Rocky Mountain Diabetes and Osteoporosis Center

Somapacitan is a long-acting GH approved for once-weekly treatment of GH deficiency (GHD). This study aims to evaluate the efficacy and tolerability of somapacitan after 3 years of treatment and 2 years after switch from daily GH in children with GHD. Randomized, multi-national, open-labelled, active-controlled parallel-group phase 3 trial, with a 52-week main phase and 3-year safety extension (NCT03811535). Treatment-naïve children with GHD were randomized (2:1) to continuous somapacitan (0.16 mg/kg/week; "soma/soma" group) or daily GH (Norditropin®; 0.034 mg/kg/day) followed by somapacitan (0.16 mg/kg/week; "switch" group). Of 200 participants, 188 completed 3 years of treatment. Sustained growth was observed in both groups. At week 156, mean (SD) height velocity (HV) between weeks 104 and 156 was 7.4 (1.5) cm/year in the soma/soma group and 7.8 (1.4) cm/year in the switch group. At week 156, the soma/soma and switch groups had reached a mean (SD) height SD score (HSDS) of -0.95 (0.98) and -1.08 (0.93), respectively, and were approaching the mean mid-parental HSDS of -0.74 (for both groups). Mean total insulin-like growth factor I (IGF-I) SDS during year 3 was similar between groups and within normal range (-2.0 to +2.0). Bioactive IGF-I and bioactive IGF-I to IGF-I ratio were similar between groups. Somapacitan was well tolerated, with low proportions reporting injection-site reactions. Sustained efficacy and tolerability were observed for continuous somapacitan treatment for 3 years, and for 2 years after the switching from daily GH treatment. HSDS in both groups was approaching mean mid-parental HSDS. NCT03811535.

IntroductionWe have evaluated the performance of the FreeStyle Libre® 3 continuous glucose monitoring system (FSL3) compared to (1) the venous plasma reference for participants aged ≥ 6 years and (2) the fingerstick capillary blood glucose (BG) reference for pediatric participants aged 4 and 5 years. The analytical performance of the third-generation factory-calibrated FSL3 CGM system was compared to the plasma venous blood glucose reference using the YSI 2300 STAT PLUS Glucose and Lactate Analyzer (the YSI reference) and the self-monitoring blood glucose (SMBG) reference for participants aged ≥ 6 years and participants aged 4 and 5 years, respectively.MethodsA total of 108 participants aged ≥ 4 years with type 1 or type 2 diabetes from four sites in the USA were enrolled in the study. The data of 100 participants were ultimately evaluated. Adult participants (aged ≥ 18 years) participated in three in-clinic sessions, and pediatric participants (aged 4–17 years) participated in up to two in-clinic sessions, all stratified to provide data for days 1, 2, 3, 7, 8, 9, 12, 13 or 14 of sensor wear. Performance evaluation included accuracy measures, such as proportion of CGM values that fell within ± 20% or ± 20 mg/dL (1.1 mmol/L) of the reference glucose values, and difference measures, such as the mean absolute relative difference (MARD) between the CGM and reference values.ResultsData from the 100 study participants were analyzed. The overall MARD was 7.8%, and 93.4% of the CGM values were within ± 20% or ± 20 mg/dL of the YSI reference for participants aged ≥ 6 years, with 6845 CGM-YSI matched pairs. The performance was stable over the 14-day wear period. For participants aged 4–5 years, MARD was 10.0%, and 88.9% of the CGM values were within 20%/20 mg/dL compared to a SMBG reference. No serious adverse events were reported.ConclusionsThe FSL3 CGM system demonstrated accurate performance across the dynamic glycemic range during the 14-day sensor wear period.

Background: The COVID-19 pandemic and the rapid expansion of telemedicine have increased the need for accurate and reliable capillary hemoglobin A1c (HbA1c) testing. Nevertheless, validation studies of commercially available products suitable for home use have been in short supply. Methods: Three commercial home-use capillary blood sample HbA1c tests (Home Access, CoreMedica, and A1cNow+) were evaluated in 219 participants with type 1 or type 2 diabetes (4-80 years years of age, HbA1c 5.1%-13.4% [32-123 mmol/mol]) at four clinical sites. Comparisons were made between HbA1c measurements from the commercial tests and paired venous samples for which HbA1c was measured at two central reference laboratories. The primary outcome was percentage of commercial HbA1c values within 5% of the corresponding reference values. Results: HbA1c values were within 5% (relative difference) of paired reference values for 82% of Home Access samples, 29% of CoreMedica samples, and 46% of A1cNow+ samples. Absolute differences were within 0.3% of the reference value for 75% of Home Access samples, 28% of CoreMedica samples, and 44% of A1cNow+ samples and exceeded 0.5% for 8%, 55%, and 37%, respectively. Conclusions: None of the commercial home-use HbA1c tests produced the National Glycohemoglobin Standardization Program goal of ≥90% measurements within 5% of a DCCT venous reference. However, the Home Access product performed substantially better than the CoreMedica or A1cNow+ products. Telemedicine is likely to persist as a mainstay of diabetes care well after the COVID-19 era. As such, accurate home-based HbA1c assessment represents an urgent need for the diabetes community.

