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IntroductionGestational diabetes mellitus (GDM) is common in pregnancy and is increasing in prevalence. It is associated with an increased risk of maternal and perinatal complications if not diagnosed and managed early. Most guidelines suggest making a diagnosis of GDM using an oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy at which stage there still is an increased risk of complications. Increased beta-cell secretory product concentrations have been observed prior to changes in glycaemia and can potentially be used as an early marker to diagnose and assess risk of developing GDM.MethodsThe study was a prospective, longitudinal cohort study. OGTTs were carried out at visit one: 16–18 weeks and visit two: 24–28 weeks gestation in pregnant women with at least one risk factor for GDM [Body Mass Index >30 kg/m2, previous macrosomic baby (>4.5 kg), previous GDM, first degree relative with type 2 diabetes mellitus (T2DM)]. Blood sampling was performed at fasting, 30 min, 1 and 2 hours following a 75-g oral glucose load. Samples were analysed for glucose, total and intact proinsulin, insulin and C-peptide. Hormonal concentrations at visit 1 were compared between those that remained normal glucose tolerant (NGT) and those that progressed to GDM at visit 2 using receiver operator characteristic (ROC) area under the curve (AUC) to assess for discrimination between the two groups.ResultsUnfortunately, a smaller than planned sample size was recruited due to the start of COVID-19 pandemic midway through the study. 83 pregnant women had OGTT at visit 1. Of these, 12 reached the threshold for GDM at visit 1 and were excluded. In total, data from 66 patients were included for analysis (5 Did Not Attend). Visit 1 hormone comparisons were carried out between 51 who remained NGT and 15 who progressed to GDM at visit 2. There were no significant differences at each time point in ROC AUC between the two groups for total and intact proinsulin and insulin. However, there were significant differences observed in C-peptide ROC AUC at 30 (p=0.041) and 60 min (p=0.003) between the two groups.ConclusionsThis study did not demonstrate significant increase in early proinsulin concentrations in patients that developed GDM. However, there were differences in C-peptide concentrations. The COVID-19 pandemic restricted the recruitment of patient numbers and further studies in a larger cohort will be needed to validate these findings.Trial registration numberISRCTN16416602.

The 75-g oral glucose tolerance test (OGTT) remains the optimal diagnostic test for use in pregnancy but needs to be performed in the clinical setting. The GTT@home OGTT device offers the potential to enable patients to perform the test at home using capillary blood samples. This study aimed to determine the accuracy of the GTT@home device compared to the routine National Health Service laboratory reference method using blood samples during an OGTT from pregnant women at high risk of developing gestational diabetes mellitus (GDM). A total of 65 women (aged >18 y), at high risk for GDM (per the National Institute for Health and Care Excellence guidelines) were recruited for this performance evaluation. Following an overnight fast, participants went for a 75-g OGTT. Fasting and 2-hour capillary glucose levels were measured using the GTT@home device with corresponding venous samples measured in the laboratory. The complete data for analysis was available for 61/65 devices. The overall bias for the GTT@home device was +0.16 mmol/L. Correlation analysis of the clinical performance of the two methods using a surveillance error grid showed 79.8% of results in the lowest, 16.9% in the \"slight, lower\" and 2.4% in the \"slight, higher\" risk categories. Only 0.8% were \"moderate, lower\" risk, and none were in any higher risk categories. There was agreement in the classification in 54/61 cases. The GTT@home device under-classified 2 cases and over-classified 5 cases. The GTT@home device worked well in a controlled, antenatal clinical setting. Differences in classification observed were generally due to small differences in glucose values close to the diagnostic cut-offs. The GTT@home device shows promise for home testing of glucose tolerance in pregnant women.

Introduction The glucagon-like peptide-1 receptor analogue (GLP-1RA) semaglutide is associated with improvements in glycaemia and cardiovascular risk factors in clinical trials. The aim of this study was to examine the real-world impact of semaglutide administered by injection in people with type 2 diabetes (T2D) across three secondary care sites in Wales. Methods A retrospective evaluation of 189 patients with T2D initiated on semaglutide between January 2019 and June 2020 with at least one follow-up visit was undertaken. Results At baseline, participants had a mean age of 61.1 years, mean glycated haemoglobin (HbA1c) of 77.8 mmol/mol (9.3%) and mean body weight of 101.8 kg. At 6 and 12 months of follow-up, mean HbA1c reductions of 13.3 mmol/mol (1.2%) and 16.4 mmol/mol (1.5%), respectively, were observed, and mean weight loss at 6 months was 3.0 kg (all p  < 0.001). At 12 months, there were significant reductions in total cholesterol (0.5 mmol/L) and alanine transaminase (4.8 IU/L). Patients naïve to GLP-1RAs or with higher baseline HbA1c at baseline had greater glycaemic reductions, although clinically significant HbA1c reductions were also observed in those who switched from other GLP-1RAs, whose body mass index was < 35.0 and > 35.0 kg/m 2 or who had lower baseline HbA1c. Semaglutide was generally well tolerated, although adverse-effects limited use in 18 patients (9.5%). Conclusion Semaglutide provided clinically and statistically significant reductions in HbA1c, body weight, lipids and liver enzymes.

