees of Renal Dysfunction: Relationship to Body Weight.

Diabetes mellitus is a chronic metabolic disorder and is associated with depleted vitamin C status. The underlying aetiologies and pathogeneses responsible for this association are poorly understood. This retrospective study explored the vitamin C status of 136 adult outpatients with types 1 and 2 diabetes mellitus (T1DM/T2DM), with a focus on indices of renal function and metabolic health, including body weight. In the T1DM group (n = 73), the median plasma vitamin C concentration was 33 (18, 48) µmol/L, with 37% hypovitaminosis C and 12% deficiency. In the T2DM group (n = 63), the median plasma concentration was 15 (7, 29) µmol/L, with 68% hypovitaminosis C and 38% deficiency. Lower vitamin C was associated with macroalbuminuria (p = 0.03), renal dysfunction (p = 0.08), and hypertension (p = 0.0005). Inverse associations were also observed between plasma vitamin C and various other metabolic health parameters (p < 0.05), especially body weight (p < 0.0001), which was higher in those with hypovitaminosis C (<23 µmol/L; p = 0.0001). The association with bodyweight remained, even after multivariable analysis. In summary, body weight was a significant predictor of low vitamin C status in people with diabetes. This suggests that people with both diabetes and a high body weight may have greater than average vitamin C requirements.

Applying Parkes Grid Method to Evaluate Impact of Variation in Blood Glucose Monitoring (BGM) Strip Accuracy Performance in Type 1 Diabetes Highlights the Potential for Amplification of Imprecision With Less Accurate BGM Strips.

BACKGROUND: The National Health Service spends £170 million on blood glucose monitoring (BGM) strips each year and there are pressures to use cheaper less accurate strips. Technology is also being used to increase test frequency with less focus on accuracy.Previous modeling/real-world data analysis highlighted that actual blood glucose variability can be more than twice blood glucose meter reported variability (BGMV). We applied those results to the Parkes error grid to highlight potential clinical impact. METHOD: BGMV is defined as the percent of deviation from reference that contains 95% of results. Four categories were modeled: laboratory (<5%), high accuracy strips (<10%), ISO 2013 (<15%), and ISO 2003 (<20%) (includes some strips still used).The Parkes error grid model with its associated category of risk including "alter clinical decision" and "affect clinical outcomes" was used, with the profile of frequency of expected results fitted into each BGM accuracy category. RESULTS: Applying to single readings, almost all strip accuracy ranges derived in a controlled setting fell within the category: clinically accurate/no effect on outcomes areas.However modeling the possible blood glucose distribution in more detail, 30.6% of longer term results of the strips with current ISO accuracy would fall into the "alter clinical action" category. For previous ISO strips, this rose to 44.1%, and for the latest higher accuracy strips, this fell to 12.8%. CONCLUSION: There is a minimum standard of accuracy needed to ensure that clinical outcomes are not put at risk. This study highlights the potential for amplification of imprecision with less accurate BGM strips.

Metformin increases plasma ghrelin in Type 2 diabetes.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Metformin, unlike the other major antihyperglycaemic drugs, is not associated with weight gain. * Ghrelin is an appetite-stimulating hormone whose concentrations vary in relation to food, obesity and diabetes control. * Reports are conflicting about how metformin affects ghrelin concentrations, and this study was aimed at resolving this issue in patients with Type 2 diabetes. WHAT THIS STUDY ADDS: * In this study an increase in ghrelin concentrations was seen in response to metformin treatment in patients with Type 2 diabetes. * This effect was opposite to what might be expected if the effect of metformin on weight control was mediated via suppression of ghrelin. * It is likely that the ghrelin response was secondary to improved glycaemic control. * Meal time changes in appetite and satiety did not correlate with changes in ghrelin, which suggests ghrelin may not be important in meal initiation. AIMS: Metformin treatment of Type 2 diabetes is not usually associated with weight gain, and may assist with weight reduction. Plasma ghrelin concentrations are inversely associated with obesity and food intake. Metformin might therefore affect ghrelin concentrations, although previous studies have shown variable results in this regard. The primary aim of this study was to determine the effect of metformin on plasma ghrelin, appetite and satiety in patients with Type 2 diabetes. METHODS: Eighteen patients with Type 2 diabetes were studied before and after 6 weeks of metformin treatment, which was titrated to 1 g b.d. On the study days patients were fed standard meals of 390 kcal at 08.00 and 12.30 h, plasma samples were collected at 15- and 30-min intervals, and appetite and satiety were measured on visual analogue scales. Changes in the area under the concentration-time curves (AUCs) of plasma ghrelin, insulin, glucose, appetite and satiety were assessed and examined for correlations with metformin AUCs. Changes in fasting adiponectin and leptin were also measured. RESULTS: Treatment with metformin increased the mean AUC (07.30-16.30 h) of plasma ghrelin by 24% (P= 0.003), while decreasing those of glucose by 19% (P < 0.001) and insulin by 19% (P= 0.001). No changes were detected in hunger and satiety, or in fasting adiponectin or leptin concentrations. There were no clear correlations between metformin plasma concentrations (AUC) and changes in plasma glucose, insulin or ghrelin. CONCLUSIONS: Treatment of Type 2 diabetes with metformin was associated with increased plasma ghrelin concentrations, without associated changes in hunger and satiety.

