Autoimmune retinopathy in a patient with smoldering multiple myeloma: a case report.

PURPOSE: Multiple myeloma (MM) is a plasma cell dyscrasia leading to proliferation of monoclonal plasma cells. Ocular involvement in multiple myeloma is uncommon but can occur. The ocular manifestations of MM may include the cornea, uvea, and retinal vasculature. We present a rare case of autoimmune retinopathy associated with smoldering MM. CASE: A 76-year-old female with no significant past medical or ocular history presented with four months of worsening vision, difficulty with night driving, and loss of peripheral vision. Examination was notable for pallor of the optic nerves and vascular attenuation. Visual field testing demonstrated significant and progressive field loss in both eyes. An electroretinogram was extinguished under all conditions. Serum protein electrophoresis showed a significant elevation of IgG with an M-spike, and a subsequent bone marrow biopsy was performed showing 12.5% plasma cells, consistent with the diagnosis of MM. CAR antibody testing was positive for anti-enolase, anti-GAPDH, and anti-Rab6 antibodies, consistent with autoimmune retinopathy. DISCUSSION: Autoimmune retinopathy associated with MM is exceedingly rare. Management of this condition is challenging, as treatment of the underlying disease does not often lead to improvement in visual symptoms. Ultimately, visual prognosis is very poor, and both patients and clinicians should be aware of the guarded visual potential. CONCLUSION: The association of autoimmune retinopathy with multiple myeloma is rare. It is crucial for physicians to be aware of such manifestations to ensure timely and appropriate diagnosis and management for patients.

Patient-Reported Outcomes Improve with a Virtual Diabetes Care Model that Includes Continuous Glucose Monitoring.

Background: The objective was to examine patient-reported outcomes (PROs) associated with access to a virtual clinic model for diabetes care. Methods: Adults with diabetes (N = 234) received virtual care, including support for continuous glucose monitoring (CGM) over a 6-month study period. Care was led by a Certified Diabetes Care and Education Specialist and focused on optimizing self-management skills and response to glucose values observed on CGM. After 6 months of CGM use and access to diabetes education, participants could opt in to another 6 months of follow-up with access to the virtual care team. Participants completed PRO surveys and had health and glycemic measures collected at baseline, 3, 6, and 12 months. Results: Participants with type 1 diabetes (N = 160) were 44 ± 14 years and had mean baseline HbA1c of 61 mmol/mol (7.7%). Participants with type 2 diabetes (N = 74) were 52 ± 12 years and had mean baseline HbA1c of 66 mmol/mol (8.2%). Compared with baseline levels, at 6 months participants experienced less depression, diabetes distress, and hypoglycemic fears while also experiencing greater satisfaction with glucose monitoring, diabetes technology and specifically with CGM, and confidence for managing hypoglycemic (p < 0.05). For participants with type 1 diabetes, more time in the target range for glucose levels (70-180 mg/dL) was associated with less depression, diabetes distress, and hypoglycemic fears. Conclusions: PROs improved for adults with diabetes utilizing virtual diabetes care, including support for CGM use. Paired with the glycemic improvements observed in this virtual clinic study, there were robust benefits on the quality of life of adults with diabetes. ClinicalTrials.gov Identifier: NCT04765358.

Autistic Characteristics, Cognitive Impairment, and Sex as Predictors of Anxiety and Depression among Autistic Youth.

Although it is well established that autistic youth are at high risk for anxiety and depression, factors associated with heightened risk within this population are poorly understood. The purpose of this study was to evaluate whether autistic characteristics and cognitive impairment interact to predict anxiety and depression symptoms, and whether the impacts of autistic characteristics and cognitive impairment on anxiety and depression differ for male and female children. Participants comprised 7989 youth (M = 11.23 years) enrolled in SPARK, a national cohort of autistic individuals. Autistic characteristics were assessed via the Social Communication Questionnaire. Anxiety and depression were assessed via the Child Behavior Checklist. Linear regressions were conducted to examine associations between autistic characteristics, cognitive impairment, and symptoms and to test for interactions. The effect of parent-reported autistic characteristics on anxiety was stronger for males than for females, while the effect of cognitive impairment on anxiety was stronger for females than for males. A different pattern was observed for depression. The effect of autistic characteristics on depression was the same for males and females, while cognitive impairment was not associated with depression per parent report. Findings indicate that both male and female children with high levels of autistic characteristics are susceptible to experiencing anxiety and depression, and that autistic female children with intact cognitive abilities are uniquely vulnerable to experiencing anxiety based on parent report. Results have implications for the prevention of internalizing problems in autistic youth, and highlight future directions for longitudinal work examining mechanisms of comorbidity.