Objective Examine the health and economic impact of extending screening intervals in people with Type 2 diabetes (T2DM) and Type 1 diabetes (T1DM) without diabetes-related retinopathy (DR). Setting Diabetic Eye Screening Wales (DESW). Study design Retrospective observational study with cost-utility analysis (CUA) and Decrementai Cost-Effectiveness Ratios (DCER) study. Intervention Biennial screening versus usual care (annual screening). Inputs Anonymised data from DESW were linked to primary care data for people with two prior screening events with no DR. Transition probabilities for progression to DR were estimated based on a subset of 26,812 and 1232 people with T2DM and T1DM, respectively. DCER above £20,000 per QALY was considered cost-effective. Results The base case analysis DCER results of £71,243 and £23,446 per QALY for T2DM and T1DM respectively at a 3.5% discount rate and £56,822 and £14,221 respectively when discounted at 1.5%. Diabetes management represented by the mean HbA1c was 7.5% for those with T2DM and 8.7% for T1DM. Sensitivity analysis Extending screening to biennial based on HbA1c, being the strongest predictor of progression of DR, at three levels of HbA1c 6.5%, 8.0% and 9.5% lost one QALY saving the NHS £106,075; £58,653 and £31,626 respectively for T2DM and £94,696, £37,646 and £11,089 respectively for T1DM. In addition, extending screening to biennial based on the duration of diabetes > 6 years for T2DM per QALY lost, saving the NHS £54,106 and for 6-12 and > 12 years for T1DM saving £83,856, £23,446 and £13,340 respectively. Conclusions Base case and sensitivity analyses indicate biennial screening to be cost-effective for T2DM irrespective of HbA1c and duration of diabetes. However, the uncertainty around the DCER indicates that annual screening should be maintained for those with T1DM especially when the HbA1c exceeds 80 mmol/mol (9.5%) and duration of diabetes is greater than 12 years.

IntroductionGestational diabetes mellitus (GDM) is a common metabolic disorder occurring in up to 10% of pregnancies in the western world. Most women with GDM are asymptomatic; therefore, it is important to screen, diagnose and manage the condition as it is associated with an increased risk of maternal and perinatal complications. Diagnosis of GDM is made in the late second trimester or early third trimester because accurate diagnosis or risk stratification in the first trimester is still lacking. An increase in serum proinsulin may be seen earlier in pregnancy and before a change in glycaemic control can be identified. This study will aim to establish if fasting proinsulin concentrations at 16–18 weeks gestation will help to identify or risk stratify high-risk pregnant women with GDM.Methods and analysisThis is a prospective, longitudinal cohort study. Two oral glucose tolerance tests will be carried out at 16–18 and 24–28 weeks gestation in 200 pregnant women with at least one risk factor for GDM (body mass index>30 kg/m2, previous macrosomic baby (>4.5 kg), previous gestational diabetes, first degree relative with type 2 diabetes mellitus) recruited from antenatal clinics. Blood samples will be taken fasting and at 30 min, 1 and 2 hours following the 75 g glucose load. In addition, a fasting blood sample will be taken 6-weeks post delivery. All samples will be analysed for glucose, insulin, C peptide and proinsulin. Recruitment began in November 2017. Optimal cut-off points for proinsulin to diagnose gestational diabetes according to National Institute for Health and Care Excellence (2015) criteria will be established by the receiver operating characteristic plot and sensitivity and specificity will be calculated to assess the diagnostic accuracy of proinsulin at 16–18 weeks gestation.Ethics and disseminationThis study received ethical approval from the Wales Research Ethics Committee (Panel 6) (Ref. 17/WA/0194). Data will be presented at international conferences and published in peer-reviewed journals.Trial registration number ISRCTN16416602; Pre-results.