Background Efficacy and safety of novel dual GIP/GLP-1 receptor agonist tirzepatide versus insulin glargine was assessed in adults with type 2 diabetes inadequately controlled on metformin, sulfonylurea, and/or SGLT-2i and increased cardiovascular risk.

In this study, we evaluated the analytical performance of the second-generation factory-calibrated FreeStyle Libre Flash Glucose Monitoring (FreeStyle Libre 2) System compared to plasma venous blood glucose reference, Yellow Springs Instrument 2300 (YSI). The study enrolled participants aged four and above with type 1 or type 2 diabetes at seven sites in the United States. Adult participants (18+ years) participated in three in-clinic sessions and pediatric participants (4-17 years) participated in up to two in-clinic sessions stratified to provide data for days 1, 2, 3, 7, 8, 9, 12, 13, or 14 of sensor wear. Participants aged 11+ underwent supervised glycemic manipulation during in-clinic sessions to achieve glucose levels across the measurement range of the System. Performance evaluation included accuracy measures such as the proportion of continuous glucose monitoring (CGM) values that were within ±20% or ±20 mg/dL of reference glucose values, and bias measures such as the mean absolute relative difference (MARD) between CGM and reference values. Data from the 144 adults and 129 pediatric participants were analyzed. Percent of sensor results within ±20%/20 mg/dL of YSI reference were 93.2% and 92.1%, and MARD was 9.2% and 9.7% for the adults and pediatric participants, respectively. The System performed well in the hypoglycemic range, with 94.3% of the results for the adult population and 96.1% of the data for pediatric population being within 15 mg/dL of the YSI reference. The time lag was 2.4 ± 4.6 minutes for adults and 2.1 ± 5.0 minutes for pediatrics. The System demonstrated improved analytical accuracy performance across the dynamic range during the 14-day sensor wear period as compared to the previous-generation device.NCT#: NCT03607448 and NCT03820050.

Venous thromboembolism has become an increasingly recognized clinical entity in children over the past decade. Recently, important efforts have been made to track post thrombotic outcomes. The present review discusses the knowledge gained from seminal studies in the field over the past decade, with particular emphasis on the findings of numerous published reports on outcomes of various types of venous thromboembolism in the pediatric literature from January 2003 to January 2005. Large cohort studies involving acute venous thromboembolism of all types in children have recently confirmed a rather low frequency of recurrent venous thromboembolism, but have shown a lack of thrombus resolution following standard-duration anticoagulant therapy in as many as 50% of patients. In addition, the development of the post thrombotic syndrome has been demonstrated in greater than one third of children with venous thromboembolism involving the extremities. Persistent thrombosis despite adequate anticoagulation has been independently associated with complete vaso-occlusion at diagnosis. Furthermore, the presence of elevated levels of factor VIII and D-dimer either at diagnosis or following three to six months anticoagulation has now been defined as a predictor of adverse long-term outcomes of pediatric thrombosis. This body of work indicates that the various forms of venous thromboembolism in children are in general associated with a considerable degree of adverse outcomes, particularly in the form of venous thromboembolism-related mortality, recurrent thromboembolism, and development of post thrombotic syndrome. Advances in the prediction of post thrombotic outcomes have begun, and must continue to facilitate a risk-stratified approach to antithrombotic management in children, and to ultimately achieve meaningful improvements in long-term outcomes.

Severe genetic protein C deficiency is rare and is associated with severe, often fatal thrombosis. The authors report the use of recombinant activated protein C (APC) to treat an episode of purpura fulminans (PF) in a teenage girl with severe protein C deficiency who had developed anaphylaxis to fresh-frozen plasma that was given in the past to treat recurrent episodes of PF. Concomitant with an infusion of APC, 20 microg/kg/h for 10 hours, a d-dimer level that was markedly positive (6,450 ng/mL) prior to the onset of PF decreased to 847 ng/mL following the APC. The teenager was treated with heparin along with warfarin for four days until the INR was more than 3.5 and the d-dimer level was less than 230 ng/mL. At the end of the APC infusion all skin lesions of PF were resolved. There were no adverse reactions to APC. APC was safe and effective for treatment of PF in severe genetic protein C deficiency.

We hypothesized that magnetic resonance imaging (MRI) scans taken prior to radiosynoviorthesis may be predictive of response to the procedure in persons with haemophilia. Specifically, response would be inversely related to the severity of synovial hyperplasia. Radiosynoviorthesis was administered to 21 joints with recurrent haemorrhage (target joints). A detailed self-report of haemorrhage history, joint evaluation with scoring according to the World Federation of Haemophilia orthopaedic joint and pain scales, plain radiographs, and MRI studies of the joints were performed pre- and post-radiosynoviorthesis. To augment comparison of the MRI findings to those assessed using the Arnold-Hilgartner and Pettersson scales, a provisional MRI scale for evaluation of haemophilic arthropathy was designed. We found the MRI findings prior to the procedure were not predictive of clinical response; independent of the severity of synovial hyperplasia, most joints bled less and showed improvement by the WFH orthopaedic score. There was generally no change in the severity of synovial hyperplasia after the procedure. We conclude that MRI evaluation is not routinely indicated prior to radiosynoviorthesis.