Health care costs and utilization of progressive fibrosing lung disease by underlying interstitial lung disease type.

BACKGROUND: Fibrosing interstitial lung disease (ILD) encompasses more than 200 diverse pulmonary disorders, of which up to 40% become progressive. The 4 underlying ILD types most likely to result in progression are unclassified ILD/idiopathic interstitial pneumonia (IIP), autoimmune ILDs, exposure-related ILD/hypersensitivity pneumonitis, and sarcoidosis. OBJECTIVE: To compare health care resource utilization (HCRU) and costs among patients with fibrosing ILD that has progressed ("progressive" fibrosing cohort) vs patients whose fibrosis did not meet criteria set for progression ("not yet progressed" cohort). METHODS: This was a noninterventional study of commercial enrollees and Medicare Advantage with Part D beneficiaries, which used administrative claims data for the period from October 1, 2015, through May 31, 2021. Adult patients (aged ≥18 years) with fibrosing ILD and 12 months of continuous health plan enrollment were included. Patients with idiopathic pulmonary fibrosis, baseline ILD diagnoses, or missing demographic data were excluded. Patients were first classified according to the underlying type of fibrosing ILD. For statistical analyses of outcomes, 2 cohorts were compared within each subtype: progressive fibrosing ILD vs not yet progressed ILD. The final study population included propensity score-matched (PSM) patients (1:1) based on pre-ILD baseline demographic and clinical characteristics. HCRU categories included inpatient hospitalization counts and the number of inpatient days and total costs (in 2021 US dollars), analyzed descriptively and weighted by the per-patient-per-month cost. Lin's regression was used to predict 12-month total cost estimates for comparison by cohort. RESULTS: The distribution by underlying conditions was as follows: autoimmune ILD (n = 4,156), HP (n = 8,181), sarcoidosis (n = 775), and unclassified ILD/IIP (n = 18,635). After PSM, pre-ILD baseline variables were generally well balanced between the progressive and not yet progressed fibrosing ILD cohorts. For all underlying subtypes of ILD, patients in the progressive cohort had significantly more utilization and higher costs compared with patients in the not yet progressed cohort. Progressive cohorts had significantly higher adjusted rates of inpatient days among patients with at least 1 inpatient stay compared with the not yet progressed cohorts (all P < 0.01). In addition, the progressive cohorts had significantly higher adjusted 12-month total costs, with the differences ranging from $24,493 to $55,072 (all comparisons P < 0.001). CONCLUSIONS: Irrespective of underlying ILD type, patients with progressive fibrosing ILD had significantly increased HCRU and cost relative to those whose fibrosing ILD had not yet progressed.

Outcomes of Patients with COPD Treated with ICS/LABA Before and After Initiation of Single-Inhaler Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI).