OBJECTIVE:--Our objectives were to determine the prevalence of previously undiagnosed abnormal glucose tolerance, i.e., diabetes and impaired glucose tolerance (IGT) in patients with acute coronary syndrome and to assess the utility of admission and fasting glucose in identifying diabetes in these patients. RESEARCH DESIGN AND METHODS--Glycemic status was characterized on the basis of admission plasma glucose (APG), fasting plasma glucose (FPG), and an oral glucose tolerance test (OGTT) in 140 patients admitted to the hospital with acute coronary syndrome, who were not known to have diabetes (mean ± SD age 67.3 ± 13.4 years; 79% men). OGTTs were performed on days 5-7 after admission. RESULTS:--The prevalences of diabetes and IGT were 27 and 39%, respectively, according to OGTT criteria. Receiver operating characteristic curves showed that the area under the curve for diagnosing diabetes was 0.83 (P < 0.001) for FPG, 0.79 (P < 0.001) for APG, and 0.84 (P < 0.001) for FPG and APG applied in combination. A FPG cutoff >=5.6 mmol/l (100 mg/dl) and/or APG >=7.8 mmol/l (140 mg/dl) yielded a sensitivity of 89.5% and a positive predictive value of 43.6% for detecting diabetes. CONCLUSIONS:--A high prevalence of abnormal glucose tolerance was seen in patients with acute coronary syndrome. The combination of FPG >=5.6 mmol/l (100 mg/dl) and/or APG >=7.8 mmol/l (140 mg/dl) was highly sensitive for identifying diabetes. Although weakly specific, this simple algorithm could offer a practical initial screening tool at the acute setting in the high-risk population with acute coronary syndrome.

Effects of Exercise on the Absorption of Insulin Glargine in Patients With Type 1 Diabetes Rajesh Peter , MRCP 1 , Stephen D. Luzio , PHD 1 , Gareth Dunseath , MPHIL 1 , Andy Miles , PHD 2 , Barry Hare , PHD 2 , Karianne Backx , PHD 2 , Vassen Pauvaday , MRCP 1 and David R. Owens , MD 1 1 Diabetes Research Unit, Llandough Hospital, Penarth, South Glamorgan, U.K 2 School of Sport, PE and Recreation, University of Wales Institute, Cardiff, South Glamorgan, U.K Address correspondence and reprint requests to Prof. D.R. Owens, Diabetes Research Unit, First Floor, Academic Centre, Llandough Hospital, Penlan Road, Penarth, South Glamorgan CF64 2XX, Wales, U.K. E-mail: owensdr{at}cf.ac.uk Abstract OBJECTIVE —To study the effects of exercise on the absorption of the basal long-acting insulin analog insulin glargine (Lantus), administered subcutaneously in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS —A total of 13 patients (12 men, 1 woman) with type 1 diabetes on a basal-bolus insulin regimen were studied. 125 I-labeled insulin glargine at the usual basal insulin dose was injected subcutaneously into the thigh on the evening (2100) before the study day on two occasions 1 week apart. Patients were randomly assigned to 30 min intense exercise (65% peak oxygen uptake [ V o 2peak ]) on one of these visits. The decay of radioactive insulin glargine was compared on the two occasions using a thallium-activated Nal gamma counter. Blood samples were collected at regular intervals on the study days to assess plasma glucose and insulin profiles. RESULTS —No significant difference was found in the 125 I-labeled insulin glargine decay rate on the two occasions (exercise vs. no exercise; repeated-measures ANOVA, P = 0.548). As expected, a significant fall in plasma glucose was observed over the exercise period (area under curve above fasting [ΔAUC] glucose: −0.39 ± 0.11 vs. −1.30 ± 0.16 mmol · l −1 · h −1 ; nonexercise vs. exercise; P = 0.001), but insulin levels did not differ significantly on the two occasions (ΔAUC insulin: −2.1 ± 3.9 vs. 1.5 ± 6.2 pmol · l −1 · h −1 ; nonexercise versus exercise; P = 0.507). CONCLUSIONS —An intense 30-min period of exercise does not increase the absorption rate of the subcutaneously injected basal long-acting insulin analog insulin glargine in patients with type 1 diabetes. ΔAUC, area under the curve above fasting Footnotes D.R.O. is a member of the Aventis European Advisory Board and has received consultation fees and research grant funding from Aventis Pharma. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Accepted November 24, 2004. Received July 22, 2004. DIABETES CARE