Mitigating the impact of disasters and emergencies on clinical trials site conduct: A site perspective following major and minor unforeseen events.

Internationally, the frequency of emergencies and disasters affecting the built environment is increasing. Clinical trials sites that experience an event that affects their clinical trials research infrastructure and site functionality, may find their ability to follow optimal clinical trials conduct is compromised. There is however minimal published information on how clinical trials sites should best undertake emergency planning and develop resilience. We provide a description (case study) from a site perspective of two unforeseen events, one major and one minor, and discuss 'lessons learnt'. International collation of post-event information about what worked and what did not, collected across a spectrum of disasters and emergencies affecting facilities undertaking clinical trials, would provide a repository of shared knowledge and help inform the development of strategies aimed at enhancing the resilience of clinical trials sites to extreme events.

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.

Laboratory diagnosis of gestational diabetes: An in silico investigation into the effects of pre-analytical processing on the diagnostic sensitivity and specificity of the oral glucose tolerance test.

INTRODUCTION: Delayed separation of red cells from plasma causes pre analytical glucose loss, which in turn results in an under-diagnosis of GDM (gestational diabetes) based on the OGTT (oral glucose tolerance test). In silico investigations may help laboratory decision making, when exploring pragmatic improvements to sample processing. METHODS: Late pregnancy 0, 1 and 2h 75g OGTT values were obtained from two distinct populations of pregnant women: 1. Values derived from the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) Study and 2. New Zealand women identified as at higher risk of GDM by their caregivers, undergoing OGTT during routine antenatal care. In both populations studied, in silico modelling focussed on the effects of pre-analytical delays in plasma separation, when using fluoride collection tubes. RESULTS: Using a model that 'batched' samples from the three OGTT collection times, diagnostic sensitivity was estimated as follows: 66.1% for HAPO research population and 48.4% for the 1305 women receiving routine antenatal care. If samples were not batched, but processed shortly after each blood sample was collected, then sensitivity increased to 81%. CONCLUSION: Exploration of a range of clinical and laboratory scenarios using in silico modelling, showed that delaying the processing of pregnancy OGTT samples, using batched sample collection into fluoride tubes, causes unacceptable loss of GDM diagnostic sensitivity across two distinct population groups. This modelling approach will hopefully provide information that helps with final decision making around improved laboratory processing techniques.

How Satisfied Are Patients When Their Choice of Funded Glucose Meter Is Restricted to a Single Brand?

BACKGROUND: Many governments and insurers are driving down the cost of medical devices, including glucose meters, by the central management of purchasing decisions. We report patients' responses to an "enforced" change in brand of glucose meter, one year after the introduction of a national sole supplier arrangement for funded glucose meters and strips. METHOD: Specialist diabetes clinic attendees from two geographical locations completed a questionnaire one year after the final meter changeover date. In the first location, consecutive patients were asked to complete a glucose meter satisfaction questionnaire during their clinic visit. In the second location, this questionnaire was mailed to clinic attendees. Responses to open questions were analyzed thematically. RESULTS: Response rates were 85% and 31% from the first and second locations, respectively and 378 questionnaires were suitable for analysis, 309 from the first and 69 from the second location. Insulin users composed 90% of participants. Results from the two locations were broadly similar. Most participants adapted well to the changeover, however 36% reported ongoing dissatisfaction with their "new" meter. The commonest concern, expressed by 23% of participants, related to meter accuracy and precision. CONCLUSIONS: One year after glucose meter changeover, a third of participants expressed dissatisfaction with their meter, with many participants describing a failure to adapt to the sole supplier arrangement. Providing a choice of meters and strips, ideally from two or more brands that have demonstrable differences in technical and ergonomic features, is likely to produce higher overall patient satisfaction than is a sole supplier arrangement.