INTRODUCTION: Triple therapy (fluticasone furoate/umeclidinium/vilanterol; FF/UMEC/VI) has been shown to improve symptoms and reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. This real-world study compared exacerbation rates and healthcare resource utilization (HCRU) before and after initiation of FF/UMEC/VI in patients with COPD previously treated with inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA). METHODS: This retrospective cohort study included commercial and Medicare Advantage with Part D administrative claims data from September 01, 2016, to March 31, 2020, of patients diagnosed with COPD. The index date was the date of the first FF/UMEC/VI claim (September 2017-March 2019). The 12 months prior to index (baseline) were used to assess patient characteristics and outcomes; the 12 months following index (follow-up) were used to assess study outcomes. All patients had ≥ 30 consecutive days' supply of any ICS/LABA dual therapy during the 12 months prior to FF/UMEC/VI initiation. Subgroup analyses included patients with ≥ 30 consecutive days' supply of budesonide/formoterol (BUD/FORM) during baseline. Analyses of patients with ≥ 1 COPD exacerbation during baseline were reported as well. RESULTS: The overall population included 1449 patients (mean age 70.75 years; 54.18% female), of whom 540 were patients in the BUD/FORM subgroup. Significantly fewer patients experienced any exacerbation during follow-up versus baseline (overall population 53.49% vs 62.59%; p < 0.001; BUD/FORM subgroup 55.00% vs 62.41%; p = 0.004). Effects on exacerbation reduction were more pronounced among patients with ≥ 1 exacerbation during baseline. Lower COPD-related HCRU was observed during the follow-up compared with baseline for both the overall population and the BUD/FORM subgroup. CONCLUSION: Patients with COPD treated with ICS/LABA during baseline, including patients specifically treated with BUD/FORM and those with a history of ≥ 1 exacerbation, had fewer COPD exacerbations and lower COPD-related HCRU after initiating FF/UMEC/VI.

Highly selective pressure-dependent (transfer) hydrogenative depolymerization of polybutylene succinate.

Ru-MACHO®-BH is an effective catalyst for controlled depolymerization of polybutylene succinate. Under low pressure hydrogen the catalyst produces gamma-butyrolactone via a novel transfer hydrogenation wherein dehydrogenation and hydrogenation deconstruct the polymer chain. Simply increasing the hydrogen pressure selectively generates 1,4-butanediol.

Outcomes Following Initiation of Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol versus Multiple-Inhaler Triple Therapy Among Medicare Advantage with Part D Beneficiaries and Those Commercially Enrolled for Health Care Insurance in the United States.

Purpose: Patients with chronic obstructive pulmonary disease (COPD) have been shown to benefit from triple therapy commonly delivered by multiple-inhaler triple therapy (MITT); however, the complexity of MITT regimens may decrease patient adherence. Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), a once-daily single-inhaler triple therapy (SITT), became available in the United States (US) in 2017, but real-world data comparing outcomes for SITT versus MITT are currently limited. This study compared outcomes among patients with COPD initiating MITT versus SITT with FF/UMEC/VI who were either Medicare Advantage with Part D (MAPD) beneficiaries or commercial enrollees in the US. Methods: Retrospective study using administrative claims data from the Optum Research Database for patients with COPD who initiated FF/UMEC/VI or MITT between September 1, 2017, and March 31, 2019 (index date: first pharmacy claim for FF/UMEC/VI cohort; earliest day of ≥30 consecutive days-long period of overlap in the day's supply of all triple therapy components for MITT cohort). COPD exacerbations, adherence to triple therapy, and all-cause and COPD-related health care resource utilization (HCRU) and costs were compared between FF/UMEC/VI and MITT initiators. Results: In total, 4659 FF/UMEC/VI initiators and 9845 MITT initiators for the MAPD population, and 821 FF/UMEC/VI initiators and 1893 MITT initiators for the commercial population were included in the study. MAPD beneficiaries initiating FF/UMEC/VI had a significantly lower annual rate of severe exacerbations compared to MITT initiators (0.26 vs 0.29; p=0.014). They also had a significantly higher mean adherence (proportion of days covered) (0.51 vs 0.37; p<0.001) and significantly lower all-cause and COPD-related inpatient stays compared to MITT initiators ([32.02% vs 34.27%; p=0.017], [16.09% vs 17.72%; p=0.037]). Trends were similar among the commercial population, but the results were not statistically significant. Conclusion: FF/UMEC/VI initiators had significantly fewer severe exacerbations, higher triple therapy adherence, and lower HCRU costs compared to MITT initiators for MAPD beneficiaries.

Association of Short-Term Increases in Ambient Fine Particulate Matter With Hospitalization for Asthma or COPD During Wildfire Season and Other Time Periods.

BACKGROUND: Short-term increases in air pollution are associated with poor asthma and COPD outcomes. Short-term elevations in fine particulate matter (PM2.5) due to wildfire smoke are becoming more common. RESEARCH QUESTION: Are short-term increases in PM2.5 and ozone in wildfire season and in winter inversion season associated with a composite of emergency or inpatient hospitalization for asthma and COPD? STUDY DESIGN AND METHODS: Case-crossover analyses evaluated 63,976 and 18,514 patients hospitalized for primary discharge diagnoses of asthma and COPD, respectively, between January 1999 and March 2022. Patients resided on Utah's Wasatch Front where PM2.5 and ozone were measured by Environmental Protection Agency-based monitors. ORs were calculated using Poisson regression adjusted for weather variables. RESULTS: Asthma risk increased on the same day that PM2.5 increased during wildfire season (OR, 1.057 per + 10 µg/m3; 95% CI, 1.019-1.097; P = .003) and winter inversions (OR, 1.023 per +10 µg/m3; 95% CI, 1.010-1.037; P = .0004). Risk decreased after 1 week, but during wildfire season risk rebounded at a 4-week lag (OR, 1.098 per +10 µg/m3; 95% CI, 1.033-1.167). Asthma risk for adults during wildfire season was highest in the first 3 days after PM2.5 increases, but for children, the highest risk was delayed by 3 to 4 weeks. PM2.5 exposure was weakly associated with COPD hospitalization. Ozone exposure was not associated with elevated risks. INTERPRETATION: In a large urban population, short-term increases in PM2.5 during wildfire season were associated with asthma hospitalization, and the effect sizes were greater than for PM2.5 during inversion season.

Continuous Glucose Monitoring Prediction of Gestational Diabetes Mellitus and Perinatal Complications.

Objective: To assess the performance of continuous glucose monitoring (CGM)-measured glycemic metrics in predicting development of gestational diabetes mellitus (GDM) and select perinatal complications. Research Methods: In a prospective observational study, CGM data were collected from 760 pregnant females throughout gestation after study enrollment. GDM was diagnosed using the oral glucose tolerance test (OGTT) at 24-34 weeks of gestation. Predictive models were built using logistic and elastic net regression. Predictive performance was assessed by the area under the receiver-operating characteristic (AUROC) curve. Results: The AUROCs of using second trimester percent time >140 mg/dL (TA140) and week 13-14 TA140 in predicting GDM were 0.81 and 0.74, respectively. The AUROCs for predicting large-for-gestational-age (LGA) births and hypertensive disorders of pregnancy (HDP) using second trimester TA140 were both 0.58. When matching the specificity of OGTT, a model using TA140 in weeks 13-14 achieved similar sensitivity to OGTT in predicting HDP (13% vs. 10%, respectively) and LGA (6% for both methods). Elastic net also demonstrated similar AUROC and diagnostic performance with no meaningful improvement by using multiple predictors. Conclusion: CGM-measured hyperglycemic metrics such as TA140 predicted GDM with high AUROCs as early as 13-14 weeks of gestation. These metrics were also similar statistically to the OGTT at 24-34 weeks in predicting perinatal complications, although sensitivity was low for both. CGM could potentially be used as an early screening tool for elevated hyperglycemia during gestation, which could be used in addition to or instead of the OGTT.

Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

OBJECTIVE: We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments. RESEARCH DESIGN AND METHODS: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) of adults with T2DM of <10 years' duration, HbA1c 6.8-8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or the dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean [SD] age 58.0 [10.2] years, 32% female, 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every 6 months. Analyses examined differences at 1 year and over the 3-year follow-up. RESULTS: Across treatments, diabetes distress (-0.24, P < 0.0001) and depressive symptoms (-0.67, P < 0.0001) decreased over 1 year. Diabetes distress was lower at 1 year for the glargine group than for the other groups combined (-0.10, P = 0.002). Diabetes distress was also lower for liraglutide than for glimepiride or sitagliptin (-0.10, P = 0.008). Over the 3-year follow-up, there were no significant group differences in total diabetes distress; interpersonal diabetes distress remained lower for those assigned to liraglutide. No significant differences were observed for depressive symptoms. CONCLUSIONS: Contrary to expectations, this randomized trial found no evidence for a deleterious effect of basal insulin on emotional distress. Glargine lowered diabetes distress modestly at 1 year rather than increasing it. Liraglutide also reduced diabetes distress at 1 year. Results can inform treatment decisions for adults with early T2DM.

Continuous Glucose Monitoring-Derived Differences in Pregnancies With and Without Adverse Perinatal Outcomes.

OBJECTIVE: To evaluate whether continuous glucose monitoring (CGM)-derived glycemic patterns observed throughout pregnancy were associated with adverse perinatal outcomes, specifically fetal growth disorders and hypertensive disorders of pregnancy (HDP). METHODS: We conducted a prospective observational study of individuals with viable singleton pregnancies and screening hemoglobin A1c levels less than 6.5%. Those with preexisting diabetes were excluded. Enrollment occurred at the earliest gestational age before 17 weeks. Participants wore blinded continuous glucose monitors consecutively as willing until delivery. Those with at least 14 days of CGM data were included in analysis. Rates of large-for-gestational-age (LGA) neonates, small-for-gestational age (SGA) neonates, and HDP were assessed. Continuous glucose monitoring-derived glycemic metrics were calculated, including mean glucose level and percent time above and below thresholds. Two-sample t tests were used to compare glycemic metrics between participants with and without adverse perinatal outcomes. RESULTS: Of 937 participants enrolled, 760 met inclusion criteria. Those delivering LGA neonates or who were diagnosed with HDP had higher mean glucose levels (102±9 vs 100±8, P=.01 and 103±8 vs 99±8, P<.001) and spent more time above 120 mg/dL (median 16% vs 12%, P=.006, and 16% vs 12%, P<.001, respectively) and above 140 mg/dL (median 3.9% vs 2.8%, P=.006, and 3.5% vs 2.8%, P<.001, respectively) throughout gestation than those without these outcomes. These findings were present regardless of gestational diabetes mellitus status. Participants with SGA neonates had lower mean glucose levels (97±7 vs 101±8, P=.01) and spent less time above 140 mg/dL (median 1.6% vs 2.3%, P=.01) and more time below 63 mg/dL (median 3.0% vs 2.3%, P=.02) than those without SGA neonates. CONCLUSION: Individuals with LGA neonates or HDP exhibit a slightly higher mean glucose levels and spend more time hyperglycemic in early pregnancy than those who do not experience these outcomes.

Glucose levels measured with continuous glucose monitoring in uncomplicated pregnancies.

INTRODUCTION: To characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c <5.7% (<39 mmol/mol) in early pregnancy, and without a large-for-gestational-age birth, hypertensive disorders of pregnancy, or gestational diabetes mellitus (ie, abnormal oral glucose tolerance test). RESEARCH DESIGN AND METHODS: Two sites enrolled 937 pregnant individuals aged 18 years and older prior to reaching 17 gestational weeks; 413 had an uncomplicated pregnancy (mean±SD body mass index (BMI) of 25.3±5.0 kg/m2) and wore Dexcom G6 continuous glucose monitoring (CGM) devices throughout the observed gestational period. Mealtimes were voluntarily recorded. Glycemic levels during gestation were characterized using CGM-measured glycemic metrics. RESULTS: Participants wore CGM for a median of 123 days each. Glucose levels were nearly stable throughout all three trimesters in uncomplicated pregnancies. Overall mean±SD glucose during gestation was 98±7 mg/dL (5.4±0.4 mmol/L), median per cent time 63-120 mg/dL (3.5-6.7 mmol/L) was 86% (IQR: 82-89%), median per cent time <63 mg/dL (3.5 mmol/L) was 1.8%, median per cent time >120 mg/dL (6.7 mmol/L) was 11%, and median per cent time >140 mg/dL (7.8 mmol/L) was 2.5%. Mean post-prandial peak glucose was 126±22 mg/dL (7.0±1.2 mmol/L), and mean post-prandial glycemic excursion was 36±22 mg/dL (2.0±1.2 mmol/L). Higher mean glucose levels were low to moderately associated with pregnant individuals with higher BMIs (103±6 mg/dL (5.7±0.3 mmol/L) for BMI ≥30.0 kg/m2 vs 96±7 mg/dL (5.3±0.4 mmol/L) for BMI 18.5-<25 kg/m2, r=0.35). CONCLUSIONS: Mean glucose levels and time 63-120 mg/dL (3.5-6.7 mmol/L) remained nearly stable throughout pregnancy and values above 140 mg/dL (7.8 mmol/L) were rare. Mean glucose levels in pregnancy trend higher as BMI increases into the overweight/obesity range. The glycemic metrics reported during uncomplicated pregnancies represent treatment targets for pregnant individuals.

Personalized Exercise Prescription in Long COVID: A Practical Toolbox for a Multidisciplinary Approach.

Objective: To describe our methodology and share the practical tools we have developed to operationalize a multidisciplinary Long COVID clinic that incorporates progressive, personalized exercise prescription as a cornerstone feature. Background: There is a lack of evidence-based guidance regarding optimal rehabilitation strategies for people with Long COVID. Existing guidelines lack precision regarding exercise dosage. As one of Australia's few established multidisciplinary Long COVID clinics, we describe our novel approach to safely incorporating exercise of both peripheral and respiratory muscles, with essential monitoring and management of post-exertional symptom exacerbation. Methods: Working closely with primary health-care providers, our multidisciplinary team screens referrals for people aged 16 and older with Long COVID. Staff apply a three tier model of triage, dependent on the consumer's presenting problems. Exercise-based interventions necessitate detailed monitoring for post-exertional symptom exacerbation both in the clinic and at home. Personalized exercise prescription includes resistance training at a submaximal threshold (4-6 exercises, 3 days/week); whole-body endurance exercise titrated to the individual's progress, at an intensity 4-6/10 (Rate of Perceived Exertion); and for those limited by dyspnoea, high-intensity inspiratory muscle training using a threshold-based handheld device (30 repetitions per day, ≥50% of their maximum inspiratory pressure). Discussion: We have used these approaches for the past 2 years in 250 consumers with no serious adverse events and promising consumer feedback. Our exercise prescription is less conservative than the methods advocated in international guidelines for people with Long COVID, and these more progressive tools may be valuable in other contexts. Conclusion: In our experience, a multidisciplinary clinic-based approach to safely prescribing progressive exercise in Long COVID is feasible. Both peripheral and inspiratory muscle exercise can be effectively titrated to each individual's symptoms, and careful monitoring for post-exertional symptom exacerbation is crucial.

Long COVID affects 5-10% of people following COVID infection. There is little specific guidance on how exercise can be safely prescribed in Long COVID. This paper is the first to provide a detailed description of an Australian multidisciplinary Long COVID clinic, including specific tools and guidance about how exercise can be prescribed while minimising post-exertional symptom exacerbation. The tools described could be valuable to other health facilities striving to optimise multidisciplinary care for people with Long COVID, incorporating safe exercise prescription.

Continuous Glucose Monitoring Profiles in Pregnancies With and Without Gestational Diabetes Mellitus.

OBJECTIVE: To determine whether continuous glucose monitoring (CGM)-derived glycemic patterns can characterize pregnancies with gestational diabetes mellitus (GDM) as diagnosed by standard oral glucose tolerance test at 24-28 weeks' gestation compared with those without GDM. RESEARCH DESIGN AND METHODS: The analysis includes 768 individuals enrolled from two sites prior to 17 weeks' gestation between June 2020 and December 2021 in a prospective observational study. Participants wore blinded Dexcom G6 CGMs throughout gestation. Main outcome of interest was a diagnosis of GDM by oral glucose tolerance test (OGTT). Glycemic levels in participants with GDM versus without GDM were characterized using CGM-measured glycemic metrics. RESULTS: Participants with GDM (n = 58 [8%]) had higher mean glucose (109 ± 13 vs. 100 ± 8 mg/dL [6.0 ± 0.7 vs. 5.6 ± 0.4 mmol/L], P < 0.001), greater glucose SD (23 ± 4 vs. 19 ± 3 mg/dL [1.3 ± 0.2 vs. 1.1 ± 0.2 mmol/L], P < 0.001), less time in range 63-120 mg/dL (3.5-6.7 mmol/L) (70% ± 17% vs. 84% ± 8%, P < 0.001), greater percent time >120 mg/dL (>6.7 mmol/L) (median 23% vs. 12%, P < 0.001), and greater percent time >140 mg/dL (>7.8 mmol/L) (median 7.4% vs. 2.7%, P < 0.001) than those without GDM throughout gestation prior to OGTT. Median percent time >120 mg/dL (>6.7 mmol/L) and time >140 mg/dL (>7.8 mmol/L) were higher as early as 13-14 weeks of gestation (32% vs. 14%, P < 0.001, and 5.2% vs. 2.0%, P < 0.001, respectively) and persisted during the entire study period prior to OGTT. CONCLUSIONS: Prior to OGTT at 24-34 weeks' gestation, pregnant individuals who develop GDM have higher CGM-measured glucose levels and more hyperglycemia compared with those who do not develop GDM.

GAD65Abs Are Not Associated With Beta-Cell Dysfunction in Patients With T2D in the GRADE Study.

Context: Autoantibodies directed against the 65-kilodalton isoform of glutamic acid decarboxylase (GAD65Abs) are markers of autoimmune type 1 diabetes (T1D) but are also present in patients with Latent Autoimmune Diabetes of Adults and autoimmune neuromuscular diseases, and also in healthy individuals. Phenotypic differences between these conditions are reflected in epitope-specific GAD65Abs and anti-idiotypic antibodies (anti-Id) against GAD65Abs. We previously reported that 7.8% of T2D patients in the GRADE study have GAD65Abs but found that GAD65Ab positivity was not correlated with beta-cell function, glycated hemoglobin (HbA1c), or fasting glucose levels. Context: In this study, we aimed to better characterize islet autoantibodies in this T2D cohort. This is an ancillary study to NCT01794143. Methods: We stringently defined GAD65Ab positivity with a competition assay, analyzed GAD65Ab-specific epitopes, and measured GAD65Ab-specific anti-Id in serum. Results: Competition assays confirmed that 5.9% of the patients were GAD65Ab positive, but beta-cell function was not associated with GAD65Ab positivity, GAD65Ab epitope specificity or GAD65Ab-specific anti-Id. GAD65-related autoantibody responses in GRADE T2D patients resemble profiles in healthy individuals (low GAD65Ab titers, presence of a single autoantibody, lack of a distinct epitope pattern, and presence of anti-Id to diabetes-associated GAD65Ab). In this T2D cohort, GAD65Ab positivity is likely unrelated to the pathogenesis of beta-cell dysfunction. Conclusion: Evidence for islet autoimmunity in the pathophysiology of T2D beta-cell dysfunction is growing, but T1D-associated autoantibodies may not accurately reflect the nature of their autoimmune process.

Expert Panel Recommendations for a Standardized Ambulatory Glucose Profile Report for Connected Insulin Pens.

Background: Connected insulin pens capture data on insulin dosing/timing and can integrate with continuous glucose monitoring (CGM) devices with essential insulin and glucose metrics combined into a single platform. Standardization of connected insulin pen reports is desirable to enhance clinical utility with a single report. Methods: An international expert panel was convened to develop a standardized connected insulin pen report incorporating insulin and glucose metrics into a single report containing clinically useful information. An extensive literature review and identification of examples of current connected insulin pen reports were performed serving as the basis for creation of a draft of a standardized connected insulin pen report. The expert panel participated in three virtual standardization meetings and online surveys. Results: The Ambulatory Glucose Profile (AGP) Report: Connected Insulin Pen brings all clinically relevant CGM-derived glucose and connected insulin pen metrics into a single simplified two-page report. The first page contains the time in ranges bar, summary of key insulin and glucose metrics, the AGP curve, and detailed basal (long-acting) insulin assessment. The second page contains the bolus (mealtime and correction) insulin assessment periods with information on meal timing, insulin-to-carbohydrate ratio, average bolus insulin dose, and number of days with bolus doses recorded. The report's second page contains daily glucose profiles with an overlay of the timing and amount of basal and bolus insulin administered. Conclusion: The AGP Report: Connected Insulin Pen is a standardized clinically useful report that should be considered by companies developing connected pen technology as part of their system reporting/output.